Co-reporter:Dr. Michiel Dusselier;Jong Hun Kang;Dr. Dan Xie;Dr. Mark E. Davis
Angewandte Chemie 2017 Volume 129(Issue 43) pp:13660-13663
Publication Date(Web):2017/10/16
DOI:10.1002/ange.201707452
AbstractA synthetic, fault-free gmelinite (GME) zeolite is prepared using a specific organic structure-directing agent (OSDA), cis-3,5-dimethylpiperidinium. The cis-isomers align in the main 12-membered ring (MR) channel of GME. Trans-isomer OSDA leads to the small-pore zeolite SSZ-39 with the OSDA in its cages. Data from N2-physisorption and rotation electron diffraction provide evidence for the openness of the 12 MR channel in the GME 12×8×8 pore architecture and the absence of stacking faults, respectively. CIT-9 is hydrothermally stable when K+-exchanged, while in the absence of exchange, the material transforms into an aluminous AFI-zeolite. The process of this phase-change was followed by in situ variable temperature powder X-ray diffraction. CIT-9 has the highest Si/Al ratio reported for GME, and along with its good porosity, opens the possibility of using GME in a variety of applications including catalysis.
Co-reporter:Joel E. Schmidt;Stephen K. Brand;Michael W. Deem;Frits Daeyaert;Yanhang Ma;Marat Orazov;Osamu Terasaki;Mark E. Davis
PNAS 2017 Volume 114 (Issue 20 ) pp:5101-5106
Publication Date(Web):2017-05-16
DOI:10.1073/pnas.1704638114
Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis.
Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would
enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples
of a molecular sieve. Enantiopure organic structure directing agents are designed with the assistance of computational methods
and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results
correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electron
microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts.
The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective
adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity
compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).
Co-reporter:Mark A. Deimund, Luke Harrison, Jonathan D. Lunn, Yu Liu, Andrzej Malek, Ramzy Shayib, and Mark E. Davis
ACS Catalysis 2016 Volume 6(Issue 2) pp:542
Publication Date(Web):December 22, 2015
DOI:10.1021/acscatal.5b01450
SSZ-13 materials have been synthesized with varying amounts of Al to produce samples with different concentrations of Brønsted acid sites, and consequently, these SSZ-13 materials contain increasing numbers of paired Al heteroatoms with increasing Al content. These materials were then characterized and tested as catalysts for the methanol-to-olefins (MTO) reaction at 400 °C and 100% methanol conversion under atmospheric pressure. A SAPO-34 sample was also synthesized and tested for comparison. SSZ-13 materials exhibited significant differences in MTO reactivity as Si/Al ratios varied. Reduced Al content (higher Si/Al ratio) and, consequently, fewer paired Al sites led to more stable light olefin selectivities, with a reduced initial transient period, lower initial propane selectivities, and longer catalyst lifetime. To further support the importance of paired Al sites in the formation of propane during this initial transient period, a series of experiments was conducted wherein an H-SSZ-13 sample was exchanged with Cu2+, steamed, and then back-exchanged to the H form. The H-SSZ-13 sample exhibited high initial propane selectivity, while the steamed H-SSZ-13, the Cu2+-exchanged SSZ-13 sample, and the steamed Cu-SSZ-13 sample did not, as expected since steaming selectively removes paired Al sites and Cu2+ exchanges onto these sites. However, when it was back-exchanged to the proton form, the steamed Cu-SSZ-13 sample still exhibited the high initial alkane selectivity and transient period typical of the higher Al content materials. This is attributed to protection of paired Al sites during steaming via the Cu2+ cation. Post-reaction coke analyses reveal that the degree of methylation for each aromatic species increases with increasing Si/Al in SSZ-13. Further, SAPO-34 produces more polycyclic species than SSZ-13 samples. From these data, the paired Al site content appears to be correlated with both MTO reaction behavior and coke species formation in SSZ-13 samples.Keywords: CHA; hydrocarbon pool; methanol-to-olefins; silicoaluminophosphates; zeolite
Co-reporter:Jong Hun Kang, Dan Xie, Stacey I. Zones, Stef Smeets, Lynne B. McCusker, and Mark E. Davis
Chemistry of Materials 2016 Volume 28(Issue 17) pp:6250
Publication Date(Web):August 18, 2016
DOI:10.1021/acs.chemmater.6b02468
The synthesis of the germanosilicate CIT-13, a molecular sieve that is the first to have a two-dimensional (2D) pore system possessing pores that are bounded by 14- and 10-rings, is accomplished using a family of monoquaternary, benzyl-imidazolium organic structure-directing agents (OSDAs) in aqueous media containing fluoride. CIT-13 is prepared using either hydrogen fluoride (HF) or ammonium fluoride (NH4F). The structure refinement suggests that most of the Ge atoms are located in the d4r (double-4-rings) units, and that there are framework disorders in the arrangement of those d4r units. Other characterizations of CIT-13 such as 29Si MAS NMR spectra, Ar-adsorption isotherms, and so forth are presented and compared to those of IM-12 (UTL), a previously reported germanosilicate with 14- and 12-ring pores.
Co-reporter:Marat Orazov and Mark E. Davis
Chemical Science 2016 vol. 7(Issue 3) pp:2264-2274
Publication Date(Web):04 Jan 2016
DOI:10.1039/C5SC03889H
Microporous and mesoporous zincosilicates (e.g., CIT-6, VPI-8, Zn-MFI, and Zn-MCM-41) synthesized in the presence of alkali cations contain two broad types of Zn sites: one that is a dication analog of the monocation ion-exchangeable Al-site in aluminosilicates, while the other resembles isolated Zn sites on amorphous silica. The ratio of these sites varies, depending on the synthesis conditions of the zincosilicate. Post-synthetic strategies based on ion-exchange can alter the site distribution towards either population. Furthermore, post-synthetic introduction of isolated Zn sites of the latter type is possible for materials possessing silanol nests. Both types of sites behave as Lewis acid centers in probe-molecule IR spectroscopy, but have very different catalytic properties. Due to the unusually high adsorption energies of Lewis bases on such materials, Lewis acid catalysis is difficult at low temperatures and in solvents bearing Lewis basic functionality. However, at high temperatures, in hydrocarbon solvents, CIT-6 (Zn-beta) is able to selectively catalyze the Lewis-acid-catalyzed Diels–Alder cycloaddition–dehydration reactions of ethylene with methyl 5-(methoxymethyl)furan-2-carboxylate, a furan that can be derived quantitatively by partial oxidation of biomass-based 5-hydroxymethylfurfural. Additionally, zinc in silica-based molecular sieves is shown here to enable chemistries previously not accessible with framework Sn-, Ti- and Zr-based Lewis acid sites, e.g., the direct production of dimethyl terephthalate by Diels–Alder cycloaddition–dehydration reactions of ethylene and the dimethyl ester of furan-2,5-dicarboxilic acid.
Co-reporter:Yuewei Ji, John Birmingham, Mark A. Deimund, Stephen K. Brand, Mark E. Davis
Microporous and Mesoporous Materials 2016 Volume 232() pp:126-137
Publication Date(Web):15 September 2016
DOI:10.1016/j.micromeso.2016.06.012
•Two 8MR zeolites prepared without using OSDAs are steamed and tested for MTO.•Steaming of RHO and KFI zeolites improves olefin selectivities and lifetimes.•Olefins do not undergo oligomerization reactions at mesoporous or surface acid sites.RHO and KFI-type zeolites are synthesized in the absence of organic structure-directing agents (OSDAs), post-synthetically dealuminated via high temperature (600–800 °C) steam treatments, and evaluated as catalysts for converting methanol-to-light olefins (MTO). The proton forms of the as-made zeolites deactivate rapidly when tested for the MTO reaction (conducted at 400 °C and atmospheric pressure) due to their high aluminum content. Steam treatments lead to improvements in olefin selectivities and catalyst lifetimes with samples steamed at 600 °C giving the best combination of lifetime and olefin selectivity. Zeolite characterizations by 27Al NMR, 29Si NMR and argon physisorption indicate that the steam treatments extract framework aluminum, leading to reductions in the total number of Brønsted acid sites and the creation of mesopores that can facilitate transport of reactants. Poisoning of the acid sites external to the 8MR pores of the zeolites by treatments with trimethylphosphite results in longer catalyst lifetimes but do not affect the observed olefin selectivities, suggesting that olefins do not undergo secondary dimerization or methylation reactions at these sites.
Co-reporter:Dr. Joel E. Schmidt;Dr. Cong-Yan Chen;Stephen K. Br;Dr. Stacey I. Zones; Mark E. Davis
Chemistry - A European Journal 2016 Volume 22( Issue 12) pp:4022-4029
Publication Date(Web):
DOI:10.1002/chem.201504717
Abstract
Large-pore microporous materials are of great interest to process bulky hydrocarbon and biomass-derived molecules. ITQ-27 (IWV) has a two-dimensional pore system bounded by 12-membered rings (MRs) that lead to internal cross-sections containing 14 MRs. Investigations into the catalytic behavior of aluminosilicate (zeolite) materials with this framework structure have been limited until now due to barriers in synthesis. The facile synthesis of aluminosilicate IWV in both hydroxide and fluoride media is reported herein using simple, diquaternary organic structure-directing agents (OSDAs) that are based on tetramethylimidazole. In hydroxide media, a zeolite product with Si/Al=14.8–23.2 is obtained, while in fluoride media an aluminosilicate product with Si/Al up to 82 is synthesized. The material produced in hydroxide media is tested for the hydroisomerization of n-hexane, and results from this test reaction suggest that the effective pore size of zeolites with the IWV framework structure is similar to but slightly larger than that of ZSM-12 (MTW), in fairly good agreement with crystallographic data.
Co-reporter:Dr. Joel E. Schmidt;Dr. Cong-Yan Chen;Stephen K. Br;Dr. Stacey I. Zones; Mark E. Davis
Chemistry - A European Journal 2016 Volume 22( Issue 12) pp:
Publication Date(Web):
DOI:10.1002/chem.201600173
Co-reporter:Stephen K. Br;Dr. Jay A. Labinger ; Mark E. Davis
ChemCatChem 2016 Volume 8( Issue 1) pp:121-124
Publication Date(Web):
DOI:10.1002/cctc.201501067
Abstract
The use of biomass as a resource to produce value-added products has garnered significant interest as a means of reducing reliance on fossil fuels. This task is complicated by the complex, highly functionalized nature of abundant biomass derivatives, such as glucose. Tin-containing zeolite Beta (Sn-Beta) can selectively isomerize glucose to fructose through a 1,2-intramolecular hydride shift (1,2-HS) or selectively produce mannose through a 1,2-intramolecular carbon shift (1,2-CS) by titration of the silanol groups with sodium (Na-Sn-Beta). To understand the structure–activity relationships between the conditions of the active sites in the zeolite, two molecular models (tin silsesquioxanes) of the tin sites in the zeolite were synthesized. Tin silsesquioxanes that contain an octahedral tin site with and without an adjacent silanol group selectively form fructose through a 1,2-HS and mannose through a 1,2-CS, respectively, and provide further evidence for the nature of the active sites in Sn-Beta.
Co-reporter:Andrew J. Clark;Devin T. Wiley;Jonathan E. Zuckerman;Paul Webster;Joseph Chao;James Lin;Yun Yen;Mark E. Davis;
Proceedings of the National Academy of Sciences 2016 113(14) pp:3850-3854
Publication Date(Web):March 21, 2016
DOI:10.1073/pnas.1603018113
Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown
to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles
localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies
are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered
the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either
the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from
the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected
24–48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles
in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and
topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment
tumors.
Co-reporter:Joshua J. Pacheco, Jay A. Labinger, Alex L. Sessions, and Mark E. Davis
ACS Catalysis 2015 Volume 5(Issue 10) pp:5904
Publication Date(Web):September 3, 2015
DOI:10.1021/acscatal.5b01309
Silica molecular sieves that have the zeolite beta topology and contain framework Lewis acid centers (e.g., Zr-β, Sn-β) are useful catalysts in the Diels–Alder and dehydrative aromatization reactions between ethylene and various renewable furans for the production of biobased terephthalic acid precursors. Here, the main side products in the synthesis of methyl 4-(methoxymethyl)benzene carboxylate that are obtained by reacting ethylene with methyl 5-(methoxymethyl)-furan-2-carboxylate are identified, and an overall reaction pathway is proposed. Madon–Boudart experiments using Zr-β samples of varying Si/Zr ratios clearly indicate that there are no transport limitations to the rate of reaction for the synthesis of p-xylene from 2,5-dimethylfuran and ethylene and strongly suggest no mass transport limitations in the synthesis of methyl p-toluate from methyl 5-methyl-2-furoate and ethylene. Measured apparent activation energies for these reaction-limited systems are small (<10.5 kcal/mol), suggesting that apparent activation energies are derived from a collection of parameters and are not true activation energies for a single chemical step. In addition, 13C kinetic isotope effects (KIE) in the synthesis of MMBC and MPT measured by gas chromatography/isotope-ratio mass spectrometry in reactant-depletion experiments support the Madon–Boudart result that these systems are not transport-limited and the KIE values agree with those previously reported for Diels–Alder cycloadditions.Keywords: 5-(hydroxymethyl)furfural; dehydration; Diels−Alder cycloaddition; dimethyl terephthalate; ethylene; kinetic isotope effect; terephthalic acid; tin-β; zirconium-β
Co-reporter:Ben W. Boal, Joel E. Schmidt, Mark A. Deimund, Michael W. Deem, Lawrence M. Henling, Stephen K. Brand, Stacey I. Zones, and Mark E. Davis
Chemistry of Materials 2015 Volume 27(Issue 22) pp:7774
Publication Date(Web):November 5, 2015
DOI:10.1021/acs.chemmater.5b03579
Zeolite A (LTA) has many large-scale uses in separations and ion exchange applications. Because of the high aluminum content and lack of high-temperature stability, applications in catalysis, while highly desired, have been extremely limited. Herein, we report a robust method to prepare pure-silica, aluminosilicate (product Si/Al = 12–42), and titanosilicate LTA in fluoride media using a simple, imidazolium-based organic structure-directing agent. The aluminosilicate material is an active catalyst for the methanol-to-olefins reaction with higher product selectivities to butenes as well as C5 and C6 products than the commercialized silicoalumniophosphate or zeolite analogue that both have the chabazite framework (SAPO-34 and SSZ-13, respectively). The crystal structures of the as-made and calcined pure-silica materials were solved using single-crystal X-ray diffraction, providing information about the occluded organics and fluoride as well as structural information.
Co-reporter:Joel E. Schmidt, Dan Xie and Mark E. Davis
Chemical Science 2015 vol. 6(Issue 10) pp:5955-5963
Publication Date(Web):27 Jul 2015
DOI:10.1039/C5SC02325D
There are several distinct two-dimensional zeolite building layers that can condense through different stacking arrangements of the layers to form various three-dimensional framework materials. All known building layers are dense layers in that they do not contain 8-membered ring (MR) or larger pores perpendicular to the two-dimensional layers. Herein, we report a new material (CIT-10) that consists of a two-dimensional layer (termed “rth” layer) that contains an 8 MR perpendicular to the layer. Calcination of CIT-10 forms pure-silica RTH (SSZ-50). CIT-10 can be pillared to form a new framework material with a three-dimensional pore system of 8 and 10 MRs, denoted CIT-11, that can be calcined to form a new microporous material, denoted CIT-12.
Co-reporter:Joel E. Schmidt, Dan Xie, Thomas Rea and Mark E. Davis
Chemical Science 2015 vol. 6(Issue 3) pp:1728-1734
Publication Date(Web):23 Jan 2015
DOI:10.1039/C4SC03935A
A new crystalline molecular sieve, denoted CIT-7, is synthesized using an imidazolium-based diquaternary organic structure directing agent (OSDA). The framework structure is determined from a combination of rotation electron diffraction and synchrotron X-ray powder diffraction data. The structure has 10 crystallographically unique tetrahedral atoms (T-atoms) in the unit cell, and can be described as an ordered arrangement of the [425462] mtw building unit and a previously unreported [4452] building unit. The framework contains a 2-dimensional pore system that is bounded by 10 T-atom rings (10-ring, 5.1 Å × 6.2 Å opening) that are connected with oval 8-rings (2.9 Å × 5.5 Å opening) through medium-sized cavities (∼7.9 Å) at the channel intersections. CIT-7 can be synthesized over a broad range of compositions including pure-silica and heteroatom, e.g., aluminosilicate and titanosilicate, containing variants.
Co-reporter:Michiel Dusselier, Joel E. Schmidt, Roger Moulton, Barry Haymore, Mark Hellums, and Mark E. Davis
Chemistry of Materials 2015 Volume 27(Issue 7) pp:2695
Publication Date(Web):March 30, 2015
DOI:10.1021/acs.chemmater.5b00651
The aluminosilicate molecular sieve with the AEI framework topology (SSZ-39) is currently of great interest for use in a number of important applications such as exhaust gas NOx reduction and the methanol-to-olefins reaction. It is likely that advances in the synthesis of this molecular sieve will be needed for applications to proceed. Here, dimethylpiperidine based organic structure directing agents (OSDAs) are used to prepare SSZ-39, and the influence of diastereo- and structural isomeric mixtures on the synthesis of SSZ-39 is reported. Although differences in the rates of molecular sieve formation as well as preferential isomer incorporation occur, the synthesis of SSZ-39 is possible over a wide range of isomeric mixtures. These findings demonstrate that the synthesis of SSZ-39 can be accomplished with OSDA isomer mixtures that naturally occur from the synthesis of the organic precursors used to prepare the OSDAs.
Co-reporter:Joel E. Schmidt, Mark A. Deimund, Dan Xie, and Mark E. Davis
Chemistry of Materials 2015 Volume 27(Issue 10) pp:3756
Publication Date(Web):May 6, 2015
DOI:10.1021/acs.chemmater.5b01003
RTH-type zeolites are promising catalytic materials for applications that include the important methanol-to-olefins (MTO) and NOX reduction reactions. Here, RTH-type zeolites are prepared using a wide-range of imidazolium-based, cationic organic structure directing agents (OSDAs), that greatly expand the methodologies and compositions that can be used to synthesize these materials. The abilities of the OSDAs to produce RTH-type zeolites agree well with results from molecular modeling studies of predicted stabilization energies of the OSDAs in the RTH framework. The RTH-type zeolites are stable to steaming up to 900 °C and are shown to be active MTO catalysts.
Co-reporter:Yuewei Ji, Mark A. Deimund, Yashodhan Bhawe, and Mark E. Davis
ACS Catalysis 2015 Volume 5(Issue 7) pp:4456
Publication Date(Web):June 23, 2015
DOI:10.1021/acscatal.5b00404
Chabazite (CHA)-type zeolites are prepared from the hydrothermal conversion of faujasite (FAU)-type zeolites, dealuminated by high-temperature steam treatments (500–700 °C), and evaluated as catalysts for the methanol-to-olefins (MTO) reaction. The effects of temperature and partial pressure of water vapor during steaming are investigated. Powder X-ray diffraction (XRD) and Ar physisorption data show that the steam treatments cause partial structural collapse of the zeolite with the extent of degradation increasing with steaming temperature. 27Al MAS NMR spectra of the steamed materials reveal the presence of tetrahedral, pentacoordinate, and octahedral aluminum. NH3 and i-propylamine temperature-programmed desorption (TPD) demonstrate that steaming removes Brønsted acid sites, while simultaneously introducing larger pores into the CHA materials that make the remaining acid sites more accessible. Acid washing the steamed CHA-type zeolites removes a significant portion of the extra-framework aluminum, producing an increase in the bulk Si/Al ratio as well as the adsorption volume. The proton form of the as-synthesized CHA (Si/Al = 2.4) rapidly deactivates when tested for MTO at a reaction temperature of 400 °C and atmospheric pressure. CHA samples steamed at 600 °C performed the best among the samples tested, showing increased olefin selectivities as well as catalyst lifetime compared to the unsteamed CHA. Both lifetime and C2–C3 olefin selectivities are found to increase with increasing reaction temperature. At 450 °C, CHA steamed at 600 °C reached a combined C2–C3 olefin selectivity of 74.2% at 100% methanol conversion, with conversion remaining above 80% for more than 130 min of time-on-stream (TOS) before deactivating. More stable time-on-stream behavior is observed for 600 °C-steamed CHA that underwent acid washing: conversion above 90% for more than 200 min of TOS at 450 °C with a maximum total C2–C3 olefin selectivity of 71.4% at 100% conversion.Keywords: CHA; methanol-to-olefins; organic-free; steaming; zeolite
Co-reporter:Michiel Dusselier, Mark A. Deimund, Joel E. Schmidt, and Mark E. Davis
ACS Catalysis 2015 Volume 5(Issue 10) pp:6078
Publication Date(Web):September 17, 2015
DOI:10.1021/acscatal.5b01577
Zeolite SSZ-39 is evaluated for catalyzing the methanol-to-olefins (MTO) reaction. By steaming NH4–SSZ-39, Al can be removed from framework positions, resulting in an increase in framework-Si/AlT and thus a lowered active acid site density. The Si/AlT ratios can be controlled by the steaming temperatures. SSZ-39 steamed at 750 °C, with preserved pore volume and morphology, is an excellent MTO catalyst, as high, stable olefin selectivities, long time-on-stream activity, and low alkane production are observed. Moreover, interesting propylene/ethylene/butylene ratios of 2.8/1/1.1 are obtained, likely related to the shape of the AEI cage. By Cu2+-exchanging SSZ-39, evidence is provided to show that AlT sites in close proximity (high AlT density) produce the unwanted effects (higher alkane-make and carbonaceous deposits) in nonsteamed materials during MTO.Keywords: AEI; heterogeneous catalysis; methanol-to-olefins; SSZ-39; steaming; zeolite
Co-reporter:Joel E. Schmidt, Dan Xie and Mark E. Davis
Journal of Materials Chemistry A 2015 vol. 3(Issue 24) pp:12890-12897
Publication Date(Web):27 May 2015
DOI:10.1039/C5TA02354H
There are both natural minerals and synthetic zeolites that possess the HEU framework topology. These materials have a limited compositional range (Si/Al < 6), and the natural zeolites often contain a large amount of impurities such as Fe3+. The preparation of impurity-free HEU-type zeolites with higher Si/Al ratio could open many areas of application, particularly in catalysis. Here, we report the first high-silica HEU-type zeolite that can be prepared via two different procedures. In the first method high-silica HEU (denoted CIT-8) is prepared using a topotactic condensation mechanism (layered precursor denoted CIT-8P); CIT-8P is obtained from a low-water synthesis in fluoride media. CIT-8 prepared in this manner has a product Si/Al ratio of 9.8 ± 0.7 and a micropore volume of 0.10 cm3 g−1 (measured by nitrogen adsorption). The variable temperature powder X-ray diffraction shows that CIT-8 forms via topotactic condensation from CIT-8P along the b axis. Additionally, high-silica heulandite can be synthesized directly from a hydroxide-mediated reaction mixture (denoted CIT-8H), and has a Si/Al ratio of 6.4 ± 0.3 and a micropore volume of 0.10 cm3 g−1. Both synthesis methods produce zeolites that expand the compositional range of HEU-type zeolites. These synthetic methods allow for the addition of other heteroatoms, and titanium-containing CIT-8 is prepared as an illustrative example.
Co-reporter:Dorothy W. Pan and Mark E. Davis
Bioconjugate Chemistry 2015 Volume 26(Issue 8) pp:1791
Publication Date(Web):July 8, 2015
DOI:10.1021/acs.bioconjchem.5b00324
Nanoparticle (NP) delivery systems for small interfering RNA (siRNA) that have good systemic circulation and high nucleic acid content are highly desired for translation into clinical use. Here, a family of cationic mucic acid-containing polymers is synthesized and shown to assemble with siRNA to form NPs. A cationic mucic acid polymer (cMAP) containing alternating mucic acid and charged monomers is synthesized. When combined with siRNA, cMAP forms NPs that require steric stabilization by poly(ethylene glycol) (PEG) that is attached to the NP surface via a 5-nitrophenylboronic acid linkage (5-nitrophenylboronic acid–PEGm (5-nPBA–PEGm)) to diols on mucic acid in the cMAP in order to inhibit aggregation in biological fluids. As an alternative, cMAP is covalently conjugated with PEG via two methods. First, a copolymer is prepared with alternating cMAP–PEG units that can form loops of PEG on the surface of the formulated siRNA-containing NPs. Second, an mPEG–cMAP–PEGm triblock polymer is synthesized that could lead to a PEG brush configuration on the surface of the formulated siRNA-containing NPs. The copolymer and triblock polymer are able to form stable siRNA-containing NPs without and with the addition of 5-nPBA–PEGm. Five formulations, (i) cMAP with 5-nPBA–PEGm, (ii) cMAP–PEG copolymer both (a) with and (b) without 5-nPBA–PEGm, and (iii) mPEG–cMAP–PEGm triblock polymer both (a) with and (b) without 5-nPBA–PEGm, are used to produce NPs in the 30–40 nm size range, and their circulation times are evaluated in mice using tail vein injections. The mPEG–cMAP–PEGm triblock polymer provides the siRNA-containing NP with the longest circulation time (5–10% of the formulation remains in circulation at 60 min postdosing), even when a portion of the excess cationic components used in the formulation is filtered away prior to injection. A NP formulation using the mPEG–cMAP–PEGm triblock polymer that is free of excess components could contain as much as ca. 30 wt % siRNA.
Co-reporter:Ben W. Boal, Stacey I. Zones, Mark E. Davis
Microporous and Mesoporous Materials 2015 Volume 208() pp:203-211
Publication Date(Web):15 May 2015
DOI:10.1016/j.micromeso.2015.01.045
•Synthesis of triptycene-based OSDAs.•Extra-large pored aluminophosphate synthesis.•Synthesis of VPI-5.The synthesis of aluminophosphates is investigated using a number of triptycene-based organic structure-directing agents (OSDA). These OSDAs are designed to synthesize extra-large pore and/or large cavity-containing molecular sieves. Starting from the hydrophobic triptycene molecule, OSDAs are prepared by introducing three amine-based centers that can be charged either by protonation in the acidic aluminophosphate reaction media or through quaternization. VPI-5 is synthesized using these tripytycene OSDAs, and the OSDAs are occluded inside the pores. This synthesis marks the first time VPI-5 has been made as a single phase with an OSDA occluded inside the framework of the as-made material that is not removed by simple washing with water or other solvents. Additionally, several other aluminophosphates with unknown structures are synthesized using these new OSDAs.
Co-reporter:Marat Orazov;Mark E. Davis
PNAS 2015 112 (38 ) pp:11777-11782
Publication Date(Web):2015-09-22
DOI:10.1073/pnas.1516466112
Retro-aldol reactions have been implicated as the limiting steps in catalytic routes to convert biomass-derived hexoses and
pentoses into valuable C2, C3, and C4 products such as glycolic acid, lactic acid, 2-hydroxy-3-butenoic acid, 2,4-dihydroxybutanoic acid, and alkyl esters thereof.
Due to a lack of efficient retro-aldol catalysts, most previous investigations of catalytic pathways involving these reactions
were conducted at high temperatures (≥160 °C). Here, we report moderate-temperature (around 100 °C) retro-aldol reactions
of various hexoses in aqueous and alcoholic media with catalysts traditionally known for their capacity to catalyze 1,2-intramolecular
carbon shift (1,2-CS) reactions of aldoses, i.e., various molybdenum oxide and molybdate species, nickel(II) diamine complexes,
alkali-exchanged stannosilicate molecular sieves, and amorphous TiO2–SiO2 coprecipitates. Solid Lewis acid cocatalysts that are known to catalyze 1,2-intramolecular hydride shift (1,2-HS) reactions
that enable the formation of α-hydroxy carboxylic acids from tetroses, trioses, and glycolaldehyde, but cannot readily catalyze
retro-aldol reactions of hexoses and pentoses at these moderate temperatures, are shown to be compatible with the aforementioned
retro-aldol catalysts. The combination of a distinct retro-aldol catalyst with a 1,2-HS catalyst enables lactic acid and alkyl
lactate formation from ketohexoses at moderate temperatures (around 100 °C), with yields comparable to best-reported chemocatalytic
examples at high temperature conditions (≥160 °C). The use of moderate temperatures enables numerous desirable features such
as lower pressure and significantly less catalyst deactivation.
Co-reporter:Mark E. Davis;Robert Langer
PNAS 2015 Volume 112 (Issue 47 ) pp:14423
Publication Date(Web):2015-11-24
DOI:10.1073/pnas.1517450112
Co-reporter:Andrew J. Clark;Mark E. Davis
PNAS 2015 Volume 112 (Issue 40 ) pp:12486-12491
Publication Date(Web):2015-10-06
DOI:10.1073/pnas.1517048112
Most therapeutic agents are excluded from entering the central nervous system by the blood–brain barrier (BBB). Receptor mediated
transcytosis (RMT) is a common mechanism used by proteins, including transferrin (Tf), to traverse the BBB. Here, we prepared
Tf-containing, 80-nm gold nanoparticles with an acid-cleavable linkage between the Tf and the nanoparticle core to facilitate
nanoparticle RMT across the BBB. These nanoparticles are designed to bind to Tf receptors (TfRs) with high avidity on the
blood side of the BBB, but separate from their multidentate Tf–TfR interactions upon acidification during the transcytosis
process to allow release of the nanoparticle into the brain. These targeted nanoparticles show increased ability to cross
an in vitro model of the BBB and, most important, enter the brain parenchyma of mice in greater amounts in vivo after systemic
administration compared with similar high-avidity nanoparticles containing noncleavable Tf. In addition, we investigated this
design with nanoparticles containing high-affinity antibodies (Abs) to TfR. With the Abs, the addition of the acid-cleavable
linkage provided no improvement to in vivo brain uptake for Ab-containing nanoparticles, and overall brain uptake was decreased
for all Ab-containing nanoparticles compared with Tf-containing ones. These results are consistent with recent reports of
high-affinity anti-TfR Abs trafficking to the lysosome within BBB endothelium. In contrast, high-avidity, Tf-containing nanoparticles
with the acid-cleavable linkage avoid major endothelium retention by shedding surface Tf during their transcytosis.
Co-reporter:Mark A. Deimund;Joel E. Schmidt;Mark E. Davis
Topics in Catalysis 2015 Volume 58( Issue 7-9) pp:416-423
Publication Date(Web):2015 May
DOI:10.1007/s11244-015-0384-y
Six eight-membered-ring (8MR), microporous materials are synthesized and evaluated as catalysts for the methanol-to-olefins (MTO) reaction. The molecular sieves SSZ-13, SAPO-34, SAPO-39, MCM-35, ERS-7 and RUB-37 are investigated since they have 8MR access to the crystal interior but have differences in pore structure and cage size. The polymethylbenzene species that are the proposed reaction intermediates of the MTO reaction should only be able to form in materials with intra-molecular sieve void spaces of sufficient size to accommodate them. Thus, it is hypothesized that 8MR materials without adequately large pores or cages will be inactive for the MTO reaction. SSZ-13 and SAPO-34 (both with CHA framework topology) have interconnected 3-dimensional pore-and-cage systems sufficiently large for formation of the proposed reaction intermediates, while the other 8MR materials have intra-molecular sieve void spaces that are too small to allow formation of these species. The molecular sieves are tested as MTO catalysts at 400 °C, and only the molecular sieves with the CHA topology show MTO activity. Post-reaction analysis of the organic content of each solid material is accomplished by HF acid digestion with subsequent 1H NMR analysis of the extracted hydrocarbon products to confirm the presence of aromatics in the 8MR materials with sufficiently large cages (those with CHA topology), and absence with materials that have smaller void spaces. These data provide further support for the necessity of polymethylbenzene species in the hydrocarbon pool for MTO activity.
Co-reporter:Mark E. Davis
Topics in Catalysis 2015 Volume 58( Issue 7-9) pp:405-409
Publication Date(Web):2015 May
DOI:10.1007/s11244-015-0386-9
The synthesis of commodity polymers from biomass presents interesting challenges and opportunities for new catalytic chemistries. Starting from glucose, reaction pathways to a variety of monomers for commodity polymers are presented. The first step for each pathway is the isomerization of glucose to fructose. This reaction can now be accomplished in aqueous media with hydrophobic, large pore molecular sieves that contain Lewis acid sites as catalysts. A typical catalyst is a pure-silica molecular sieve having the zeolite beta topology and containing a small amount of framework Sn4+ (Sn-Beta). Dehydration of fructose into 5-hydroxymethylfurfural (HMF) provides a convenient path that can lead to 2,5-furandicarboxylic acid (FDCA) for the synthesis of polyethylene furanoate (PEF) or purified terephthalic acid (PTA) (via Diels–Alder reactions) for the synthesis of polyethylene terephthalate (PET). Recent progress on the dehydration of lactic acid could open new routes to acrylic acid and acrylonitrile that are used to produce polyacrylic acid and polyacrylonitrile, respectively, provided more selective catalysts for the retro-aldol deconstruction of fructose are developed.
Co-reporter:Joel E. Schmidt, Mark A. Deimund, and Mark E. Davis
Chemistry of Materials 2014 Volume 26(Issue 24) pp:7099
Publication Date(Web):December 5, 2014
DOI:10.1021/cm503625u
RTH type zeolite (aluminosilicate) is a potentially useful catalytic material that is limited by the inability to easily prepare the material over a wide composition range. Here, we report the use of pentamethylimidazolium to prepare aluminosilicate RTH across a wide range of compositions in both fluoride and hydroxide inorganic systems. RTH type zeolites are crystallized with a calcined product Si/Al of 7–27 from fluoride media and 6–59 from hydroxide media. The use of this new, simple organic structure-directing agent that can be prepared in one step allows for dramatic improvement in the compositional space where aluminosilicate RTH can be formed. RTH is tested as a catalyst for the methanol-to-olefins reaction and at complete conversion shows a high propylene/ethylene ratio of 3.9 at a propylene selectivity of 43%.
Co-reporter:Mark A. Deimund, Jay Labinger, and Mark E. Davis
ACS Catalysis 2014 Volume 4(Issue 11) pp:4189
Publication Date(Web):October 14, 2014
DOI:10.1021/cs501313z
Two nickel-containing zincosilicates (Ni-CIT-6 and Ni–Zn-MCM-41) and two nickel-containing aluminosilicates (Ni-HiAl-BEA and Ni-USY) are synthesized and used as catalysts to oligomerize propylene into C3n (C6 and C9) products. Both Ni-CIT-6 and Ni-HiAl-BEA have the *BEA topology and are investigated to assess the effects of framework zinc versus aluminum because the former gives two framework charges per atom, whereas the latter, only one. Ni-CIT-6 and Ni–Zn-MCM-41 enable the comparison of a microporous to a mesoporous zincosilicate. Ni2+ ion-exchanged into zeolite Y has been previously reported to oligomerize propylene and is used here for comparison. Reaction data are obtained at 180 and 250 °C, atmospheric pressure, and WHSV = 1.0 h–1 in a feed stream of 85 mol % propylene (in inert). At these conditions, all catalysts are capable of oligomerizing propylene with steady-state conversions ranging from 3 to 16%. With the exception of Ni-HiAl-BEA, all catalysts have higher propylene conversions at 250 °C than at 180 °C. Both *BEA materials exhibit similar propylene conversions at each temperature, but Ni-HiAl-BEA is not as selective to C3n products as Ni-CIT-6. Zincosilicates demonstrate higher average selectivities to C3n products than the aluminosilicates at both reaction temperatures tested. Hexene products other than those expected by simple oligomerization are present, likely formed by double-bond isomerization catalyzed at acid sites. Additionally, both of the aluminosilicate materials catalyzed cracking reactions, forming non-C3n products. The reduced acidity of the zincosilicates relative to the aluminosilicates likely accounts for higher C3n product selectivity of the zincosilicates. Zincosilicates also exhibited higher linear-to-branched hexene isomer ratios (typically 1.0–1.5) when compared with the aluminosilicates, which had ratios on the order of 0.3. The mesoporous zincosilicate shows the best reaction behavior (including C3n product selectivity: ∼99% at both temperatures for Ni–Zn-MCM-41) of the catalytic materials tested here.Keywords: *BEA; nickel; oligomerization; propylene; zincosilicate
Co-reporter:Ricardo Bermejo-Deval, Marat Orazov, Rajamani Gounder, Son-Jong Hwang, and Mark E. Davis
ACS Catalysis 2014 Volume 4(Issue 7) pp:2288
Publication Date(Web):June 2, 2014
DOI:10.1021/cs500466j
Framework Lewis acidic tin sites in hydrophobic, pure-silica molecular sieves with the zeolite beta topology (Sn-Beta) have been reported previously to predominantly catalyze glucose−fructose isomerization via 1,2 intramolecular hydride shift in water and glucose–mannose epimerization via 1,2 intramolecular carbon shift in methanol. Here, we show that alkali-free Sn-Beta predominantly isomerizes glucose to fructose via 1,2 intramolecular hydride shift in both water and methanol. Increasing extents of postsynthetic Na+ exchange onto Sn-Beta, however, progressively shifts the reaction pathway toward glucose–mannose epimerization via 1,2 intramolecular carbon shift. Na+ remains exchanged onto silanol groups proximal to Sn centers during reaction in methanol solvent, leading to nearly exclusive selectivity toward epimerization. In contrast, decationation occurs with increasing reaction time in aqueous solvent and gradually shifts the reaction selectivity to isomerization at the expense of epimerization. Decationation and the concomitant selectivity changes are mitigated by the addition of NaCl to the aqueous reaction solution. Preadsorption of ammonia onto Sn-Beta leads to near complete suppression of infrared and 119Sn nuclear magnetic resonance spectroscopic signatures attributed to open Sn sites and of glucose−fructose isomerization pathways in water and methanol. These data provide evidence that Lewis acidic open Sn sites with either proximal silanol groups or Na-exchanged silanol groups are respectively the active sites for glucose–fructose isomerization and glucose–mannose epimerization.Keywords: Bilik reaction; closed site; epimerization; fructose; glucose; isomerization; mannose; open site; silanol; sodium exchange; tin-beta
Co-reporter:Joshua J. Pacheco;Mark E. Davis
PNAS 2014 111 (23 ) pp:8363-8367
Publication Date(Web):2014-06-10
DOI:10.1073/pnas.1408345111
Terephthalic acid (PTA), a monomer in the synthesis of polyethylene terephthalate (PET), is obtained by the oxidation of petroleum-derived
p-xylene. There is significant interest in the synthesis of renewable, biomass-derived PTA. Here, routes to PTA starting from
oxidized products of 5-hydroxymethylfurfural (HMF) that can be produced from biomass are reported. These routes involve Diels-Alder
reactions with ethylene and avoid the hydrogenation of HMF to 2,5-dimethylfuran. Oxidized derivatives of HMF are reacted with
ethylene over solid Lewis acid catalysts that do not contain strong Brønsted acids to synthesize intermediates of PTA and
its equally important diester, dimethyl terephthalate (DMT). The partially oxidized HMF, 5-(hydroxymethyl)furoic acid (HMFA),
is reacted with high pressure ethylene over a pure-silica molecular sieve containing framework tin (Sn-Beta) to produce the
Diels-Alder dehydration product, 4-(hydroxymethyl)benzoic acid (HMBA), with 31% selectivity at 61% HMFA conversion after 6
h at 190 °C. If HMFA is protected with methanol to form methyl 5-(methoxymethyl)furan-2-carboxylate (MMFC), MMFC can react
with ethylene in the presence of Sn-Beta for 2 h to produce methyl 4-(methoxymethyl)benzenecarboxylate (MMBC) with 46% selectivity
at 28% MMFC conversion or in the presence of a pure-silica molecular sieve containing framework zirconium (Zr-Beta) for 6
h to produce MMBC with 81% selectivity at 26% MMFC conversion. HMBA and MMBC can then be oxidized to produce PTA and DMT,
respectively. When Lewis acid containing mesoporous silica (MCM-41) and amorphous silica, or Brønsted acid containing zeolites
(Al-Beta), are used as catalysts, a significant decrease in selectivity/yield of the Diels-Alder dehydration product is observed.
Co-reporter:Joel E. Schmidt;Dr. Michael W. Deem;Dr. Mark E. Davis
Angewandte Chemie 2014 Volume 126( Issue 32) pp:8512-8514
Publication Date(Web):
DOI:10.1002/ange.201404076
Abstract
Crystalline molecular sieves are used in numerous applications, where the properties exploited for each technology are the direct consequence of structural features. New materials are typically discovered by trial and error, and in many cases, organic structure-directing agents (OSDAs) are used to direct their formation. Here, we report the first successful synthesis of a specified molecular sieve through the use of an OSDA that was predicted from a recently developed computational method that constructs chemically synthesizable OSDAs. Pentamethylimidazolium is computationally predicted to have the largest stabilization energy in the STW framework, and is experimentally shown to strongly direct the synthesis of pure-silica STW. Other OSDAs with lower stabilization energies did not form STW. The general method demonstrated here to create STW may lead to new, simpler OSDAs for existing frameworks and provide a way to predict OSDAs for desired, theoretical frameworks.
Co-reporter:Joel E. Schmidt;Dr. Michael W. Deem;Dr. Mark E. Davis
Angewandte Chemie International Edition 2014 Volume 53( Issue 32) pp:8372-8374
Publication Date(Web):
DOI:10.1002/anie.201404076
Abstract
Crystalline molecular sieves are used in numerous applications, where the properties exploited for each technology are the direct consequence of structural features. New materials are typically discovered by trial and error, and in many cases, organic structure-directing agents (OSDAs) are used to direct their formation. Here, we report the first successful synthesis of a specified molecular sieve through the use of an OSDA that was predicted from a recently developed computational method that constructs chemically synthesizable OSDAs. Pentamethylimidazolium is computationally predicted to have the largest stabilization energy in the STW framework, and is experimentally shown to strongly direct the synthesis of pure-silica STW. Other OSDAs with lower stabilization energies did not form STW. The general method demonstrated here to create STW may lead to new, simpler OSDAs for existing frameworks and provide a way to predict OSDAs for desired, theoretical frameworks.
Co-reporter:Jonathan E. Zuckerman;Ismael Gritli;Anthony Tolcher;Jeremy D. Heidel;Dean Lim;Robert Morgan;Bartosz Chmielowski;Antoni Ribas;Mark E. Davis;Yun Yen
PNAS 2014 Volume 111 (Issue 31 ) pp:11449-11454
Publication Date(Web):2014-08-05
DOI:10.1073/pnas.1411393111
Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01
is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA
interference (RNAi)–based, experimental therapeutic to be administered to cancer patients. Here, we report the results from
the initial phase I clinical trial where 24 patients with different cancers were treated with CALAA-01 and compare those results
to data obtained from multispecies animal studies to provide a detailed example of translating this class of nanoparticles
from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys, and humans show fast elimination and reveal
that the maximum concentration obtained in the blood after i.v. administration correlates with body weight across all species.
The safety profile of CALAA-01 in animals is similarly obtained in humans except that animal kidney toxicities are not observed
in humans; this could be due to the use of a predosing hydration protocol used in the clinic. Taken in total, the animal models
do appear to predict the behavior of CALAA-01 in humans.
Co-reporter:Rajamani Gounder and Mark E. Davis
ACS Catalysis 2013 Volume 3(Issue 7) pp:1469
Publication Date(Web):May 20, 2013
DOI:10.1021/cs400273c
Pure-silica zeolite beta containing Lewis acidic framework Ti4+ centers (Ti-Beta) is shown to catalyze the isomerization of d-glucose to l-sorbose via an intramolecular C5–C1 hydride shift. Glucose–sorbose isomerization occurs in parallel to glucose–fructose isomerization on Ti-Beta in both water and methanol solvents, with fructose formed as the predominant product in water and sorbose as the predominant product in methanol (at 373 K) at initial times and over the course of >10 turnovers. Isotopic tracer studies demonstrate that 13C and D labels placed respectively at the C1 and C2 positions of glucose are retained respectively at the C6 and C5 positions of sorbose, consistent with its formation via an intramolecular C5–C1 hydride shift isomerization mechanism. This direct Lewis acid-mediated pathway for glucose–sorbose isomerization appears to be unprecedented among heterogeneous or biological catalysts and sharply contrasts indirect base-mediated glucose–sorbose isomerization via 3,4-enediol intermediates or via retro-aldol fragmentation and recombination of sugar fragments. Measured first-order glucose–sorbose isomerization rate constants (per total Ti; 373 K) for Ti-Beta in methanol are similar for glucose and glucose deuterated at the C2 position (within a factor of ∼1.1), but are a factor of ∼2.3 lower for glucose deuterated at each carbon position, leading to H/D kinetic isotope effects expected for kinetically relevant intramolecular C5–C1 hydride shift steps. Optical rotation measurements show that isomerization of d-(+)-glucose (92% enantiomeric purity) with Ti-Beta in water (373 K) led to the formation of l-(−)-sorbose (73% enantiomeric purity) and d-(−)-fructose (87% enantiomeric purity) as the predominant stereoisomers, indicating that stereochemistry is preserved at carbon centers not directly involved in intramolecular C5–C1 or C2–C1 hydride shift steps, respectively. This new Lewis acid-mediated rearrangement of glucose to sorbose does not appear to have a metalloenzyme analog.Keywords: fructose; glucose; hydride shift; isomerization; Lewis acid; sorbose; stereospecific; titanium-Beta
Co-reporter:Bingjun Xu, Yashodhan Bhawe, and Mark E. Davis
Chemistry of Materials 2013 Volume 25(Issue 9) pp:1564
Publication Date(Web):March 20, 2013
DOI:10.1021/cm3038747
A manganese oxide-based, thermochemical cycle for water splitting below 1000 °C has recently been reported. The cycle involves the shuttling of Na+ into and out of manganese oxides via the consumption and formation of sodium carbonate, respectively. Here, we explore the combinations of three spinel metal oxides and three alkali carbonates in thermochemical cycles for water splitting and CO2 reduction. Hydrogen evolution and CO2 reduction reactions of metal oxides with a given alkali carbonate occur in the following order of decreasing activity: Fe3O4 > Mn3O4 > Co3O4, whereas the reactivity of a given metal oxide with alkali carbonates declines as Li2CO3 > Na2CO3 > K2CO3. While hydrogen evolution and CO2 reduction reactions occur at a lower temperature on the combinations with the more reactive metal oxide and alkali carbonate, higher thermal reduction temperatures and more difficult alkali ion extractions are observed for the combinations of the more reactive metal oxides and alkali carbonates. Thus, for a thermochemical cycle to be closed at low temperatures, all three reactions of hydrogen evolution (CO2 reduction), alkali ion extraction, and thermal reduction must proceed within the specified temperature range. Of the systems investigated here, only the Na2CO3/Mn3O4 combination satisfies these criteria with a maximum operating temperature (850 °C) below 1000 °C.Keywords: alkali carbonate; CO2 reduction; spinel metal oxide; thermochemical cycle; water splitting;
Co-reporter:Han Han and Mark E. Davis
Bioconjugate Chemistry 2013 Volume 24(Issue 4) pp:669
Publication Date(Web):March 6, 2013
DOI:10.1021/bc300640j
The delivery of therapeutics via nanoscaled vehicles for solid cancer treatment can be enhanced by the incorporation of a targeting capability. Here, we describe a new method for assembling a targeted nanoparticle that utilizes the reversible covalent complexation between boronic acids and diols to achieve a targeted nanoparticle for the delivery of the anticancer drug camptothecin (CPT). CPT is conjugated to a biocompatible, hydrophilic copolymer of mucic acid and PEG (MAP). When this polymer–drug conjugate is placed in water, it self-assembles into MAP–CPT nanoparticles of ca. 30 nm (diameter) and slightly negative zeta potential. The antibody Herceptin is attached to a boronic acid via a polyethylene glycol (PEG) spacer, and this boronic acid-containing targeting moiety is complexed with the diol-containing MAP to form a targeted MAP–CPT nanoparticle. The addition of Herceptin targeting agent to the MAP–CPT nanoparticles yields targeted MAP–CPT nanoparticles with increased nanoparticle size to ca. 40 nm (diameter). The main mechanisms of CPT release from MAP–CPT nanoparticles are found by in vitro analysis to be hydrolysis and nanoparticle disruption by fat. Cellular uptake of nanoparticles is enhanced by 70% compared to nontargeted version by the incorporation of a single Herceptin antibody targeting agent per nanoparticle. This single Herceptin antibody targeted MAP–CPT nanoparticle system carries ca. 60 CPT molecules per nanoparticle and shows prolonged plasma circulation with an elimination half-life of 21.2 h and AUC value of 2766 μg.h/mL at a 10 mg CPT/kg tail vein injection in mice.
Co-reporter:Han Han and Mark E. Davis
Molecular Pharmaceutics 2013 Volume 10(Issue 7) pp:2558-2567
Publication Date(Web):May 15, 2013
DOI:10.1021/mp300702x
We have developed a new method for assembling targeted nanoparticles that utilizes the complexation between targeting agents that contain boronic acids and polymer–drug conjugates that possess diols. Here, we report the first in vivo, antitumor results of a nanoparticle formed via this new assembly methodology. A nanoparticle consisting of a mucic acid polymer conjugate of camptothecin (CPT), MAP–CPT, and containing on average one Herceptin antibody is investigated in nude mice bearing HER2 overexpressing BT-474 human breast cancer tumors. Nontargeted MAP–CPT and antibody-containing MAP–CPT nanoparticles of ca. 30–40 nm diameter and slightly negative zeta potential show prolonged in vivo circulation and similar biodistributions after intravenous tail vein injections in mice. The maximum tolerated dose (MTD) of the nontargeted and Herceptin-containing MAP–CPT nanoparticles is found to be 10 and 8 mg of CPT/kg, respectively, in mice. Mice bearing BT-474 human breast tumors treated with nontargeted MAP–CPT nanoparticles at 8 mg of CPT/kg show significant tumor growth inhibition (mean tumor volume of 63 mm3) when compared to irinotecan at 80 mg/kg (mean tumor volume of 575 mm3) and CPT at 8 mg/kg (mean tumor volume of 808 mm3) at the end of the study. Herceptin antibody treatment at 5.9 mg/kg results in complete tumor regressions in 5 out of 8 mice, with a mean tumor volume of 60 mm3 at the end of the study. Mice treated with MAP–CPT nanoparticles at 1 mg of CPT/kg do not show tumor inhibition. However, all mice receiving administrations of MAP–CPT nanoparticles (1 mg of CPT/kg) that contain on average a single Herceptin molecule per nanoparticle (5.9 mg of Herceptin equivalent/kg) show complete tumor regression by the end of the study. These results demonstrate that the antitumor efficacy of nanoparticles carrying anticancer drugs can be enhanced by incorporating on average a single antibody.Keywords: antitumor efficacy; biodistribution; camptothecin; Herceptin; targeted nanoparticles;
Co-reporter:Devin T. Wiley;Paul Webster;Aaron Gale;Mark E. Davis
PNAS 2013 Volume 110 (Issue 21 ) pp:8662-8667
Publication Date(Web):2013-05-21
DOI:10.1073/pnas.1307152110
Receptor-mediated transcytosis across the blood–brain barrier (BBB) may be a useful way to transport therapeutics into the
brain. Here we report that transferrin (Tf)-containing gold nanoparticles can reach the brain parenchyma from systemic administration
in mice through a receptor-mediated transcytosis pathway. This transport is aided by tuning the nanoparticle avidity to Tf
receptor (TfR), which is correlated with nanoparticle size and total amount of Tf decorating the nanoparticle surface. Nanoparticles
of both 45 nm and 80 nm diameter reach the brain parenchyma, and their accumulation there (visualized by silver enhancement
light microscopy in combination with transmission electron microscopy imaging) is observed to be dependent on Tf content (avidity);
nanoparticles with large amounts of Tf remain strongly attached to brain endothelial cells, whereas those with less Tf are
capable of both interacting with TfR on the luminal side of the BBB and detaching from TfR on the brain side of the BBB. The
requirement of proper avidity for nanoparticles to reach the brain parenchyma is consistent with recent behavior observed
with transcytosing antibodies that bind to TfR.
Co-reporter:Scott Eliasof;Roy I. Case;Douglas Lazarus;Thomas Schluep;Christian G. Peters;Jungyeon Hwang;Joseph Chao;Yun Yen;James Lin;Roderic O. Cole;Han Han;Devin T. Wiley;Jonathan E. Zuckerman;Mark E. Davis
PNAS 2013 Volume 110 (Issue 37 ) pp:15127-15132
Publication Date(Web):2013-09-10
DOI:10.1073/pnas.1309566110
Nanoparticles are currently being investigated in a number of human clinical trials. As information on how nanoparticles function
in humans is difficult to obtain, animal studies that can be correlative to human behavior are needed to provide guidance
for human clinical trials. Here, we report correlative studies on animals and humans for CRLX101, a 20- to 30-nm-diameter,
multifunctional, polymeric nanoparticle containing camptothecin (CPT). CRLX101 is currently in phase 2 clinical trials, and
human data from several of the clinical investigations are compared with results from multispecies animal studies. The pharmacokinetics
of polymer-conjugated CPT (indicative of the CRLX101 nanoparticles) in mice, rats, dogs, and humans reveal that the area under
the curve scales linearly with milligrams of CPT per square meter for all species. Plasma concentrations of unconjugated CPT
released from CRLX101 in animals and humans are consistent with each other after accounting for differences in serum albumin
binding of CPT. Urinary excretion of polymer-conjugated CPT occurs primarily within the initial 24 h after dosing in animals
and humans. The urinary excretion dynamics of polymer-conjugated and unconjugated CPT appear similar between animals and humans.
CRLX101 accumulates into solid tumors and releases CPT over a period of several days to give inhibition of its target in animal
xenograft models of cancer and in the tumors of humans. Taken in total, the evidence provided from animal models on the CRLX101
mechanism of action suggests that the behavior of CRLX101 in animals is translatable to humans.
Co-reporter:Ricardo Bermejo-Deval, Rajamani Gounder, and Mark E. Davis
ACS Catalysis 2012 Volume 2(Issue 12) pp:2705
Publication Date(Web):October 29, 2012
DOI:10.1021/cs300474x
Here, we show that framework tin sites in pure silica zeolite Beta (Sn-Beta) can isomerize glucose to fructose by a Lewis acid-mediated intramolecular hydride shift in aqueous solvent, but not in methanol solvent. Mechanistic studies using isotopically labeled (2H, 13C) glucose reactants show that in methanol, Sn-Beta instead epimerizes glucose to mannose by a Lewis acid-mediated intramolecular carbon shift mechanism known as the Bilik reaction. We also provide evidence that extraframework tin sites located within the hydrophobic channels of zeolite Beta can isomerize glucose to fructose in both water and methanol solvent, but through a base-catalyzed proton-transfer mechanism. SnO2 particles located at external zeolite crystal surfaces or supported on amorphous silica catalyze isomerization in methanol but not in water, suggesting that contact with bulk water inhibits isomerization at SnO2 surfaces. 119Sn MAS NMR spectroscopy was used to unambiguously identify framework Sn sites, which give resonances for octahedral Sn (−685 to −700 ppm) in hydrated Sn-Beta that disappear upon dehydration, with the concomitant appearance of resonances for tetrahedral Sn (−425 to −445 ppm). In sharp contrast, spectra of hydrated samples containing extraframework SnO2 show resonances for octahedral Sn centered at −604 ppm that do not change upon dehydration. These findings demonstrate that aldose–ketose isomerization reactivity on Sn-zeolite samples cannot be ascribed to the presence of framework Sn sites in the absence of isotopic labeling studies. They also indicate that any Sn-zeolite samples that initially convert glucose to fructose, instead of mannose, in methanol solvent contain Sn species that are structurally different from framework Sn centers.Keywords: Bilik reaction; epimerization; glucose; isomerization; mannose; methanol; tin-Beta; water;
Co-reporter:Yashodhan Bhawe, Manuel Moliner-Marin, Jonathan D. Lunn, Yu Liu, Andrzej Malek, and Mark Davis
ACS Catalysis 2012 Volume 2(Issue 12) pp:2490
Publication Date(Web):October 18, 2012
DOI:10.1021/cs300558x
Zeolites that contain eight-membered ring pores but different cavity geometries (LEV, CHA, and AFX structure types) are synthesized at similar Si/Al ratios and crystal sizes. These materials are tested as catalysts for the selective conversion of methanol to light olefins. At 400 °C, atmospheric pressure, and 100% conversion of methanol, the ethylene selectivity decreases as the cage size increases. Variations in the Si/Al ratio of the LEV and CHA show that the maximum selectivity occurs at Si/Al = 15–18. Because lower Si/Al ratios tend to produce faster deactivation rates and poorer selectivities, reactivity comparisons between frameworks are performed with solids having a ratio Si/Al = 15–18. With LEV and AFX, the data are the first from materials with this high Si/Al. At similar Si/Al and primary crystallite size, the propylene selectivity for the material with the CHA structure exceeds those from either the LEV or AFX structure. The AFX material gives the shortest reaction lifetime, but has the lowest amount of carbonaceous residue after reaction. Thus, there appears to be an intermediate cage size for maximizing the production of light olefins and propylene selectivities equivalent to or exceeding ethylene selectivities.Keywords: AFX; CHA; LEV; methanol-to-olefins; zeolite
Co-reporter:Bingjun Xu;Yashodhan Bhawe;Mark E. Davis
PNAS 2012 Volume 109 (Issue 24 ) pp:
Publication Date(Web):2012-06-12
DOI:10.1073/pnas.1206407109
Thermochemical cycles that split water into stoichiometric amounts of hydrogen and oxygen below 1,000 °C, and do not involve
toxic or corrosive intermediates, are highly desirable because they can convert heat into chemical energy in the form of hydrogen.
We report a manganese-based thermochemical cycle with a highest operating temperature of 850 °C that is completely recyclable
and does not involve toxic or corrosive components. The thermochemical cycle utilizes redox reactions of Mn(II)/Mn(III) oxides.
The shuttling of Na+ into and out of the manganese oxides in the hydrogen and oxygen evolution steps, respectively, provides the key thermodynamic
driving forces and allows for the cycle to be closed at temperatures below 1,000 °C. The production of hydrogen and oxygen
is fully reproducible for at least five cycles.
Co-reporter:Jonathan E. Zuckerman;Chung Hang J. Choi;Han Han;Mark E. Davis
PNAS 2012 Volume 109 (Issue 8 ) pp:3137-3142
Publication Date(Web):2012-02-21
DOI:10.1073/pnas.1200718109
Despite being engineered to avoid renal clearance, many cationic polymer (polycation)-based siRNA nanoparticles that are used
for systemic delivery are rapidly eliminated from the circulation. Here, we show that a component of the renal filtration
barrier—the glomerular basement membrane (GBM)—can disassemble cationic cyclodextrin-containing polymer (CDP)-based siRNA
nanoparticles and, thereby, facilitate their rapid elimination from circulation. Using confocal and electron microscopies,
positron emission tomography, and compartment modeling, we demonstrate that siRNA nanoparticles, but not free siRNA, accumulate
and disassemble in the GBM. We also confirm that the siRNA nanoparticles do not disassemble in blood plasma in vitro and in
vivo. This clearance mechanism may affect any nanoparticles that assemble primarily by electrostatic interactions between
cationic delivery components and anionic nucleic acids (or other therapeutic entities).
Co-reporter:Ricardo Bermejo-Deval;Rajeev S. Assary;Son-Jong Hwang;Yuriy Román-Leshkov;Arna Palsdottir;Eranda Nikolla;Manuel Moliner;Larry A. Curtiss;Dorothy Silverman;Raul F. Lobo;Mark E. Davis
PNAS 2012 Volume 109 (Issue 25 ) pp:
Publication Date(Web):2012-06-19
DOI:10.1073/pnas.1206708109
Isomerization of sugars is used in a variety of industrially relevant processes and in glycolysis. Here, we show that hydrophobic
zeolite beta with framework tin or titanium Lewis acid centers isomerizes sugars, e.g., glucose, via reaction pathways that
are analogous to those of metalloenzymes. Specifically, experimental and theoretical investigations reveal that glucose partitions
into the zeolite in the pyranose form, ring opens to the acyclic form in the presence of the Lewis acid center, isomerizes
into the acyclic form of fructose, and finally ring closes to yield the furanose product. The zeolite catalysts provide processing
advantages over metalloenzymes such as an ability to work at higher temperatures and in acidic conditions that allow for the
isomerization reaction to be coupled with other important conversions.
Co-reporter:Eranda Nikolla, Yuriy Román-Leshkov, Manuel Moliner, and Mark E. Davis
ACS Catalysis 2011 Volume 1(Issue 4) pp:408
Publication Date(Web):March 7, 2011
DOI:10.1021/cs2000544
Conversion of carbohydrates to 5-(hydroxymethyl)furfural (HMF) may provide a step forward toward achieving a renewable biomass-based chemicals and fuels platform. Recently, we reported that a tin-containing, high-silica molecular sieve with the zeolite beta topology (Sn-Beta) can efficiently catalyze the isomerization of glucose to fructose in aqueous media at low pH. Herein, we describe the combination of Sn-Beta with acid catalysts in a one vessel, biphasic reactor system to synthesize HMF from carbohydrates such as glucose, cellobiose, and starch with high efficiency. HMF selectivities over 70% were obtained using this “one-pot” biphasic water/tetrahydrofuran (THF) reactor system. The key to successfully achieving the conversions/selectivities reported is that Sn-Beta is able to convert glucose to fructose at pH near 1 and in saturated aqueous salt solutions.Keywords: carbohydrate conversion; glucose isomerization; heterogeneous catalysis; HMF; Zeolite
Co-reporter:Yuriy Román-Leshkov and Mark E. Davis
ACS Catalysis 2011 Volume 1(Issue 11) pp:1566
Publication Date(Web):September 28, 2011
DOI:10.1021/cs200411d
Current interest in reacting carbonyl-containing molecules in aqueous media is primarily due to the growing emphasis on conversion of biomass to fuels and chemicals. Recently, solid Lewis acids have been shown to perform catalytic reactions with carbonyl-containing molecules such as sugars in aqueous media. Here, catalysis mediated by Lewis acids is briefly discussed, Lewis acid solids that perform catalysis in aqueous media are then described, and the review is concluded with a few comments on the outlook for the future.Keywords: biomass; Lewis acid; water-resistant catalysts;
Co-reporter:Jeremy D. Heidel;Mark E. Davis
Pharmaceutical Research 2011 Volume 28( Issue 2) pp:187-199
Publication Date(Web):2011 February
DOI:10.1007/s11095-010-0178-7
Nanoparticle approaches to drug delivery for cancer offer exciting and potentially “game-changing” ways to improve patient care and quality of life in numerous ways, such as reducing off-target toxicities by more selectively directing drug molecules to intracellular targets of cancer cells. Here, we focus on technologies being investigated clinically and discuss numerous types of therapeutic molecules that have been incorporated within nanostructured entities such as nanoparticles. The impacts of nanostructured therapeutics on efficacy and safety, including parameters like pharmacokinetics and biodistribution, are described for several drug molecules. Additionally, we discuss recent advances in the understanding of ligand-based targeting of nanoparticles, such as on receptor avidity and selectivity.
Co-reporter:Yuriy Román-Leshkov ; Manuel Moliner ;Mark E. Davis
The Journal of Physical Chemistry C 2011 Volume 115(Issue 4) pp:1096-1102
Publication Date(Web):September 9, 2010
DOI:10.1021/jp106247g
Zeolites with the ferrierite (FER) topology are synthesized using a combination of tetramethylammonium (TMA) cations with differently sized cyclic amines (pyrrolidine (Pyr), hexamethyleneimine (HMI), and 1,4-diazabicyclo[2.2.2]octane (DAB)). Using these organic structure-directing agents (SDAs), low Si/Al ratios and concentrated synthesis mixtures favor the crystallization of FER materials. Increasing the size of the cyclic amine or decreasing the aluminum content leads to the crystallization of other phases or the creation of excessive amounts of connectivity defects. TMA cations play a decisive role in the synthesis of the FER materials, and their presence allows the use of HMI to synthesize FER. Proton MAS NMR is used to quantify the accessibility of pyridine to acid sites in these FER samples, where it is found that the FER + HMI + TMA sample contains only 27% acid sites in the 8-MR channels, whereas FER + Pyr and FER + Pyr + TMA contain 89% and 84%, respectively. The constraint index (CI) test and the carbonylation of dimethyl ether (DME) with carbon monoxide are used as probe reactions to evaluate how changes in the aluminum distribution in these FER samples affect their catalytic behavior. Results show that the use of Pyr as an SDA results in the selective population of acid sites in the 8-MR channels, whereas the use of HMI generates FER zeolites with an increased concentration of acid sites in the 10-MR channels.
Co-reporter:Chung Hang J. Choi;Jonathan E. Zuckerman;Paul Webster;Mark E. Davis
PNAS 2011 Volume 108 (Issue 16 ) pp:6656-6661
Publication Date(Web):2011-04-19
DOI:10.1073/pnas.1103573108
Nanoparticles are being investigated for numerous medical applications and are showing potential as an emerging class of carriers
for drug delivery. Investigations on how the physicochemical properties (e.g., size, surface charge, shape, and density of
targeting ligands) of nanoparticles enable their ability to overcome biological barriers and reach designated cellular destinations
in sufficient amounts to elicit biological efficacy are of interest. Despite proven success in nanoparticle accumulation at
cellular locations and occurrence of downstream therapeutic effects (e.g., target gene inhibition) in a selected few organs
such as tumor and liver, reports on effective delivery of engineered nanoparticles to other organs still remain scarce. Here,
we show that nanoparticles of ~75 ± 25-nm diameters target the mesangium of the kidney. These data show the effects of particle
diameter on targeting the mesangium of the kidney. Because many diseases originate from this area of the kidney, our findings
establish design criteria for constructing nanoparticle-based therapeutics for targeting diseases that involve the mesangium
of the kidney.
Co-reporter:Yuriy Román-Leshkov, Manuel Moliner and Mark E. Davis
Chemistry of Materials 2010 Volume 22(Issue 8) pp:2646
Publication Date(Web):March 3, 2010
DOI:10.1021/cm100108e
Hybrid organic−inorganic solids featuring millimolar/gram concentrations of intracrystalline organic moieties and shape-selectivity are synthesized. Pure-silica zeolite beta crystals are coated with zirconia and treated in aqueous sodium hydroxide to create defects and mesoporosity within the crystalline structure. Aminopropyl organic groups are subsequently grafted onto the generated intracrystalline silanol groups. After grafting, characterization data indicate a high organic concentration localized primarily within the intracrystalline voids. Specifically, thermogravimetric analysis shows an organic loading of 0.7 mmol of NH2/g, 29Si solid-state nuclear magnetic resonance (NMR) spectra display a quantitative decrease in Q3 silicon atoms with a corresponding resharpening of the Q4 resonances, and N2 adsorption data show a decrease in micropore volume to 0.10 cm3/g. Knoevenagel condensation reactions are catalyzed by the aminopropyl-functionalized materials using differently sized aldehydes and the results show that the zirconia-protected functionalized solid have shape selective properties.
Co-reporter:Raymond H. Archer, John R. Carpenter, Son-Jong Hwang, Allen W. Burton, Cong-Yan Chen, Stacey I. Zones and Mark E. Davis
Chemistry of Materials 2010 Volume 22(Issue 8) pp:2563
Publication Date(Web):March 4, 2010
DOI:10.1021/cm9035677
SSZ-70 is synthesized using 1,3-bis(isobutyl)imidazolium, 1,3-bis(cyclohexyl)imidazolium, and 1,3-bis(cycloheptyl)imidazolium structure directing agents (SDAs), and the solids obtained are characterized by powder X-ray diffraction (XRD), 29Si magic angle spinning nuclear magnetic resonance (MAS NMR), electron microscopy, nitrogen and hydrocarbon adsorption, and thermogravimetric analyses. The physicochemical properties of SSZ-70 show that it is a new molecular sieve that has similarities to MWW-type materials. The catalytic behavior of SSZ-70 is evaluated through the use of the constraint index (CI) test. Distinct differences in the reactivity between Al-SSZ-70 and SSZ-25 (MWW) are observed and are the consequences of the structural differences between these two molecular sieves.
Co-reporter:Heather K. Hunt, Christopher M. Lew, Minwei Sun, Yushan Yan, Mark E. Davis
Microporous and Mesoporous Materials 2010 Volume 128(1–3) pp:12-18
Publication Date(Web):March 2010
DOI:10.1016/j.micromeso.2009.07.023
A new method to synthesize pure-silica zeolite films is presented. Specifically, this method uses fluoride-mediated syntheses that involve the vapor phase transport of the mineralizing agent, fluoride, to crystallize a precursor film deposited by dip-coating techniques to obtain thin films of pure-silica zeolites with LTA, CHA, and ITW topologies. The films are characterized by a combination of X-ray diffraction, field emission scanning electron microscopy, and X-ray energy dispersive analyses. The films are polycrystalline, intergrown, continuous and well-adhered to their substrates. The usefulness of these thin films as low-k materials, that are needed to reduce cross-talk noise and energy dissipation between transistors in an integrated circuit, is demonstrated via evaluation of the pure-silica LTA film. The LTA topology has the lowest framework density (FD = 14.2) of the 19 known pure-silica zeolites, and theoretically could have the lowest dielectric constant. The average dielectric constants of the LTA films are calculated from capacitance measurements at a frequency of 1 MHz with metal–insulator–metal structures on low-resistivity silicon substrates, and yield an average k = 1.69, well within the ultra low-k material requirements (k between 2.3 and 2.6).
Co-reporter:Manuel Moliner;Yuriy Román-Leshkov;Mark E. Davis;
Proceedings of the National Academy of Sciences 2010 107(14) pp:6164-6168
Publication Date(Web):March 22, 2010
DOI:10.1073/pnas.1002358107
The isomerization of glucose into fructose is a large-scale reaction for the production of high-fructose corn syrup (HFCS;
reaction performed by enzyme catalysts) and recently is being considered as an intermediate step in the possible route of
biomass to fuels and chemicals. Here, it is shown that a large-pore zeolite that contains tin (Sn-Beta) is able to isomerize
glucose to fructose in aqueous media with high activity and selectivity. Specifically, a 10% (wt/wt) glucose solution containing
a catalytic amount of Sn-Beta (1∶50 Sn:glucose molar ratio) gives product yields of approximately 46% (wt/wt) glucose, 31%
(wt/wt) fructose, and 9% (wt/wt) mannose after 30 min and 12 min of reaction at 383 K and 413 K, respectively. This reactivity
is achieved also when a 45 wt% glucose solution is used. The properties of the large-pore zeolite greatly influence the reaction
behavior because the reaction does not proceed with a medium-pore zeolite, and the isomerization activity is considerably
lower when the metal centers are incorporated in ordered mesoporous silica (MCM-41). The Sn-Beta catalyst can be used for
multiple cycles, and the reaction stops when the solid is removed, clearly indicating that the catalysis is occurring heterogeneously.
Most importantly, the Sn-Beta catalyst is able to perform the isomerization reaction in highly acidic, aqueous environments
with equivalent activity and product distribution as in media without added acid. This enables Sn-Beta to couple isomerizations
with other acid-catalyzed reactions, including hydrolysis/isomerization or isomerization/dehydration reaction sequences [starch
to fructose and glucose to 5-hydroxymethylfurfural (HMF) demonstrated here].
Co-reporter:Chung Hang J. Choi;Christopher A. Alabi;Paul Webster;Mark E. Davis
PNAS 2010 Volume 107 (Issue 3 ) pp:1235-1240
Publication Date(Web):2010-01-19
DOI:10.1073/pnas.0914140107
PEGylated gold nanoparticles are decorated with various amounts of human transferrin (Tf) to give a series of Tf-targeted
particles with near-constant size and electrokinetic potential. The effects of Tf content on nanoparticle tumor targeting
were investigated in mice bearing s.c. Neuro2A tumors. Quantitative biodistributions of the nanoparticles 24 h after i.v.
tail-vein injections show that the nanoparticle accumulations in the tumors and other organs are independent of Tf. However,
the nanoparticle localizations within a particular organ are influenced by the Tf content. In tumor tissue, the content of
targeting ligands significantly influences the number of nanoparticles localized within the cancer cells. In liver tissue,
high Tf content leads to small amounts of the nanoparticles residing in hepatocytes, whereas most nanoparticles remain in
nonparenchymal cells. These results suggest that targeted nanoparticles can provide greater intracellular delivery of therapeutic
agents to the cancer cells within solid tumors than their nontargeted analogs.
Co-reporter:Dr. Yuriy Román-Leshkov;Dr. Manuel Moliner;Dr. Jay A. Labinger ; Mark E. Davis
Angewandte Chemie International Edition 2010 Volume 49( Issue 47) pp:8954-8957
Publication Date(Web):
DOI:10.1002/anie.201004689
Co-reporter:Dr. Yuriy Román-Leshkov;Dr. Manuel Moliner;Dr. Jay A. Labinger ; Mark E. Davis
Angewandte Chemie 2010 Volume 122( Issue 47) pp:9138-9141
Publication Date(Web):
DOI:10.1002/ange.201004689
Co-reporter:Mark E. Davis,
Jonathan E. Zuckerman,
Chung Hang J. Choi,
David Seligson,
Anthony Tolcher,
Christopher A. Alabi,
Yun Yen,
Jeremy D. Heidel
&
Antoni Ribas
Nature 2010 464(7291) pp:1067
Publication Date(Web):2010-03-21
DOI:10.1038/nature08956
It has previously been shown in mice and non-human primates that systemically delivered short RNA molecules can inhibit gene expression. Here it is shown that a short interfering RNA (siRNA) can be systemically delivered, using nanoparticles, to a solid tumour in humans. The siRNA mediates cleavage of its target mRNA, thereby also reducing levels of the encoded protein. This proof-of-principle study confirms the potential of this technology for treating human disease.
Co-reporter:Raymond H. Archer, Stacey I. Zones, Mark E. Davis
Microporous and Mesoporous Materials 2010 130(1–3) pp: 255-265
Publication Date(Web):
DOI:10.1016/j.micromeso.2009.11.018
Co-reporter:Heather K. Hunt, Christopher M. Lew, Minwei Sun, Yushan Yan, Mark E. Davis
Microporous and Mesoporous Materials 2010 130(1–3) pp: 49-55
Publication Date(Web):
DOI:10.1016/j.micromeso.2009.10.011
Co-reporter:Christopher A. Alabi, Zhongwei Chen, Yushan S. Yan and Mark E. Davis
Chemistry of Materials 2009 Volume 21(Issue 19) pp:4645
Publication Date(Web):September 8, 2009
DOI:10.1021/cm901772q
A nitrogen-containing heterocycle (NCH), 4,4-1H-1H-bi-1,2,3-triazole (bitriazole), capable of mimicking the hydrogen bonding of water in the solid state is synthesized and its ability to conduct protons in the presence of poly(ethylene oxides) under anhydrous conditions is investigated. Bitriazole is shown to have sufficient thermal and electrochemical stability for fuel cell applications. The composites formed between bitriazole and poly(ethylene oxides) give proton conductivities that can be described by the Vogel−Tamman−Fulcher (VTF) equation. These characteristics suggest coupling between polymer segmental motion and ion transport. The bitriazole N-H proton is shown to be the source of conductivity, and bitriazole and poly(ethylene oxides) function synergistically through specific intermolecular interactions and polymer-induced segmental motion to create a pathway for proton transport via structural diffusion.
Co-reporter:Brendan C. Mack, Kenneth W. Wright, Mark E. Davis
Journal of Controlled Release 2009 Volume 139(Issue 3) pp:205-211
Publication Date(Web):3 November 2009
DOI:10.1016/j.jconrel.2009.06.020
Biodegradable filaments (diameters of 250–300 μm) for the controlled delivery of dexamethasone or levofloxacin are described. Filaments are prepared by wet-spinning solutions of poly(lactide-co-glycolide) (PLGA) and drug dissolved in dimethyl sulfoxide (DMSO) into a coagulation bath of water. Compositional analyses of the filaments by independent measurements of drug, DMSO, water, and polymer give drug loadings up to 40% of filament mass and drug retention (drug in filament per drug in solution) greater than 40%. Drug release kinetics, and thermal and mechanical properties, of the filaments are reported. Three filaments with levofloxacin contents of 46 ± 2, 85 ± 4, and 36 ± 2 μg/cm (denoted 506-L1, 506-L2, and 506-L3, respectively) are implanted in the conjunctiva of New Zealand white rabbits. The time dependent, in-vivo tear concentrations of levofloxacin from filament implants in New Zealand white rabbit eyes are in general agreement with the results from the in-vitro release profiles, with one of the filaments (506-L1) showing effective levels of levofloxacin in the tears for 6 days. The filaments are generally well tolerated by the rabbits. Filament failure occurs at 6–8 days within the rabbit eyes, essentially the same time to failure observed from in-vitro mechanical properties testing results.
Co-reporter:Mark E. Davis
Molecular Pharmaceutics 2009 Volume 6(Issue 3) pp:659-668
Publication Date(Web):March 6, 2009
DOI:10.1021/mp900015y
Experimental therapeutics developed to exploit RNA interference (RNAi) are now in clinical studies. Here, the translation from concept to clinic for the first experimental therapeutic to provide targeted delivery of synthetic, small interfering RNA (siRNA) in humans is described. This targeted, nanoparticle formulation of siRNA, denoted as CALAA-01, consists of a cyclodextrin-containing polymer (CDP), a polythethylene glycol (PEG) steric stabilization agent, and human transferrin (Tf) as a targeting ligand for binding to transferrin receptors (TfR) that are typically upregulated on cancer cells. The four component formulation is self-assembled into nanoparticles in the pharmacy and administered intravenously (iv) to patients. The designed features of this experimental therapeutic are described, and their functions illustrated.Keywords: CALAA-01; clinical trial; siRNA; targeted delivery; targeted nanoparticle;
Co-reporter:John C. McKeen and Mark E. Davis
The Journal of Physical Chemistry C 2009 Volume 113(Issue 22) pp:9870-9877
Publication Date(Web):May 12, 2009
DOI:10.1021/jp902235z
Impedance spectroscopy is used to investigate the long-range ionic conductivity of the microporous, zincosilicate VPI-9 (Si/Zn = 4.0) (International Zeolite Association framework type VNI) containing the alkali cations Li+, Na+, K+, Rb+, and Cs+, and the alkaline earth cations Mg2+, Ca2+, and Sr2+. Monovalent cation-exchanged samples Li- and Na-VPI-9 lose X-ray crystallinity upon vacuum dehydration at 450 °C, whereas K-, Rb-, and Cs-VPI-9 remain crystalline and exhibit conductivities of 1.7 × 10−4, 3.5 × 10−4, and 4.9 × 10−4 S/cm, respectively, at 450 °C and activation energies of 0.72, 0.64, and 0.69 eV, respectively, in the temperature range 150−450 °C. Divalent cation-exchanged sample Mg-VPI-9 also loses X-ray crystallinity, but Ca- and Sr-VPI-9 remain crystalline and exhibit conductivities of 2.3 × 10−6 S/cm and 7.7 × 10−7 S/cm, respectively, at 450 °C, and activation energies of 0.88 and 0.91 eV, respectively, over the temperature range 150−450 °C. When compared to aluminosilicate zeolite X (Si/Al = 1.25) exchanged with the same cations, all crystalline M-VPI-9 materials have greater conductivities than M-X, with the exception of K-X (1.6 × 10−3 S/cm at 450 °C), with the greatest differences arising between the divalent exchanged materials. Dense, crystalline zincosilicate samples with the compositions K2ZnSixO2(x+1) (x = 2−5), Rb2ZnSi5O12, and Cs2ZnSi5O12 are also prepared and characterized for comparison with the microporous materials and exhibit much lower conductivities than their microporous counterparts at the same composition.
Co-reporter:Thomas Schluep;Jungyeon Hwang;Isabel J. Hildebrandt;Johannes Czernin;Chung Hang J. Choi;Christopher A. Alabi;Brendan C. Mack;Mark E. Davis;
Proceedings of the National Academy of Sciences 2009 106(27) pp:11394-11399
Publication Date(Web):June 29, 2009
DOI:10.1073/pnas.0905487106
IT-101, a cyclodextrin polymer-based nanoparticle containing camptothecin, is in clinical development for the treatment of
cancer. Multiorgan pharmacokinetics and accumulation in tumor tissue of IT-101 is investigated by using PET. IT-101 is modified
through the attachment of a 1,4,7,10-tetraazacyclododecane-1,4,7-Tris-acetic acid ligand to bind 64Cu2+. This modification does not affect the particle size and minimally affects the surface charge of the resulting nanoparticles.
PET data from 64Cu-labeled IT-101 are used to quantify the in vivo biodistribution in mice bearing Neuro2A s.c. tumors. The 64Cu-labeled IT-101 displays a biphasic plasma elimination. Approximately 8% of the injected dose is rapidly cleared as a low-molecular-weight
fraction through the kidneys. The remaining material circulates in plasma with a terminal half-life of 13.3 h. Steadily increasing
concentrations, up to 11% injected dose per cm3, are observed in the tumor over 24 h, higher than any other tissue at that time. A 3-compartment model is used to determine
vascular permeability and nanoparticle retention in tumors, and is able to accurately represent the experimental data. The
calculated tumor vascular permeability indicates that the majority of nanoparticles stay intact in circulation and do not
disassemble into individual polymer strands. A key assumption to modeling the tumor dynamics is that there is a “sink” for
the nanoparticles within the tumor. Histological measurements using confocal microscopy show that IT-101 localizes within
tumor cells and provides the sink in the tumor for the nanoparticles.
Co-reporter:Mark E. Davis,
Zhuo (Georgia) Chen
&
Dong M. Shin
Nature Reviews Drug Discovery 2008 7(9) pp:771
Publication Date(Web):2008-09-01
DOI:10.1038/nrd2614
Nanoparticles — particles in the size range 1–100 nm — are emerging as a class of therapeutics for cancer. Early clinical results suggest that nanoparticle therapeutics can show enhanced efficacy, while simultaneously reducing side effects, owing to properties such as more targeted localization in tumours and active cellular uptake. Here, we highlight the features of nanoparticle therapeutics that distinguish them from previous anticancer therapies, and describe how these features provide the potential for therapeutic effects that are not achievable with other modalities. While large numbers of preclinical studies have been published, the emphasis here is placed on preclinical and clinical studies that are likely to affect clinical investigations and their implications for advancing the treatment of patients with cancer.
Co-reporter:John C. McKeen, Yushan S. Yan and Mark E. Davis
Chemistry of Materials 2008 Volume 20(Issue 12) pp:3791
Publication Date(Web):June 3, 2008
DOI:10.1021/cm800762x
Co-reporter:John C. McKeen, Yushan S. Yan and Mark E. Davis
Chemistry of Materials 2008 Volume 20(Issue 16) pp:5122
Publication Date(Web):August 6, 2008
DOI:10.1021/cm801418r
Co-reporter:Jeremy D. Heidel;Zhongping Yu;Joanna Yi-Ching Liu;Shyam M. Rele;Yongchao Liang;Ryan K. Zeidan;Douglas J. Kornbrust;Mark E. Davis;
Proceedings of the National Academy of Sciences 2007 104(14) pp:5715-5721
Publication Date(Web):March 22, 2007
DOI:10.1073/pnas.0701458104
The results of administering escalating, i.v. doses of targeted nanoparticles containing a siRNA targeting the M2 subunit
of ribonucleotide reductase to non-human primates are reported. The nanoparticles consist of a synthetic delivery system that
uses a linear, cyclodextrin-containing polycation, transferrin (Tf) protein targeting ligand, and siRNA. When administered
to cynomolgus monkeys at doses of 3 and 9 mg siRNA/kg, the nanoparticles are well tolerated. At 27 mg siRNA/kg, elevated levels
of blood urea nitrogen and creatinine are observed that are indicative of kidney toxicity. Mild elevations in alanine amino
transferase and aspartate transaminase at this dose level indicate that the liver is also affected to some extent. Analysis
of complement factors does not reveal any changes that are clearly attributable to dosing with the nanoparticle formulation.
Detection of increased IL-6 levels in all animals at 27 mg siRNA/kg and increased IFN-γ in one animal indicate that this high
dose level produces a mild immune response. Overall, no clinical signs of toxicity clearly attributable to treatment are observed.
The multiple administrations spanning a period of 17–18 days enable assessment of antibody formation against the human Tf
component of the formulation. Low titers of anti-Tf antibodies are detected, but this response is not associated with any
manifestations of a hypersensitivity reaction upon readministration of the targeted nanoparticle. Taken together, the data
presented show that multiple, systemic doses of targeted nanoparticles containing nonchemically modified siRNA can safely
be administered to non-human primates.
Co-reporter:Derek W. Bartlett;Helen Su;Isabel J. Hildebrandt;Wolfgang A. Weber;Mark E. Davis
PNAS 2007 104 (39 ) pp:15549-15554
Publication Date(Web):2007-09-25
DOI:10.1073/pnas.0707461104
Targeted delivery represents a promising approach for the development of safer and more effective therapeutics for oncology
applications. Although macromolecules accumulate nonspecifically in tumors through the enhanced permeability and retention
(EPR) effect, previous studies using nanoparticles to deliver chemotherapeutics or siRNA demonstrated that attachment of cell-specific
targeting ligands to the surface of nanoparticles leads to enhanced potency relative to nontargeted formulations. Here, we
use positron emission tomography (PET) and bioluminescent imaging to quantify the in vivo biodistribution and function of nanoparticles formed with cyclodextrin-containing polycations and siRNA. Conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic
acid to the 5′ end of the siRNA molecules allows labeling with 64Cu for PET imaging. Bioluminescent imaging of mice bearing luciferase-expressing Neuro2A s.c. tumors before and after PET
imaging enables correlation of functional efficacy with biodistribution data. Although both nontargeted and transferrin-targeted
siRNA nanoparticles exhibit similar biodistribution and tumor localization by PET, transferrin-targeted siRNA nanoparticles
reduce tumor luciferase activity by ≈50% relative to nontargeted siRNA nanoparticles 1 d after injection. Compartmental modeling
is used to show that the primary advantage of targeted nanoparticles is associated with processes involved in cellular uptake
in tumor cells rather than overall tumor localization. Optimization of internalization may therefore be key for the development
of effective nanoparticle-based targeted therapeutics.
Co-reporter:Swaroop Mishra, Jeremy D. Heidel, Paul Webster, Mark E. Davis
Journal of Controlled Release 2006 Volume 116(Issue 2) pp:179-191
Publication Date(Web):28 November 2006
DOI:10.1016/j.jconrel.2006.06.018
The linear, cyclodextrin-containing polycation (CDP) is one of many non-viral gene delivery vectors that show improved transfection efficiency when modified to have pH-buffering capacity. The buffering activity is presumed to confer enhanced ability to escape the endocytic pathway. Here, the differences in delivery behavior between CDP and its pH-buffering, imidazole-containing variant (CDPim) are investigated in order to elucidate the mechanism(s) by which these related materials exhibit differences in gene delivery. In cell-free assays that include dye exclusion and heparan sulfate displacement, CDP appears to have weaker binding strength with nucleic acids than CDPim. Numerous analyses involving transfected cells, however, indicate that CDPim more readily releases nucleic acids in the intracellular setting. Together, these data suggest that differences in transfection efficiency between CDP and CDPim result from factors beyond buffering activity and endosomal escape.
Co-reporter:Hyunjoo Lee, Stacey I. Zones, Mark E. Davis
Microporous and Mesoporous Materials 2006 Volume 88(1–3) pp:266-274
Publication Date(Web):21 January 2006
DOI:10.1016/j.micromeso.2005.09.018
Molecular sieves are synthesized using degradable, ketal-containing structure-directing agents (SDA). Eight quaternary ammonium compounds that contain ketal groups are synthesized and used as degradable SDAs for the synthesis of ZSM-5, mordenite, ZSM-12 and VPI-8. The ketal-containing SDAs are degraded into smaller fragments by acidic hydrolysis while in the micropore space, and the degradation products observed by 13C CP MAS NMR. This synthetic methodology is used to circumvent the need for SDA removal by calcination. The effects of organic content, hydrophilicity and pore connectivity of the synthesized molecular sieves on the ability to degrade the entrapped SDA are investigated. The SDAs are degraded more readily inside molecular sieves with more hydrophilic character and higher pore connectivity. This is likely due to better mass transfer of H2O and H+ that are necessary for the hydrolysis of the SDA within the micropore space.
Co-reporter:Jonathan Galownia, James Martin, Mark E. Davis
Microporous and Mesoporous Materials 2006 Volume 92(1–3) pp:61-63
Publication Date(Web):20 June 2006
DOI:10.1016/j.micromeso.2005.12.020
Water absorption and mouse blood clotting experiments show that aluminophosphate molecular sieve VPI-5 containing Ca2+ ions can clot blood like the zeolite-containing QuikClot, but with 50% less heat release. These data suggest that Ca2+ containing microporous aluminophosphates may be useful as inexpensive human blood clotting agents.
Co-reporter:Ryan K. Zeidan;Son-Jong Hwang;Mark E. Davis
Angewandte Chemie 2006 Volume 118(Issue 38) pp:
Publication Date(Web):28 AUG 2006
DOI:10.1002/ange.200602243
Doppelfunktion: Die Immobilisierung von primären Aminen und Sulfonsäuren auf mesoporösem Siliciumdioxid (SBA-15-A/B; siehe Schema) ergibt einen kooperativen Heterogenkatalysator für Aldolkondensationen. Die chemischen Reaktivitäten der sauren und basischen Gruppen bleiben jeweils erhalten, ohne sich, wie in homogener Lösung, zu neutralisieren. TEOS: Tetraethoxysilan.
Co-reporter:Ryan K. Zeidan;Son-Jong Hwang;Mark E. Davis
Angewandte Chemie International Edition 2006 Volume 45(Issue 38) pp:
Publication Date(Web):28 AUG 2006
DOI:10.1002/anie.200602243
Dual functions: The simultaneous immobilization of primary amines and sulfonic acids on mesoporous silica SBA-15 (SBA-15-A/B; see scheme) creates a heterogeneous catalyst that exhibits cooperative catalytic behavior in the aldol condensation reaction. The respective chemical reactivities of the acid and base groups are maintained, whereas homogeneous analogues are neutralized in solution. TEOS=tetraethoxysilane.
Co-reporter:Rajan P. Kulkarni;David D. Wu;Mark E. Davis;Scott E. Fraser
PNAS 2005 102 (21 ) pp:7523-7528
Publication Date(Web):2005-05-24
DOI:10.1073/pnas.0501950102
Quantitatively understanding how nonviral gene delivery vectors (polyplexes) are transported inside cells is essential before
they can be optimized for gene therapy and medical applications. In this study, we used spatio-temporal image correlation
spectroscopy (ICS) to follow polymer-nucleic acid particles (polyplexes) of various sizes and analyze their diffusive-like
and flow behaviors intracellularly to elucidate the mechanisms responsible for their transport. ICS is a quantitative imaging
technique that allows the assessment of particle motion in complex systems, although it has not been widely used to date.
We find that the internalized polyplexes are able to use microtubule motors for intracellular trafficking and exhibit different
transport behaviors for short (<10 s) versus long (≈60 s) correlation times. This motion can be explained by a memory effect
of the microtubule motors. These results reveal that, although microtubule motor biases may be present for short periods of
time, resulting in a net directional velocity, the overall long-term motion of the polyplexes is best described as a random
walk-like process. These studies suggest that spatio-temporal ICS is a powerful technique for assessing the nature of intracellular
motion and provides a quantitative tool to compare the transport of different objects within a living cell.
Co-reporter:Mark E. Davis
&
Marcus E. Brewster
Nature Reviews Drug Discovery 2004 3(12) pp:1023
Publication Date(Web):
DOI:10.1038/nrd1576
Cyclodextrins are cyclic oligomers of glucose that can form water-soluble inclusion complexes with small molecules and portions of large compounds. These biocompatible, cyclic oligosaccharides do not elicit immune responses and have low toxicities in animals and humans. Cyclodextrins are used in pharmaceutical applications for numerous purposes, including improving the bioavailability of drugs. Current cyclodextrin-based therapeutics are described and possible future applications discussed. Cyclodextrin-containing polymers are reviewed and their use in drug delivery presented. Of specific interest is the use of cyclodextrin-containing polymers to provide unique capabilities for the delivery of nucleic acids.
Co-reporter:I Ogino, M.E Davis
Microporous and Mesoporous Materials 2004 Volume 67(Issue 1) pp:67-78
Publication Date(Web):8 January 2004
DOI:10.1016/j.micromeso.2003.09.027
(-)-Sparteine is alkylated to prepare a series of compounds that are used as structure-directing agents (SDAs) to specifically crystallize large pore molecular sieves. Two new sparteine derivatives, N-ethylsparteinium (EtSPA) and N,N′-dimethylsparteinium (Me2SPA), are synthesized and their single crystal X-ray structures obtained. The results from molecular sieve syntheses using EtSPA and Me2SPA are compared to previously reported preparations that employed N (16)-methylsparteinium (MeSPA). In general, crystalline phases obtained with MeSPA, e.g., SSZ-24, CIT-5, ITQ-21, can also be prepared using EtSPA and Me2SPA. However, Me2SPA did produce what appears to be a new phase from a reaction mixture containing Zn2+.
Co-reporter:Hyunjoo Lee,
Stacey I. Zones
and
Mark E. Davis
Nature 2003 425(6956) pp:385
Publication Date(Web):
DOI:10.1038/nature01980
Zeolites are mainly used for the adsorption and separation of ions and small molecules, and as heterogeneous catalysts. More recently, these materials are receiving attention in other applications, such as medical diagnosis and as components in electronic devices1. Modern synthetic methodologies for preparing zeolites and zeolite-like materials typically involve the use of organic molecules that direct the assembly pathway and ultimately fill the pore space2, 3, 4, 5, 6. Removal of these enclathrated species normally requires high temperature combustion that destroys this high cost component, and the associated energy release in combination with the formed water can be extremely detrimental to the inorganic structure7. Here we report a synthetic methodology that avoids these difficulties by creating organic structure-directing agents (SDAs) that can be disassembled within the zeolite pore space to allow removal of their fragments for possible use again by reassembly. The methodology is shown for the synthesis of zeolite ZSM-5 using a SDA that contains a cyclic ketal group that is removed from the SDA while it is inside the zeolite without destruction of the inorganic framework. This approach should be applicable to the synthesis of a wide variety of inorganic and organometallic structures.
Co-reporter:José G. Nery, Son-Jong Hwang, Mark E. Davis
Microporous and Mesoporous Materials 2002 Volume 52(Issue 1) pp:19-28
Publication Date(Web):March 2002
DOI:10.1016/S1387-1811(02)00274-3
SSZ-43 and SSZ-48 are new high-silica molecular sieves prepared with organic structure-directing agents (SDAs) derived from the decahydroquinolinium cation. SSZ-48 has a related theoretical 14 member-ring (MR) net, and computer modeling with energy minimization has been used to predict SDAs suitable for stablilizing this theoretical 14MR structure. Three SDAs derived from decahydroquinolinium cation were indicated as plausible candidates for the synthesis of the 14MR material. These SDAs are investigated here using several reaction chemistries. The results show that in addition to SSZ-43 and SSZ-48, other materials including known, large-pore, high-silica molecular sieves such as SSZ-31, CIT-6 and zeolite beta can be synthesized with these SDAs. NMR data show that some of the newly synthesized materials contain a significant amount of Q3 sites. The removal of the SDAs through calcination converts these Q3 sites to Q4 silicons, and generates microporosity.
Co-reporter:Mark E. Davis ;Christopher J. Dillon;Joseph H. Holles;Jay Labinger Dr.
Angewandte Chemie International Edition 2002 Volume 41(Issue 5) pp:
Publication Date(Web):7 MAR 2002
DOI:10.1002/1521-3773(20020301)41:5<858::AID-ANIE858>3.0.CO;2-7
A niobium and pyridine salt of molybdo(vanado)phosphoric acid (see formula) leads to a catalyst that achieves excellent yield and productivity for both the conversion of propane into acrylic acid and n-butane into maleic acid. The catalyst is active under either hydrocarbon-rich or -lean reaction conditions.
Co-reporter:Mark E. Davis ;Christopher J. Dillon;Joseph H. Holles;Jay Labinger Dr.
Angewandte Chemie 2002 Volume 114(Issue 5) pp:
Publication Date(Web):7 MAR 2002
DOI:10.1002/1521-3757(20020301)114:5<886::AID-ANGE886>3.0.CO;2-K
Das Geheimnis des Erfolgs ist die Anwesenheit eines Amins, hier Pyridin: Ein Niob/Pyridiniumsalz von Molybdo(vanado)phosphorsäure (siehe Formel) ergibt einen besonders produktiven Katalysator, der bei der Umsetzung von Propan zu Acrylsäure und von n-Butan zu Maleinsäure ausgezeichnete Ausbeuten gewährleistet. Er ist sowohl unter Kohlenwasserstoffreichen als auch -armen Reaktionsbedingungen aktiv.
Co-reporter:Patrick M Piccione, Mark E Davis
Microporous and Mesoporous Materials 2001 Volume 49(1–3) pp:163-169
Publication Date(Web):15 November 2001
DOI:10.1016/S1387-1811(01)00414-0
A new synthetic procedure for the preparation of pure-phase ZSM-11 (MEL) is reported. Pure-phase ZSM-11 is synthesized at 135 °C using 2,2-diethoxyethyltrimethylammonium as a structure-directing agent (SDA). The effects of the incorporation of boron in the reaction chemistry are also reported. A very high SDA–ZSM-11 specificity is observed since the inclusion of ZSM-5 (MFI) into the synthesis mixture at levels as high as 24 wt.% of the total silica content still leads to the crystallization of ZSM-11.
Co-reporter:Christopher W Jones, Katsuyuki Tsuji, Takahiko Takewaki, Larry W Beck, Mark E Davis
Microporous and Mesoporous Materials 2001 Volume 48(1–3) pp:57-64
Publication Date(Web):1 November 2001
DOI:10.1016/S1387-1811(01)00330-4
Pure-silica molecular sieves with the MFI topology and zincosilicates, aluminosilicates, borosilicates and pure silicates with the *BEA topology are synthesized and subjected to solvent extraction treatments in an effort to remove the organic structure-directing agents (SDAs) from the micropores. For both molecular sieve topologies, the amount of SDA that can be removed by extraction is found to be dependent on the size of the SDA and the strength of interaction of the SDA with the molecular sieve framework. Furthermore, the potential for extraction of SDAs from the micropores of the material is shown to correlate well with the temperature at which the SDA combusts in thermogravimetric analyses experiments. For materials with SDAs that are small relative to the size of the micropores, the fraction of SDA that can be removed is found to correlate well with the fraction of the SDA that decomposes below 400°C in the materials studied here. SDA that burns or decomposes at temperatures exceeding this value is strongly bound to the framework via ionic charge-balancing interactions. The ease of liberation of charge-balancing tetraethylammonium (TEA) cations from the various metallosilicates is shown to be Zn>B>Al, following the reverse trend of known Bronsted acidity of the various types of sites. It is shown that this tightly bound SDA is removed by extraction under conditions that simultaneously hydrolyze part of the framework. For example, TEA cations charge-balancing boron atoms in the silicate framework are removed with concomitant hydrolysis of the B–O–Si bonds, releasing the tightly bound TEA cation with subsequent desorption of the boron and TEA from the molecular sieve pores. A borosilicate with the *BEA topology synthesized with TEA fluoride as an SDA is shown to be a precursor to a variety of molecular sieves as was previously demonstrated for the zincosilicate with the *BEA topology, CIT-6.
Co-reporter:Christopher W Jones, Michael Tsapatsis, Tatsuya Okubo, Mark E Davis
Microporous and Mesoporous Materials 2001 Volume 42(Issue 1) pp:21-35
Publication Date(Web):January 2001
DOI:10.1016/S1387-1811(00)00268-7
Several organic-functionalized molecular sieves (OFMSs) are investigated for use as shape-selective catalysts. OFMSs with the ∗BEA topology containing ethylcyclohexenyl, phenethyl and mercaptopropyl functional groups are synthesized and characterized by X-ray diffraction, FT-Raman spectroscopy, solid-state 13C NMR spectroscopy, thermogravimetric analysis, nitrogen physisorption, scanning electron microscopy, energy dispersive spectroscopy, field emission scanning electron microscopy, and transmission electron microscopy. Acidic OFMSs derived from phenethyl and mercaptopropyl containing OFMSs are used in catalytic tests. Sulfonated phenethyl-containing OFMSs can exhibit poor shape selectivity in discriminating between cyclohexanone and 1-pyrenecarboxaldehyde reactions with ethylene glycol at low temperatures in the liquid phase. This poor selectivity is shown to be due to the introduction of silanol-bound sulfonic acid species on the external surface by sulfonation of extracted phenethyl-functionalized beta samples. Sulfonic acid containing OFMSs derived from the oxidation of mercaptopropyl groups are very selective for the conversion of cyclohexanone relative to 1-pyrenecarboxaldehyde, with an initial rate ratio (RHEX/RPYC) that can exceed 200. The rate of reaction over this shape-selective catalyst is significantly slower than over commercial zeolite beta, organic-functionalized mesoporous materials, and homogeneous acids.
Co-reporter:Wen Li, Lin Luo, Hiromi Yamashita, Jay A Labinger, Mark E Davis
Microporous and Mesoporous Materials 2000 Volume 37(1–2) pp:57-65
Publication Date(Web):May 2000
DOI:10.1016/S1387-1811(99)00193-6
Individual and mixed metal oxide clusters of antimony and vanadium are synthesized within the pore space of zeolite beta and investigated by powder X-ray diffraction, N2 physisorption, electron spin resonance spectroscopy, temperature-programmed reduction and X-ray adsorption fine structure. Vanadium species (VO2+) are highly dispersed in zeolite beta by ion exchange of the hydrogen form with VOSO4. Upon calcination in air and subsequent reduction at 550°C in hydrogen, the vanadium species do not aggregate into large oxide clusters. On the contrary, intrazeolitic antimony species obtained via the impregnation of antimony acetate into zeolite beta do aggregate during calcination in air. However, if antimony acetate is impregnated into a zeolite beta containing vanadium at an Sb/V ratio near unity, mixed metal oxide clusters are formed with physicochemical properties different from either intrazeolitic vanadium or antimony or bulk SbVO4. At Sb/V ratios above unity, phase-separated antimony oxide is obtained in addition to the intrazeolitic mixed metal oxide clusters.
Co-reporter:Osamu Chiyoda, Mark E Davis
Microporous and Mesoporous Materials 2000 Volume 38(2–3) pp:143-149
Publication Date(Web):1 August 2000
DOI:10.1016/S1387-1811(99)00287-5
Synthetic gmelinite zeolites are prepared via (i) hydrothermal conversion of strontium-containing zeolite Y and (ii) the use of a DABCO (1,4-diazabicyclo [2,2,2] octane) polymer structure-directing agent. The synthetic materials are compared to a sample of natural gmelinite. The adsorption capacities of the three gmelinites after ion exchange with Na+, Sr2+ and La3+ for adsorbates such as water, methanol, ethanol, propanol, nitrogen, n-hexane and cyclohexane are presented. It is shown on each type of gmelinite and independent of the degree of faulting, the adsorption capacities of nitrogen, propanol, n-hexane and cyclohexane increase when monovalent cations are replaced by multivalent cations. However, adsorbates such as water, methanol and ethanol do not show significant variations in adsorption capacity with exchangeable ion valency.
Co-reporter:Alexander Katz
and
Mark E. Davis
Nature 2000 403(6767) pp:286
Publication Date(Web):
DOI:10.1038/35002032
Molecular imprinting aims to create solid materials containing chemical
functionalities that are spatially organized by covalent1 or
non-covalent2 interactions with imprint (or template) molecules
during the synthesis process. Subsequent removal of the imprint molecules
leaves behind designed sites for the recognition of small molecules, making
the material ideally suited for applications such as separations, chemical
sensing and catalysis2, 3, 4, 5. Until now, the molecular imprinting
of bulk polymers2, 3, 4, 5 and polymer6, 7 and
silica8, 9 surfaces has been reported, but the extension of
these methods to a wider range of materials remains problematic. For example,
the formation of substrate-specific cavities within bulk silica, while conceptually
straightforward10, has been difficult to accomplish experimentally11, 12. Here we describe the imprinting of bulk amorphous silicas
with single aromatic rings carrying up to three 3-aminopropyltriethoxysilane
side groups; this generates and occupies microporosity and attaches functional
organic groups to the pore walls in a controlled fashion. The triethoxysilane
part of the molecules' side groups is incorporated into the silica framework
during sol–gel synthesis, and subsequent removal of the aromatic core
creates a cavity with spatially organized aminopropyl groups covalently anchored
to the pore walls. We find that the imprinted silicas act as shape-selective
base catalysts. Our strategy can be extended to imprint other functional groups,
which should give access to a wide range of functionalized materials.
Co-reporter:O. Chiyoda, M.E. Davis
Microporous and Mesoporous Materials 1999 Volume 32(Issue 3) pp:257-264
Publication Date(Web):1 December 1999
DOI:10.1016/S1387-1811(99)00112-2
Hydrothermal synthesis of the natural, alkaline-earth zeolites via the alteration of Y-zeolite is presented. Synthetic versions of the zeolites harmotome, heulandite, brewsterite and gmelinite are synthesized from Y-zeolite using alkaline-earth cation containing solutions. The effect of the composition of the starting zeolite, the composition of the solution phase, the presence or absence of seeds and the experimental conditions are discussed.
Co-reporter:Christopher W Jones, Katsuyuki Tsuji, Mark E Davis
Microporous and Mesoporous Materials 1999 Volume 33(1–3) pp:223-240
Publication Date(Web):15 December 1999
DOI:10.1016/S1387-1811(99)00141-9
Organic-functionalized molecular sieves (OFMSs) with a beta-type structure (∗BEA) containing intracrystalline phenethyl (PE) groups were synthesized and characterized by X-ray diffraction, thermogravimetric analysis, FT Raman spectroscopy, 29Si, 13C and 27Al solid-state nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, bulk elemental analysis, scanning electron microscopy and physisorption techniques. The OFMSs are synthesized from monomeric silicon sources such as tetraethylorthosilicate and phenethyltrimethoxysilane and via the solid-state conversion of extracted, PE-functionalized MCM-41. Occluded structure-directing agent (tetraethylammonium fluoride; TEAF) is removed by solvent extraction techniques. By varying the extraction conditions, OFMSs with varying hydrophobicity and porosity are synthesized. Bulk and surface elemental analysis indicate that there is an even distribution of organic functionalities throughout the material at levels of PE incorporation below 5% (silicon basis). The phenethyl groups are sulfonated using SO3 vapor to produce a microporous solid containing intracrystalline sulfonic acids.
Co-reporter:Christopher W. Jones,
Katsuyuki Tsuji
and
Mark E. Davis
Nature 1998 393(6680) pp:52
Publication Date(Web):
DOI:10.1038/29959
Zeolites and related crystalline molecular sieves can possess catalytically active acid sites, as well as uniformly sized and shaped pores and voids, that allow for their industrial use as shape-selective catalysts1. Some catalytic reactions that are not mediated by acids (such as oxidation) have also been shown to occur in zeolites in a shape-selective manner2, but the diversity in active sites in these materials remains restricted. For mesoporous materials3, the diversity in catalytic activity has been broadened by grafting organosilanes that contain organic functional groups onto the internal pore surfaces4, 5, 6 or by incorporating them into the structure during the synthesis process7, 8, 9, 10, 11, 12. The former approach has not proven straightforward for microporous zeolites because a large fraction of the grafted functional groups become attached instead to the exterior surfaces of the crystal, where there is no shape selectivity13. The synthesis of zeolites and molecular sieves using organosilanes as structure-directing agents has been accomplished14,15, but the subsequent creation of porosity requires the complete loss of the organic functional groups. Here we report a new methodology that overcomes these problems and allows the production of microporous molecular sieves containing organic functionalities within their pores. During the initial synthesis phase, phenethyl groups covalently tethered to silicon atoms are incorporated into the framework. The external surface-bound functionalities and the structure-directing agents residing within the intracrystalline spaces are then removed to create a microporous material. Subsequent sulphonation of the phenyl rings produces intrapore sulphonic acid sites that perform shape-selective catalysis. Different active-site types can be created by attaching other functional groups to the framework silicon, and we therefore expect that our method will lead to the formation of a wide range of shape-selective catalysts.
Co-reporter:Mark E. Davis
Chemistry - A European Journal 1997 Volume 3(Issue 11) pp:
Publication Date(Web):20 JAN 2006
DOI:10.1002/chem.19970031104
The definition and reasons for desiring extralarge pore, crystalline molecular sieves are ennumerated. A historical perspective on the development of these materials is presented with emphasis on critical features important for practical application. Based on the known physiochemical properties of extra-large pore materials, several avenues for their synthesis are suggested. Finally, a few issues of concern when dealing with this class of materials are presented.
Co-reporter:Stephen K. Brand, Tyler R. Josephson, Jay A. Labinger, Stavros Caratzoulas, Dionisios G. Vlachos, Mark E. Davis
Journal of Catalysis (September 2016) Volume 341() pp:62-71
Publication Date(Web):1 September 2016
DOI:10.1016/j.jcat.2016.06.013
•A methyl tin silsesquioxane is studied as a model for the closed site in Sn-Beta.•Glucose is catalyzed through equivalent pathways to the heterogeneous open site.•The closed site is catalytically active, but less so than the open site.Tin-containing zeolite Beta (Sn-Beta) has been investigated as a catalyst for isomerizing aldohexoses into ketohexoses through a Lewis acid mediated hydride shift. Recent studies on the reactivities of Lewis base-doped and alkali-exchanged Sn-Beta samples have conclusively demonstrated that the “open” tin site performs the glucose isomerization reaction. With Lewis base doped Sn-Beta, glucose conversion is almost completely eliminated and product selectivity is shifted predominantly to mannose. These data suggest that glucose reactions may occur through pathways that do not involve the “open” site in Sn-Beta; albeit at significantly lower rates. To examine this possibility, reactions of glucose catalyzed by a homogeneous model of Sn-Beta that does not contain “open” sites, methyl-ligated tin silsesquioxane 1a, is experimentally and theoretically examined. 1a is an active glucose conversion catalyst selectively producing mannose, although the rates of reaction are far below those obtained from Sn-Beta. A hybrid quantum mechanical/molecular mechanics model is constructed, and the complete catalytic cycle is computationally examined, considering ring-opening, three distinct pathways for each hydride- and carbon-shift reaction, and ring-closing. The combined experimental and computational results suggest that there could be reaction pathways that involve Si–O–Sn cleavage that give much slower reaction rates than the open tin site in Sn-Beta.Download high-res image (107KB)Download full-size image
Co-reporter:Rajamani Gounder, Mark E. Davis
Journal of Catalysis (December 2013) Volume 308() pp:176-188
Publication Date(Web):1 December 2013
DOI:10.1016/j.jcat.2013.06.016
Lewis acid sites isolated within low-defect, hydrophobic molecular sieves (Sn-Beta-F, Ti-Beta-F) catalyze monosaccharide (glucose–fructose) and disaccharide (lactose–lactulose) aldose–ketose isomerization reactions in liquid water at initial turnover rates (per total metal atom; 373 K) that are, respectively, ∼10–30 and ∼103–104 factors higher than sites isolated within highly defective, hydrophilic molecular sieves (Ti-Beta-OH) or amorphous co-precipitated oxides (TiO2–SiO2). Glucose-H2/glucose-D2 kinetic isotope effects of ∼2 (at 373 K) for intramolecular C2–C1 hydride shift isomerization to fructose indicate that glucose transport to active sites within Ti-Beta-F or Ti-Beta-OH does not limit turnover rates in liquid water or methanol, in spite of dramatic differences in the volumetric occupation of hydrophobic and hydrophilic void spaces by physisorbed solvent molecules. Glucose isomerization turnover rates (per total Ti; 373 K) in liquid water are first-order in aqueous glucose concentration (at least up to 1.5% (w/w)). The mechanistic interpretation of measured first-order isomerization rate constants indicates that they reflect free energies of kinetically relevant isomerization transition states relative to two bound solvent molecules, which adsorb competitively with sugars at Lewis acid sites and are the most abundant surface intermediates during steady-state catalysis. The lower isomerization rate constants on Ti centers in highly defective environments, in part, reflect stronger coordination of solvent molecules to Ti centers via additional hydrogen bonding interactions with proximal surface hydroxyl groups. The direct measurement of glucose isomerization rate constants in the liquid phase provides a rigorous and quantitative description of the catalytic differences prevalent among Lewis acidic silica-based solids with hydrophobic or hydrophilic properties, and their interpretation using a mechanism-based rate equation provides further clarity into the inhibition of catalytic turnovers at Lewis acid sites by solvent coordination.Graphical abstractDownload high-res image (83KB)Download full-size imageHighlights•Glucose and lactose isomerization are catalyzed by Lewis acidic zeolites.•Order-of-magnitude higher turnover rates on hydrophobic than hydrophilic solids.•Reactant diffusion does not limit rates even when pores are filled with solvent.•Rate constants reflect transition state stability relative to bound solvent.•Solvent molecules bind more strongly at Ti centers in defective environments.
Co-reporter:Ryan K. Zeidan, Mark E. Davis
Journal of Catalysis (25 April 2007) Volume 247(Issue 2) pp:379-382
Publication Date(Web):25 April 2007
DOI:10.1016/j.jcat.2007.02.005
Acid–base bifunctionalized heterogeneous catalysts may be capable of exhibiting reactivity not achievable with homogeneous catalysts. We investigated the effect of pKa of the acid component of mesoporous solids containing acid–base bifunctionality on their catalytic ability toward aldol condensation between 4-nitrobenzaldehyde and acetone. We found that higher levels of aldol product conversion were obtained when weaker acid components (phosphoric, carboxylic vs sulfonic) were used, an indication of the importance of the equilibrium between free acid and free base and the resulting neutralized ion pair in the catalytic capability of acid–base functionalized materials. A catalyst containing primary amine groups in combination with carboxylic acid groups (with similar chemical functionalities to proline) was found to be a superior catalyst in this aldol reaction with a number of different electrophilic components.
Co-reporter:Mark E. Davis
Advanced Drug Delivery Reviews (12 November 2009) Volume 61(Issue 13) pp:1189-1192
Publication Date(Web):12 November 2009
DOI:10.1016/j.addr.2009.05.005
IT-101 (Insert Therapeutics-101) is a linear, cyclodextrin-containing polymer conjugate of camptothecin (CPT). When formulated properly, the polymer conjugate self-assembles into nanoparticles of ca. 30 nm diameter and near neutral zeta potential. The nanoparticles show long circulation half-lives in animals and humans and localize in tumors. The nanoparticles enter the tumor cells and slowly release the CPT causing them to disassemble into individual polymer chains that are sufficiently small to be cleared renally. IT-101 is currently being investigated in human clinical trials. Here, the design and development of IT-101 is described with emphasis on features distinguishing it from other polymer-containing therapeutics.
Co-reporter:John R. Carpenter, Sheila Yeh, Stacey I. Zones, Mark E. Davis
Journal of Catalysis (1 January 2010) Volume 269(Issue 1) pp:64-70
Publication Date(Web):1 January 2010
DOI:10.1016/j.jcat.2009.10.016
Zeolites such as SSZ-25 and SSZ-35 exhibit Constraint Indexes (CI) lower than expected. Two hypotheses for the origin of the lower CI values are that partial cages on the external surface of the zeolites significantly contribute to the overall conversions and that the large cages within the crystalline structures provide less steric hinderence at the active site than would be expected from the size of the pores. The effect of external surface activity is observed by comparing the as-synthesized materials to those passivated via dealumination with ammonium hexafluorosilicate. The external surface dealumination is verified by XPS and by the reduction in reactivity toward isopropanol dehydration observed from materials still containing their SDAs. The external surface of calcined zeolites is shown to have little influence on the CI value. Cage accessibility is investigated by comparisons of structures having larger cages to those that do not and by following the time dependent behavior of the CI values for these materials. The presence of large cages in the zeolites is shown to lower the CI values below those expected from the pore sizes, and the time dependence of the CI value can provide insight into the existence of these larger cage structures.External surface activity and increased internal space are investigated to understand the low Constraint Index results compared to the pore size of SSZ-25 and SSZ-35, zeolites with large internal cages.Download high-res image (70KB)Download full-size image
Co-reporter:Joel E. Schmidt, Dan Xie and Mark E. Davis
Journal of Materials Chemistry A 2015 - vol. 3(Issue 24) pp:NaN12897-12897
Publication Date(Web):2015/05/27
DOI:10.1039/C5TA02354H
There are both natural minerals and synthetic zeolites that possess the HEU framework topology. These materials have a limited compositional range (Si/Al < 6), and the natural zeolites often contain a large amount of impurities such as Fe3+. The preparation of impurity-free HEU-type zeolites with higher Si/Al ratio could open many areas of application, particularly in catalysis. Here, we report the first high-silica HEU-type zeolite that can be prepared via two different procedures. In the first method high-silica HEU (denoted CIT-8) is prepared using a topotactic condensation mechanism (layered precursor denoted CIT-8P); CIT-8P is obtained from a low-water synthesis in fluoride media. CIT-8 prepared in this manner has a product Si/Al ratio of 9.8 ± 0.7 and a micropore volume of 0.10 cm3 g−1 (measured by nitrogen adsorption). The variable temperature powder X-ray diffraction shows that CIT-8 forms via topotactic condensation from CIT-8P along the b axis. Additionally, high-silica heulandite can be synthesized directly from a hydroxide-mediated reaction mixture (denoted CIT-8H), and has a Si/Al ratio of 6.4 ± 0.3 and a micropore volume of 0.10 cm3 g−1. Both synthesis methods produce zeolites that expand the compositional range of HEU-type zeolites. These synthetic methods allow for the addition of other heteroatoms, and titanium-containing CIT-8 is prepared as an illustrative example.
Co-reporter:Joel E. Schmidt, Dan Xie and Mark E. Davis
Chemical Science (2010-Present) 2015 - vol. 6(Issue 10) pp:NaN5963-5963
Publication Date(Web):2015/07/27
DOI:10.1039/C5SC02325D
There are several distinct two-dimensional zeolite building layers that can condense through different stacking arrangements of the layers to form various three-dimensional framework materials. All known building layers are dense layers in that they do not contain 8-membered ring (MR) or larger pores perpendicular to the two-dimensional layers. Herein, we report a new material (CIT-10) that consists of a two-dimensional layer (termed “rth” layer) that contains an 8 MR perpendicular to the layer. Calcination of CIT-10 forms pure-silica RTH (SSZ-50). CIT-10 can be pillared to form a new framework material with a three-dimensional pore system of 8 and 10 MRs, denoted CIT-11, that can be calcined to form a new microporous material, denoted CIT-12.
Co-reporter:Marat Orazov and Mark E. Davis
Chemical Science (2010-Present) 2016 - vol. 7(Issue 3) pp:NaN2274-2274
Publication Date(Web):2016/01/04
DOI:10.1039/C5SC03889H
Microporous and mesoporous zincosilicates (e.g., CIT-6, VPI-8, Zn-MFI, and Zn-MCM-41) synthesized in the presence of alkali cations contain two broad types of Zn sites: one that is a dication analog of the monocation ion-exchangeable Al-site in aluminosilicates, while the other resembles isolated Zn sites on amorphous silica. The ratio of these sites varies, depending on the synthesis conditions of the zincosilicate. Post-synthetic strategies based on ion-exchange can alter the site distribution towards either population. Furthermore, post-synthetic introduction of isolated Zn sites of the latter type is possible for materials possessing silanol nests. Both types of sites behave as Lewis acid centers in probe-molecule IR spectroscopy, but have very different catalytic properties. Due to the unusually high adsorption energies of Lewis bases on such materials, Lewis acid catalysis is difficult at low temperatures and in solvents bearing Lewis basic functionality. However, at high temperatures, in hydrocarbon solvents, CIT-6 (Zn-beta) is able to selectively catalyze the Lewis-acid-catalyzed Diels–Alder cycloaddition–dehydration reactions of ethylene with methyl 5-(methoxymethyl)furan-2-carboxylate, a furan that can be derived quantitatively by partial oxidation of biomass-based 5-hydroxymethylfurfural. Additionally, zinc in silica-based molecular sieves is shown here to enable chemistries previously not accessible with framework Sn-, Ti- and Zr-based Lewis acid sites, e.g., the direct production of dimethyl terephthalate by Diels–Alder cycloaddition–dehydration reactions of ethylene and the dimethyl ester of furan-2,5-dicarboxilic acid.
Co-reporter:Joel E. Schmidt, Dan Xie, Thomas Rea and Mark E. Davis
Chemical Science (2010-Present) 2015 - vol. 6(Issue 3) pp:NaN1734-1734
Publication Date(Web):2015/01/23
DOI:10.1039/C4SC03935A
A new crystalline molecular sieve, denoted CIT-7, is synthesized using an imidazolium-based diquaternary organic structure directing agent (OSDA). The framework structure is determined from a combination of rotation electron diffraction and synchrotron X-ray powder diffraction data. The structure has 10 crystallographically unique tetrahedral atoms (T-atoms) in the unit cell, and can be described as an ordered arrangement of the [425462] mtw building unit and a previously unreported [4452] building unit. The framework contains a 2-dimensional pore system that is bounded by 10 T-atom rings (10-ring, 5.1 Å × 6.2 Å opening) that are connected with oval 8-rings (2.9 Å × 5.5 Å opening) through medium-sized cavities (∼7.9 Å) at the channel intersections. CIT-7 can be synthesized over a broad range of compositions including pure-silica and heteroatom, e.g., aluminosilicate and titanosilicate, containing variants.
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