We report the pressure-induced crystallographic transitions and optical behavior of MAPbI₃ (MA=methylammonium) using in situ synchrotron X-ray diffraction and laser-excited photoluminescence spectroscopy, supported by density functional theory (DFT) calculations using the hybrid functional B3PW91 with spin-orbit coupling. The tetragonal polymorph determined at ambient pressure transforms to a ReO₃-type cubic phase at 0.3 GPa. Upon continuous compression to 2.7 GPa this cubic polymorph converts into a putative orthorhombic structure. Beyond 4.7 GPa it separates into crystalline and amorphous fractions. During decompression, this phase-mixed material undergoes distinct restoration pathways depending on the peak pressure. In situ pressure photoluminescence investigation suggests a reduction in band gap with increasing pressure up to ≈0.3 GPa and then an increase in band gap up to a pressure of 2.7 GPa, in excellent agreement with our DFT calculation prediction.

We report the pressure-induced crystallographic transitions and optical behavior of MAPbI₃ (MA=methylammonium) using in situ synchrotron X-ray diffraction and laser-excited photoluminescence spectroscopy, supported by density functional theory (DFT) calculations using the hybrid functional B3PW91 with spin-orbit coupling. The tetragonal polymorph determined at ambient pressure transforms to a ReO₃-type cubic phase at 0.3 GPa. Upon continuous compression to 2.7 GPa this cubic polymorph converts into a putative orthorhombic structure. Beyond 4.7 GPa it separates into crystalline and amorphous fractions. During decompression, this phase-mixed material undergoes distinct restoration pathways depending on the peak pressure. In situ pressure photoluminescence investigation suggests a reduction in band gap with increasing pressure up to ≈0.3 GPa and then an increase in band gap up to a pressure of 2.7 GPa, in excellent agreement with our DFT calculation prediction.

The promiscuous encapsulation of π-electron-rich guests by the π-electron-deficient host, cyclobis(paraquat-p-phenylene) (CBPQT⁴⁺), involves the formation of 1:1 inclusion complexes. One of the most intensely investigated charge-transfer (CT) bands, assumed to result from inclusion of a guest molecule inside the cavity of CBPQT⁴⁺, is an emerald-green band associated with the complexation of tetrathiafulvalene (TTF) and its derivatives. This interpretation was called into question recently in this journal based on theoretical gas-phase calculations that reinterpreted this CT band in terms of an intermolecular side-on interaction of TTF with one of the bipyridinium (BIPY²⁺) units of CBPQT⁴⁺, rather than the encapsulation of TTF inside the cavity of CBPQT⁴⁺. We carried out DFT calculations, including solvation, that reveal conclusively that the CT band emerging upon mixing TTF with CBPQT⁴⁺ arises from the formation of a 1:1 inclusion complex. In support of this conclusion, we have performed additional experiments on a [2]rotaxane in which a TTF unit, located in the middle of its short dumbbell, is prevented sterically from interacting with either one of the two BIPY²⁺ units of a CBPQT⁴⁺ ring residing on a separate [2]rotaxane in a side-on fashion. This [2]rotaxane has similar UV/Vis and ¹H NMR spectroscopic properties with those of 1:1 inclusion complexes of TTF and its derivatives with CBPQT⁴⁺. The [2]rotaxane exists as an equimolar mixture of cis- and trans-isomers associated with the disubstituted TTF unit in its dumbbell component. Solid-state structures were obtained for both isomers, validating the conclusion that the TTF unit, which gives rise to the CT band, resides inside CBPQT⁴⁺.

Human somatostatin receptor subtype 5 (hSSTR5) regulates cell proliferation and hormone secretion. However, the identification of effective therapeutic small-molecule ligands is impeded because experimental structures are not available for any SSTR subtypes. Here, we predict the ensemble of low-energy 3D structures of hSSTR5 using a modified GPCR Ensemble of Structures in Membrane BiLayer Environment (GEnSeMBLE) complete sampling computational method. We find that this conformational ensemble displays most interhelical interactions conserved in class A G protein-coupled receptors (GPCRs) plus seven additional interactions (e.g., Y2.43–D3.49, T3.38–S4.53, K5.64–Y3.51) likely conserved among SSTRs. We then predicted the binding sites for a series of five known antagonists, leading to predicted binding energies consistent with experimental results reported in the literature. Molecular dynamics (MD) simulation of 50 ns in explicit water and lipid retained the predicted ligand-bound structure and formed new interaction patterns (e.g. R3.50–T6.34) consistent with the inactive μ-opioid receptor X-ray structure. We suggest more than six mutations for experimental validation of our prediction. The final predicted receptor conformations and antagonist binding sites provide valuable insights for designing new small-molecule drugs targeting SSTRs.

A series of rhodium(III) bis(quinolinyl)benzene (bisq^x) complexes was studied as candidates for the homogeneous partial oxidation of methane. Density functional theory (DFT) (M06 with Poisson continuum solvation) was used to investigate a variety of (bisq^x) ligand candidates involving different functional groups to determine the impact on Rh^III(bisq^x)-catalyzed methane functionalization. The free energy activation barriers for methane CH activation and Rh–methyl functionalization at 298 K and 498 K were determined. DFT studies predict that the best candidate for catalytic methane functionalization is Rh^III coordinated to unsubstituted bis(quinolinyl)benzene (bisq). Support is also found for the prediction that the η²-benzene coordination mode of (bisq^x) ligands on Rh encourages methyl group functionalization by serving as an effective leaving group for S_N2 and S_R2 attack.

Human Urotensin-II (U-II) is the most potent mammalian vasoconstrictor known.1 Thus, a U-II antagonist would be of therapeutic value in a number of cardiovascular disorders.2 Here, we describe our work on the prediction of the structure of the human U-II receptor (hUT₂R) using GEnSeMBLE (GPCR Ensemble of Structures in Membrane BiLayer Environment) complete sampling Monte Carlo method. With the validation of our predicted structures, we designed a series of new potential antagonists predicted to bind more strongly than known ligands. Next, we carried out R-group screening to suggest a new ligand predicted to bind with 7 kcal mol⁻¹ better energy than 1-{2-[4-(2-bromobenzyl)-4-hydroxypiperidin-1-yl]ethyl}-3-(thieno[3,2-b]pyridin-7-yl)urea, the designed antagonist predicted to have the highest affinity for the receptor. Some of these predictions were tested experimentally, validating the computational results. Using the pharmacophore generated from the predicted structure for hUT₂R bound to ACT-058362, we carried out virtual screening based on this binding site. The most potent hit compounds identified contained 2-(phenoxymethyl)-1,3,4-thiadiazole core, with the best derivative exhibiting an IC₅₀ value of 0.581 μM against hUT₂R when tested in vitro. Our efforts identified a new scaffold as a potential new lead structure for the development of novel hUT₂R antagonists, and the computational methods used could find more general applicability to other GPCRs.

Hydrogen fuel cells (FC) are considered essential for a sustainable economy based on carbon-free energy sources, but a major impediment are the costs. First-principles quantum mechanics (density functional theory including solvation) is used to predict how the energies and barriers for the mechanistic steps of the oxygen reduction reaction (ORR) over the fcc(111) platinum surface depend on the dielectric constant of the solvent. The ORR kinetics can be strongly accelerated by decreasing the effective medium polarizability from the high value it has in water. Possible ways to realize this experimentally are suggested. The calculated volcano structure for the dependence of rate on solvent polarization is considered to be general, and should be observed in other electrochemical systems.

Urotensin-II (U-II) has been shown to be the most potent mammalian vasoconstrictor known. Thus, a U-II antagonist might be of therapeutic value in a number of cardiovascular disorders. However, interspecies variability of several nonpeptidic ligands complicates the interpretation of in vivo studies of such antagonists in preclinical animal disease models. ACT058362 is a selective antagonist for the human U-II receptor (hUT2R) with a reported K_d value of ∼4 nM in a molecular binding assay, but it is reported to bind weakly to rat UT2R (rUT2R), with a K_d value of ∼1 500 nM. In contrast, the arylsulphonamide SB706375 is a selective antagonist against both hUT2R (K_d=∼9 nM) and rUT2R (K_d=∼21 nM). To understand the species selectivity of the UT2R, we investigated the binding site of ACT058362 and SB706375 in both hUT2R and rUT2R to explain the dramatically lower (∼400-fold) affinity of ACT058362 for rUT2R and the similar affinity (∼10 nM) of SB706375 for both UT2Rs. These studies used MembStruk and MSCDock to predict the UT2R structure and the binding site of ACT058362 and SB706375. Based on binding energies, we found two binding modes each with D130^3.32 as the crucial anchoring point (Ballesteros–Weinstein numbering given in superscript). We predict that ACT058362 (an aryl–amine–aryl or ANA ligand) binds in the transmembrane (TM) 3456 region, while SB706375 (an aryl–aryl–amine or AAN ligand) binds in the TM 1237 region. These predicted sites explain the known differences in binding of the ANA ligand to rat and human receptors, while explaining the similar binding of the AAN compound to rat and human receptors. Moreover the predictions explain currently available structure–activity relationship (SAR) data. To further validate the predicted binding sites of these ligands in hUT2R and rUT2R, we propose several mutations that would help define the structural origins of differential responses between UT2R of different species, potentially indicating novel UT2R antagonists with cross-species high affinity.