Hydrogenation reactions can be used to store energy in chemical bonds, and if these reactions are reversible, that energy can be released on demand. Some of the most effective transition metal catalysts for CO2 hydrogenation have featured pyridin-2-ol-based ligands (e.g., 6,6′-dihydroxybipyridine (6,6′-dhbp)) for both their proton-responsive features and for metal–ligand bifunctional catalysis. We aimed to compare bidentate pyridin-2-ol based ligands with a new scaffold featuring an N-heterocyclic carbene (NHC) bound to pyridin-2-ol. Toward this aim, we have synthesized a series of [Cp*Ir(NHC-pyOR)Cl]OTf complexes where R = tBu (1), H (2), or Me (3). For comparison, we tested analogous bipy-derived iridium complexes as catalysts, specifically [Cp*Ir(6,6′-dxbp)Cl]OTf, where x = hydroxy (4Ir) or methoxy (5Ir); 4Ir was reported previously, but 5Ir is new. The analogous ruthenium complexes were also tested using [(η6-cymene)Ru(6,6′-dxbp)Cl]OTf, where x = hydroxy (4Ru) or methoxy (5Ru); 4Ru and 5Ru were both reported previously. All new complexes were fully characterized by spectroscopic and analytical methods and by single-crystal X-ray diffraction for 1, 2, 3, 5Ir, and for two [Ag(NHC-pyOR)2]OTf complexes 6 (R = tBu) and 7 (R = Me). The aqueous catalytic studies of both CO2 hydrogenation and formic acid dehydrogenation were performed with catalysts 1–5. In general, NHC-pyOR complexes 1–3 were modest precatalysts for both reactions. NHC complexes 1–3 all underwent transformations under basic CO2 hydrogenation conditions, and for 3, we trapped a product of its transformation, 3SP, which we characterized crystallographically. For CO2 hydrogenation with base and dxbp-based catalysts, we observed that x = hydroxy (4Ir) is 5–8 times more active than x = methoxy (5Ir). Notably, ruthenium complex 4Ru showed 95% of the activity of 4Ir. For formic acid dehydrogenation, the trends were quite different with catalytic activity showing 4Ir ≫ 4Ru and 4Ir ≈ 5Ir. Secondary coordination sphere effects are important under basic hydrogenation conditions where the OH groups of 6,6′-dhbp are deprotonated and alkali metals can bind and help to activate CO2. Computational DFT studies have confirmed these trends and have been used to study the mechanisms of both CO2 hydrogenation and formic acid dehydrogenation.

Metallo prodrugs that take advantage of the inherent acidity surrounding cancer cells have yet to be developed. We report a new class of pH-activated metallo prodrugs (pHAMPs) that are activated by light- and pH-triggered ligand dissociation. These ruthenium complexes take advantage of a key characteristic of cancer cells and hypoxic solid tumors (acidity) that can be exploited to lessen the side effects of chemotherapy. Five ruthenium complexes of the type [(N,N)2Ru(PL)]2+ were synthesized, fully characterized, and tested for cytotoxicity in cell culture (1A: N,N = 2,2′-bipyridine (bipy) and PL, the photolabile ligand, = 6,6′-dihydroxybipyridine (6,6′-dhbp); 2A: N,N = 1,10-phenanthroline (phen) and PL = 6,6′-dhbp; 3A: N,N = 2,3-dihydro-[1,4]dioxino[2,3-f][1,10]phenanthroline (dop) and PL = 6,6′-dhbp; 4A: N,N = bipy and PL = 4,4′-dimethyl-6,6′-dihydroxybipyridine (dmdhbp); 5A: N,N = 1,10-phenanthroline (phen) and PL = 4,4′-dihydroxybipyridine (4,4′-dhbp). The thermodynamic acidity of these complexes was measured in terms of two pKa values for conversion from the acidic form (XA) to the basic form (XB) by removal of two protons. Single-crystal X-ray diffraction data is discussed for 2A, 2B, 3A, 4B, and 5A. All complexes except 5A showed measurable photodissociation with blue light (λ = 450 nm). For complexes 1A–4A and their deprotonated analogues (1B–4B), the protonated form (at pH 5) consistently gave faster rates of photodissociation and larger quantum yields for the photoproduct, [(N,N)2Ru(H2O)2]2+. This shows that low pH can lead to greater rates of photodissociation. Cytotoxicity studies with 1A–5A showed that complex 3A is the most cytotoxic complex of this series with IC50 values as low as 4 μM (with blue light) versus two breast cancer cell lines. Complex 3A is also selectively cytotoxic, with sevenfold higher toxicity toward cancerous versus normal breast cells. Phototoxicity indices with 3A were as high as 120, which shows that dark toxicity is avoided. The key difference between complex 3A and the other complexes tested appears to be higher uptake of the complex as measured by inductively coupled plasma mass spectrometry, and a more hydrophobic complex as compared to 1A, which may enhance uptake. These complexes demonstrate proof of concept for dual activation by both low pH and blue light, thus establishing that a pHAMP approach can be used for selective targeting of cancer cells.

A new pincer ligand with N-heterocyclic carbene (NHC) and 4-pyridinol-derived rings supports ruthenium complexes for photocatalytic CO2 reduction. The methoxy group on the pyridine ring offers unique catalysis advantages not seen with the unsubstituted analog. Our best catalyst offers selective CO formation, ∼250 turnover cycles, and a 40 h lifetime.

•We report a bidentate ligand that merges N-heterocyclic carbene and pyridinol rings.•Ag, Ru, and Ir complexes been synthesized and characterized including by SC-XRD.•Catalytic CO2 hydrogenation and formic acid dehydrogenation have been studied.•The PF6− anion associated with the metal complexes transforms to PO2F2−.We report the synthesis and characterization of new ruthenium(II) and iridium(III) complexes of a new bidentate chelate, NHCR′-pyOR (OR = OMe, OtBu, OH and R′ = Me, Et). Synthesis and characterization studies were done on the following compounds: four ligand precursors (1–4); two silver complexes of these NHCR′-pyOR ligands (5–7); six ruthenium complexes of the type [η6-(p-cymene)Ru(NHCR′-pyOR)Cl]X with R′ = Me, Et and R = Me, tBu, H and X = OTf−, PF6− and PO2F2− (8–13); and two iridium complexes, [Cp∗Ir(NHCMe-pyOtBu)Cl]PF6 (14) and [Cp∗Ir(NHCMe-pyOH)Cl]PO2F2 (15). The complexes are air stable and were isolated in moderate yield. However, for the PF6− salts, hydrolysis of the PF6− counter anion to PO2F2− during t-butyl ether deprotection was observed. Most of the complexes were characterized by 1H and 13C NMR, MS, IR, and X-ray diffraction. The ruthenium complexes [η6-(p-cymene)Ru(NHCMe-pyOR)Cl]OTf (R = Me (8) and tBu (9)) were tested for their ability to accelerate CO2 hydrogenation and formic acid dehydrogenation. However, our studies show that the complexes transform during the reaction and these complexes are best thought of as pre-catalysts.Download high-res image (106KB)Download full-size image

•Ttz ligands provide a site for remote protonation that alters electronic features.•The reduction of copper(II) to (I) is a key step in enzymatic nitrite reduction.•Here we explore the use of protonation to alter the redox potential.•Electronic changes were verified by cyclic voltammetry and UV–Vis spectroscopy.Tris(triazolyl)borate (Ttz) is a proton responsive ligand, and the redox potential of Ttz complexes can be altered by protonation. Protonation events can therefore alter the thermodynamics of reduction of copper complexes, and this is relevant to nitrite reduction mediated by copper complexes wherein Cu(II) reduction to Cu(I) is the first step. The electrochemical behavior of tris(triazolyl)borate and the corresponding copper complexes, TtztBu,MeCuCl (1) and TtztBu,MeCuNO2 (2), was investigated under both neutral and acidic conditions. Upon protonation, reduction of 1 is shifted more positive (ΔEpc = 290 mV) upon addition of 1.0 equiv. of acid. This result indicates that ligand protonation facilitates the reduction process, which is also evident from the UV–Vis spectral data. In contrast, with the TtztBuMeCuNO2 (2) analog, the reduction peak shifted towards a more negative potential while UV–Vis spectra shows no significant changes as acid is added. This suggests that the protons may not be involved in assisting the redox process but rather lead to decomposition events at reducing potentials. Other electrochemical control studies on a series of compounds, namely (TtztBu,Me)ZnCl (3), (TtztBu,Me)K (4), H(TtztBu,Me) (5), and HtztBu,Me (6), were also conducted with and without acid present. These studies have shown that triazole rings, by themselves and in metal complexes, are not redox active under the conditions we have used. We therefore conclude that the Ttz ligand (including in 1 and 2) is not a site for reduction in our studies.Ttz ligands can bind to copper(II) and provide a site for remote protonation to alter the electronic properties. The reduction of copper(II) to (I) is a key step in enzymatic nitrite reduction. Here we investigate the use of protonation of Ttz to alter the redox potential.Download high-res image (61KB)Download full-size image

The hydrogen bonding ligand, 3-NH(t-butyl)-5-methyl-pyrazole, forms “scorpionate-like” first row transition metal complexes that are held together by hydrogen bonds rather than covalent bonds. The formulae of these complexes are (LH)nMX2, where n = 3, 4; X = Cl, Br; and LH = 3-NH(t-butyl)-5-methyl-pyrazole. The amino-substituted pyrazole can hydrogen bond via both the amino group and the pyrazole NH to form intramolecular NH to halide hydrogen bonds. These complexes have been well characterized and show a 3:1 ratio of ligand to metal for zinc and cobalt (1 and 2), and a 4:1 ratio of ligand to metal for manganese and nickel (3 and 4). The hydrogen bonding interactions appear to be stronger for the 3:1 complexes. The crystallographic and spectroscopic studies (EPR and NMR) have shown that these hydrogen-bonding interactions are strong enough to perturb metal halogen bond distances and, with non-hydrogen bonding solvents, the hydrogen bonds appear to hold these complexes together in solution.Amino-substituted pyrazole ligands form 3:1 and 4:1 transition metal complexes with zinc(II), cobalt(II), manganese(II), and nickel(II). These complexes exhibit hydrogen bonds between NH groups and halide ions. Thus these are “scorpionate-like” metal complexes that are held together by hydrogen bonds rather than covalent bonds.