Synthesis, Crystal Structure, Inhibitory Activity and Molecular Docking of Coumarins/Sulfonamides Containing Triazolyl Pyridine Moiety as Potent Selective Carbonic Anhydrase IX and XII Inhibitors

In this work, two classes of Carbonic Anhydrase (CA) inhibitors, sulfonamide and coumarin derivatives linked to pyta moiety (2a-b) and their corresponding rhenium complexes (3a-b), were designed. These compounds were synthesized and fully characterized by classical analytical methods and X-ray diffraction. All the synthesized compounds were evaluated for their inhibitory activity against the hCA isoforms I, II, IX and XII. They exhibited high inhibitory activities in the range of nanomolar for both hCA IX and hCA XII isoforms. The sulfonamide compound 2a showed the strongest inhibition against the tumour-associated hCA IX isoform with a Ki of 11.7 nM. The tumour-associated isoforms hCA IX and hCA XII were selectively inhibited by all the coumarin derivatives, with inhibition constants ranging from 12.7 nM (2b) to 44.5 nM (3b), while the hCA I and II isoforms were slightly inhibited (in the micromolar range), as expected. In terms of selectivity, compared to previously published rhenium complex-based CA inhibitors, complex 3b showed one of the highest selectivities against hCA IX and hCA XII compared to the off-target isoforms hCA I and hCA II, making it a potential anti-cancer drug candidate. Molecular docking calculations were performed to investigate the inhibition profiles of the investigated compounds at the tumour-associated hCA IX active site and to rationalize our results.

Photocatalytic Deoxygenation of N–O Bonds with Rhenium Complexes: From the Reduction of Nitrous Oxide to Pyridine N-Oxides

The accumulation of nitrogen oxides in the environment calls for new pathways to interconvert the various oxidation states of nitrogen, and especially their reduction. The large spectrum of reduction potentials covered by nitrogen oxides makes it however difficult to find general systems capable of efficiently reducing various N-oxides. Here photocatalysis unlocks high energy species able to both circumvent the inherent low reactivity of the greenhouse gas and oxidant N₂O (E°(N₂O/N₂) = +1.77 V vs. SHE), and reduce pyridine N-oxides (E_1/2(pyridine N-oxide/pyridine) = –1.04 V vs. SHE). The rhenium complex [Re(4,4’-tBu-bpy)(CO)₃Cl] proved to be efficient to perform both reactions under ambient conditions, enabling the deoxygenation of N₂O as well as synthetically relevant and functionalized pyridine N-oxides.<br>

Photocatalytic Deoxygenation of N–O Bonds with Rhenium Complexes: From the Reduction of Nitrous Oxide to Pyridine N-Oxides

The accumulation of nitrogen oxides in the environment calls for new pathways to interconvert the various oxidation states of nitrogen, and especially their reduction. The large spectrum of reduction potentials covered by nitrogen oxides makes it however difficult to find general systems capable of efficiently reducing various N-oxides. Here photocatalysis unlocks high energy species able to both circumvent the inherent low reactivity of the greenhouse gas and oxidant N₂O (E°(N₂O/N₂) = +1.77 V vs. SHE), and reduce pyridine N-oxides (E_1/2(pyridine N-oxide/pyridine) = –1.04 V vs. SHE). The rhenium complex [Re(4,4’-tBu-bpy)(CO)₃Cl] proved to be efficient to perform both reactions under ambient conditions, enabling the deoxygenation of N₂O as well as synthetically relevant and functionalized pyridine N-oxides.<br>

Decarboxylation-triggered homo-Nazarov cyclization of cyclic enol carbonates catalyzed by rhenium complex

Decarboxylative homo-Nazarov cyclization catalyzed by a rhenium complex was achieved using a cyclic enol carbonate bearing a cyclopropane moiety as a substrate.

Temperature and Solvent Effects on H2 Splitting and Hydricity: Ramifications on CO2 Hydrogenation by a Rhenium Pincer Catalyst

The catalytic hydrogenation of carbon dioxide holds immense promise for applications in sustainable fuel synthesis and hydrogen storage. Mechanistic studies that connect thermodynamic parameters with the kinetics of catalysis can provide new understanding and guide predictive design of improved catalysts. Reported here are thermochemical and kinetic analyses of a new pincer-ligated rhenium complex (^tBuPOCOP)Re(CO)₂(^tBuPOCOP = 2,6-bis(di-<i>tert</i>-butylphosphinito)phenyl) that catalyzes CO₂ hydrogenation to formate with faster rates at lower temperature. Because the catalyst follows the prototypical “outer sphere” hydrogenation mechanism, comprehensive studies of temperature and solvent effects on the H₂splitting and hydride transfer steps are expected to be relevant to many other catalysts. Strikingly large entropy associated with cleavage of H₂ results in a strong temperature dependence on the concentration of [(^tBuPOCOP)Re(CO)₂H]^– present during catalysis, which is further impacted by changing the solvent from toluene to tetrahydrofuran to acetonitrile. New methods for determining the hydricity of metal hydrides and formate at temperatures other than 298 K were developed, providing insight into how temperature can influence the favorability of hydride transfer during catalysis. These thermochemical insights guided the selection of conditions for CO₂ hydrogenation to formate with high activity (up to 364 h^–1 at 1 atm or 3330 h^–1 at 20 atm of 1:1 H₂ CO₂). In cases where hydride transfer is the highest individual kinetic barrier, entropic contributions to outer sphere H₂ splitting lead to a unique temperature dependence: <i>catalytic activity increases as temperature decreases</i> in tetrahydrofuran (200-fold increase upon cooling from 50 to 0 °C) and toluene (4-fold increase upon cooling from 100 to 50 °C). Ramifications on catalyst structure-function relationships are discussed, including comparisons between “outer sphere” mechanisms and metal–ligand cooperation mechanisms.

Temperature and Solvent Effects on H2 Splitting and Hydricity: Ramifications on CO2 Hydrogenation by a Rhenium Pincer Catalyst

The catalytic hydrogenation of carbon dioxide holds immense promise for applications in sustainable fuel synthesis and hydrogen storage. Mechanistic studies that connect thermodynamic parameters with the kinetics of catalysis can provide new understanding and guide predictive design of improved catalysts. Reported here are thermochemical and kinetic analyses of a new pincer-ligated rhenium complex (^tBuPOCOP)Re(CO)₂(^tBuPOCOP = 2,6-bis(di-<i>tert</i>-butylphosphinito)phenyl) that catalyzes CO₂ hydrogenation to formate with faster rates at lower temperature. Because the catalyst follows the prototypical “outer sphere” hydrogenation mechanism, comprehensive studies of temperature and solvent effects on the H₂splitting and hydride transfer steps are expected to be relevant to many other catalysts. Strikingly large entropy associated with cleavage of H₂ results in a strong temperature dependence on the concentration of [(^tBuPOCOP)Re(CO)₂H]^– present during catalysis, which is further impacted by changing the solvent from toluene to tetrahydrofuran to acetonitrile. New methods for determining the hydricity of metal hydrides and formate at temperatures other than 298 K were developed, providing insight into how temperature can influence the favorability of hydride transfer during catalysis. These thermochemical insights guided the selection of conditions for CO₂ hydrogenation to formate with high activity (up to 364 h^–1 at 1 atm or 3330 h^–1 at 20 atm of 1:1 H₂ CO₂). In cases where hydride transfer is the highest individual kinetic barrier, entropic contributions to outer sphere H₂ splitting lead to a unique temperature dependence: <i>catalytic activity increases as temperature decreases</i> in tetrahydrofuran (200-fold increase upon cooling from 50 to 0 °C) and toluene (4-fold increase upon cooling from 100 to 50 °C). Ramifications on catalyst structure-function relationships are discussed, including comparisons between “outer sphere” mechanisms and metal–ligand cooperation mechanisms.

A dinuclear rhenium complex in the electrochemically driven homogeneous and heterogeneous H+/CO2-reduction

Herein, we report on the homogeneous and heterogeneous H+/CO2-reduction forming syngas with a binuclear Re complex having a proton rely.