Biomimetic models for cysteine proteases. 3. Acylation of imidazolium-thiolate zwitterions by p-nitrophenylacetate as a model for the acylation step and demonstration of intramolecular general-base-catalyzed delivery of water by imidazole to thiol esters as a model for the deacylation step

Abstract

The pH dependence of the acylation of (I) and the deacylation of (III) shows a plateau region in the intermediate range.

Intramolecular Catalysis of Thiol Ester Hydrolysis by a Tertiary Amine and a Carboxylate

“…Rates of disappearance of the starting esters were followed at 270 nm using instrumentation and methods previously described. − Reactions were initiated by injecting 20−25 μL of a 0.009−0.012 M solution of the ester in dry acetonitrile into 3 mL of buffer solution held in 1-cm quartz cuvettes which were thermally equilibrated at 50 ± 0.7 °C in the cell holder for 10 min prior to initiation of the run. The pseudo-first-order rate constant for the reaction ( k obs ) was obtained by NLLSQ fitting of absorbance vs time data to a standard exponential model ( A t = A ∞ + ( A 0 − A ∞ )exp(− kt )).…”

“…The catalytic cycle of these enzymes is known to proceed through an intermediate thioester which is subsequently hydrolyzed with general base assistance of the histidine imidazole to regenerate the native enzyme. In ongoing efforts to develop small molecule biomics of the cysteine proteases, we have synthesized 1 − 3 − which contain reasonable approximations for the histidine and cysteine active site residues, and studied their reactions with activated esters 5 3,4 and the distorted amide 6 . , In addition, we have recently reported the reaction of thioglycolic acid ( 4) with 6 as a potential model for a hypothetical enzymatic site containing SH and COOH.

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Imidazolium silanethiolates relevant to the active site of cysteine proteases. A cooperative effect in a chain of NH+⋯S− hydrogen bonds

“…In the middle eighties the solvolysis of 2-[2-(acetylthio)phenyl]-4,5-dimethylimidazole has been studied in ethanol-water solution as a model for the thiol ester intermediates occurring during the catalytic cycle of cysteine proteases. [20][21][22] All the studied compounds feature one-dimensional networks of hydrogen bonds. Hydrogen bonding interactions play a very important role in functioning of natural systems since hydrogen bonded chains are common proton pathways in biology.…”

Stepwise Construction of Polynuclear Complexes of Rhodium and Iridium Assisted by Benzimidazole-2-thiol. NMR and X-ray Diffraction Studies

“…An additional interest arises when the polydentate bridging ligands are molecules of relevant importance in biological processes, because their coordination to metals serves as model of reference in bioinorganic chemistry. In this context, the imidazole-thiol derivatives, structurally analogous to the thionucleosides, have potential pharmacological activity as found for H1-Meimt (methimazole ) and they are used as biomimetic models for cysteine proteases . We have decided to investigate the coordination ability of one of them, benzimidazole-2-thiol (H 2 Bzimt) which contains an imidazole ring together with a thiol group (Figure A) or alternatively two donor entities HNCS (Figure B), that should be useful for the construction of polynuclear complexes.…”