Reaction mechanism of NO with hydrolysates of NAMI‐A: an MD simulation by combining the QM/MM(ABEEM) with the MD‐FEP method

Nitrosylation reaction mechanisms of the hydrolysates of NAMI‐A and hydrolysis reactions of ruthenium nitrosyl complexes were investigated in the triplet state and the singlet state. Activation free energies were calculated by combining the QM/MM(ABEEM) method with free energy perturbation theory, and the explicit solvent environment was simulated by an ABEEMσπ polarizable force field. Our results demonstrate that nitrosylation reactions of the hydrolysates of NAMI‐A occur in both the triplet and the singlet states. The Ru‐N‐O angle of the triplet ruthenium nitrosyl complexes is in the range of 132.0°–138.2°. However, all the ruthenium nitrosyl complexes at the singlet state show an almost linear Ru‐N‐O angle. The nitrosylation reaction happens prior to the hydrolysis reaction for the first‐step hydrolysates. The activation free energies of the nitrosylation reactions show that the H2O‐NO exchange reaction of [RuCl4(Im)(H2O)] in the singlet spin sate is the most likely one. Comparing with the activation free energies of the hydrolysis reactions of the ruthenium nitrosyl complexes, the results indicate that the rate of the DMSO–H2O exchange reaction of [RuCl3(NO)(Im)(DMSO)] is faster than that of [RuCl3(H2O)(Im)(DMSO)] in both the triplet spin state and the singlet spin state. © 2018 Wiley Periodicals, Inc. Ab initio method and ABEEM/MM‐FEP method have been combined to investigate reaction mechanism of the interactions of NO with NAMI‐A hydrolysates in both the triplet and singlet spin states. The combined QM/MM(ABEEM polarizable force field) method with MD‐FEP was employed to calculate the activation free energies. The rates of nitrosylation reactions are faster than those of further hydrolysis reactions for the first step hydrolysates of NAMI‐A. The activation free energies of the nitrosylation reactions show that the H2O‐NO exchange reaction of [RuCl4(Im)(H2O)] in the singlet spin sate is the most likely one.