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

Abstract

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 firststep hydrolysates. The activation free energies of the nitrosylation reactions show that the H 2 O-NO exchange reaction of [RuCl 4 (Im)(H 2 O)] 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-H 2 O exchange reaction of [RuCl 3 (NO)(Im)(DMSO)] is faster than that of [RuCl 3 (H 2 O)(Im) (DMSO)] in both the triplet spin state and the singlet spin state.

Development of QM/MM (ABEEM polarizable force field) method to simulate the excision reaction mechanism of damaged cytosine

“…The initial temperature during the simulation was 298 K with Berendsen thermostats, and the cutoff radius was 12.0 Å. Since the MD simulations were performed in the NVT ensemble, the experimental values were measured in the NPT ensemble, the energy compensation term needed to be increased to 0.5921 kcal/mol when calculating the activation free energy of the reaction 62 . MD simulations were performed for multiple trajectories, and the simulation time for each trajectory was 1 ns.…”

“…And the last 500 ps data were used for statistical average calculation of the activation free energy of the reaction, and then the fluctuation ranges of the activation free energy were obtained 63,64 . ABEEM‐7P water model was adopted to describe the interaction of water solvent in QM/MM(ABEEM) method 62 …”

Electronic structure and mechanism for the uptake of nitric oxide by the Ru(iii) antitumor complex NAMI-A

“…In a detailed recent work, Li and co-workers 31 investigated the mechanism for the nitrosylation reaction of NAMI-A mono-hydrolysate complexes in the singlet and triplet states, in aqueous solution, using QM/MM methods. Their results showed the possible coexistence of the singlet and triplet spin states in the ruthenium nitrosyl complex in aqueous solution leading to a competitive interaction between spin states.…”

ABEEM/MM OH– Models for OH–(H2O)n Clusters and Aqueous OH–: Structures, Charge Distributions, and Binding Energies

“…It calculates the charge distribution by solving a set of linear equations without any iteration. There are some FQ models, including the electronegativity equalization method (EEM), , the charge equilibration (QEq), the chemical potential equalization principle (CPE), and the atom-bond electronegativity equalization method (ABEEM). , A few PFFs with fluctuating charge models have also been developed and applied by some groups, such as Patel and Brooks III, Rick, Rappé and Goddard, , van der Graaf, Chelli and Procacci, , Stern and Berne, , Yang and co-workers, − and so on. The ABEEM/MM proposed and developed by Yang and his co-workers can deal with the charge transfer and the electrostatic polarization effect.…”

“…The ABEEM/MM proposed and developed by Yang and his co-workers can deal with the charge transfer and the electrostatic polarization effect. It has been successfully applied to gas-phase water clusters and bulk water, − aqueous ionic solutions, ,− biomolecules, inorganic and organic molecules, − and metalloproteins …”