Formation and Release of NO from Ruthenium Nitrosyl Ammine Complexes [Ru(NH₃)₅(NO)]^2+/3+ in Aqueous Solution: A Theoretical Investigation

Abstract

In this article, density functional theory in conjunction with Monte Carlo statistical mechanical simulation was used to investigate the electronic structure, reduction potential, solvation, and solvent effects on the electronic spectra of nitrosyl ammine complexes using [Ru(NH)(NO)] as model compounds. In addition, ligand exchange reactions with solvent water molecules were also investigated. It is shown that the complexes are involved in strong hydrogen bonds in aqueous solution, with mean average energies of -13.5 ± 0.4 and -22.4 ± 0.4 kcal mol for Ru(II) and Ru(III), respectively. Interestingly, for all the complexes studied, the NO ligand is not involved in hydrogen bonding interactions in aqueous solution. These strong hydrogen bonds are responsible for the high stability of these complexes in aqueous solution, showing formation constants K greater than 10. The complex [Ru(NH)(NO)] can easily be reduced by biological reducing agents in both the singlet and triplet states; however, the reduction is easier in the triplet state, which has a positive reduction potential of 1.70 V. The formation of [Ru(NH)(NO)] in its most stable singlet state may take place through at least two singlet-triplet surface crossings leading to nonadiabatic effects. The existence of the minimum-energy crossing points makes the release of NO from the triplet state more favorable, with an activation energy almost seven times lower (∼6 kcal mol).

Reduction Potential of RuIII-Based Complexes with Potential Antitumor Activity and Thermodynamics of their Hydrolysis Reactions and Interactions with Possible Biological Targets: a Theoretical Investigation

“…For the Ru III species with d 5 configuration, only the S = 1 / 2 configuration was evaluated since it is the most stable spin state of Ru III complexes. [50][51][52] The optimized Cartesian coordinates of all species studied in this work can be found in the Supplementary Information (SI) section.…”

“…56 We have shown that this combination of methods/basis set provides good reduction potentials for ruthenium complexes. 52 The Gibbs free energy for the interactions involving the Ru II -monoaquo species and the biomolecules (GN3 and GN7 sites, Cys and GSH) were computed using the thermodynamic cycle exemplified in Figure 3 (for the KP1019 monohydrated compound), at the TPSSh/def2-TZVP level of theory.…”

“…However, we have recently shown that the procedure used in this work produces excellent results for the reduction potential of ruthenium complexes with amine ligands. 52 The TPSSh/def2-TZVP optimized structures for the products of the hydrolysis reactions of NAMI-A, in the +3 and +2 oxidation states, are shown in Figures 5 and 6, respectively, which highlight the main structural parameters around the metallic center. The optimized structures for the products of the hydrolysis reactions of KP1019, in the +3 and +2 oxidation states, are shown in Figures S3 and S4 (SI section), respectively.…”

Nitric oxide (NO) photo-release in a series of ruthenium–nitrosyl complexes: new experimental insights in the search for a comprehensive mechanism

“…7 The presence of this resulting diamagnetic singlet ground state has been further supported by several computational studies. [8][9][10][11] Under these assumptions, the photo-release of the NO· radical depicted in equation 1occurs after a formal electron transfer to the nitrosyl ligand, achieved within an intense low-lying electron transition having a strong charge transfer character towards the strongly withdrawing nitrosyl, in any case.…”

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

“…Their investigation showed that NO coordinates linearly with the NAMI‐A‐HAS adduct, and Ru(III) is reduced to Ru(II). Recent theoretical investigation results published by Rodrigues and Rocha showed that the formation of [Ru(NH 3 ) 5 (NO)] 3+ in its most stable singlet state may take place through at least two singlet–triplet surfaces crossing.…”