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Azanone (nitroxyl, HNO) is a highly reactive compound whose biological role is still a matter of debate. One possible route for its formation is NO reduction by biological reductants. These reactions have been historically discarded due to the negative redox potential for the NO,H+/HNO couple. However, the NO to HNO conversion mediated by vitamins C, E, and aromatic alcohols has been recently shown to be feasible from a chemical standpoint. Based on these precedents, we decided to study the reaction of NO with thiols as potential sources of HNO. Using two complementary approaches, trapping by a Mn porphyrin and an HNO electrochemical sensor, we found that under anaerobic conditions aliphatic and aromatic thiols (as well as selenols) are able to convert NO to HNO, albeit at different rates. Further mechanistic analysis using ab initio methods shows that the reaction between NO and the thiol produces a free radical adduct RSNOH, which reacts with a second NO molecule to produce HNO and a nitrosothiol. The nitrosothiol intermediate reacts further with RSH to produce a second molecule of HNO and RSSR, as previously reported.

The Lennard-Jones (12-6) parameters were obtained for all atoms of cisplatin molecule using the ab initio quantum mechanical potential energy surface for the water-cisplatin interaction as reference data. The parameters found were (epsilon/kcal.mol(-1) and sigma/angstroms) 1.0550, 3.6590 (Pt); 0.0381, 4.6272 (Cl); 0.0455, 3.3783 (N); and 0.0185, 0.0936 (H) and provided very good results for the description of the aqueous solution of cisplatin through Monte Carlo simulation. From statistical analysis of solute-solvent interactions, we observed that the NH3 groups are involved in 53% of the calculated hydrogen bonds with a significant contribution from chlorides (41%) and only 6% involving the Pt center. This is in agreement with the expected behavior for such molecules. Two hydration shells with 22 and 81 water molecules, respectively, centered around 4.6 and 7.3 angstroms were found from the center of mass pair correlation function analysis. The cisplatin atomic Lennard-Jones parameters are reported for the first time, and they might be useful for studying the structure, properties, and processes of cisplatin-like molecules in aqueous solution, including explicitly the solvent effect.

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The hydrolysis process of the cisplatin analog cis-dichloro(ethylenediamine)platinum(II) (cis-DEP) was theoretically investigated at the Hartree–Fock, density functional theory and the second order Møller–Plesset perturbation theory levels of calculation. The stationary points on the gas phase potential energy surface for the first and second hydrolysis steps were fully optimized and characterized. For the first aquation process the gas phase results are in satisfactory agreement with the experimental data. However in order to reproduce the observed rate constant for the second hydrolysis step it is essential to include the solvent effect. The structures and energetic properties are similar to the values found for the parent compound cisplatin, showing that the cis-DEP analog should be considered as a potential drug concerning its hydrolysis process.

A combined Monte Carlo and quantum mechanical study was carried out to analyze the tautomeric equilibrium of 2-mercaptopyrimidine in the gas phase and in aqueous solution. Second- and fourth-order Møller-Plesset perturbation theory calculations indicate that in the gas phase thiol (Pym-SH) is more stable than the thione (Pym-NH) by ca. 8 kcal/mol. In aqueous solution, thermodynamic perturbation theory implemented on a Monte Carlo NpT simulation indicates that both the differential enthalpy and Gibbs free energy favor the thione form. The calculated differential enthalpy is DeltaH(SH)(-->)(NH)(solv) = -1.7 kcal/mol and the differential Gibbs free energy is DeltaG(SH)(-->)(NH)(solv) = -1.9 kcal/mol. Analysis is made of the contribution of the solute-solvent hydrogen bonds and it is noted that the SH group in the thiol and NH group in the thione tautomers act exclusively as a hydrogen bond donor in aqueous solution. The proton transfer reaction between the tautomeric forms was also investigated in the gas phase and in aqueous solution. Two distinct mechanisms were considered: a direct intramolecular transfer and a water-assisted mechanism. In the gas phase, the intramolecular transfer leads to a large energy barrier of 34.4 kcal/mol, passing through a three-center transition state. The proton transfer with the assistance of one water molecule decreases the energy barrier to 17.2 kcal/mol. In solution, these calculated activation barriers are, respectively, 32.0 and 14.8 kcal/mol. The solvent effect is found to be sizable but it is considerably more important as a participant in the water-assisted mechanism than the solvent field of the solute-solvent interaction. Finally, the calculated total Gibbs free energy is used to estimate the equilibrium constant.

In this article, we investigated the hydroxylation of methane catalyzed by the binuclear copper site of a pMMO enzyme, through a radical rebound mechanism. All intermediates and transition states along the reaction coordinate were located and the energies involved in the mechanism calculated using the B3LYP functional including dispersion effects. Our B3LYP-D2 results show that the singlet state of the (μ-1,2-peroxo)Cu(II)2 complex plays an important role as the lowest energy species prior to C-H bond activation. A crossing between the singlet and triplet PES is suggested to occur before the cleavage of the C-H bond of methane, where the triplet (bis-μ-oxo)Cu(III)2 is very reactive towards activation of the strong C-H bond of methane. The C-H bond activation is the rate-determining step of the reaction, with an activation energy of 18.6 kcal mol(-1) relative to the singlet (μ-1,2-peroxo)Cu(II)2 species. Comparison with previous theoretical results for a non-synchronous concerted mechanism suggests the radical rebound mechanism as a possible alternative pathway.

Ammonia oxide is revealed as a stable molecule in a crystal structure and as a likely reactive species in many reactions of hydroxylamine.