A Personal Account on Inorganic Reaction Mechanisms.

The presented Review is focused on the latest research in the field of inorganic chemistry performed by the van Eldik group and his collaborators. The first part of the manuscript concentrates on the interaction of nitric oxide and its derivatives with biologically important compounds. We summarized mechanistic information on the interaction between model porphyrin systems (microperoxidase) and NO as well as the recent studies on the formation of nitrosylcobalamin (CblNO). The following sections cover the characterization of the Ru(II)/Ru(III) mixed-valence ion-pair complexes, including Ru(II)/Ru(III)(edta) complexes. The last part concerns the latest mechanistic information on the DFT techniques applications. Each section presents the most important results with the mechanistic interpretations.

Unraveling the Molecular Mechanism of S-Nitrosation Mediated by N-Acetylmicroperoxidase-11.

Conversion of NO to stable S-nitrosothiols is perceived as a biologically important strategy of NO storage and a signal transduction mechanism. Transition-metal ions and metalloproteins are competent electron acceptors that may promote the formation of S-nitrosothiols from NO. We selected N-acetylmicroperoxidase (AcMP-11), a model of protein heme centers, to study NO incorporation to three biologically relevant thiols (glutathione, cysteine, and N-acetylcysteine). The efficient formation of S-nitrosothiols under anaerobic conditions was confirmed with spectrofluorimetric and electrochemical assays. AcMP-11-assisted incorporation of NO to thiols occurs via an intermediate characterized as an N-coordinated S-nitrosothiol, (AcMP-11)Fe2+(N(O)SR), which is efficiently converted to (AcMP-11)Fe2+(NO) in the presence of NO excess. Two possible mechanisms of S-nitrosothiol formation at the heme-iron were considered: a nucleophilic attack on (AcMP-11)Fe2+(NO+) by a thiolate and a reaction of (AcMP-11)Fe3+(RS) with NO. Kinetic studies, performed under anaerobic conditions, revealed that the reversible formation of (AcMP-11)Fe2+(N(O)SR) occurs in a reaction of RS- with (AcMP-11)Fe2+(NO+) and excluded the second mechanism, indicating that the formation of (AcMP-11)Fe3+(RS) is a dead-end equilibrium. Theoretical calculations revealed that N-coordination of RSNO to iron, forming (AcMP-11)Fe2+(N(O)SR), shortens the S-N bond and increases the complex stability compared to S-coordination. Our work unravels the molecular mechanism of heme-iron-assisted interconversion of NO and low-molecular-weight thiols to S-nitrosothiols and recognizes the reversible NO binding in the form of a heme-Fe2+(N(O)SR) motif as an important biological strategy of NO storage.