Can a Nonorganometallic Ruthenium(II) Polypyridylamine Complex Catalyze Hydride Transfer? Mechanistic Insight from Solution Kinetics on the Reduction of Coenzyme NAD+ by Formate

Application of organometallic ruthenium(II) arene complexes has been successful for the modulation of cellular redox processes via their interaction with species such as formate to control the NAD+/NADH balance in cells. Here we present the first evidence that similar effects can be reached with the application of a nonorganometallic ruthenium(II) polypyridyl complex. Kinetic studies performed demonstrate the ability of [RuII(terpy)(en)(H2O/EtOH)]2+ in water/ethanol (1:9, v/v) solution, where terpy = 2,2′:6′,2″-terpyridine and en = ethylenediamine, to catalyze the reduction of the NAD+ coenzyme to NADH in the presence of formate as hydride transfer source. In this case, terpy instead of arene is responsible for the labilization of coordinated solvent. The suggested catalytic cycle begins with the fast anation of the [RuII(terpy)(en)(H2O/EtOH)]2+ complex by formate. This is followed by the rate-determining formate-catalyzed decarboxylation of the generated ruthenium(II) formato complex to form [RuII(terpy)(en)H]+. Rapid hydride transfer to NAD+ from [RuII(terpy)(en)H]+ to form NADH and to regenerate the starting ruthenium(II) solvato complex, closes the overall catalytic cycle

Electrochemistry of Ru(edta) complexes relevant to small molecule transformations: Catalytic implications and challenges

Electrochemistry of Ru(edta) complexes (edta4 = ethylenediaminetetraacetate) progressed over a period of several decades, with significant increase in understanding of the electro-catalytic processes involving the substrate coordinated to the metal center. While electrochemistry studies of many Ru(edta) complexes were published in several papers, no attempt has been made to provide a comprehensive and systematic overview of its electrochemical properties, evaluating its application to catalytic electrochemical transformation of small molecules. In this article, results of the electrochemical studies of both mononuclear and binuclear complexes of Ru(edta) are reviewed with regard to electron-transfer reaction mechanism and activity. Their potential to act as redox mediators or catalysts in electrochemical transformations of small molecules and enzymatic reactions, are highlighted. This review aims to contribute to the mechanistic understanding of Ru(edta) complexes in catalysis of such electrochemical transformations

Tuning the lability of a series of Ru(II) polypyridyl complexes: a comparison of experimental-kinetic and DFT-predicted reaction mechanisms

This report deals with a comparison of experimentally obtained kinetic and activation parameter data, and theoretical DFT computations, in terms of mechanistic information on the water exchange and water displacement reactions by thiourea for a series of complexes of the type [RuII(terpy)(N^N)(H2O)]2+, where terpy = 2,2′:6′,2″-terpyridine and N^N represents ethylenediamine (en), 2-(aminomethyl)pyridine (ampy), 2,2′-bipyridine (bipy), 1,10-phenantroline (phen), and N,N,N′,N′-tetramethylethylenediamine (tmen). The complexes were all isolated in the form of [Ru(terpy)(N^N)Cl]X (X = Cl– or ClO4–) compounds and fully characterized in both the solid state and in solution. The DFT calculations revealed further mechanistic insight into the water exchange reactions as well as the water displacement reactions by thiourea. Both the experimental activation parameters and the DFT calculations suggest the operation of an associative interchange (Ia) mechanism for both reaction types studied

Structure and reactivity of [RuII(terpy)(N^N)Cl]Cl complexes: consequences for biological applications

The crystal structures of [RuII(terpy)(bipy)Cl]Cl·2H2O and [RuII(terpy)(en)Cl]Cl·3H2O, where terpy = 2,2′:6′,2′′-terpyridine, bipy = 2,2′-bipyridine and en = ethylenediamine, were determined and compared to the structure of the complexes in solution obtained by multi-nuclear NMR spectroscopy in DMSOd-6 as a solvent. In aqueous solution, both chlorido complexes aquate fully to the corresponding aqua complexes, viz. [RuII(terpy)(bipy)(H2O)]2+ and [RuII(terpy)(en)(H2O)]2+, within ca. 2 h and ca. 2 min at 37 °C, respectively. The spontaneous aquation reactions can only be suppressed by chloride concentrations as high as 2 to 4 M, i.e. concentrations much higher than that found in human blood. The corresponding aqua complexes are characterized by pKa values of ca. 10 and 11, respectively, which suggest a more labile coordinated water molecule in the case of the [RuII(terpy)(en)(H2O)]2+ complex. Substitution reactions of the aqua complexes with chloride, cyanide and thiourea show that the [RuII(terpy)(en)(H2O)]2+ complex is 30-60 times more labile than the [RuII(terpy)(bipy)(H2O)]2+ complex at 25 °C. Water exchange reactions for both complexes were studied by 17O-NMR and DFT calculations (B3LYP(CPCM)/def2tzvp//B3LYP/def2svp and ωB97XD(CPCM)/def2tzvp//B3LYP/def2svp). Thermal and pressure activation parameters for the water exchange and ligand substitution reactions support the operation of an associative interchange (Ia) process. The difference in reactivity between these complexes can be accounted for in terms of π-back bonding effects of the terpy and bipy ligands and steric hindrance on the bipy complex. Consequences for eventual biological application of the chlorido complexes are discussed

Inorganic reaction mechanisms. A personal journey

This review covers highlights of the work performed in the van Eldik group on inorganic reaction mechanisms over the past two decades in the form of a personal journey. Topics that are covered include, from NO to HNO chemistry, peroxide activation in model porphyrin and enzymatic systems, the wonder-world of RuIII(edta) chemistry, redox chemistry of Ru(iii) complexes, Ru(ii) polypyridyl complexes and their application, relevant physicochemical properties and reaction mechanisms in ionic liquids, and mechanistic insight from computational chemistry. In each of these sections, typical examples of mechanistic studies are presented in reference to related work reported in the literature

Electronic effects on the mechanism of the NAD+ coenzyme reduction catalysed by a non-organometallic ruthenium(ii) polypyridyl amine complex in the presence of formate

In the present study, electronic effects on the mechanism of the NAD+ coenzyme reduction in the presence of formate, catalysed by a non-organometallic ruthenium(II) polypyridyl amine complex, were investigated. The [RuII(terpy)(ampy)Cl]Cl (terpy ¼ 2,20 :60 ,200-terpyridine, ampy ¼ 2-(aminomethyl)pyridine) complex was employed as the catalyst. The reactions were studied in a water/ethanol mixture as a function of formate, catalyst, and NAD+ concentrations at 37 C. The overall process was found to be 11 to 18 times slower than for the corresponding ethylenediamine (en) complex as the result of p-back bonding effects of the ampy ligand. The mechanistic studies revealed a complete set of reactions that accounted for the overall catalytic cycle based on a formate-induced hydride transfer reaction to form the reduced coenzyme, NADH. The geometries of the ruthenium(II)-ampy complexes involved in the catalytic cycle and free energy changes for the main steps were predicted by DFT calculations. Similar calculations were also performed for the analogues ruthenium(II)-en and ruthenium(II)-bipy complexes (bipy ¼ 2,20 - bipyridine). The DFT calculated energies show that both the solvent-formato exchange and the formatohydrido conversion reactions have negative (favourable) energies to proceed spontaneously. The reactions involving the en complex have the more negative (favourable) reaction energies, followed by the ampy complex, in agreement with faster reactions for en complexes and slower reactions for bipy complexes than for ampy complexes