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.

Investigation of water substitution at RuII complexes by conceptual density function theory approach.

In this paper, we investigated water exchange reactions and substitution of aqua RuII complexes of general formula [Ru(terpy)(N^N)(H2 O)]2+ (where N^N = ethylenediamine (en), 1,2-(aminomethyl)pyridine (ampy) and 2,2'-bipyridine (bipy)) by ammonia and thioformaldehyde. These reactions were studied in detail by applying conceptual density functional theory. This approach enabled us to gain further insight into the underlying reaction mechanism at the microscopic level (involving only direct participants of the reaction, without the influence of the solvent) and to put the concept of reaction mechanism on a quantitative basis. The course of the chemical reaction along the reaction coordinate ξ, is rationalized in terms of reaction energy, force, dipole moment, and reaction electronic flux (REF). The results yield and characterize the significant influence of an intermolecular hydrogen bond formed between the entering and the spectator ligand to the overall energy barrier of the reactions.

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.

Characterization of a Mixed-Valence Ru(II)/Ru(III) Ion-Pair Complex. Unexpected High-Frequency Electron Paramagnetic Resonance Evidence for Ru(III)-Ru(III) Dimer Coupling.

In this contribution, we report the synthesis and full characterization of the first mixed-valence Ru(II)/Ru(III) ion-pair complex, [RuII(bipy)2(pic)]+[cis-RuIIICl2(pic)2]-, in the solid state and in aqueous solution, where bipy = 2,2'-bipyridine and pic- = picolinate. In addition, unexpected high-frequency electron paramagnetic resonance evidence for interactions between two neighboring Ru(III) ions, resulting in a triplet state, S = 1, was found.

Reactivity of non-organometallic ruthenium(II) polypyridyl complexes and their application as catalysts for hydride transfer reactions.

Recently, we investigated the substitution behavior of a series of ruthenium(II) complexes of the general formula [RuII(terpy)(N∧N)Cl]Cl, where terpy = 2,2':6',2″-terpyridine, N∧N = bidentate ligand, in aqueous solutions. We have shown that the most and least reactive complexes of the series are [RuII(terpy)(en)Cl]Cl (en = ethylenediamine) and [RuII(terpy)(phen)Cl]Cl (phen = 1, 10-phenantroline), respectively, as a result of different electronic effects provided by the bidentate spectator chelates. Polypyridyl amine Ru(II) complex, viz. [Ru(terpy)(en)Cl]Cl and [Ru(terpy)(ampy)Cl]Cl (where ampy = 2-(aminomethyl)pyridine), in which the terpy chelate labilizes the metal center, are able to catalyze the conversion of NAD+ to 1,4-NADH using sodium formate as a source of hydride. We showed that this complex can control the [NAD+]/[NADH] ratio and potentially induce reductive stress in living cells, which is accepted as an effective method to kill cancer cells. Polypyridyl Ru(II) complexes, characterized in terms of the behavior in aqueous solutions, can be used as model systems to monitor heterogeneous multiphase ligand substitution reactions at the solid-liquid interface. Colloidal coordination compounds in the submicron range were synthesized from Ru(II)-aqua derivatives of starting chlorido complexes via the anti-solvent procedure and stabilized by a surfactant shell layer.

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 = 2,2':6',2''-terpyridine, ampy = 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 π-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 = 2,2'-bipyridine). The DFT calculated energies show that both the solvent-formato exchange and the formato-hydrido 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.

RuIII(edta) complexes as molecular redox catalysts in chemical and electrochemical reduction of dioxygen and hydrogen peroxide: inner-sphere versus outer-sphere mechanism.

The reduction of molecular oxygen (O2) and hydrogen peroxide (H2O2) by [RuII(edta)(pz)]2- (edta4- = ethylenediaminetetraacetate; pz = pyrazine) has been studied spectrophotometrically and kinetically in aqueous solution. Exposure of the aqua-analogue [RuII(edta)(H2O)]2- to O2 and H2O2 resulted in the formation of [RuIII(edta)(H2O)]- species, with subsequent formation of the corresponding RuV[double bond, length as m-dash]O complex. A working mechanism for the O2 and H2O2 reduction reactions mediated by the RuII(edta) complexes is proposed. The role of the coordinated water molecule (by its absence or presence in the primary coordination sphere) in controlling the mechanistic pathways, outer-sphere or inner-sphere, is discussed.

Reaction mechanisms relevant to the formation and utilization of [Ru(edta)(NO)] complexes in aqueous media.

The advancement of Ru(edta) complexes (edta4- = ethylenediamineteraacetate) mediated reactions, including NO generation and its utilization, has not been systematically reviewed to date. This review aims to report the research progress that has been made in exploring the application of Ru(edta) complexes in trapping and generation of NO. Furthermore, utilization of the potential of Ru(edta) complexes to mimic NO synthase and nitrite reductase activity, including thermodynamics and kinetics of NO binding to Ru(edta) complexes, their NO scavenging (in vitro), and antitumor activity will be discussed. Also, the role of [Ru(edta)(NO)] in mediating electrochemical reduction of nitrite, S-nitrosylation of biological thiols, and cross-talk between NO and H2S, will be covered. Reports on the NO-related chemistry of Fe(edta) complexes showing similar behavior are contextualized in this review for comparison purposes. The research contributions compiled herein will provide in-depth mechanistic knowledge for understanding the diverse routes pertaining to the formation of the [Ru(edta)(NO)] species, and its role in effecting the aforementioned reactions of biochemical significance.

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.

Structure and reactivity of [RuII(terpy)(N

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.