Mechanism Elucidation of thecis–transIsomerization of an Azole Ruthenium–Nitrosyl Complex and Its Osmium Counterpart

Abstract

Synthesis and X-ray diffraction structures of cis and trans isomers of ruthenium and osmium metal complexes of general formulas (nBu4N)[cis-MCl4(NO)(Hind)], where M = Ru (1) and Os (3), and (nBu4N)[trans-MCl4(NO)(Hind)], where M = Ru (2) and Os (4) and Hind = 1H-indazole are reported. Interconversion between cis and trans isomers at high temperatures (80–130 °C) has been observed and studied by NMR spectroscopy. Kinetic data indicate that isomerizations correspond to reversible first order reactions. The rates of isomerization reactions even at 110 °C are very low with rate constants of 10–5 s–1 and 10–6 s–1 for ruthenium and osmium complexes, respectively, and the estimated rate constants of isomerization at room temperature are of ca. 10–10 s–1. The activation parameters, which have been obtained from fitting the reaction rates at different temperatures to the Eyring equation for ruthenium [ΔHcis-trans‡= 122.8 ± 1.3; ΔHtrans-cis‡= 138.8 ± 1.0 kJ/mol; ΔScis-trans‡= −18.7 ± 3.6; ΔStrans-cis‡= 31.8 ± 2.7 J/(mol·K)] and osmium [ΔHcis-trans‡= 200.7 ± 0.7; ΔHtrans-cis‡= 168.2 ± 0.6 kJ/mol; ΔScis-trans‡= 142.7 ± 8.9; ΔStrans-cis‡= 85.9 ± 3.9 J/(mol·K)] reflect the inertness of these systems. The entropy of activation for the osmium complexes is highly positive and suggests the dissociative mechanism of isomerization. In the case of ruthenium, the activation entropy for the cis to trans isomerization is negative [−18.6 J/(mol·K)], while being positive [31.0 J/(mol·K)] for the trans to cis conversion. The thermodynamic parameters for cis to trans isomerization of [RuCl4(NO)(Hind)]−, viz. ΔH° = 13.5 ± 1.5 kJ/mol and ΔS° = −5.2 ± 3.4 J/(mol·K) indicate the low difference between the energies of cis and trans isomers. The theoretical calculation has been carried out on isomerization of ruthenium complexes with DFT methods. The dissociative, associative, and intramolecular twist isomerization mechanisms have been considered. The value for the activation energy found for the dissociative mechanism is in good agreement with experimental activation enthalpy. Electrochemical investigation provides further evidence for higher reactivity of ruthenium complexes compared to that of osmium counterparts and shows that intramolecular electron transfer reactions do not affect the isomerization process. A dissociative mechanism of cis↔trans isomerization has been proposed for both ruthenium and osmium complexes.

Ruthenium-Nitrosyl Complexes with Glycine, l-Alanine, l-Valine, l-Proline, d-Proline, l-Serine, l-Threonine, and l-Tyrosine: Synthesis, X-ray Diffraction Structures, Spectroscopic and Electrochemical Properties, and Antiproliferative Activity

“…Ruthenium and osmium analogues showed a striking difference in antiproliferative activity in three human cancer cell lines, A549 (nonsmall cell lung carcinoma), CH1 (ovarian carcinoma), and SW480 (colon carcinoma). 14,15 These results were in strong contrast to previous comparative studies on homologous ruthenium and osmium complexes (with metal ion in different oxidation states) showing either similar activities 16,17 or much smaller differences 18−20 than those observed for compounds reported in reference (15). We are now trying to find out whether their behavior toward amino acids can provide an explanation for their different antiproliferative activity.…”

Striking Difference in Antiproliferative Activity of Ruthenium- and Osmium-Nitrosyl Complexes with Azole Heterocycles

“…27,28 ( n -Bu 4 N)[ cis -OsCl 4 (NO)(Hind)] ( 5c ) and ( n -Bu 4 N)[ trans -OsCl 4 (NO)(Hind)] ( 5t ) were prepared by reaction of ( n -Bu 4 N) 2 [OsCl 5 (NO)] with 1 H -indazole and separated by fractional crystallization. 29 l (+)-Ascorbic acid was obtained from Acros, and ubiquitin (bovine erythrocytes) and myoglobin (equine heart) from Sigma. The solvents for ESI-MS studies were methanol (VWR Int., HiPerSolv CHROMANORM), formic acid (Fluka), and Milli-Q water (18.2 MΩ, Synergy 185 UV Ultrapure Water System, Millipore, France).…”

“…To a solution of ( n -Bu 4 N)[ trans -OsCl 4 (NO)(Hind)] 29 ( 5t ) (200 mg, 0.27 mmol) in water/ethanol 1:1 (250 mL) was added ion exchanger Dowex Marathon C Na + -form (25 g). The suspension was stirred for 12 h, the ion exchanger was separated by filtration, and the solution lyophilized to give a blue solid.…”

cis-Tetrachlorido-bis(indazole)osmium(iv) and its osmium(iii) analogues: paving the way towards the cis-isomer of the ruthenium anticancer drugs KP1019 and/or NKP1339

“…59 The reduction of osmium(IV) to osmium(III) with NaBH 4 was performed as described previously for [ 3 ] − 29 and [ 1 ] − was isolated as its tetra- n -butylammonium salt ( n Bu 4 N[ 1 ]). Cation metathesis employing an ion exchange resin 60 afforded the sodium salt Na[ 1 ].…”