Synthesis and Structural, Spectroscopic, and Electrochemical Characterization of New Ruthenium Dimethyl Sulfoxide Nitrosyls

Abstract

The reactivity of ruthenium(II)- and ruthenium(III)-chloride-dimethyl sulfoxide precursors and of the antimetastatic drug [ImH][trans-RuCl(4)(dmso-S)(Im)] (NAMI-A, Im = imidazole, dmso = dimethyl sulfoxide) toward NO was investigated. Treatment of [(dmso)(2)H][trans-RuCl(4)(dmso-S)(2)] and mer-RuCl(3)(dmso)(3) with gaseous NO yielded [(dmso)(2)H][trans-RuCl(4)(dmso-O)(NO)] (1) and mer,cis-RuCl(3)(dmso-O)(2)(NO) (2), respectively. Thus, coordination of the strong pi-acceptor NO induces a S to O linkage isomerization of the dmso trans to it to avoid competition for pi-electrons. In light-protected nitromethane solutions, complex 2 equilibrates slowly with the two isomers mer-RuCl(3)(dmso-S)(dmso-O)(NO) (3), with NO trans to Cl, and mer-RuCl(3)(dmso-S)(dmso-O)(NO) (4), with NO trans to dmso-O; the equilibrium mixture consists of ca. 64% 2, 3% 3, and 33% 4. Treatment of the Ru(II) precursor trans-RuCl(2)(dmso-S)(4) with gaseous NO in CH(2)Cl(2) solution yielded the nitrosyl-nitro derivative trans,cis,cis-RuCl(2)(dmso-O)(2)(NO)(NO(2)) (5). Finally, [(Im)(2)H][trans-RuCl(4)(Im)(NO)] (6) was prepared by treatment of [ImH][trans-RuCl(4)(dmso-O)(NO)] (1Im) with an excess of imidazole in refluxing acetone. The spectroscopic features are consistent with the [Ru(NO)](6) formulation for all complexes, that is, a diamagnetic Ru(II) nucleus bound to NO(+). Compounds 1, 2, 5, and 6 were characterized also by X-ray crystallography; they all show a linear nitrosyl group, with short Ru-NO bond distances consistent with a strong d(pi) --> pi NO back-bonding. An unusual inertness of O-bonded dmso was observed in compound 1. Complexes 1, 2, 3, 5, and 6 are all redox active in DMF solutions showing irreversible reductions whose peak potentials depend on the other ligands attached to the Ru metal center. The site of reduction is the NO(+) moiety. The reduced complexes are not stable and release a Cl(-) or NO(2)(-) ligand followed by the NO(*) radical. The chemical reactions following electron transfer are all fast (rate constant >100 s(-1) at 293 K). The Ru product species are not redox active within the DMF window.

{RuII(NO+)}3+-core complexes with 4-methyl-pyrimidine and ethyl-isonicotinate: Synthesis, X-ray structure, spectroscopy, and computational and NO-release studies upon UVA irradiation

“…S1). The value is in agreement with the corresponding ones for rutheniumnitrosyl compounds previously reported by others [36][37][38]. The band is shifted some 50 cm À1 towards lower energies when compared to the corresponding one for the starting compound, RuCl 3 (NO) Á H 2 O.…”

“…Fig. 6), when compared to experimental values from this work and from the literature [24,38,40]. On passing the effect of solvent (PCM, CHCl 3 ) is quite small ( Table 5).…”

Novel ruthenium complex K2[Ru(dmgly)Cl4]·2H2O is toxic to C6 astrocytoma cell line, but not to primary rat astrocytes

“…However, NO produced at higher quantities by tumor-infiltrating macrophages or by tumor cells themselves efficiently destroys tumors [17,20]. For example, one possibility for explaining the activity of NAMI-A is that it interferes with NO metabolism in vivo [24]. There are several data that prevention of NO synthesis in macrophages co-cultivated with tumor cells in vitro prevents macrophage anti-tumor action [25][26][27].…”

On the Electronic Structure ofmer,trans‐[RuCl3(1H‐indazole)2(NO)], a Hypothetical Metabolite of the Antitumor Drug Candidate KP1019: An Experimental and DFT Study

“…[6] The high affinity of ruthenium for NO is well documented in the literature. [7] The pronounced effect of NAMI-A on angiogenesis was confirmed in the chick allantoic membrane and in the rabbit eye cornea model.…”