Behaviour of the Antitumor Agent Vanadocene Dichloride in Physiological and Therapeutic Media, Blood Plasma and Human Blood ‐ An EPR Study

Abstract

By means of EPR spectroscopy the behaviour of the vanadocene dichloride (I), Cp2VCl2 (Cp=η5-C5H5), in various deoxygenated and non-deoxygenated physiological media and therapeutic solution as well as in blood plasma and stabilized human blood was studied. On the basis of measured values of isotropic spectroscopic splitting factor giso and isotropic hyperfine coupling constant Aiso, the vanadocene species, [Cp2V(H2O)Cl]+ (II; giso= 1.985, |Aiso| = 7.68 mT), [Cp2V(H2O)2]2+ (III; giso= 1.983, |Aiso| = 7.92 mT), [Cp2V(OH2 (IV; giso= 1.991, |Aiso| = 6.285 mT), [Cp2VCl(DMSO)]+ (V; giso= 1.985, |Aiso| = 7.69 mT), the vanadyl species [VO(DMSO)5]2+ (VI; giso= 1.964, |Aiso| = 10.78mT) and [VO(H2O)5]2+ (VII; giso= 1.955, |Aiso| = 11.56 mT) have been identified. From the measurements it follows that I does not react in its first coordination sphere with any component of a system used other than water and DMSO, resp. As to water-containing media, its behaviour is fully consistent with that of I in pure aqueous media. It was found the only vanadocene species present after application of the therapeutic solution of I into human blood to be IV not interacting in its first coordination sphere with any blood component.

An experimental and theoretical study of the Cp2VO2CO: use of 13CO32− for structure investigation of d1‐metallocene complexes

“…11 Carbonates seem to be components that are present in all these media and they are able to interact with the vanadocene moiety. It was found that complex 1 introduced into the solution of carbonates at physiological pH gave one simple eight-line EPR spectrum with magnetic parameters corresponding to compound 2 (jA iso 51 V j D 175.1 MHz, g iso D 1.9861).…”

“…11 Bidentate bonded carbonate ligand stabilizes the complex due to chelate effect. So the vanadocene fragment is resistant to degradation at physiological pH.…”

“…8 -10 EPR measurements have shown that in blood plasma and with whole human blood vanadocene dichloride (1) forms paramagnetic compound (2), the structure of which has not been determined reliably. 11 The aim of this study was the isolation of compound 2 and the determination of its structure on the basis of spectral measurements. Now it is possible to calculate EPR hyperfine coupling (HFC) tensors of transition metal complexes on the density functional level of theory.…”

Spermicidal activity of chelated complexes of bis(cyclopentadienyl)vanadium(IV)

“…(Kopf-Maier andKopf, 1987, 1988;Kopf-Maier, 1993). At present, the potential biomedical applications of these vanadocene diacido complexes are limited because of their variable dissociation, aquation, and subsequent hydrolysis in aqueous media (Toney and Marks, 1985;Vinklarek et al, 1997).…”

Ansa-vanadocene complexes with short interannular bridges

“…An EPR spectroscopy was appeared as very efficient method for investigation of such paramagnetic d 1 -complexes. This method should be used at concentration range that is used in biological experiments [13].…”