Organometallic anticancer agents. 2. Aqueous chemistry and interaction of niobocene dichloride with nucleic acid constituents and amino acids

Abstract

The solution chemistry and interactions of niobocene dichloride, Cp2NbCl2, with nucleosides, nucleotides, and amino acids has been studied by 1H and 31P NMR spectroscopy. The 1H NMR spectrum of Cp2NbCl2 in 10% DMSO-d6/D2O contains two sharp singlets consistent with hydrolysis of the halide ligands and oxidation of the paramagnetic Nb(IV) complex to a diamagnetic Nb(V) complex. Cp2NbCl2 does not dissolve in the absence of oxygen, and Cp2NbCl'2(OH) and Cp2NbCl2 when dissolved in 10% DMSO/D2O have identical 1H NMR spectra, consistent with formation of a Nb(V) complex as the antitumor active species in solution. With all nucleosides and nucleotides, except adenosine-5'-monophosphate (dAMP), no evidence of binding was detected on addition of up to 2.0 equiv of niobocene dichloride. In the case of dAMP, a minor complex (10%) was detected with 0.5 equiv of Cp2NbCl2 (pH 5.2). No evidence for interaction of aqueous solutions of Cp2NbCl2 with glutamic acid, serine, or histidine was found. The lack of interaction of niobocene dichloride with nucleic acid constituents and amino acids is markedly different from the chemistry exhibited by antitumor active metallocenes Cp2MCl2 (M = Ti, Mo, V) and suggests that the mechanism of antitumor action of Cp2NbCl2 is significantly different from other metallocene dihalides. Show more