Peroxides of vanadium and related metals in biological and medicinal chemistry

Abstract

Ions of vanadium and other transition metals of d o or low d n electron configuration are present in substantial amount in selected human tissues and blood. Vanadium is one of the elements recently recognised as essential for mammals [1]. In a very low concentration [2] it is thought to be widely distributed in tissues, but its biological function remains unknown. Complexes of vanadium and related metals with peroxo group, stabilized in specific ligand fields [3], exist in solid state and aqueous solutions. Such compounds of biologically important metals can help us understand the metal interactions with dioxygen moiety in living matter [4]. We have prepared and characterized a number of peroxo complexes of vanadium, niobium, tantalum and lanthanides, some containing various heteroligands ( e.g., oxalates, amino-carboxylates). Antitumor activity (ILS 25–32%), using L1210 murine leukemia test systems, have been found for some of these vanadium complexes [5]. They represent a new type of antitumor metal agents, quite different from a previously reported vanadocene dichloride [6]. A change in toxicity have been observed among analogous peroxo and nonperoxo niobate complexes. The relationship between the chemical properties of these compounds and their biological effects is studied by observing properties of complex peroxo species in aqueous solutions. Proton and 13C NMR spectra of heteroligands offer an indirect evidence for peroxo group presence in the metal ligand sphere. Individual resonance patterns and specific chemical shifts are observed in saturated deuterium oxide solutions for particular complex polyhedra present in the solid state. Peroxo → metal charge transfer band is pH dependent and distinct for different spheres. Redox potentials measured upon oxidation by various oxidants depend upon the type of the complex, showing significant differences (⩾300 mV). Vanadium complexes are particularly interesting in this respect because of a conceivable intramolecular redox process [7]. Under proper tuning by heteroligands the reactivity of coordinated peroxo group is expected to be modified, and eventually undergo one electron oxidation. Antitumor activity and toxicity of vanadium complexes can accordingly be associated with free radical processes [8], in addition to previously observed perturbation of enzymes involving phosphate metabolism, and perhaps sodium pump. For such speculations more reliable analyses of vanadium in tissue are of primary importance [9].