Reaction chemistry of BMOV, bis(maltolato)oxovanadium(IV) - A potent insulin mimetic agent

Article abstract of DOI:10.1021/ja00156a013

The reaction chemistry of the potent insulin-mimetic agent bis(maltolato)oxovanadium(IV) (abbreviated BMOV or VO(ma)₂) is reported. VO(ma)₂ (log K₁ = 8.80(2), log K₂ = 7.51 (2), log β₂ = 16.31(3)) has a rich coordination chemistry, forming a number of V(IV) and V(V) derivatives. In aqueous solution it is slowly oxidized by molecular oxygen to [VO₂(ma)₂]^- (log K₁ = 7.5(1), log K₂ = 6.2(1), log β₂ = 13.7(1)); in alcohols a variety of V(V) analogs VO(OR)(ma)₂ (R = CH₃, C₂H₅, i-C₃H₇) are formed by aerial oxidation. All these vanadate complexes can be interconverted by reaction with the appropriate alcohol or water. In addition, the six-coordinate V(IV) pyridine adduct VO(ma)₂py can be formed and this undergoes oxidation to V(V) complexes much more slowly, demonstrating that a vacant coordinate site is required for the coordination of O₂ to VO(ma)₂ before inner-sphere oxidation can take place. ⁵¹V NMR and electrochemistry have been studied as a function of pH; a complete study of the aqueous chemistry of VO(ma)₂ and [VO₂(ma)₂]^- has been undertaken because the oral activity of VO(ma)₂ as an insulinmimetic may be related to the chemical properties of the two compounds in water. Oral gavage studies in STZ-diabetic rats have been performed which showed that the intact complex is required for activity and that the presence of a biologically compatible reducing agent, ascorbic acid, neither interferes with nor augments the insulin-mimetic effect of VO(ma)₂. The X-ray structures of VO(ma)₂ and the cis-VO₂ compound K[VO₂(ma)₂]·H₂O have been determined; crystals of VO(ma)₂ [BMOV] are monoclinic, P2₁/n, a = 7.366(1), b = 12.759(2), c = 13.190(1) A?, β = 97.31(1)°, Z = 4, and those of K[VO₂(ma)₂]·H₂O are monoclinic, P2₁/n, a = 7.1841(9), b = 12.196(1), c = 17.147(1) A?, β = 96.64(1)°, Z = 4. The structure of VO(ma)₂ was solved by direct methods and that of K[VO₂(ma)₂]·H₂O by the Patterson method. The structures were refined by full-matrix least-squares procedures to R = 0.076 and 0.033 (R(w) = 0.075 and 0.034) for 1078 and 3232 reflections with 1 ≥ 3σ(I), respectively. VO(ma)₂ forms a square pyramid with the O₄ set from the two maltolato ligands in the base and the vanadyl V = O apical. [VO₂(ma)₂]^- is roughly octahedral with a cis-[VO₂]⁺ unit being completed by two ma^- ligands. The macroscopic structure is a chain with six-coordinate K⁺ ions linking adjacent [VO₂(ma)₂]^- units through coordination to the chelating ligand O atoms and water molecules.