Structural and functional characterization of seven spermicidal vanadium(IV) complexes: potentiation of activity by methyl substitution on the cyclopentadienyl rings

Abstract

In a systematic effort to identify and develop effective vanadocene(IV) complexes as a new class of contraceptive agents, the effect of methyl substitution in the cyclopentadienyl rings of Cp x 2VCl 2 on their spermicidal activity has been examined. The spermicidal activities of compounds Cp x 2VCl 2 [Cp x =Me 5Cp (Cp *) ( 1), Cp ( 3), MeCp (Cp′) ( 5)], as well as two of their corresponding vanadium(V) oxidation products Cp *V(O)Cl 2 ( 2) and CpV(O)Cl 2 ( 4), were examined by computer-assisted sperm analysis (CASA). These analyses have established that penta-substitution of the Cp ring by electron-donating methyl groups augments the spermicidal activity 10-fold. The corresponding V(V) oxo compounds, Cp *V(O)Cl 2 ( 2) and CpV(O)Cl 2 ( 4), tested under identical conditions did not show as effective spermicidal activity even though these complexes have a pseudo-tetrahedral geometry similar to the active vanadocene(IV) dichlorides. Two pseudo-octahedral V(IV) complexes with tris-pyrazolyl borate as ligand, (HBpz 3)V(O)Cl ·DMF ( 6) and (HB(3,5-Me 2pz) 3)V(O)Cl ·DMF ( 7), were also found to exhibit potent spermicidal activity. Although some vanadium(IV) complexes may immobilize sperm due to the generation of · OH radicals, the lack of spermicidal activity of VOSO 4 which generates · OH radicals, and the potent spermicidal activity of [Cp 2V(acac)][O 3SCF 3] ( 8), and [Cp 2V(DeDtc)][O 3SCF 3] ( 9) which do not generate · OH radicals, indicate that · OH radical mediated reactions may not be essential for the spermicidal activity of vanadium(IV) complexes.