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

In a systematic effort to identify and develop effective vanadocene(IV) com plexes as a new class of contraceptive agents, the effect of methyl substit ution in the cyclopentadienyl rings of (Cp2VCl2)-V-x on their spermicidal a ctivity has been examined. The spermicidal activities of compounds (Cp2VCl2 )-V-x [Cp-x = Me5Cp (Cp*) (1), Cp (3), MeCp (Cp') (5)], as well as two of t heir 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 electro n-donating methyl groups augments the spermicidal activity 10-fold. The cor responding V(V) oxo compounds, Cp*V(O)Cl-2 (2) and CpV(O)Cl-2 (4), tested u nder identical conditions did not show as effective spermicidal activity ev en though these complexes have a pseudo-tetrahedral geometry similar to the active vanadocene(IV) dichlorides. Two pseudooctahedral V(IV) complexes wi th tris-pyrazolyl berate as ligand, (HBpz(3))V(O)Cl . DMF (6) and (HB(3,5-M e(2)pz)(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)-O-. radicals, the lack of spermicidal activity of VO SO4 which generates (OH)-O-. radicals, and the potent spermicidal activity of [Cp2V(acac)][O3SCF3] (8), and [Cp2V(DeDtc)][O3SCF3] (9) which do not gen erate (OH)-O-. radicals, indicate that (OH)-O-. radical mediated reactions may not be essential for the spermicidal activity of vanadium( IV) complexe s. (C) 1999 Elsevier Science Inc. All rights reserved.