title: Spermicidal activity of metallocene complexes containing vanadium(IV) in humans.
abstract: We have used computer-assisted sperm analysis (CASA) to evaluate the spermicidal activity of 8 metallocene dihalides (vanadocene dichloride [VDC], titanocene dichloride [TDC], zirconocene dichloride [ZDC], molybdocene dichloride [MDC], hafnocene dichloride [HDC], vanadocene dibromide [VDB], bis[methylcyclopentadienyl] vanadium dichloride [VMDC], and vanadocene diiodide [VDI]); 5 vanadocene di-pseudohalides (vanadocene diazide [VDA], vanadocene dicyanide [VDCN], vanadocene dioxycyanate [VDOCN], vanadocene dithiocyanate [VDSCN], and vanadocene diselenocyanate [VDSeCN]); and 3 disubstituted derivatives (vanadocene ditriflate [VDT], vanadocene monochloro oxycyanate [VDCO], and vanadocene monochloro acetonitrilo tetrachloro ferrate [VDFe]). Whereas the metallocene complexes containing titanium, zirconium, molybdenum, and hafnodium were inactive, all 12 vanadocene complexes elicited potent spermicidal activity at nano-micromolar concentrations with an order of efficacy VDSeCN > VDSCN > VDB > VMDC > VDCN > VDA > VDC > VDOCN > VDI > VDT > VDFe > VDCO without disrupting the acrosomal membrane, as determined by high-resolution low-voltage scanning electron microscopy. The sperm-immobilizing activity of the vanadocene complexes was rapid and irreversible, since the treated sperm underwent apoptosis as determined by the flow cytometric annexin V binding assay, DNA nick end-labeling, and confocal laser scanning microscopy. These results provide unprecedented evidence that metallocene complexes containing vanadium(IV), especially VDSeCN, may be useful as contraceptive agents.
authors.affiliation: Department of Reproductive Biology, Wayne Hughes Institute, Roseville, Minnesota 55113, USA. odcruz@ih.org
authors.forename: O J
authors.initials: OJ
authors.lastname: D'Cruz
authors.forename: P
authors.initials: P
authors.lastname: Ghosh
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D003676:Deferoxamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology; D013081:Sperm Motility / Q000187:drug effects; D013089:Spermatocidal Agents; D013094:Spermatozoa / Q000187:drug effects* / Q000648:ultrastructure; D017968:Vanadium Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D009942:Organometallic Compounds; D013089:Spermatocidal Agents; D017968:Vanadium Compounds; C013108:metallocene; C030754:vanadocene dichloride; D003676:Deferoxamine