title: Solution speciation, kinetics, and observing reaction intermediates in the alkylation of oxidovanadium compounds.
abstract: Contact with environmental alkylating agents brings about modification of DNA bases, mispairing, mutations, and cancer. Nucleophilic compounds may be able to consume these toxins, thereby providing an alternative reaction pathway and preventing DNA damage. Owing to promising results from animal trials, oxidovanadium compounds present a potential class of nucleophilic complexes for preventing cancer. We are studying the reactivity of alkylating toxins with oxidovanadium-ligand compounds. The complexes K[VO(2)(salhyph(R)(2))], where salhyph is the salicylidenehydrazide ligand, are the focus of this study. By changing the electron donating or withdrawing ability of the -R substituents upon the salhyph(R)(2) ligand (R = -NO(2), -H, -CH(3), -OCH(3)), a family of compounds is obtained to investigate. Conductivity measurements reveal significant ion-pairing of all compounds in dimethyl sulfoxide (DMSO) solutions. Kinetic analysis shows that this ion-pairing causes a reduction in reaction rates. Reactivity of K[VO(2)(salhyph(R)(2))] is attributed exclusively to the non-ion-paired "free" [VO(2)(salhyph(R)(2))](-) anion in solution. Both (1)H and (51)V NMR spectroscopic studies show that direct alkylation of K[VO(2)(salhyph(H)(2))].CH(3)OH generates a VO(OCH(2)CH(3))(salhyph(H)(2)) intermediate which then protonates to release CH(3)CH(2)OH and a proposed [VO(salhyph(H)(2))](+) compound. Upon hydrolysis the dinuclear {[VO(salhyph(H)(2))](2)O} end product is formed. This mechanistic understanding and ability to exert control over reactions between inorganic compounds and alkylating toxins may aid in the future development of pharmaceuticals for preventing DNA damage.
authors.affiliation: Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907-2084, USA.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Fautch
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Wilker
mesh_terms: D000478:Alkylation; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D012996:Solutions; D014639:Vanadium / Q000737:chemistry*
chemical_list: D009942:Organometallic Compounds; D012996:Solutions; D014639:Vanadium