Oxovanadium compounds and reactions with alkylating agent toxins
Abstract
We are constantly exposed to alkylating carcinogenic by-products from cooked foods, tobacco smoke, and exhaust, which all react with DNA, cause genetic damage and eventual cancerous growth. Results in the area of cancer prevention demonstrate that vanadium can prevent cancers induced by these alkylating toxins, but little is known about the underlying mechanism. We hypothesize a “toxin interception” mechanism of cancer prevention in which these inorganic species may be nucleophilic, react directly with the electrophilic alkylating toxins, and prevent DNA damage. However, these compounds equilibrate to several species in a physiological environment, may mimic phosphate, and thus may have cellular uptake difficulties and toxicity. These issues led us to examine the interactions of oxovanadium ligand compounds with alkylating agents. Dioxovanadium(V) salicylidenehydrazide, K[VO2(salhyph)], and its derivatives were examined kinetically with alkylating toxins. Variation of the electron donating ability of the ligand with different Hammett groups allows for a degree of control over the reactivity of the compounds. Varying the electron density and reactivity of the oxovanadium compounds systematically may provide a basis for the development of compounds for the prevention of DNA damage.
Degree
Ph.D.
Advisors
Wilker, Purdue University.
Subject Area
Toxicology|Surgery|Inorganic chemistry
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