R. C. Gurira, L. Bowers
Apr 1, 1983
Citations
0
Influential Citations
26
Citations
Journal
Journal of Electroanalytical Chemistry
Abstract
Abstract The electrochemical reduction of methotrexate has been studied in the pH range of 2 to 11. Methotrexate exhibits three two-electron/two-proton reduction steps in neutral and acidic media. Based on the results of cyclic voltammetry and high performance liquid chromatographic analysis of the products formed in controlled potential electrolysis, the first reduction produces 5,8-dihydro-MTX which undergoes either a heretofore unreported proton-dependent cleavage or proton-dependent tautomerization to 7,8-dihydro-MTX. The rate constant for the tautomerization was pH dependent and varied from 0.41 s−1 to 0.019 s−1 in the pH range of 3.5 to 7.6. The second reduction cleaves the C(9)−N(10) bond of the 7,8-dihydro-MTX. The final reduction produces a 5,6,7,8-tetrahydro derivative of the substituted pteridine. In alkaline media, a single two-electron/two-proton reduction is observed due to the very slow tautomerization process required to produce the reactant for subsequent reductions.