Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

Abstract

Redox properties of a set of aryldiketo acids (ADKs), small organic molecules that comprise 2,4-dioxobutanoic acid moiety, were studied. Along with well-known HIV-1 integrase (IN) inhibition, ADKs exert widespread biological activities. The aim of this work was to evaluate effects of aryl substitutions on properties of dioxobutanoic moiety that is involved in key interactions with metal ions within active sites of target enzymes. The effect of pH on electronic properties of nine congeners was examined using cyclic voltammetry and differential pulse polarography. Compounds were chosen as a simple set of congeners, bearing Me-groups on phenyl ring which should not be involved in electrochemical reactions, leaving diketo moiety as sole electrophore. Substitution pattern was systematically varied, yielding a set having different torsion between phenyl ring and aryl keto group (Ar-C(O)). Protonation state of ADKs at different pH values was determined from experimentally obtained pKas. The results showed that the equal number of protons and electrons is involved in the oxidation and reduction reactions at the surface of electrode. Quantitative linear correlations between reduction potentials and energies of frontier orbitals, calculated for neutral, monoanionic and corresponding radical anionic species, and steric parameter were found.