Chemical reactivity of lumazine derivatives. Acid–base and redox reactions of a number of lumazines, deazalumazines, and isoalloxazines. An unusual effect of methyl substitution

Abstract

Three lumazines, seven deazalumazines, and two isoalloxazines have been studied and the following chemical properties measured; equilibrium acidity (pKa), equilibrium basicity [Formula: see text] polarographic reduction potential [Formula: see text] and, where applicable, the rates of the general acid and general base catalyzed dissociation of the protons in the C-5 and C-7 methyl groups [Formula: see text] The latter quantities were determined by means of isotope exchange or iodination. Structural variations in the substrate produce compatible results in pKa and [Formula: see text] and, to lesser extents, in [Formula: see text] and in the catalytic rate data. Anomalies in the rate constants appear when a methyl group is present at C-6; it facilitates ionization of the C-5 and C-7 methyl groups, reversing the quite large effect of more distant methyl. Buttressing effects appear to be absent. The effects of methyl substitution are attributed, in part, to (a) resonance stabilization by 5- and 7-methyl groups in the reactant molecules (neutral substrate and conjugate acid), and (b) relief of steric strain in going from essentially aromatic reactants to nonplanar intermediates. The significance of the 6-methyl group in the lumazine–flavin conversion is noted.