Reactions of semiquinones in aqueous solution. A comparison of the one electron reduction of kalafungin and analogues with other semiquinones using pulse radiolysis

Abstract

The radical anions of the pyranonaphthoquinone antibiotic kalafungin 1 and analogues have been studied in aqueous solution by pulse radiolysis using transient absorption spectrophotometry. Radical absorption spectra were similar regardless of the nature of the substituent at C-5 or C-7 and the decay followed second-order kinetics showing any potential first-order ring opening was too slow to compete with bimolecular disproportionation at the concentration of radicals produced by pulse radiolysis. Spectral studies using steady-state radiolysis confirmed the absence of ring opening. The pK_a of each of the semiquinones of compounds 1–5 were determined and whereas replacing a hydrogen at C-7 by a methoxy, 2 and 4, raises the pK_a by 2.5–2.9 units demonstrating a significant substituent effect, no such increase occurs for OH, 1. This and the fact that kalafungin, 1, has the most positive one-electron reduction potential E(1), –63 ± 10 mV in neutral solution, is attributed to H-bonding between the 7-OH and the oxygen of the semiquinone, with the H-bonding effectively nullifying the substituent effect. The presence of an OH on C-5 has a much less significant effect on the E(1) and pK_a values. Comparison of kinetics and products in systems with and without tert-butanol brings into question a report that 2-(methoxymethyl)benzo-1,4-quinone and 2-(phenoxymethyl)benzo-1,4-quinone undergo dissociation on one-electron reduction.