Photochemical oxidation of tetracycline in aqueous solution

Abstract

Irradiation of an aqueous solution of tetracycline at pH 9 with u.v. light from a medium pressure mercury lamp (filtered through Pyrex glass to give wavelengths >290 nm) produces a red product with λ_max. 534 nm. The red product is only produced in the presence of oxygen, one mole of oxygen being absorbed per mole of tetracycline photolysed. When the photolysis is carried out at ca. 3 °C an intermediate compound is produced (λ_max. 357 nm). On warming this irradiated solution the red product is formed in a dark reaction for which the activation energy is 90 kJ mol^–1. The red product has a pK_a value of 7.6, the protonated form being orange-yellow (λ_max. 442 nm). The red product is reduced by sodium dithionite solution to a leuco form which is reoxidised to the original compound by oxygen of the air. The red product is also reduced photochemically; flash photolysis reveals the intermediacy of a semiquinone radical in this process. These properties are typical of a quinone ring system. The spectral and chemical properties of the red product are consistent with its being 4a, 12a-anhydro-4-oxo-4-dedi-methylaminotetracycline. The mechanism of formation of the red product involves photodeamination followed by reaction of the tetracycline radical with molecular oxygen to form a peroxyl radical, which abstracts a hydrogen atom to give a hydroperoxide. Decomposition of the hydroperoxide by loss of water yields an oxo group at position 4. In the final dark reaction, water is lost across the C(4a)–C(12a) bond to form the red quinone.