Study of the photochemistry of tetracyclines
Abstract
The formation and identification of tetracycline (TC) photoproducts was examined. The proposed structure for the tetracycline photoproduct, lumitetracycline (LTC), was verified using advanced NMR techniques, and the quantum yield of its formation was determined. It was also discovered that other members of tetracycline's family, oxytetracycline, doxycycline, chlorotetracycline, demeclocycline, and minocycline, give rise to analogues of lumitetracycline when they are irradiated with long wavelength UV light ($\lambda >$ 330 nm) in deoxygenated aqueous solutions. These products were characterized by UV, NMR and mass spectral analysis, and quantum yields for their formation were determined. The photochemistry of TC was studied under a variety of conditions using HPLC analysis. It was seen that LTC forms in aqueous media as well as organic media, and that its formation was pH dependent, maximizing at pH 6.5. Anhydrotetracycline (ATC), another known TC photoproduct, formation in aqueous media was also studied. ATC formation was dependent upon the presence of thiols in solution, and it was also pH dependent, forming best under basic conditions. Mechanisms for the formation of both products are proposed. The relative ability of doxycycline (DOX) and its photoproduct, lumidoxycycline (LDOX), to produce singlet oxygen was determined by examining sensitized histidine destruction. LDOX was seen to be better able to sensitize histidine destruction, and DOX was shown to be more susceptible to singlet oxygen degradation. Other studies showed that measurements of TC binding to DNA may be complicated by the formation of apparent TC polymer that may co-precipitate with the DNA.
Degree
Ph.D.
Advisors
Morrison, Purdue University.
Subject Area
Organic chemistry
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