Conformations and Tautomers of Tetracycline

Abstract

Density functional theory (DFT) has been used to investigate the conformations and tautomeric forms of neutral tetracycline in aqueous solution. The results suggest that the extended conformation is 3−3.5 kcal mol-1 more stable than the twisted one for equivalent tautomers and that as many as six different tautomeric forms lie within 10 kcal mol-1 of the most stable one. The energetic preference for the extended conformation is a solvent effect. Calculated infrared, NMR, and UV/vis spectra are used to suggest ways of differentiating between tautomers and conformations experimentally. It is shown that the 13C chemical shifts of C4a, C5, and C6 can be used to distinguish between the twisted and extended conformations.