A nitrogen-15 nuclear magnetic resonance study of the tetracycline antibiotics

Abstract

Natural abundance 15N NMR has been used to study several tetracycline antibiotics in the solid state and in solution. In the solid state, the 15N chemical shifts of the tetracycline free bases are sensitive to the site of protonation in the "A" ring. A high frequency shift of 14 ppm is observed for the keto form of oxytetracycline (N protonated) relative to the enol form of oxytetracycline (O protonated). Comparison of 15N chemical shifts in the solid and solution states indicates for the first time that the structural integrity (site of protonation and hence conformation) of the tetracyclines is maintained in (CD3)2SO solutions. In addition, the solid state 15N CP/MAS NMR spectra are sensitive to subtle conformational changes of the "A" ring amide substituent. Key words: antibiotics, tetracyclines, 15N NMR, molecular structure.