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

Natural abundance 15 N NMR has been used to study several tetracycline antibiotics in the solid state and in solution. In the solid state, the 15 N 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 15 N 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 (CD 3 ) 2 SO solutions. In addition, the solid state 15 N CP/MAS NMR spectra are sensitive to subtle conformational changes of the "A" ring amide substituent. Key words: antibiotics, tetracyclines, 15 N NMR, molecular structure.