A carbon-13 nuclear magnetic resonance study of solid tetracyclines

Abstract

SANDRA MOO~BROEK and RODERICK E. WASYLISHEN. Can. J. Chem. 65, 357 (1987). Magic angle sample spinning and proton/carbon-13 cross-polarization techniques have been used to obtain high resolution solid state I3c nuclear magnetic resonance spectra of several tetracycline antibiotics. Carbon-13 resonances in the solid state are assigned by measuring the extent of dipolar broadening due to neighbouring quadrupolar nuclei and by using a pulse sequence that suppresses non-quaternary carbon resonances. The observed I3C chemical shifts are discussed in light of the known solid state structures derived from X-ray diffraction, and are compared with those in solution. It is shown that the solid state nuclear magnetic reosnance technique is capable of clearly distinguishing between the neutral and zwitterionic forms of the tetracycline free bases.SANDRA MOOIBROEK et RODERICK E. WASYLISHEN. Can. J. Chem. 65, 357 (1987). On a utilist les techniques de I'angle magique de couplage de I'echantillon et de polarisation croiste proton/carbone-13 pour obtenir des spectres rmn 13c B l'ttat solide de plusieurs antibiotiques de la famille des tttracyclines. On a attribue les rtsonances en I3C du spectre B l'ttat solide en mesurant I'amplitude de I'Clargissement dip6laire provenant du noyau quadrup8laire voisin et en utilisant une stquence pulste qui su prime les rtsonances de carbones qui ne sont pas quaternaires. On discute des deplacements chimiques observes pour les ' C en fonction des structures B l'etat solide qui ont ttt obtenues par diffraction des rayons-X et on les compare avec ceux observts en solutions. On dtmontre que la technique rmn B l'ttat solide peut distinguer sans ambigui'tts entre les formes neutre et zwitterioniques des tttracyclines existant sous la forme de bases neutres.[Traduit par la revue]

13C CP MAS NMR of halogenated (Cl, Br, I) pharmaceuticals at ultrahigh magnetic fields

“…13 C CP MAS spectra of Chlortetracycline recorded at 9.4 T were reported previously. [12] Chloroquine diphosphate (5) is a drug of choice for treatment of malaria. Again, its 13 C CP MAS NMR spectra recorded at 21.1 T are of extremely high resolution, and allow for easy assignment of the chlorine-bonded carbon atoms (Fig.…”

“…5). Not only every carbon resonance in every one of the three compounds can now be unambiguously assigned (Table 5), but also when compounds (11) and (12) are mixed together to simulate a pharmaceutical formulation, both compounds in the mixture can still be readily identified.…”

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

“…The inherent sensitivity of the 1 5~ chemical shifts to N-protonation and the conclusive evidence obtained with the dipolar dephasing experiments provide an even more sensitive probe of the structure of the "A" ring than previous 13c CP/MAS NMR experiments (18). In addition, comparison of solid state ' 5~ chemical shifts with corresponding values in (CD3)$0 and pyridine-d5 solutions provides the first definitive evidence that the structural integrity of the tetracyclines is maintained in solution.…”

“…A previous investigation of several solid tetracyclines in this laboratory demonstrated the utility of high-resolution solid state I3C CP/MAS NMR for distinguishing the en01 and keto forms (2 vs. 3) of the tetracycline free bases (18). This method relied on the nature of the line shapes observed in 13c CP/MAS NMR spectra for the carbon atoms that are directly bonded to a quadrupolar nitrogen nucleus (19,20).…”

Quantitation of a polymorphic mixture of an active pharmaceutical ingredient with solid state 13C CPMAS NMR spectroscopy

“…Magic angle spinning does not completely average out the dipolar coupling between 14 N and 13 C. This can be seen as splitting or broadening of signals from those sites that have 14 N attached directly to them, as often reported in the literature (Opella et al, 1979;Reutzel-Edens et al, 2003;Hughes et al, 2002;Mooibroek and Wasylishen, 1987). The presence of this residual coupling can be seen in the case of API-X in the signals C13 and C14, both giving the typical 2:1 doublet for this kind of interaction.…”