MRC: Magn. Reson. Chem. (Wiley) up to Feb. 2, 2009

MRC: Magn. Reson. Chem. (Wiley) up to Feb. 2, 2009

13C CP MAS NMR of halogenated (Cl, Br, I) pharmaceuticals at ultrahigh magnetic fields
from Magnetic Resonance in Chemistry by Victor V. Terskikh, Stephen J. Lang, Peter G. Gordon, Gary D. Enright, John A. Ripmeester
1 Steacie Institute for Molecular Sciences, National Research Council Canada, Ottawa, Canada K1A 0R6
2 Department of Chemistry, Carleton University, Ottawa, Canada K1S 5B6

This work reports significantly improved spectral resolution of 13C CP MAS NMR spectra of chlorinated, brominated and iodinated solid organic compounds when such spectra are recorded at ultrahigh magnetic field strengths. The cause of this is the residual dipolar coupling between carbon atoms and quadrupolar halogen nuclides (chlorine-35/37, bromine-79/81 or iodine-127), an effect inversely proportional to the magnetic field strength which declines in importance markedly at 21.1 T as compared to lower fields. In favorable cases, the fine structure observed can be used for spectral assignment, e.g. for Cl-substituted aromatics where the substituted carbon as well as the ortho-carbons show distinct doublets. The experimental results presented are supported by theoretical modeling and calculations. The improved spectral resolution in the studied systems and similar halogenated materials will be of particular interest and importance for polymorph identification, drug discovery and quality control in the pharmaceutical industry.

Digital Object Identifier (DOI) 10.1002/mrc.2399


Studies on drug-DNA complexes, adriamycin-d-(TGATCA)2 and 4[prime]-epiadriamycin-d-(CGATCG)2, by phosphorus-31 nuclear magnetic resonance spectroscopy
from Magnetic Resonance in Chemistry by Prashansa Agrawal, Girjesh Govil, Ritu Barthwal
1 Department of Biotechnology, Indian Institute of Technology Roorkee, Roorkee 247667, India
2 Chemical Physics Group, Tata Institute of Fundamental Research, Homi Bhabha Road, Navy Nagar, Colaba, Mumbai 400 005, India

The complexes of adriamycin-d-(TGATCA)2 and 4[prime]-epiadriamycin-d-(CGATCG)2 are studied by one- and two-dimensional 31P nuclear magnetic resonance spectroscopy (NMR) at 500 MHz in the temperature range 275-328 K and as a function of drug to DNA ratio (0.0-2.0). The binding of drug to DNA is clearly evident in 31P[bond]31P exchange NOESY spectra that shows two sets of resonances in slow chemical exchange. The phosphate resonances at the intercalating steps, T1pG2/C1pG2 and C5pA6/C5pG6, shift downfield up to 1.7 ppm and that at the adjacent step shift downfield up to 0.7 ppm, whereas the central phosphate A3pT4 is relatively unaffected. The variations of chemical shift with drug to DNA ratio and temperature as well as linewidths are different in each of the two complexes. These observations reflect change in population of BI/BII conformation, stretching of backbone torsional angle [zeta], and distortions in O[bond]P[bond]O bond angles that occur on binding of drug to DNA. To the best of our knowledge, there are no solution studies on 4[prime]-epiadriamycin, a better tolerated drug, and binding of daunomycin or its analogue to d-(TGATCA)2 hexamer sequence. The studies report the use of 31P NMR as a tool to differentiate various complexes. The specific differences may well be the reasons that are responsible for different antitumor action of these drugs due to different binding ability and distortions in DNA. Copyright © 2009 John Wiley & Sons, Ltd.

Digital Object Identifier (DOI) 10.1002/mrc.2398