A proton nuclear magnetic resonance investigation of the conformation of daunomycin.
The 500 MHz proton NMR spectra of 4.95 mM daunomycin in D2O have been investigated in the temperature range 277-350 K. Down field shifts of approximately 0.15 to 0.20 ppm in 1H, 2H and 3H protons with increasing temperature indicate that daunomycin exists in aggregated form at 277 K which is stabilized by stacking of aromatic rings. The 7H, 10axH and 10eqH protons show a change in chemical shift of 0.12 to 0.16 ppm, while other ring A/sugar protons shift by 0.0 to 0.08 ppm due to self association. The drug exists in monomer state at about 350 K. The conformational features have been ascertained from NOESY spectra at 297 K. The 7H proton is found to be strongly coupled to 8axH (J = 5 Hz) as compared to 8eqH (J = 2 Hz), while the 4'H-5'H connectivity is not observed in the COSY spectra. Besides the NOESY cross peaks between the spin-spin coupled protons, several intramolecular NOEs are seen. The 8axH and 8eqH are equally distant from 5'H proton. The distances of 3'H and 4'H daunosamine sugar protons from the ring A protons--7H, 8eqH, 9COCH3--are in the range 2.9-3.1 A, giving moderate cross peaks in NOESY spectra. The observed results imply the existence of predominantly 9H8 half chair conformation of ring A in aqueous solution, which is marginally different from that obtained by X-ray crystal analysis.
Barthwal
R
R
Department of Biosciences and Biotechnology, University of Roorkee, India. biost%rurkeu@sirnetd.ernet.in
Mujeeb
A
A
Srivastava
N
N
Sharma
U
U
D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D003630:Daunorubicin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D013696:Temperature
D000903:Antibiotics, Antineoplastic; D003630:Daunorubicin