Nuclear magnetic resonance investigations of calcium-antagonist drugs. Part 4. Conformational and dynamic features of nicardipine {methyl 2-[methyl(phenylmethyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate } in deuterium oxide

Abstract

Conformation and dynamics of nicardipine in deuterium oxide were investigated by ¹H and ¹³C NMR spectroscopy. Molecular motions were characterised by effective correlation times calculated by ¹³C spin–lattice relaxation rates and verified by the frequency dependence of ¹H spin–lattice relaxation rates or by double-selective proton relaxation rates. ¹H–¹H dipole–dipole connectivities were observed in 2D NOE spectra and quantified by measuring absolute values of cross-relaxation rates or by fitting the experimental ¹H spin–lattice relaxation rates to a model of a sum of independent pairwise interactions. A molecular model was built showing extensive folding of the (phenylmethyl)-amino-ethyl chair and a chair conformation of the dihydropyridine moiety.