Studies of Dihydropyridines by X-Ray Diffraction and Solid State ¹³C NMR

Abstract

Fourteen dimethyl 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates (DHPs) were evaluated by means of single crystal X-ray diffraction in order to investigate the effects of the structure in the crystals on the solid state 13C NMR chemical shifts. These include the analysis of three DHPs containing two molecules per asymmetric unit. The chiral rotamer unit generated by the s-cis/s-trans orientation of the carbonyl groups, as well as by rotation of the 4-phenyl ring out of the bisecting plane containing the N1, C4, C7 atoms, resulted in a significant magnetic non-equivalence for the C2-CH3/C6-CH3 and the COOCH3 pairs of signals. The solid state 13C NMR data reveal that the substitution pattern of the phenyl ring has a marked effect on the extent to which the signals of the carbonyl carbon atoms and those of C-2/C-6 peaks are split.

Partial Dehydration of Levothyroxine Sodium Pentahydrate in a Drug Product Environment: Structural Insights into Stability

“…The changes in the peak positions for all carbon atoms can also be explained by the high conformational flexibility of the molecules. − For example, the conformational difference of dihydropyridine variants are observed by 13 C peak splitting in a combined X-ray and ssNMR study . Previous studies of levothyroxine have indicated the existence of two different conformations for the biological “free” or un-ionized form. , These conformations differ in the orientation of the diiodophenyl ring with respect to the amine group (cisoid and transoid conformers).…”

On the molecular dynamics in long-acting calcium channel blocker lacidipine: solid-state NMR, neutron scattering and periodic DFT study

“…Solid-state 13 C NMR has been found as a valuable tool to characterize the rst-generation calcium antagonists and the polymorphism therein. [20][21][22] In order to provide a valuable support for polymorph screening and drug control, the high-resolution solid-state 13 C NMR spectrum of LCDP has been recorded and is presented in Fig. 2, along with the results of theoretical GIPAW calculations.…”