The Structure of Papaverine in Solution as Determined by 1H Nuclear Magnetic Relaxation Methods

Abstract

Hydrogen relaxation in the papaverine molecule in CDCl3 solution has been studied so as to derive the conformation about the C1-CH2 bond. This was done for papaverine itself, in which the resonances of H5 and H8 were reassigned on the basis of NOESY spectra, and in the 7-OC2H3 analogue, the spectrum of which confirms the reassignment. The value for the torsional angle C 8a-C1-CH2-C lays between 70 and 92�, in good agreement with those found in crystals of papaverine , its hydrochloride, and the related alkaloid isosevanine (all in the range 68-94�). Conformational energy calculations show a broad energy minimum over the range 60-70�. The 6,7-methylenedioxy analogue of papaverine has essentially the same conformation but tumbles more rapidly in solution, the Tc value for it being 1.9×10-1ls whereas values for papaverine were 5.6×10-11 s (from 1H relaxation) and 3.1×1011 s (from 13C relaxation).