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 92º, in good agreement with those found in crystals of papaverine , its hydrochloride, and the related alkaloid isosevanine (all in the range 68-94º). Conformational energy calculations show a broad energy minimum over the range 60-70º. The 6,7-methylenedioxy analogue of papaverine has essentially the same conformation but tumbles more rapidly in solution, the T_c 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).