Interaction of papaverine with micelles of surfactants with different charge studied by 1H-NMR

Abstract

The interaction of the vasodilator drug papaverine (PAV) with micelles of surfactants with different charge of headgroups as well as the properties of PAV in D 2O solution were studied by 1H-NMR. At pD values above 6.4 deprotonated PAV molecules tend to precipitate, the signals of the heterocycle protons of solubilized PAV molecules being shifted to high field. At PAV concentration above 1 mM its protons experience upfield shifts which increase with pD value and are due to the stacking of aromatic rings. Incorporation into micelles caused shifts of all resonances. This effect is due to changes in the local chemical environment of PAV rather than to stacking, and, possibly, involves the deprotonation of the N atom of PAV heterocycle. Line broadening of PAV protons at the molar ratio surfactant/ PAV > 16 indicated their restricted mobility. Different complexes were formed due to interaction between the heterocycle of PAV and polar headgroups of cationic cetyltrimethylammonium chloride (CTAC) or anionic sodium dodecylsulfate (SDS). The binding of PAV to zwitterionic N- hexadecyl-N,N- dimethyl-3- ammonio-1- propanesulfonate (HPS) is similar to that of PAV to CTAC. Association constants were estimated from NMR data as 20, 60 and 350 M −1 at pD = 4.9±0.1 for HPS, CTAC and SDS, respectively. Thus, the mode of binding of PAV to HPS is defined by the cationic dimethylammonium headgroup fragment, whereas the negative sulfate fragment attenuates the effective charge of HPS headgroup.