Yushmanov V E, Perussi J R, Imasato H, Tabak M
Institute of Physics and Chemistry of São Carlos, University of São Paulo, Brazil.
Biochim Biophys Acta. 1994 Jan 3;1189(1):74-80. doi: 10.1016/0005-2736(94)90282-8.
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 D2O 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 fragment attenuates the effective charge of HPS headgroup.
采用¹H-NMR研究了血管舒张药物罂粟碱（PAV）与具有不同头基电荷的表面活性剂胶束之间的相互作用以及PAV在D₂O溶液中的性质。在pD值高于6.4时，去质子化的PAV分子倾向于沉淀，溶解的PAV分子杂环质子的信号向高场移动。当PAV浓度高于1 mM时，其质子发生高场位移，该位移随pD值增加，这是由于芳香环的堆积所致。掺入胶束会导致所有共振峰发生位移。这种效应是由于PAV局部化学环境的变化而非堆积引起的，并且可能涉及PAV杂环N原子的去质子化。当表面活性剂与PAV的摩尔比>16时，PAV质子的谱线变宽表明其迁移受限。由于PAV的杂环与阳离子十六烷基三甲基氯化铵（CTAC）或阴离子十二烷基硫酸钠（SDS）的极性头基之间的相互作用，形成了不同的复合物。PAV与两性离子N-十六烷基-N,N-二甲基-3-铵基-1-丙烷磺酸盐（HPS）的结合类似于PAV与CTAC的结合。根据NMR数据估计，在pD = 4.9±0.1时，HPS、CTAC和SDS的缔合常数分别为20、60和350 M⁻¹。因此，PAV与HPS的结合模式由阳离子二甲基铵头基片段决定，而负性片段减弱了HPS头基的有效电荷。
