CALORIMETRIC, C-13 NMR, AND P-31 NMR-STUDIES ON INTERACTION OF SOME PHENOTHIAZINE DERIVATIVES WITH DIPALMITOYL PHOSPHATIDYLCHOLINE MODEL MEMBRANES
CALORIMETRIC, C-13 NMR, AND P-31 NMR-STUDIES ON INTERACTION OF SOME PHENOTHIAZINE DERIVATIVES WITH DIPALMITOYL PHOSPHATIDYLCHOLINE MODEL MEMBRANES
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DOI：
10.1016/0005-2736(78)90415-7
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发表时间：
1978-01-01
期刊：
影响因子：
--
通讯作者：
NUHN, P
中科院分区：
文献类型：
--
作者：
FRENZEL, J;ARNOLD, K;NUHN, P
采用二棕榈酰磷脂酰胆碱/水体系研究了吩噻嗪类化合物与模型膜的相互作用。采用差示扫描量热法和核磁共振光谱法研究药物对脂质相变的影响。所研究的吩噻嗪类药物具有外周（双乙嗪）或中枢（氯丙嗪）性质。观察到这两种药物降低二棕榈酰磷脂酰胆碱的相变温度。氯丙嗪的摩尔活性高于双乙嗪。在低浓度下，药物影响二棕榈酰磷脂酰胆碱预转变吸热。在13 C NMR光谱的药物含有的样品中的二棕榈酰磷脂酰胆碱的三甲基铵基团的信号被加宽，而脂肪酸链亚甲基基团的信号的缩小被观察到。吩噻嗪除了引起更高的值的有效化学位移各向异性的31 P在磷酸盐组中，在比较纯的二棕榈酰磷脂酰胆碱样品。在吩噻嗪的存在下，脂肪酸链区域中的较高流动性和二棕榈酰磷脂酰胆碱分子的极性头基的流动性降低被指示。这些现象可以很好地解释了一个模型的吩噻嗪在二棕榈酰磷脂酰胆碱双层，其中的二烷基氨基烷基链位于附近的极性头基和环系统不渗透远远超出甘油骨干到烃相的掺入。
The dipalmitoyl phosphatidylcholine/water system was employed to study the interaction of phenothiazines with model membranes. The effects of the drugs upon the lipid phase transition were examined using differential scanning calorimetry and NMR spectroscopy. The studied phenothiazines had peripheral (diethazine) or central (chlorpromazine) properties. Both drugs were observed to lower the phase transition temperature of dipalmitoyl phosphatidylcholine. The molar activity of chlorpromazine was higher than that of diethazine. At low concentrations the drugs affect the dipalmitoyl phosphatidylcholine pretransition endotherm. In the 13C NMR spectra of the drug-containing samples the signal of the trimethylammonium group of dipalmitoyl phosphatidylcholine was broadened, whereas a narrowing of the signal of the fatty-acid chain methylene groups was observed. Phenothiazine addition caused higher values of the effective chemical shift anisotropy of the 31P in the phosphate group, in comparison to the pure dipalmitoyl phosphatidylcholine sample. A higher fluidity in the fatty-acid chain region and a mobility reduction of the polar headgroup of the dipalmitoyl phosphatidylcholine molecules is indicated in the presence of the phenothiazines. These phenomena can be well accounted for by a model for the incorporation of the phenothiazines in the dipalmitoyl phosphatidylcholine bilayer, in which the dialkylaminoalkyl chains are located near the polar headgroups and the ring system does not penetrate far beyond the glycerol backbone into the hydrocarbon phase.