Interaction of phenothiazine compounds with zwitterionic lysophosphatidylcholine micelles: Small angle x-ray scattering, electronic absorption spectroscopy, and theoretical calculations

被引:39
作者
Barbosa, Leandro R. S.
Caetano, Wilker
Itri, Rosangela
Homem-de-Mello, Paula
Santiago, Patricia S.
Tabak, Marcel
机构
[1] Univ Sao Paulo, Inst Fis, BR-05315970 Sao Paulo, SP, Brazil
[2] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13560970 Sao Carlos, SP, Brazil
关键词
D O I
10.1021/jp056486t
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
In this work, small-angle X-ray scattering (SAXS) studies on the interaction of the phenothiazine cationic compounds trifluoperazine (TFP, 2-10 mM) and chlorpromazine (CPZ, 2-10 mM) with micelles of the zwitterionic surfactant L-alpha-lysophosphatidylcholine (LPC, 30 mM), at pHs 4.0 and 7.0, are reported. The SAXS results demonstrate that, upon addition of both phenothiazines, the LPC micelle of prolate ellipsoidal shape changes into a cylindrically shaped micelle, increasing its axial ratio from 1.6 +/- 0.1 ( in the absence of drug) to 2.5 +/- 0.1 (for 5 and 10 mM of phenothiazine). Such an effect is accompanied by a shrinking of the paraffinic shortest semiaxis from 22.5 +/- 0.3 to 20.0 +/- 0.5 angstrom. Besides, a significant increase in polar shell electron density from 0.39(1) to 0.45(1) e/angstrom(3) is observed, consistent with cylinder-like aggregate geometry. Moreover, an increase of the phenothiazine concentration induces the appearance of a repulsive interference function over the SAXS curve of zwitterionic micelles, which is typical of interaction between surface-charged micelles. Such a finding provides evidence that the positively charged phenothiazine molecule must be accommodated near the hydrophobic/hydrophilic inner micellar interface in such a way that a net surface charge is altered with respect to the original overall neutral zwitterionic micelle. Such phenothiazine location is favored by both electrostatic and hydrophobic contributions, giving rise to binding constant values, obtained from electronic absorption results, that are quite larger compared to their binding to another zwitterionic surfactant, 3-(N-hexadecyl-N, N-dimethylammonio) propanesulfonate (HPS) (Caetano, W., et al. J. Colloid Int. Sci. 2003, 260, 414-422). Comparisons are made by means of theoretical calculations of the surfactant headgroup dipole moments for monomers of LPC and HPS. The theoretical results show that the dipole moment in LPC is almost perpendicular to the methylene chain, while a significant contribution along the methylene chain occurs for HPS. Besides, evidence is presented for extensive delocalization of the charges in the headgroups, which could be also relevant for the binding of the drugs.
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页码:13086 / 13093
页数:8
相关论文
共 29 条
[1]   CONFORMATIONAL-ANALYSIS OF THE POLAR HEAD GROUP IN PHOSPHATIDYLCHOLINE BILAYERS - A STRUCTURAL-CHANGE INDUCED BY CATIONS [J].
AKUTSU, H ;
NAGAMORI, T .
BIOCHEMISTRY, 1991, 30 (18) :4510-4516
[2]  
ANTENEODO C, 1995, EUR BIOPHYS J, V23, P447, DOI 10.1007/BF00196833
[3]   THE MODE OF ASSOCIATION OF AMPHIPHILIC DRUGS IN AQUEOUS-SOLUTION [J].
ATTWOOD, D .
ADVANCES IN COLLOID AND INTERFACE SCIENCE, 1995, 55 :271-303
[4]   Trifluoperazine effects on anionic and zwitterionic micelles: a study by small angle X-ray scattering [J].
Caetano, W ;
Barbosa, LRS ;
Itri, R ;
Tabak, M .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2003, 260 (02) :414-422
[5]   Chlorpromazine and sodium dodecyl sulfate mixed micelles investigated by small angle X-ray scattering [J].
Caetano, W ;
Gelamo, EL ;
Tabak, M ;
Itri, R .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2002, 248 (01) :149-157
[6]   Interaction of chlorpromazine and trifluoperazine with ionic micelles: electronic absorption spectroscopy studies [J].
Caetano, W ;
Tabak, M .
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, 1999, 55 (12) :2513-2528
[7]   Interaction of chlorpromazine and trifluoperazine with anionic sodium dodecyl sulfate (SDS) micelles: Electronic absorption and fluorescence studies [J].
Caetano, W ;
Tabak, M .
JOURNAL OF COLLOID AND INTERFACE SCIENCE, 2000, 225 (01) :69-81
[8]  
FORD JM, 1990, PHARMACOL REV, V42, P155
[9]   INTERACTIONS OF A PHENOTHIAZINE TRANQUILIZER WITH PHOSPHATIDYLCHOLINE AND PHOSPHATIDYLCHOLINE CHOLESTEROL MEMBRANES [J].
FORREST, BJ ;
LINEHAN, PTP ;
MATTAI, J .
BIOCHEMISTRY, 1984, 23 (10) :2288-2293
[10]   THE PHOTOKILLING OF BLADDER-CARCINOMA CELLS-INVITRO BY PHENOTHIAZINE DYES [J].
FOWLER, GJS ;
REES, RC ;
DEVONSHIRE, R .
PHOTOCHEMISTRY AND PHOTOBIOLOGY, 1990, 52 (03) :489-494