Terpenes control Chlorodiazepoxide-membrane interaccion through micellar dipole potential modifications

TURINA A. V.; PERILLO M.A.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2003 vol. 1616 p. 112 - 120

0005-2736

The ability of several natural terpenes to affect benzodiazepine (BZD)?micelle interaction through the membrane dipolar organization was investigated. The acid?base equilibrium of chlorodiazepoxide (CDX) and the spectroscopic behavior of the electrochromic dye merocyanine were tested in the presence and in the absence of Triton X-100 micelles (used to mimic a membrane environment) containing or not cineole, menthol, geraniol or camphor. CDX?s apparent pK increased in the environment of terpene-containing micelles compared with pure Triton X-100 micelles. Decrements in electric potentials (between -111 and  -128 mV with respect to pure detergent) were calculated from Boltzmann equation. This result suggested, that in the presence of terpenes, the tendency of CDXH+  to remain in the membrane phase increased. The dielectric constant (D) of the microenvironment sensed by merocyanine within Triton X-100 micelles, determined from lmax,2 of merocyanine monomer, was D= 9 and increased in the presence of all the terpenes assayed (D @ 11). The decrease in merocyanine partitioning (Apeak1/Apeak2 increased) also reflected an increment in the negative dipole potential. The present results suggest that terpenes contributed to the whole dipolar arrangement of the micelle with a dipole moment vector which had an intense component oriented parallel to the intrinsic dipole of the Triton X-100 molecules in the micelles. This led to a more negative environment of the interface region where CDX was located, and increased the net polarity of the deepest micelle regions sensed by merocyanine.