Thermodynamic parameters for the complexation of water-soluble betulin derivatives with (2-hydroxypropyl)-β-cyclodextrin determined by affinity capillary electrophoresis

Abstract

The interaction between (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) and water-soluble betulin derivatives, betulin 3,28-disulfate (DSB) and betulin 3-acetate-28-sulfate (ASB), belonging to the class of pentacyclic lupane triterpenoids, was studied using affinity capillary electrophoresis. It was found that 1:1 and 1:2 complexes were formed. The stability constants of the complexes in the temperature range of 293.15-318.15 K were determined. The values obtained are sufficiently large; log K (1:1) and log K (1:2) are 4.25-5.02 and 6.08-7.59, respectively. This phenomenon can be explained by the presence of broad hydrophobic regions in the molecules of the compound studied. The stability constants decrease with increasing temperature. The stability constants for ASB complexes are slightly higher as compared to the constants for DSB complexes. The thermodynamic parameters for the complexation were calculated from the van't Hoff plots. The complexation was found to be controlled by the enthalpy change. The obtained values of stability constants at 298 K were compared with values for the β-CD complexes of the compounds under study and for the HP-β-CD an d β-CD complexes of water-insoluble betulin derivatives. It was found that water-soluble betulin derivatives form more stable complexes with CDs as compared to water-insoluble derivatives (betulonic and betulinic acids), and the HP-β-CD complexes are more stable than the β-CD complexes.

Determining binding constants for 1:1 and 1:2 inclusion complexes of ester betulin derivatives with (2‐hydroxypropyl)‐β‐cyclodextrin by affinity capillary electrophoresis

“…The fact that the same values of binding constants were obtained for DSB in this study and in study [8] can be explained as follows. In [8], a too low HP‐β‐CD concentration was not used, and the peaks were almost symmetric and more broadened due to the pressure application for transferring samples to the thermostatted segment of the capillary before separation and to detector after separation. For 25°C, there was no difference in the values obtained by the conventional way and by using the thermostatted capillary segment.…”

“…Betulin and its derivatives, pentacyclic lupane triterpenoids with anticancer and other types of biological activities, can be attributed to such drugs [3]. Recently, the complexation of a number of betulin derivatives (betulinic and betulonic acids, and sulphated betulin derivatives) with β‐CD, (2‐hydroxypropyl)‐β‐cyclodextrin (HP‐β‐CD), and (2‐hydroxypropyl)‐γ‐cyclodextrin (HP‐γ‐CD) has been studied [4–9], as well as the complexation of betulin 3,28‐diphthalate (DPhB) and betulin 3,28‐disuccinate (DScB) with HP‐γ‐CD [10].…”

“…(): where μ 12 is the ionic mobility of D/CD 2 . A characteristic feature of this dependence is the absence of a plateau after a sharp mobility decrease; mobility is decreasing with increasing CD concentration in BGE over a wide range of CD concentration [8,32,33]. To accurately calculate all the constants for this case, at least 10 BGEs with different CD content are recommended to use, while for a 1:1 complexation system, five to eight such BGEs can be used [33].…”

“…Few studies with simultaneous determination of binding constants for 1:1 and 1:2 CD complexes using ms ACE have been reported. These studies concern to complexes of alkylnaphthalene derivatives with carboxymethyl‐β‐CD [31], several alkyl(methyl)‐methylimidazolium‐based ionic liquid cations with α‐CD and dimethyl‐β‐CD [35], fusidic acid and three structurally related compounds with γ‐CD [32], betulin 3,28‐disulfate (DSB) and betulin 3‐acetate‐28‐sulfate (ASB) with HP‐β‐CD [8], and 4,4′‐biphenol and 4‐phenylphenol with HP‐β‐CD [33]. There are also studies with the simultaneous determination of binding constants for 1:1 and 1:2 CD complexes using other methods.…”

“…Among the early studied CDs, only HP‐β‐CD forms with betulin derivatives both 1:1 and 1:2 complexes. The HP‐β‐CD complexes of DPhB and DScB have been studied for the first time within the framework of this paper, while such complexes for DSB have been early studied in the thermostatted capillary segment and binding constants have been calculated without using the parameter a 1 of the HVL function [8].…”