Application of micellar and microemulsion electrokinetic chromatography for characterization of gallium(III) complexes of pharmaceutical significance

Abstract

CE with conventional UV detection has recently been shown as a highly effective means to assaying cytotoxic gallium(III)-based compounds with regard to desirable drug-like properties such as the stability and binding to serum proteins. In this extension of that work, different CE techniques are used to further characterize a given set of gallium coordination compounds with established antiproliferating efficacy. Using free-zone CE mode, the electrophoretic profiles of complexes are recorded in order to assess their actual charge state under physiological buffer conditions. Micellar and microemulsion electrokinetic chromatographic techniques are tested as tools for the rapid estimation of the n-octanol-water partition coefficient (log P) that provides a rationale estimate of a drug's ability to cross biological membranes. A range of electrolyte buffer systems with varying (both in the nature and concentration) organic modifiers are examined to evaluate their effect on the relationship between experimental or calculated log P and the retention factors of compounds (log k'). Both methods were found to be better applicable for neutral than for cationic Ga complexes, the microemulsion mode demonstrating superior lipophilicity estimations as well as statistically meaningful log P versus log k' correlations when all the complexes were included in one regression set.

An advanced application of the quantitative structure–activity relationship concept in electrokinetic chromatography of metal complexes

“…As is at work for organic analytes, the separation of metal complexes in EKC systems of concern is governed by differential partitioning into the micelles of a charged surfactant (i.e., SDS) or droplets of an organic solvent (n-heptane) stabilized -in the form of microemulsion -by means of the same surfactant [8]. For electrically neutral complexes, e.g., complex 1 (see Fig.…”

“…Next, both 2 and 3 behave differently (from 1) in such a way that the EEF induces significant changes in D and the energy of solvation, which are associated with considerable structural alterations of their C 1 symmetry. To our understanding, different in extent the EEF-mediated variations of these descriptors are related to dissimilar slopes of log k 0 versus isopropanol concentration dependences, which are opposite in sign for coordinatively saturated and unsaturated Ga complexes [8]. In this context, one's attention should be drawn to a difference in signs of D versus c functions (Fig.…”

“…However, it is intricate to apply these molecular parameters to explain changes in the migration upon the modification of the EKC electrolytes, e.g., by adding an organic solvent [8]. Indeed, while the structure and properties of the pseudostationary phase are known to be largely altered in the presence of alcohols [23,24] that inevitably affects k 0 , the corresponding changes in solute parameters are usually not taken into consideration when building up QSARs.…”

“…[8] were related to analyte descriptors by means of linear regression using the STATGRAPHICS program (StatPoint, Herndon, VA, USA). The regression equations derived were tested statistically with respect to their meaningfulness by taking into account the coefficient of regression (r), Rsquared test, standard error of the estimate (SE), and mean absolute error.…”

“…Among a great variety of applications using these techniques, inorganic analytes, particularly metal complexes, have attracted more and more attention [1][2][3][4][5][6][7][8]. Due to the fact that the micelles or oil droplets have a lipophilic character and are usually applied in aqueous electrolyte systems, both neutral (or highly hydrophobic ligand) and charged (or essentially hydrophilic) complexes can be separated.…”