title: Fast chromatographic determination of the bile salt critical micellar concentration.
abstract: In a line of research focused on the design, synthesis and development of new bile acid-based compounds, the physico-chemical profile of the molecules must be thoroughly explored and analyzed. In this scenario, a fast and reliable information on the critical micellar concentration (CMC) of specific compounds through a profitable chromatographic parameter can be of aid to rationally direct the synthesis of new molecular entities, mainly during the early stages of the drug-discovery process. The derived 'chromatographic hydrophobicity index' (CHI), usually employed for a fast access to the log P/log D value of physico-chemically diverse compounds and obtained via RP-gradient elution, was for the first time engaged in the bile acid field. Accordingly, 14 unconjugated bile acids harboured with a different number, position and orientation of hydroxy groups, as well as other substituents onto the steroidal backbone and side chain, were selected to build up a calibration curve. Such a collection of compounds was rationally assembled in order to manage an almost continuous range of CMC values (spanning the spectrophotometrically obtained CMCs between 5 and 25 mM). A high degree of correlation between CMC and CHI values was obtained (R(2) and cross-validated R(xv)(2) of the pCMC vs CHI plot equal to 0.975 and 0.966, respectively). A selected new subset of five confidential research bile acids with experimental CMCs in the range 6-19 mM was finally recruited to validate the proposed method. The high statistical quality of the established mathematical model turned out into a very appreciable predictive power.
authors.affiliation: Dipartimento di Chimica e Tecnologia del Farmaco, Università degli Studi di Perugia, Perugia, Italy. natalini@chimfarm.unipg.it
authors.forename: Benedetto
authors.initials: B
authors.lastname: Natalini
authors.forename: Roccaldo
authors.initials: R
authors.lastname: Sardella
authors.forename: Antimo
authors.initials: A
authors.lastname: Gioiello
authors.forename: Emiliano
authors.initials: E
authors.lastname: Rosatelli
authors.forename: Federica
authors.initials: F
authors.lastname: Ianni
authors.forename: Emidio
authors.initials: E
authors.lastname: Camaioni
authors.forename: Roberto
authors.initials: R
authors.lastname: Pellicciari
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000191:economics / Q000379:methods; D056148:Chromatography, Reverse-Phase / Q000191:economics / Q000379:methods*; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D015233:Models, Statistical; D013997:Time Factors
chemical_list: D001647:Bile Acids and Salts; D008823:Micelles