Mass Spectrometry of Self-Organizing Supramolecular Structures of Glycyrrhetic Acid and Levomycetin

Abstract

The formation of supramolecular complexes of glycyrrhetic acid (GLA) and levomycetin was detected and studied for the first time using electrospray-ionization mass spectrometry (ESI-MS). It was shown that the intermolecular complexes detected in the mass spectra were formed most effectively for a 1:1 host-guest ratio and less effectively for a 1:2 ratio. GLA aggregates (dimers and trimers) bound one or two levomycetin molecules and formed several singly and doubly charged cationic complexes. A comparison of the mass spectra of supramolecular complexes of glycyrrhizic acid (GA) and its aglycon (GLA) indicated that GLA self-aggregates and complexes with levomycetin formed more effectively than those of GA.Glycyrrhizic acid (GA, 1c), the principal bioactive constituent from roots of Glycyrrhiza glabra L. and G. uralensis Fisch. ex DC. and a natural drug of folk medicine, is a natural compound with significant medicinal value as the basis for formulating new highly effective preparations. GA and its aglycon glycyrrhetic acid (GLA, 1) are known to exhibit high antiinflammatory, antiulcer, anti-allergic, hepatoprotective, antiviral, and other types of biological activity and are currently the subjects of numerous investigations [1,2]. Despite that facts that the complexing properties of GA are rather well known [3][4][5][6][7][8][9] and that drug substances based on modified natural compounds often have biological activities surpassing those of the starting compounds [5,10], the ability of GLA to form complexes with drugs is practically unstudied [4].The goal of the present work was to study the formation of supramolecular complexes of 1 with the widely used drug levomycetin (2) using electrospray-ionization mass spectrometry. Understanding the reaction mechanisms of plant metabolites and drugs on the molecular level is one of the most important problems of biochemistry and medicinal chemistry because it can reveal the drug mechanism of action and facilitate the development of methods for monitoring it and minimizing possible in vivo side effects. Recently, mass spectrometry (ESI-MS) has been widely used to study supramolecular compounds. It has advantages over other methods for determining the qualitative composition of supramolecular complexes and their properties owing to the mild ionization conditions [11][12][13][14].