Differential conformational behaviors of alpha-mycolic acids in Langmuir monolayers and computer simulations

Phase diagrams of Langmuir monolayers of alpha-mycolic acids (alpha-MAs) from representative slow growing mycobacteria were intensively analyzed over a range of temperatures, by using so-called type-1 alpha-MAs having two cis-cyclopropyl groups from Mycobacterium tuberculosis, Mycobacterium kansasii and Mycobacterium avium-intracellulare complex (MAC) and type-3 alpha-MA, having one cis-cyclopropyl and one cis-double bond from Mycobacterium bovis BCG and MAC. Their intrachain groups are either cis-cyclopropyl or cis-double bond but the methylene chain segment lengths vary greatly. However, their monolayer features were alike: at lower temperatures and surface pressures, the molecules seemed to be in folded conformations, requiring larger mean molecular areas, whereas at higher temperatures and surface pressures, to be in extended conformations, requiring smaller average molecular areas approximately equivalent to cross sectional area of two hydrocarbon chains in a condensed film. In phase diagrams, the region for the folded forms of alpha-MAs was very limited, in contrast to the previously established behavior of ketomycolates, where complete folding predominated. Easy conversion of folded to extended conformations was indicated by thermodynamic studies of the Langmuir monolayer results and computer simulations.