Phase Behaviour of Cord Factor and Related Bacterial Glycolipid Toxins

Abstract

C-6 esters of methyl .alpha.-D-glucoside and C-6, C-6'' diesters of .alpha.,.alpha.''-D-trehalose with C18 and C32 threo and erythro mycolic acids (from chemical source) and of C80-erythro-mycolic acid (from natural source) were synthesized. Esters of a C32 deoxy analog were also prepared. Throughout a monolayer study at the air-water interface, these glycolipids formed well-organized phases in which the 2 hydrocarbon chains of mycoloyl residues must be in interaction. Compression isotherms of C32 esters suggested a transition between liquid-expanded and liquid-condensed states. Latent heat Qc and entropy changes .DELTA.S associated with these phase transitions and the critical temperature at which they occur were measured. Within the monolayer, the molecular packing of these glycolipids depends on the presence of the hydroxyl group of mycoloyl residues and on its stereochemistry. In particular, intermolecular H bonds between these groups are postulated in the case of the bis(C32-erythro-mycoloyl)-trehalose. Short chain C18 esters form fluid phases (> 10.degree. C), whereas very long chain C80 mycoloyl esters of trehalose exist in a condensed state (20.degree. C). These glycolipids interacted strongly with dipalmitoylphosphatidylcholine and egg yolk lecithins (3-sn-phosphatidylcholine). Their phase behaviors are discussed in connection with hypotheses concerning the way they can interact with mitochondrial membranes.