Location of chlorhexidine in DMPC model membranes: a neutron diffraction study

Chlorhexidine (CHX) is an effective anti-bacterial agent whose mode of action is thought to be the disruption of the cell membrane. It is known to partition into phospholipid bilayers of aqueous model-membrane preparations. Neutron diffraction data taken at 36 °C on the location of CHX in phosphatidylcholine (PC) bilayers is presented. The center of mass of the deuterated hydrocarbon chain of CHX is found to reside 16 Å from the center of the bilayer in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (14:0–14:0 PC). This places the drug near the glycerol backbone of the lipid, and suggests a mode of action whereby the molecule is bent in half and inserts wedge-like into the lipid matrix. This mechanism is distinct from detergent-like mechanisms of membrane disruption and more similar to some anti-microbial peptide action, where peptides insert obliquely into the bilayer headgroup region to disrupt its structure.