title: Location of chlorhexidine in DMPC model membranes: a neutron diffraction study.
abstract: 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 degrees 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 16A from the center of the bilayer in 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (14:0-14:0PC). 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.
authors.affiliation: Department of Physics, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3S1, Canada.
authors.forename: Ivana
authors.initials: I
authors.lastname: Komljenović
authors.forename: Drew
authors.initials: D
authors.lastname: Marquardt
authors.forename: Thad A
authors.initials: TA
authors.lastname: Harroun
authors.forename: Edward
authors.initials: E
authors.lastname: Sternin
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002710:Chlorhexidine / Q000737:chemistry*; D003903:Deuterium / Q000737:chemistry; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D008958:Models, Molecular; D033363:Neutron Diffraction
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D003903:Deuterium; D002710:Chlorhexidine; D004134:Dimyristoylphosphatidylcholine