Effect of Polymer Chain Length on Membrane Perturbation Activity of Cationic Phenylene Ethynylene Oligomers and Polymers

• Published in: Langmuir Vol. 27; no. 17; pp. 10770 - 10775
• Main Authors: Wang, Ying, Jones, Emmalee M, Tang, Yanli, Ji, Eunkyung, Lopez, Gabriel P, Chi, Eva Y, Schanze, Kirk S, Whitten, David G
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 06.09.2011
• Subjects: Animals; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Biological Interfaces: Biocolloids, Biomolecular and Biomimetic Materials; Cations - chemical synthesis; Cations - chemistry; Cations - pharmacology; Cell Membrane - drug effects; Cell Membrane - metabolism; Chemistry; Colloidal state and disperse state; Electrolytes - chemical synthesis; Electrolytes - chemistry; Electrolytes - pharmacology; Escherichia coli - cytology; Escherichia coli - drug effects; Escherichia coli - metabolism; Exact sciences and technology; General and physical chemistry; Membranes; Microbial Sensitivity Tests; Molecular Structure; Polymers - chemical synthesis; Polymers - chemistry; Polymers - pharmacology; Structure-Activity Relationship; Gas liquid interface; Vesicle; Monolayer; Dyes; Molecular structure; Chain length; Glycerol; Lipids; Polymer; Molecular size; Air water interface; Perturbation; Oligomer; Assay; Polyelectrolyte; Membrane; Models
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la201820k

The interactions of poly(phenylene ethynylene)- (PPE-) based cationic conjugated polyelectrolytes (CPEs) and oligo(phenylene ethynylene)s (OPEs) with different model lipid membrane systems were investigated to gain insight into the relationship between molecular structure and membrane perturbation ability. The CPE and OPE compounds exhibit broad-spectrum antimicrobial activity, and cell walls and membranes are believed to be their main targets. To better understand how the size, in terms of the number of repeat units, of the CPEs and OPEs affects their membrane disruption activities, a series of PPE-based CPEs and OPEs were synthesized and studied. A number of photophysical techniques were used to investigate the interactions of CPEs and OPEs with model membranes, including unilamellar vesicles and lipid monolayers at the air/water interface. CPE- or OPE-induced dye leakage from vesicles reveals that the CPEs and OPEs selectively perturb model bacterial membranes and that their membrane perturbation abilities are highly dependent on molecular size. Consistent with dye-leakage assay results, the CPEs and OPEs also exhibit chain-length-dependent ability to insert into 1,2-dipalmitoyl-sn-glycero-3-phospho-(1′-rac-glycerol) (DPPG) monolayers. Our results suggest that, for PPE-based CPE and OPE antimicrobials, chain length can be tuned to optimize their membrane perturbation ability.