title: Interactions of biocidal guanidine hydrochloride polymer analogs with model membranes: a comparative biophysical study.
abstract: Four synthesized biocidal guanidine hydrochloride polymers with different alkyl chain length, including polyhexamethylene guanidine hydrochloride and its three new analogs, were used to investigate their interactions with phospholipids vesicles mimicking bacterial membrane. Characterization was conducted by using fluorescence dye leakage, isothermal titration calorimetry, and differential scanning calorimetry. The results showed that the gradually lengthened alkyl chain of the polymer increased the biocidal activity, accompanied with the increased dye leakage rate and the increased binding constant and energy change value of polymer-membrane interaction. The polymer-membrane interaction induced the change of pretransition and main phase transition (decreased temperature and increased width) of phospholipids vesicles, suggesting the conformational change in the phospholipids headgroups and disordering in the hydrophobic regions of lipid membranes. The above information revealed that the membrane disruption actions of guanidine hydrochloride polymers are the results of the polymer's strong binding to the phospholipids membrane and the subsequent perturbations of the polar headgroups and hydrophobic core region of the phospholipids membrane. The alkyl chain structure significantly affects the binding constant and energy change value of the polymer-membrane interactions and the perturbation extent of the phospholipids membrane, which lead to the different biocidal activity of the polymer analogs. This work provides important information about the membrane disruption action mechanism of biocidal guanidine hydrochloride polymers.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, School of Bioengineering, East China University of Science and Technology, Shanghai.
authors.forename: Zhongxin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Anna
authors.initials: A
authors.lastname: Zheng
authors.forename: Jianjiang
authors.initials: J
authors.lastname: Zhong
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055592:Biophysical Phenomena; D002151:Calorimetry; D002176:Candida albicans / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D019791:Guanidine / Q000737:chemistry; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008051:Lipid Bilayers / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008956:Models, Chemical; D015394:Molecular Structure; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D021241:Spectrometry, Mass, Electrospray Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000890:Anti-Infective Agents; D006146:Guanidines; D008051:Lipid Bilayers; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D010743:Phospholipids; D011108:Polymers; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C060540:polyhexamethyleneguanidine; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C002773:dimyristoylphosphatidylglycerol; D019791:Guanidine