Antimicrobial polycarbonates: investigating the impact of balancing charge and hydrophobicity using a same-centered polymer approach.
Biodegradable antimicrobial polymers are a promising solution for combating drug resistant microbes. When designing these materials, the balance between charge and hydrophobicity significantly affects the antimicrobial activity and selectivity toward microbes over mammalian cells. Furthermore, where the charge and hydrophobicity is located on the molecules has also proven to be significant. A series of antimicrobial homopolymer polycarbonates were synthesized, where the hydrophobic/hydrophilic balance was controlled by varying the spacer between the charged quaternary ammonium moiety and the polymer backbone (a "same-centered" structure where the hydrophobic moiety is directly attached to the charged moiety). These homopolymers were active against all microbes tested but depending on the spacer length some hemolytic activity was observed. To reduce the polymer hemolytic activity we systematically varied the polymer composition by copolymerizing the different monomers used in the "same center" homopolymers. By maintaining charge on each repeat unit but copolymerizing monomers having varied hydrophobic side chain lengths, polymers with high activity and selectivity were achieved. In addition, these macromolecules act via a membrane disruption mechanism, making them less likely to induce resistance.
IBM Almaden Research Center, 650 Harry Road, San Jose, California 95120, United States.
Amanda C
AC
Engler
Jeremy P K
JP
Tan
Zhan Yuin
ZY
Ong
Daniel J
DJ
Coady
Victor W L
VW
Ng
Yi Yan
YY
Yang
James L
JL
Hedrick
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002254:Carbonates / Q000737:chemistry*; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D053878:Hemolytic Agents / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D011108:Polymers / Q000737:chemistry; D011550:Pseudomonas aeruginosa; D051381:Rats; D013211:Staphylococcus aureus / Q000187:drug effects; D013212:Staphylococcus epidermidis / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D002254:Carbonates; D053878:Hemolytic Agents; D011108:Polymers