Alternatingly Amphiphilic Antimicrobial Oligoguanidines: Structure–Property Relationship and Usage as the Coating Material with Unprecedented Hemocompatibility

Abstract

With the emergence of antibiotic resistance in recent years, the combat against bacteria is becoming more difficult and critical in human healthcare. In addition to the development of new chemical entities and derivatives of antibiotics and disinfectants, the antimicrobial surface is recognized as a potential way to prevent healthcare-associated infections, particularly those caused by medical devices such as implants and various catheters. However, traditional ways of engineering antimicrobial surfaces using coated metal nanostructures or blended-in antibiotics inevitably face the problem of metal ion or antibiotic leakage, leading to surface deactivation, toxicity, and antibiotic resistance. A new strategy developed in recent years involves the use of coated cationic antimicrobial polymers, which serve as resistance-resistant, surface-anchored antibacterial agents, but they also usually come with hemolytic activity resulting from their membrane-disrupting-type mechanism of action. In this report, we show that the combinatorial approach can be highly useful for the selection of alternatingly amphiphilic oligomers, which are essentially molecular nanorods as revealed by molecular dynamic simulations. The combinatorial process allowed the structure–property relationship of these molecular nanorods to be revealed and yielded oligoguanidine hit with high antimicrobial activity, fast killing kinetics, and extremely low hemolytic activity through assay screening. We demonstrate that the covalent conjugation of such a prescreened oligoguanidine nanorod to glass slides or polycaprolactone films could produce antimicrobial surfaces with excellent performance. A catheter prototype made using such a modified polycaprolactone film could transport bacteria-contaminated liquid, efficiently removing all bacteria without causing lysis of red blood cells.