Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers

Abstract

Antimicrobial polymers have emerged as a potential solution to the growing problem of antimicrobial resistance. Although several studies have examined the effects of various parameters on the antimicrobial and hemolytic activity of statistical copolymers, there are still numerous parameters to be explored. Therefore, in this study, we developed a library of 36 statistical amphiphilic ternary copolymers prepared via photoinduced electron transfer-reversible addition−fragmentation chain transfer polymerization to systematically evaluate the influence of hydrophobic groups [number of carbons (5, 7, and 9)] and chain type of the hydrophobic monomer (cyclic, aromatic, linear, or branched), monomer ratio, and degree of polymerization (DP n ) on antimicrobial and hemolytic activity. To guide our synthetic strategy, we developed a pre-experimental screening approach using C log P values of oligomer models, which correspond to the logarithm of the partition coefficient of compounds between n-octanol and water. This method enabled correlation of polymer hydrophobicity with antimicrobial and hemolytic activity. In addition, this study revealed that minimizing hydrophobicity and hydrophobic content were key factors in controlling hemolysis, whereas optimizing antimicrobial activity was more complex. High antimicrobial activity required hydrophobicity (i.e., C log P, hydrophobicity index) that was neither too high nor too low, an appropriate cationic/hydrophobic balance, and structural compatibility between the chosen monomers. Furthermore, these findings could guide the design of future antimicrobial ternary copolymers and suggest that C log P values between 0 and 2 have the best balance of high antimicrobial activity and low hemolytic activity.

Laser-patterned carbon coatings on flexible and optically transparent plastic substrates for advanced biomedical sensing and implant applications

“…36,37 They can also exhibit antimicrobial, self-cleaning, and anti-biofouling properties since the low adhesive forces and rough topographies reduce the contact area between an implant and its surroundings. 53 For example, DLC-modified HDPE is utilized in coronary stents due to its antithrombotic properties. 54 The sp 2 and sp 3 content of a hard carbon surface affect its contact angle value.…”

Antibacterial and cytotoxic properties of star-shaped quaternary ammonium-functionalized polymers with different pendant groups

“…The hydrophobicity of a polymer is one of the critical parameters determining its biological activity. 55 The QAD polymers were highly hydrophobic with negligible water solubility owing to their long alkyl pendant group. 56 The hydrophobicity of the…”

Macromolecular Nanotherapeutics and Antibiotic Adjuvants to Tackle Bacterial and Fungal Infections

“…Researchers throughout the world have developed numerous polymeric architecture including random copolymers, block copolymers, homopolymers, zwitterionic, and branched polymers with different polymeric backbone, such as polynorbornenes/oxanorbornenes ( Figure 2 A), [ 78–84 ] polymethacrylate/polyacrylates (Figure 2B), [ 85–91 ] poly‐ β −lactam (Figure 2C), [ 92–95 ] polymaleimides (Figure 2D), [ 95–100 ] glycosylated cationic block co‐beta‐peptides (Figure 2E), [ 101 ] polycarbonates (Figure 2F), [ 102–107 ] polyamides, [ 108 ] poly(benzyl ether)s, [ 109 ] polyionenes, [ 110,111 ] poly(2‐oxazoline), [ 112,113 ] and many other polymeric amphiphiles (Figure 2). [ 114–130 ] Readers can follow development of antimicrobial polymers which have been extensively covered in several earlier review article. [ 30,32,131–137 ] Herein, we will focus on the development antimicrobial polymers which exert their antimicrobial activity through the formation of nanoaggregates with some prominent experimental evidences.…”