Structure−Antibacterial Activity Relationships in Quaternized Cellulose-Grafted PDMAEMA: Influence of Graft Length, Degree of Quaternization, and Alkyl Chain Length

Abstract This study elucidates the structure−activity relationship governing the antibacterial activity of quaternized cellulose-graft-poly(2-(dimethylamino)ethylmethacrylate) (cellulose−g-QPDMAEMA) copolymers. Cellulose was functionalized with PDMAEMA side chains of controlled graft lengths, followed by quaternization using alkyl halides of varying chain lengths (C1, C8, and C12) to introduce permanent cationic functionalities. The effects of three key structural parameters: graft length, degree of quaternization (DQ), and alkyl chain length of the quaternizing agent were systematically investigated against the Gram-positive bacterium Staphylococcus aureus. The interplay between charge density and hydrophobicity significantly influenced antibacterial performance, where increasing graft length enhanced bacterial inhibition up to a graft length of 32 repeat units, beyond which steric hindrance and restricted chain mobility likely limited antibacterial effectiveness. Higher DQ (83%) improved antimicrobial activity due to enhanced electrostatic interactions with negatively charged bacterial membranes, while quaternizing alkyl chain lengths significantly modulated membrane-disruptive capability, where short and medium alkyl lengths (C1 and C8, respectively) provided the best antimicrobial activity against S. aureus with a bactericidal concentration producing a ≥ 4-log reduction of 0.63 mg mL−1, while a longer alkyl length (C12) displayed little to no antibacterial activity. The methyl-quaternized graft copolymer cellulose-g-C1-QPDMAEMA23 performed better relative to n-octyltrimethylammonium bromide (OTAB), a non-polymeric quaternary ammonium compound (QAC). These findings establish clear structure−antibacterial activity relationships for cellulose-based cationic polymers against S. aureus and highlight the importance of tuning chemical and architectural parameters to improve antibacterial activity for biomedical or antibacterial surface applications.