Copolymers of acrylonitrile with quaternizable thiazole and triazole side-chain methacrylates as potent antimicrobial and hemocompatible systems.

ABSTRACT

A series of six copolymeric families, P(AN-co-MTAs) with various molar fractions of acrylonitrile (fAN) and methacrylates (fMTA) based on 1,3-thiazole and 1,2,3-triazole pendant groups with several spacers of different length and nature (alkyl or succinic), have been synthesized by conventional radical polymerization. The molar fraction of acrylonitrile in the copolymers (FAN) was determined by CHNS elemental analysis. The copolymers were also characterized by ATR-FTIR and molecular weights were determined by size exclusion chromatography (SEC). Due to the nucleophilic nature of the azole heterocycles the copolymers have been easily modified by N-alkylation reaction with butyl iodide leading to polyelectrolytes of diverse amphiphilic balance, P(AN-co-MTAs-BuI). The degree of quaternization (DQ) was quantitative in all instances and was determined by (1)H NMR spectroscopy. Dynamic light scattering (DLS) measurements were performed in order to determine the particle size and the charge density of the systems. The antimicrobial activity of the copolymers was studied in terms of minimal inhibitory concentration (MIC) against the Gram-positive bacteria Staphylococcus aureus, the Gram-negative Pseudomonas aeruginosa and the yeast Candida parapsilosis, as well as the cytotoxic activity toward human red blood cells (RBCs). These types of amphiphilic copolycations presented high selectivity (>300) maintaining moderate to good antimicrobial activity (MIC=4-64 µg/mL) and being non-hemolytic even at high molar fractions of AN in the copolymers compared to PMTAs-BuI homopolymers. Moreover, two examples of acrylonitrile-enriched copolymers (FAN=0.6) presented an excellent time-killing efficiency against microorganisms with 99.9% of killing ranging from 5 to 30 min. Besides, important changes in the morphology of the cell envelop of the microorganisms after treatment with P(AN-co-MTAs) were observed by Field Emission Scanning Electron Microscopy (FE-SEM) compared to untreated samples. These results indicate that these quaternized copolymers (QUATs) behave like the corresponding PMTAs-BuI homopolymers, being microbiostatic and also highly effective microbiocidal agents.