Estudo das propriedades antimicrobianas de copolímeros derivados do eugenol

Abstract

The main objective of this work was to develop and to test a novel biologically active polymer based on macroporous PCL-co-Eugenol copolymers with potential for use in medicine. The antimicrobial element in the copolymer main chain is the bioactive compound eugenol (Eg). Eugenol (2-allyl-4-methoxyphenol) (Eg) has wide use as cement in dentistry due to their analgesic and antiseptic properties. Eugenol is able to act as antimicrobial due to their hydrogen donating capacity of the phenolic hydroxyl group. In this work bioresorbable copolymers with antimicrobial properties based on Eugenol (Eg) and caprolactone (CL) monomers were prepared by mass polymerization at 25 oC using iodine (I2) as initiator. The microstructure of the copolymer obtained was elucidated by means of 1H-NMR and FTIR spectroscopy as well by thermal analyses. The reactivity ratios of both monomers were determined by the application of the non-linear least-squares method suggested by Tidwell and Mortiner. The obtained results (rEg=0.126 and rCL=2.132) confirm that the comonomer pairs polymerizes statistically, independently of the monomer feed. To obtain more information about the factors that determine the bioactivity of the PCL-co-Eg copolymers, molecular orbital modeling was performed. The theoretical quantum-chemistry calculations indicated that the antimicrobial activity of copolymers might be significantly associated with the frontier molecular orbital energy gap (LUMO-HOMO energy difference). The present findings are consistent with our experimental studies about the antimicrobial property of PCL-Eg copolymers by in vitro techniques. According to the LUMO energy, the molecules can be classified as hard electrophiles (ELUMO>3.0 eV) and soft electrophiles (ELUMO<2.5 eV). In general, hard electrophiles show a more important biological activity, suggesting that the active site of the biomolecule could be a hard nucleophile. Despite the fact that the antimicrobial activity of the PCL-co-Eg may be also influenced by other factors, LUMO energy seems to be an adequate theoretical parameter to predict qualitatively the antimicrobial activity of these copolymers. The energy of the HOMO-LUMO orbitals in the copolymer did not show a significant dependence with the Eg composition in the PCL-co-Eg copolymer. The frontier orbital LUMO energy is inversely proportional to the Eg composition in the PCL-co-Eg copolymer. Our study confirms and supports the earlier findings regarding antimicrobial properties of PCL-co-Eg copolymers against S. Aureus and E. Coli. Further investigations need to be done to develop PCL-co-Eg copolymers into a useful therapeutic tool for treatment of periodontits. PCL-co-Eg copolymers show great potential in this respect, especially on the grounds of limitations such as development of resistance to side effects and toxicity of currently used antibiotics. However, more theoretical and experimental investigations about PCL-Eg copolymers will aid in the elucidation of its biodegradation properties and clarification about some potential health hazards before they can be safely evaluated and commercially developed as beneficial antimicrobial coating in medicine.