Oxazoline-Based Antimicrobial Oligomers: Synthesis by CROP Using Supercritical CO 2 a Vanessa G. Correia, Vasco D.B. Bonifa ´cio, Vivek P. Raje, Teresa Casimiro, Guilhermina Moutinho, Cla ´udia Lobato da Silva, Mariana G. Pinho, Ana Aguiar-Ricardo* Introduction Due to public health concerns many modern materials are supposed to be equipped with antimicrobial properties. The use of antimicrobial polymers for rendering biomaterials resistant to microbial colonization is a very convenient way. [1] Polymeric antimicrobial agents have many advan- tages as they are chemically stable, reduced residual toxicity, nonvolatile, do not permeate though the skin, and can have antimicrobial activity against different strains of bacteria and/or fungi. Significant advances have been made in the synthesis of antimicrobial polymers geared specifically for water treatment, for biomedical and food applications, or for textile products. [2,3] Synthetic polymers are much easier to synthesize than peptides but the synthetic approaches still often involve multi-step synthesis including protection and deprotection steps. New synthetic approaches for the production of inherently antimicrobial and biocompatible polymers are required. Full Paper V. G. Correia, V. D. B. Bonifa ´cio, V. P. Raje, T. Casimiro, A. Aguiar-Ricardo REQUIMTE, Faculdade de Cie ˆncias e Tecnologia, Departamento de Quı ´mica, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal E-mail: aar@dq.fct.unl.pt V. G. Correia, M. G. Pinho Bacterial Cell Biology Laboratory, Instituto de Tecnologia Quı ´mica e Biolo ´gica, Av. da Repu ´blica (EAN) 2780-157 Oeiras, Portugal G. Moutinho CPB–Centro de Polimeros Biome ´dicos, Instituto Superior de Cie ˆncias da Sau ´de Egas Moniz Quinta da Granja, Campus Universita ´rio, 2829-511b Caparica, Portugal C. L. da Silva IBB–Institute for Biotechnology and Bioengineering, Center for Biological and Chemical Engineering, Instituto Superior Te ´cnico, Avenida Rovisco Pais, 1049-001 Lisboa, Portugal a Supporting Information for this article is available from the Wiley Online Library or from the author. A method using supercritical CO 2 to obtain biocompatible 2-oxazoline-based oligomers quaternized with different amines is described. The synthesized oligo(2-oxazoline)s display partial carbamic-acid insertion at one end. The syntheses of quaternary oligo(2-bisoxazoline)s and linear oligoethylenimine hydrochlorides are reported. Oligo(2-methyl-2-oxazoline) and oligo(2-bisoxazoline) quaternized with N,N-dimethyl- dodecylamine are the most efficient biocidal agents showing fast killing rates against Staphylococcus aur- eus and Escherichia coli. Linear oligoethylenimine hydrochloride shows the lowest MIC values but higher killing times against both bacteria. Based on the anti- microbial activity studies, a cooperative action of car- bamic acid with the ammonium end group is proposed. 1128 Macromol. Biosci. 2011, 11, 1128–1137 ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim wileyonlinelibrary.com DOI: 10.1002/mabi.201100126