Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore 138669, Singapore.
Biomaterials. 2010 Mar;31(7):1751-6. doi: 10.1016/j.biomaterials.2009.11.030. Epub 2009 Dec 8.
In this paper, we have designed and synthesized well-defined pegylated-polymers with tertiary amines from readily available commodity monomers 2-(dimethylamino)ethyl methacrylate (DMAEMA) and oligo(ethylene glycol) methyl ether methacrylate (OEGMA, M(n) approximately 475 Da) by reversible addition-fragmentation chain transfer (RAFT) polymerisation. By employing a simple and efficient post-polymerisation functionalization strategy, tertiary amines were quaternized to result in cationic polymers. By the careful selection of the functional halide, X-(CH(2))q-R, (where in X=halide; R=the chemical functionality; q=the number of alkyl spacer between the quaternary ammonium group and R), a series of polymers with well-controlled molecular weight, different amphiphilic balance and chemical functionalities (such as alkyl, primary alcohol, primary amine and carboxylic acid) were readily synthesized. The antimicrobial activities of these cationic polymers were determined against Gram-positive bacteria Bacillus subtilis. Minimum inhibitory concentration (MIC), the polymer concentration to completely inhibit the bacterial growth, was found to be dependent both on the nature of functional group and the hydrophobicity of the polymer. Amongst the functional groups, both the alkyl and the alcohol groups were found to be effective, with MIC values in the range of 20-80 mg/L. The haemolytic properties of polymers were analyzed against mouse red blood cells. The polymers with a short alkyl or hydroxyl group demonstrated little haemolysis, yet retained strong antimicrobial activity. The overall hydrophobicity of the polymer influenced its haemolytic behavior. These polymers can be promising antimicrobial agents. In addition, the approach proposed in this study to atom-efficient design and synthesis of antimicrobial polymers from the commercially available monomers can also be applied to develop well-defined functional cationic polymers for various biomedical applications.
本文设计并合成了一系列具有叔胺官能团的聚乙二醇化聚合物，这些聚合物是由易得的商品化单体 2-（二甲氨基）乙基甲基丙烯酸酯（DMAEMA）和聚乙二醇甲基醚甲基丙烯酸酯（OEGMA，M(n)约为 475 Da）通过可逆加成-断裂链转移（RAFT）聚合制备的。通过采用简单有效的聚合后功能化策略，将叔胺季铵化得到阳离子聚合物。通过仔细选择功能卤化物 X-(CH(2))q-R，（其中 X=卤化物；R=化学官能团；q=季铵基团和 R 之间的烷基间隔数），可以很容易地合成一系列具有良好控制的分子量、不同的两亲平衡和化学官能团（如烷基、伯醇、伯胺和羧酸）的聚合物。这些阳离子聚合物的抗菌活性是针对革兰氏阳性细菌枯草芽孢杆菌测定的。最小抑菌浓度（MIC），即完全抑制细菌生长的聚合物浓度，既取决于官能团的性质，也取决于聚合物的疏水性。在所研究的官能团中，烷基和醇基都被证明是有效的，MIC 值在 20-80 mg/L 范围内。聚合物对小鼠红细胞的溶血性质进行了分析。具有短烷基或羟基的聚合物表现出很少的溶血，但仍保持较强的抗菌活性。聚合物的整体疏水性影响其溶血行为。这些聚合物可能是有前途的抗菌剂。此外，本研究中提出的从商业上可获得的单体高效设计和合成抗菌聚合物的方法也可用于开发用于各种生物医学应用的具有良好定义的功能性阳离子聚合物。
