抑菌型Fischer卡宾类一氧化碳缓释分子

Antibacterial Fischer Carbenoid CO-Releasing Molecules

过渡金属羰基化合物类一氧化碳释放分子(CORMs)的设计是当下无机化学、生物医学、材料化学等多学科交叉的热点.针对现有先导结构传输效率低、水溶性差的关键问题,发展了一类离子型Fischer卡宾类CORM先导结构([(CO)_5ML]^-)的化合物Fc-CORMs,其中五羰基卡宾阴离子单元可水解缓释一氧化碳,季铵盐阳离子有效调节CORM水溶性.肌红蛋白测试表明,每分子Fc-CORM可以在体外生理环境下至少缓释两分子CO.动力学分析显示,Fc-CORM释放速度取决于中心金属的种类,Fc-CORM-Mo(2a^2e)释放速度大于Fc-CORM-Cr(1a^1e),且远大于Fc-CORM-W(3a^3e).抗菌实验发现,中速释放分子1b可有效抑制大肠杆菌,其MIC为30μmol/L.对于具有耐药性的细菌,Fc-CORM-Mo(2b)和Fc-CORM-W(3b)表现出一定抗菌活性.机理研究证明,Fc-CORMs的抗菌活性取决于其释放CO的速度.

CO releasing molecules （CORMs） of transition metal carbonyl complexes are emerging as a new interdisciplinary advance of inorganic chemistry, biological medicine and materials chemistry. In this paper, new ionic Fischer carbene carbonyl complexes were devised, in which Cr, Mo and W metals as metallic center carried five CO whilst the quaternary ammonium finely tuned the water solubility of Fc-CORMs. The myoglobin assays showed that one Fc-CORM released at least two molecules of carbon monoxide in well-controlled fashion under physiological conditions. The structure-releasing correlation revealed that the central metal was the key factor governing their carbon monoxide release behavior. The CO release rate of Fc-CORM-Mo （2a^2e） is quicker than Fc-CORM-Cr （1a^1e）, much faster than Fc-CORM-W （3a^3e）. The antibacterial activity test found that Fc-CORM （1b） with medium CO release rate effectively inhibited the growth and survival of Escherichia coli, with an minimal inhibitory concentration （MIC） value of 30 μmol/L. As for drug-resistant bacteria, Fc-CORM （2a^2e） and Fc-CORM （3a^3e） showed bactericidal activity. Mechanism study indicated that the antibacterial activity relied on the CO release rate of Fc-CORMs.