有机化学 ›› 2016, Vol. 36 ›› Issue (11): 2695-2703.DOI: 10.6023/cjoc201603027 上一篇    下一篇

研究论文

抑菌型Fischer卡宾类一氧化碳缓释分子

周玲玲a, 周亚青a, 唐艳丽a, 杨科武b, 张雷c, 高玲香a, 张国防a, 高子伟a, 张伟强a   

  1. a 陕西师范大学化学化工学院 西安 710062;
    b 西北大学材料与化学科学学院 西安 710069;
    c 解放军第二医科大学上海长征医院 上海 200000
  • 收稿日期:2016-03-16 修回日期:2016-05-09 发布日期:2016-07-07
  • 通讯作者: 高子伟, 张伟强 E-mail:zwgao@snnu.edu.cn;zwq@snnu.edu.cn
  • 基金资助:

    国家自然科学基金(No.21371112)、教育部博士点新教师基金(No.20120202120005)、中央高校基金(No.GK201501005)和陕西省自然科学基金(No.2012JM2006)资助项目.

Antibacterial Fischer Carbenoid CO-Releasing Molecules

Zhou Linglinga, Zhou Yaqinga, Tang Yanlia, Yang Kewub, Zhang Leic, Gao Lingxianga, Zhang Guofanga, Gao Ziweia, Zhang Weiqianga   

  1. a Key Laboratory of Applied Surface and Colloid Chemistry, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi'an 710062;
    b College of Chemistry & Materials Science, Northwest University, Xi'an 710069;
    c Shang Hai Chang Zheng Hospital, The People's Liberation Army Second Medical University, Shanghai 200000
  • Received:2016-03-16 Revised:2016-05-09 Published:2016-07-07
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No.21371112),the Fundamental Doctoral Fund of Ministry of Education (No.20120202120005),the Fundamental Funds Research for the Central Universities (No.GK201501005) and the Natural Science Basic Research Plan in Shaanxi Province (No.2012JM2006).

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30 μmol/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.

关键词: 一氧化碳释放分子, Fischer卡宾, 季铵盐, 耐药细菌

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.

Key words: CO releasing molecules, Fischer carbene, quaternary ammonium salt, drug-resistant bacteria