Yan Yaw Kai, Melchart Michael, Habtemariam Abraha, Peacock Anna F A, Sadler Peter J
School of Chemistry, University of Edinburgh, West Mains Road, EH9 3JJ, Edinburgh, UK.
J Biol Inorg Chem. 2006 Jun;11(4):483-8. doi: 10.1007/s00775-006-0098-5. Epub 2006 Apr 8.
Ruthenium(II) arene anticancer complexes [(eta6-arene)Ru(en)Cl]PF6 (arene is hexamethylbenzene, p-cymene, indan; en is ethylenediamine) can catalyse regioselective reduction of NAD+ by formate in water to form 1,4-NADH, at pD 7.2, 37 degrees C, and in the presence of air. The catalytic activity is markedly dependent on the arene, with the hexamethylbenzene (hmb) complex showing the highest activity. For [(eta 6-hmb)Ru(en)Cl]PF6, the rate of reaction is independent of NAD+ concentration and shows saturation kinetics with respect to formate concentration. A Km value of 58 mM and a turnover frequency at saturation of 1.46 h(-1) were observed. Removal of chloride and performing the reaction under argon led to higher reaction rates. Lung cancer cells (A549) were found to be remarkably tolerant to formate even at millimolar concentrations. The possibility of using ruthenium arene complexes coadministered with formate as catalytic drugs is discussed.
钌（II）芳烃抗癌配合物[（η6-芳烃）Ru（en）Cl]PF6（芳烃为六甲基苯、对异丙基苯、茚满；en为乙二胺）在pD 7.2、37℃且有空气存在的条件下，能催化水中甲酸将NAD+区域选择性还原为1,4-NADH。催化活性显著依赖于芳烃，其中六甲基苯（hmb）配合物的活性最高。对于[（η6-hmb）Ru（en）Cl]PF6，反应速率与NAD+浓度无关，而对甲酸浓度呈现饱和动力学。观察到Km值为58 mM，饱和时的周转频率为1.46 h-1。去除氯离子并在氩气氛围下进行反应可得到更高的反应速率。发现肺癌细胞（A549）即使在毫摩尔浓度下对甲酸也具有显著的耐受性。讨论了将钌芳烃配合物与甲酸共同给药用作催化药物的可能性。
