通过光诱导的电子转移抑制光激活蛋白质的鲁 (II) - (III) 双金属复合体
Robert J Holbrook1, David J Weinberg, Mark D Peterson
1Department of Chemistry, Northwestern University , Evanston, Illinois 60208, United States.
Journal of the American Chemical Society
|February 12, 2015
概括
研究人员开发了一种光激活的复合物,用于抑制蛋白质. 光诱导的电子转移触发了连接体的释放,从而实现了针对性抑制关键蛋白质α-血. 这为无机治疗剂提供了一个新的策略.
科学领域:
- 无机化学 无机化学 有机化学
- 摄影化学的使用.
- 生物化学 生物化学
- 药用化学 医学化学
背景情况:
- 针对性治疗剂的开发对于有效的疾病治疗至关重要.
- 金属复合物为药物设计提供独特的特性,但受控的激活仍然是一个挑战.
- 生物惰性复合体可以被外部刺激激活,例如光用于时空控制.
研究的目的:
- 用 (III) 希夫基复合物来描述光激活蛋白抑制的机制.
- 为了证明光诱导电子转移 (PET) 对于无机治疗剂的受控激活的使用.
- 在暴露于光线后,研究连接体交换和蛋白质抑制的动力学.
主要方法:
- (II) 二基复合物与 (III) 希夫基复合物的共价附着.
- 光诱导电子转移 (PET) 是由455nm光暴露引起的.
- 核磁共振 (NMR) 谱学用于监测与4-methylimidazole的配体交换动力学.
- 在照射光线之前和之后对α-血抑制率的测定.
主要成果:
- 观察到从Ru (II) 复合体到Co (III) 复合体的光诱导电子转移,在纳秒时间尺度上的形状变化.
- 减小了Co(III) 复合体启动的轴性意达联体的位移.
- 在455nm光照射下,与胺仿真体的联结物交换率增加了大约5倍.
- 在暴露于光线后,α-血抑制率增加了5倍以上,证明了功能激活.
结论:
- 成功展示了一种用于光激活无机治疗剂的新策略.
- 光诱导的电子转移与氧化还原活性金属中心相结合,提供了一种可控药物递送和激活的机制.
- 这种方法可以对蛋白质抑制进行时空控制,在向治疗中有潜在的应用.
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