一种二氧化 ((IV) 抗癌复合物的光替代和光减少
Huayun Shi1, Christian Ward-Deitrich2, Fortuna Ponte3
1Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK. P.J.Sadler@warwick.ac.uk.
Dalton transactions (Cambridge, England : 2003)
|July 19, 2024
概括
用蓝光对抗癌症药物FM-190进行光辐射,产生氧化 ((IV) 种. 使用HPLC-ICP-MS和LC-MS识别的这些光产物可能是其生物活性的关键.
科学领域:
- 分析化学 分析化学
- 生物有机化学 生物有机化学
- 摄影化学的使用.
背景情况:
- (IV) 复合物被研究为可光激活的抗癌剂.
- 了解这些药物的物种化和转化对于它们的发展至关重要.
- 高性能液态染色学 (HPLC) 与感应合等离子体质谱学 (ICP-MS) 和液态染色学-质谱学 (LC-MS) 结合,可在生物矩阵中对制药进行敏感分析.
研究的目的:
- 为了研究光活性抗癌复合物trans,trans,trans-[Pt(N3)2(OH)2(py)2 (FM-190) 在水溶液和生物液中的物种化.
- 为了确定用蓝光照射后形成的光产品.
- 阐明光激活路径和潜在兴奋状态药的形成.
主要方法:
- 使用HPLC与ICP-MS进行HPLC与ICP-MS的混合,用于对制药的敏感元素分析.
- 用于种分子结构确认的LC-MS.
- 密度函数理论 (DFT) 和时间依赖 DFT (TDDFT) 计算以建模反应路径.
主要成果:
- FM-190在黑暗中在37°C的温度下显示出人类血的高稳定性.
- 用蓝光 (463nm) 对FM-190进行光照辐射,导致多氧化物种的形成,特别是[PtIV(py) 2(OH) 4} + Na]+和[PtIV(py) 2(N3) OH>3} + Na]+,这是由于酸连接体的替换.
- DFT/TDDFT计算表明,这些Pt(IV) 物种可以直接从水性介质中的单一激发状态中形成.
结论:
- 该研究成功地描述了FM-190的光转化产物,揭示了氧化物种是主要的光产物.
- 这些光置换Pt(IV) 种类可能在FM-190.0的生物活性中起着重要作用.
- 规范分析 (金属学) 提供了对基抗癌药物的光激活机制的关键见解,这对于临床前开发至关重要.
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