Intraligand Excited States Turn a Ruthenium Oligothiophene Complex into a Light-Triggered Ubertoxin with Anticancer Effects in Extreme Hypoxia.
Intraligand Excited States Turn a Ruthenium Oligothiophene Complex into a Light-Triggered Ubertoxin with Anticancer Effects in Extreme Hypoxia.
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DOI：
10.1021/jacs.2c02475
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发表时间：
2022-05-11
影响因子：
15
通讯作者：
McFarland, Sherri A.
中科院分区：
文献类型：
--
作者：
Roque, John A., III;Cole, Houston D.;Barrett, Patrick C.;Lifshits, Liubov M.;Hodges, Rachel O.;Kim, Susy;Deep, Gagan;Frances-Monerris, Antonio;Alberto, Marta E.;Cameron, Colin G.;McFarland, Sherri A.
Ru(II) complexes that undergo photosubstitution reactions from triplet metal-centered (3MC) excited states are of interest in photochemotherapy (PCT) for their potential to produce cytotoxic effects in hypoxia. Dual-action systems that incorporate this stoichiometric mode to complement the oxygen-dependent photosensitization pathways that define photodynamic therapy (PDT) are poisoned to maintain antitumor activity regardless of oxygenation status. Herein, we examine the way其中这两种途径使用[RU（DMP）2（IP-NT）] 2+序列（其中DMP = 2,9-二甲基-1,10-苯磺诺氏素和IP-NT = imidazo [4,5-F] [4,5-F] [1,10] the Store to nory to Native to n n = 0-4 RU-PHEN-RU-1T至基于配体的3ILCT状态RU-3T和RU-4T的案例。 Ru-Phen-Ru-1t具有主要的3MC状态和最大的光量量子量，在正态氧和缺氧中都是不活跃的。 SKMEL28细胞中的常氧和皮莫尔在缺氧中，在低氧中的正态氧气中的PI值为103-106，同时通过光解异的3MC状态最大化激发态的态度，这并不导致dual-daction PDT/pct剂导致研究最大的效果。生产和可能的完成I型通路通过3ilct激发态。
Ru(II) complexes that undergo photosubstitution reactions from triplet metal-centered (3MC) excited states are of interest in photochemotherapy (PCT) for their potential to produce cytotoxic effects in hypoxia. Dual-action systems that incorporate this stoichiometric mode to complement the oxygen-dependent photosensitization pathways that define photodynamic therapy (PDT) are poised to maintain antitumor activity regardless of oxygenation status. Herein, we examine the way in which these two pathways influence photocytotoxicity in normoxia and in hypoxia using the [Ru(dmp)2(IP-nT)]2+ series (where dmp=2,9-dimethyl-1,10-phenanthroline and IP-nT=imidazo[4,5-f][1,10]phenanthroline tethered to n=0–4 thiophene rings) to switch the dominant excited state from the metal-based 3MC state in the case of Ru-phen–Ru-1T to ligand-based 3ILCT state for Ru-3T and Ru-4T. Ru-phen–Ru-1T, having dominant 3MC states and the largest photosubstitution quantum yields, were inactive in both normoxia and hypoxia. Ru-3T and Ru-4T, with dominant 3IL/3ILCT states and long triplet lifetimes (τTA=20–25 μs), had the poorest photosubstitution quantum yields yet were extremely active. In the best instances, Ru-4T exhibited attomolar phototoxicity toward SKMEL28 cells in normoxia and picomolar in hypoxia, with PI values in normoxia of 105–1012 and 103–106 in hypoxia. While maximizing excited state deactivation through photodissociative 3MC states did not result in bonafide dual-action PDT/PCT agents, the study has produced the most potent photosensitizer we know of to date. The extraordinary photosensitizing capacity of Ru-3T and Ru-4T may stem from a combination of very efficient 1O2 production and possibly complementary Type I pathways via 3ILCT excited states.
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