Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy.
Interaction with a Biomolecule Facilitates the Formation of the Function-Determining Long-Lived Triplet State in a Ruthenium Complex for Photodynamic Therapy.
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DOI：
10.1021/acs.jpca.1c09968
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发表时间：
2022-03-03
期刊：
影响因子：
--
通讯作者：
Dietzek-Ivanšić B
中科院分区：
文献类型：
--
作者：
Chettri A;Cole HD;Roque Iii JA;Schneider KRA;Yang T;Cameron CG;McFarland SA;Dietzek-Ivanšić B
TLD1433是第一个基于钌（RU）的光动力疗法（PDT）剂，用于前进到临床试验，目前正在使用PDT进行非肌肉膀胱癌的II期研究。使用复合物与生物学相关的溶液阐明激发态性能的衍生型TLD1633是生物活性的关键。 [4,5-f] [1,10]分别附加到α-ter-或quaterthiyophene的苯拥ol（IP）配体，其中TLD1433 = [RU（4,4'-DMB）2（IP-3T）2（IP-3T）] CL2和TLD1633 = [RU（4,4'-DMB）2（IP-4T）] Cl2（4,4'-DMB = 4,4'-二甲基-2,2'-二吡啶; 3T =α-terthiophen; 4T = α-Quaterthihiophene）。在与生物学大分子的相互作用时（例如，DNA）。与DNA结合后的配体框架的刚度，该框架延长了T1状态的寿命。因此，为了获得构成复合物的光诱导功能的激发态动力学的现实情况，有必要在存在生物学靶标的情况下审问其光物理动力学。
TLD1433 is the first ruthenium (Ru)-based photodynamic therapy (PDT) agent to advance to clinical trials and is currently in a Phase II study for treating non-muscle bladder cancer with PDT. Herein, we present a photophysical study of TLD1433 and its derivative TLD1633 using complex, biologically relevant solvents to elucidate the excited state properties that are key for biological activity. The complexes incorporate an imidazo [4,5-f][1,10]phenanthroline (IP) ligand appended to α-ter- or quaterthiophene, respectively, where TLD1433 = [Ru(4,4′-dmb)2(IP-3T)]Cl2 and TLD1633 = [Ru(4,4′-dmb)2(IP-4T)]Cl2 (4,4′-dmb=4,4′-dimethyl-2,2′-bipyridine; 3T=α-terthiophene; 4T= α-quaterthiophene). Time-resolved transient absorption experiments demonstrate that the excited state dynamics of the complexes change upon interaction with biological macromolecules (e.g., DNA). In this case, the accessibility of the lowest energy T1 state is increased at the expense of a higher-lying triplet intraligand charge transfer (3ILCT) state. We attribute this behavior to the increased rigidity of the ligand framework upon binding to DNA, which prolongs the lifetime of the T1 state. This lowest lying state is primarily responsible for O2 sensitization and hence photoinduced cytotoxicity. Therefore, in order to gain a realistic picture of the excited-state kinetics that underlie the photoinduced function of the complexes, it is necessary to interrogate their photophysical dynamics in the presence of biological targets once they are known.
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DOI：
10.1021/acs.jpca.1c04900
发表时间：
2021-08-19
期刊：
The journal of physical chemistry. A
影响因子：
--
作者：
Chettri A;Schneider KRA;Cole HD;Roque JA 3rd;Cameron CG;McFarland SA;Dietzek B
通讯作者：
Dietzek B
影响因子：
15
作者：
Bhasikuttan, AC;Suzuki, M;Okada, T
通讯作者：
Okada, T
影响因子：
8.4
作者：
Lifshits LM;Roque Iii JA;Konda P;Monro S;Cole HD;von Dohlen D;Kim S;Deep G;Thummel RP;Cameron CG;Gujar S;McFarland SA
通讯作者：
McFarland SA
影响因子：
2.9
作者：
Kovalenko, SA;Dobryakov, AL;Ernsting, NP
通讯作者：
Ernsting, NP
影响因子：
4
作者：
Harriman, A;Khatyr, A;Ziessel, R
通讯作者：
Ziessel, R