Bozzi A S, Rocha W R
Laboratório de Estudos Computacionais em Sistemas Moleculares, eCsMolab, Departamento de Química, ICEx, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
Chem Asian J. 2024 Nov 18;19(22):e202400605. doi: 10.1002/asia.202400605. Epub 2024 Oct 23.
In this work, we used DFT and TD-DFT in the investigation of the structural parameters and photophysics of the complex [Ru(bpy)dppn] (dppn=benzo[i]-dipyrido[3,2-a:2',3'-c]phenazine) in water, and its suitability as a photosensitizer (PS) in photodynamic therapy (PDT). For that, the thermodynamics of electron transfer (ET) and energy transfer (ENT) reactions in the excited state with molecular oxygen and guanosine-5'-monophosphate (GMP) were investigated. The overall intersystem crossing (ISC) rate constant was approximately 10 s, indicating that this process is highly favorable, and the triplet excited states are populated. The triplet excited states are known to lead to photoreactions between the PS and species of the medium or directly with nucleobases. Here, we show that the Ru-dppn complex can react favorably to oxidize the GMP and generate singlet oxygen. Furthermore, this complex can also act as an intercalator between DNA base pairs and undergo dual-channel reactions. It has been proposed that the T excited state is responsible for oxidizing the GMP, but we show that T is thermodynamically capable of undergoing the same reaction. In this sense, docking simulations were carried out to investigate further the interactions of the Ru-dppn complex with a DNA fragment.
在这项工作中，我们使用密度泛函理论（DFT）和含时密度泛函理论（TD-DFT）研究了配合物[Ru(bpy)dppn]（dppn = 苯并[i] - 二吡啶并[3,2 - a:2',3' - c]吩嗪）在水中的结构参数和光物理性质，以及其作为光动力疗法（PDT）中光敏剂（PS）的适用性。为此，研究了该配合物在激发态下与分子氧和5'-鸟苷单磷酸（GMP）发生电子转移（ET）和能量转移（ENT）反应的热力学。总的系间窜越（ISC）速率常数约为10 s⁻¹，表明该过程非常有利，三重激发态得以填充。已知三重激发态会导致光敏剂与介质中的物质或直接与核碱基之间发生光化学反应。在此，我们表明Ru - dppn配合物能够顺利地氧化GMP并产生单线态氧。此外，该配合物还可作为DNA碱基对之间的嵌入剂并发生双通道反应。有人提出三重激发态T负责氧化GMP，但我们表明三重激发态T在热力学上也能够进行相同的反应。从这个意义上讲，进行了对接模拟以进一步研究Ru - dppn配合物与DNA片段之间的相互作用。
