Wei Xue, Guo Xue-Hui, Guo Jing-Fu, He Teng-Fei, Qin Gui-Ya, Zou Lu-Yi, Ren Ai-Min
Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, College of Chemistry, Jilin University, Liutiao Road #2, Changchun130061, P. R. China.
School of Physics, Northeast Normal University, Changchun130024, P. R. China.
Inorg Chem. 2022 Nov 21;61(46):18729-18742. doi: 10.1021/acs.inorgchem.2c03232. Epub 2022 Nov 9.
The high incidence and difficulties of treatment of cancer have always been a challenge for mankind. Two-photon photodynamic therapy (TP-PDT) as a less invasive technique provides a new perspective for tumor treatment due to its low-energy near-infrared excitation, high targeting, and minor damage. At present, the emerging metal complexes used as the photosensitizers (PSs) in TP-PDT have aroused great interest. However, most metal complexes as PSs in TP-PDT still face some problems, such as slow clearance, unsatisfactory two-photon absorption (TPA) characteristics, high price, low reactivity, and poor solubility. In this work, density functional theory and time-dependent density functional theory were used to characterize the one/two-photon response, solvation free energy, and lipophilicity of a series of novel PSs applied in TP-PDT. The results suggest that based on complex , replacing Ru(II) center with Zn(II) (complex ) can effectively prolong the triplet excited state lifetime while reducing the cost and environmental pollution, and the azetidine heterospirocycles were introduced into the ligand scaffold (complex ), which effectively reduced the vibration relaxation of the ligand group and improved the water solubility; further, the addition of acetylenyl groups subtly enhanced the light absorption and significantly improved the two-photon response (complex ). In addition, all complexes met the requirement of a PS and could be used as potential candidates for TP-PDT. In particular, complex has the advantages of high solvation free energy, a large TPA cross-section (1413 GM), a long triplet state lifetime (671 μs), good chemical reactivity, and low cost, and it is easy to be scavenged by organisms. Overall, this contribution may provide an important clue to formulate clear design principles for type I/II PSs and rational design of PSs with high intersystem crossing rates, a long lifetime, and therapeutic excitation wavelengths.
癌症的高发病率和治疗难题一直是人类面临的挑战。双光子光动力疗法（TP-PDT）作为一种侵入性较小的技术，因其低能量近红外激发、高靶向性和微小损伤，为肿瘤治疗提供了新的视角。目前，用作TP-PDT光敏剂（PSs）的新型金属配合物引起了极大关注。然而，大多数用作TP-PDT中PSs的金属配合物仍面临一些问题，如清除缓慢、双光子吸收（TPA）特性不理想、价格高、反应活性低和溶解性差等。在这项工作中，采用密度泛函理论和含时密度泛函理论对一系列应用于TP-PDT的新型PSs的单/双光子响应、溶剂化自由能和亲脂性进行了表征。结果表明，基于配合物，用Zn(II)取代Ru(II)中心（配合物）可有效延长三重态激发态寿命，同时降低成本和环境污染，并且将氮杂环丁烷杂螺环引入配体支架（配合物），有效降低了配体基团的振动弛豫并提高了水溶性；此外，乙炔基的引入微妙地增强了光吸收并显著改善了双光子响应（配合物）。此外，所有配合物均满足PS的要求，可作为TP-PDT的潜在候选物。特别是，配合物具有高溶剂化自由能、大TPA截面（1413 GM）、长三重态寿命（671 μs）、良好的化学反应活性和低成本等优点，且易于被生物体清除。总体而言，这一贡献可能为制定明确的I/II型PSs设计原则以及合理设计具有高系间窜越率、长寿命和治疗激发波长的PSs提供重要线索。
