Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, PR China.
Dalton Trans. 2012 Jan 14;41(2):651-7. doi: 10.1039/c1dt11401h. Epub 2011 Nov 8.
Hypocrellin B (HB), a naturally occurring photosensitizer, has been extensively and intensively studied as a promising photodynamic therapy (PDT) agent. In this work, three new oxovanadium(IV) complexes were designed and synthesized with HB as a bridging ligand and phen (1,10-phenanthroline, complex 1), tmp (3,4,7,8-tetramethyl-1,10-phenanthroline, complex 2) and dpq (dipyrido[3,2-f:2'3'-h]quinoxaline, complex 3) as terminal ligands. The use of a diimine terminal ligand avoids the formation of polymeric complexes and ensures the three VO(2+)-HB complexes possess a definite molecular formula and molecular weight to meet the single component requirement for an ideal PDT agent. Compared to HB, the VO(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window, increased binding affinity toward dsDNA, and similar singlet oxygen quantum yield, therefore advanced DNA photocleavage activity. Both the DNA binding constants and photo nuclease activities of the complexes follow the order 2 (tmp) > 3 (dpq) > 1 (phen), demonstrating the importance of the binding affinity to biomolecules, which improves the bioavailability of reactive oxygen species. Our work opens a new avenue for the development of HB-based PDT agents.
竹红菌乙素（HB）是一种天然存在的光敏剂，已被广泛深入地研究为一种有前途的光动力疗法（PDT）药物。在这项工作中，设计并合成了三个新的氧钒（IV）配合物，以 HB 作为桥联配体，并用邻菲咯啉（phen，1,10-菲咯啉，配合物 1）、3,4,7,8-四甲基-1,10-菲咯啉（tmp，配合物 2）和二吡啶并[3,2-f:2',3'-h]喹喔啉（dpq，配合物 3）作为端基配体。使用二亚胺端基配体可以避免形成聚合物配合物，并确保三个 VO(2+)-HB 配合物具有确定的分子式和分子量，以满足理想 PDT 药物的单一成分要求。与 HB 相比，VO(2+)-HB 配合物具有更好的水溶性、在光疗窗口中增强的吸光度、增加与 dsDNA 的结合亲和力以及相似的单线态氧量子产率，因此具有更高的 DNA 光裂活性。配合物的 DNA 结合常数和光核酸酶活性均遵循 2（tmp）>3（dpq）>1（phen）的顺序，这表明与生物分子的结合亲和力的重要性，这提高了活性氧的生物利用度。我们的工作为开发基于 HB 的 PDT 药物开辟了新途径。
