Oxovanadium(IV) based hypocrellin B complexes with enhanced photodynamic activity.
Oxovanadium(IV) based hypocrellin B complexes with enhanced photodynamic activity.
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DOI：
10.1039/c1dt11401h
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发表时间：
2012-01
影响因子：
4
通讯作者：
Yi Sun;Yue Zheng;Wanhua Lei;Qian-Xiong Zhou;Yuan-jun Hou;Bao-wen Zhang;Xuesong Wang
中科院分区：
文献类型：
--
作者：
Yi Sun;Yue Zheng;Wanhua Lei;Qian-Xiong Zhou;Yuan-jun Hou;Bao-wen Zhang;Xuesong Wang
Hypocrellin B （HB）是一种天然光敏剂，作为一种有前途的光动力治疗（PDT）药物已被广泛而深入地研究。本文以HB为桥接配体，以phen（1,10-菲罗啉，配合物1）、tmp（3,4,7,8-四甲基-1,10-菲罗啉，配合物2）和dpq（二吡啶[3,2-f:2'3'-h]喹诺啉，配合物3）为末端配体，设计并合成了三种新型氧钒（IV）配合物。二亚胺末端配体的使用避免了聚合物配合物的形成，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剂的单组分要求。与HB相比，VO(2+)-HB复合物具有更好的水溶性，增强的光疗窗口吸收性，对dsDNA的结合亲和力增加，单线态氧量子产率相似，因此具有更高的DNA光裂解活性。复合物的DNA结合常数和光核酸酶活性都遵循2 (tmp) > 3 (dpq) > 1 （phen）的顺序，证明了与生物分子的结合亲和力的重要性，从而提高了活性氧的生物利用度。我们的工作为基于乙肝的PDT试剂的开发开辟了一条新的途径。
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.