Ishikawa Yoshinobu, Yamakawa Naoki, Uno Tadayuki
Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-Honmachi, Kumamoto, Japan.
Bioorg Med Chem. 2007 Aug 1;15(15):5230-8. doi: 10.1016/j.bmc.2007.05.018. Epub 2007 May 10.
We have synthesized cationic bis-porphyrins and their zinc(II) complexes with two TMPyP-like chromophores bridged by p- or m-xylylenediamine to develop effective DNA photocleaving agents. The xylylene linkers and zinc ion were introduced to control interchromophoric interaction that should be involved in photosensitization of the cationic bis-porphyrins. The molar absorptivities of all the bis-porphyrins in aqueous solution remained unchanged over a wide range of concentrations, indicating the absence of self-aggregation property. In particular, the molar absorptivity of the zinc(II) complex of the p-xylylenediamine-linked bis-porphyrin in aqueous solution was 2.0 times as large as that of unichromophoric ZnTMPyP, suggesting the absence of both intermolecular and intramolecular interchromophoric interaction. The metal-free p-xylylenediamine-linked bis-porphyrin showed the more efficient conversion ability of supercoiled to nicked circular pUC18 plasmid DNA by photosensitization than the metal-free m-xylylenediamine-linked one. Furthermore, the zinc complexes of the bis-porphyrins exhibited the more potent DNA photocleavage than did the metal-free bis-porphyrins. Singlet oxygen productivity of the four cationic bis-porphyrins was determined by measuring the decomposition rate of 1,3-diphenylisobenzofuran. The amount of singlet oxygen generated by photosensitization of the zinc(II) complex of the p-xylylenediamine-linked bis-porphyrin in aqueous solution was 2.1 times as large as ZnTMPyP, indicating the full singlet oxygen productivity. A significant relationship between the DNA photocleaving abilities and the singlet oxygen productivities of the cationic porphyrins in aqueous solution was found. Hence, the degree of the intramolecular interchromophoric interaction, the DNA photocleaving ability, and the singlet oxygen productivity of the cationic bis-porphyrins in aqueous solution were successfully controlled by means of the introduction of the appropriate linker and metal ion.
我们合成了阳离子双卟啉及其锌（II）配合物，它们具有两个由对苯二甲撑二胺或间苯二甲撑二胺桥连的类TMPyP发色团，以开发有效的DNA光裂解剂。引入亚二甲苯基连接基和锌离子来控制发色团间相互作用，这种相互作用应参与阳离子双卟啉的光敏化过程。所有双卟啉在水溶液中的摩尔吸光率在很宽的浓度范围内保持不变，表明不存在自聚集性质。特别地，对苯二甲撑二胺连接的双卟啉的锌（II）配合物在水溶液中的摩尔吸光率是单发色团ZnTMPyP的2.0倍，这表明不存在分子间和分子内的发色团间相互作用。无金属的对苯二甲撑二胺连接的双卟啉通过光敏化将超螺旋pUC18质粒DNA转化为带切口的环状DNA的能力比无金属的间苯二甲撑二胺连接的双卟啉更高。此外，双卟啉的锌配合物比无金属的双卟啉表现出更强的DNA光裂解能力。通过测量1,3 - 二苯基异苯并呋喃的分解速率来测定四种阳离子双卟啉的单线态氧产生率。对苯二甲撑二胺连接的双卟啉的锌（II）配合物在水溶液中光敏化产生的单线态氧量是ZnTMPyP的2.1倍，表明单线态氧产生率高。发现阳离子卟啉在水溶液中的DNA光裂解能力与单线态氧产生率之间存在显著关系。因此，通过引入合适的连接基和金属离子，成功地控制了阳离子双卟啉在水溶液中的分子内发色团间相互作用程度、DNA光裂解能力和单线态氧产生率。
