With the aim of developing more stable Gd(Ⅲ)−porphyrin complexes,two types of ligands 1 and 2 with carboxylic acid anchors were synthesized.Due to the N-substituted pyridyl cation attached to the porphyrin core,these...With the aim of developing more stable Gd(Ⅲ)−porphyrin complexes,two types of ligands 1 and 2 with carboxylic acid anchors were synthesized.Due to the N-substituted pyridyl cation attached to the porphyrin core,these porphyrin ligands were highly water-soluble and formed the corresponding Gd(Ⅲ)chelates,Gd-1 and Gd-2.Gd-1 was sufficiently stable in neutral buffer,presumably due to the preferred conformation of the carboxylateterminated anchors connected to nitrogen in the meta position of the pyridyl group helping to stabilize Gd(Ⅲ)complexation by the porphyrin center.1H NMRD(nuclear magnetic relaxation dispersion)measurements on Gd-1 revealed high longitudinal water proton relaxivity(r_(1)=21.2 mM^(−1)s^(−1)at 60 MHz and 25℃),which originates from slow rotational motion resulting from aggregation in aqueous solution.Under visible light irradiation,Gd-1 showed extensive photoinduced DNA cleavage in line with efficient photoinduced singlet oxygen generation.Cell-based assays revealed no significant dark cytotoxicity of Gd-1,while it showed sufficient photocytotoxicity on cancer cell lines under visible light irradiation.These results indicate the potential of this Gd(Ⅲ)−porphyrin complex(Gd-1)as a core for the development of bifunctional systems acting as an efficient photodynamic therapy photosensitizer(PDT-PS)with magnetic resonance imaging(MRI)detection capabilities.展开更多
基金supported in part by the SNF,Strategic Japanese-Swiss Science and Technology Program(IZLJZ2_183660,Y.Y.)JSPS under the Joint Research Program implemented in association with SNF(20191508,H.M.and N.Y.-S.)+3 种基金the SNF Project Funding(205321_173018,Y.Y.)the ETH Research Grant(ETH-21_15-2ETH-36_20-2,Y.Y.)JSPS KAKENHI(Grantin-Aid for Scientific Research[A],6251004,H.M.,Grants-in-Aid for Scientific Research on Innovative Areas,21H00264,22H04707,H.M.,Grant-in-Aid for Scientific Research[C],15K07164,N.Y.-S.).
文摘With the aim of developing more stable Gd(Ⅲ)−porphyrin complexes,two types of ligands 1 and 2 with carboxylic acid anchors were synthesized.Due to the N-substituted pyridyl cation attached to the porphyrin core,these porphyrin ligands were highly water-soluble and formed the corresponding Gd(Ⅲ)chelates,Gd-1 and Gd-2.Gd-1 was sufficiently stable in neutral buffer,presumably due to the preferred conformation of the carboxylateterminated anchors connected to nitrogen in the meta position of the pyridyl group helping to stabilize Gd(Ⅲ)complexation by the porphyrin center.1H NMRD(nuclear magnetic relaxation dispersion)measurements on Gd-1 revealed high longitudinal water proton relaxivity(r_(1)=21.2 mM^(−1)s^(−1)at 60 MHz and 25℃),which originates from slow rotational motion resulting from aggregation in aqueous solution.Under visible light irradiation,Gd-1 showed extensive photoinduced DNA cleavage in line with efficient photoinduced singlet oxygen generation.Cell-based assays revealed no significant dark cytotoxicity of Gd-1,while it showed sufficient photocytotoxicity on cancer cell lines under visible light irradiation.These results indicate the potential of this Gd(Ⅲ)−porphyrin complex(Gd-1)as a core for the development of bifunctional systems acting as an efficient photodynamic therapy photosensitizer(PDT-PS)with magnetic resonance imaging(MRI)detection capabilities.
