title: Dinuclear Cu(II) hypocrellin B complexes with enhanced photonuclease activity.
abstract: Five new dinuclear Cu(II) complexes were designed and synthesized, using hypocrellin B, a naturally occurring photosensitizer that has received extensive studies as promising photodynamic therapy (PDT) agent, as bridging ligand, and five kinds of diimine ligands, including 2,2'-bipyridine (bpy), 1,10-phenanthroline (phen), 3,4,7,8-tetramethyl-1,10-phenanthroline (tmp), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), and dipyrido[3,2-a:2',3'-c]phenazene (dppz), as terminal ligands, respectively. The Cu(2+)-HB complexes exhibit improved water solubility, enhanced absorptivity in the phototherapeutic window of 600-900 nm, and increased binding affinity toward dsDNA than their parent HB. The biologically accessible redox potential of Cu(II)/Cu(I) couple renders the five Cu(2+)-HB complexes chemical nuclease activities in the presence of reducing agent such as ascorbic acid. Moreover, the readily available redox potential of Cu(II)/Cu(I) couple switches the photodynamic activity from type II mechanism (singlet oxygen mechanism) for HB to type I mechanism (radical mechanism) for the Cu(2+)-HB complexes. Of the five Cu(2+)-HB complexes, complex 3-5 with terminal diimine ligands of tmp, dpq, and dppz, respectively, can photocleave supercoiled pBR322 DNA more efficiently than HB. These findings open a new avenue for the development of the HB derivatives with higher photodynamic activity and better clinical applicability.
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuan-Jun
authors.initials: YJ
authors.lastname: Hou
authors.forename: Qian-Xiong
authors.initials: QX
authors.lastname: Zhou
authors.forename: Wan-Hua
authors.initials: WH
authors.lastname: Lei
authors.forename: Jing-Rong
authors.initials: JR
authors.lastname: Chen
authors.forename: Xue-Song
authors.initials: XS
authors.lastname: Wang
authors.forename: Bao-Wen
authors.initials: BW
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002417:Cattle; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D004563:Electrochemistry; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D010084:Oxidation-Reduction; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry; D010777:Photochemistry; D011809:Quinones / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D009942:Organometallic Compounds; D011809:Quinones; D014867:Water; D010569:Perylene; D003300:Copper; D004247:DNA; C427203:calf thymus DNA; C064522:hypocrellin B