Dinuclear Cu(II) Hypocrellin B Complexes with Enhanced Photonuclease Activity

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.