Potent DNA photocleavage by zinc(II) complexes of cationic bis-porphyrins linked with aliphatic diamine.
We have prepared zinc(II) complexes of cationic bis-porphyrins, as one of the attempts to improve less DNA photocleavage activities of the metal-free bis-porphyrins composed of two H(2)TMPyP-like chromophores, linked with a series of aliphatic diamines. The less activities seemed to be derived from their intermolecular self-aggregation properties in aqueous solution. The zinc(II) insertion into the metal-free cationic bis-porphyrins completely removed their self-aggregation properties, most probably due to steric hindrance between axial ligands of zinc(II) chromophores of the cationic bis-porphyrins. The DNA photocleavage activities of the zinc(II) complexes were fully enhanced, which were three times larger than that of the lead compound H(2)TMPyP. Quantitative analysis of singlet oxygen production by photosensitization of cationic bis-porphyrins was performed using 1,3-diphenylisobenzofuran, and the singlet oxygen productivities of them were found to be related to their solution properties. There is a good relationship between the activities and the productivities, which will provide insights into the further development of more effective DNA photocleavage agents.
Ishikawa
Yoshinobu
Y
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan.
Yamakawa
Naoki
N
Uno
Tadayuki
T
D002412:Cations / Q000737:chemistry / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016015:Logistic Models; D009690:Nucleic Acid Conformation / Q000187:drug effects / Q000528:radiation effects; D010782:Photolysis / Q000528:radiation effects*; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D013054:Spectrophotometry, Atomic; D017967:Zinc Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D002412:Cations; D003959:Diamines; D011166:Porphyrins; D012996:Solutions; D017967:Zinc Compounds; D026082:Singlet Oxygen; D004247:DNA