Photo-induced DNA Cleavage Activity Research Articles

Ternary iron(ii) complex with an emissive imidazopyridine arm from Schiff base cyclizations and its oxidative DNA cleavage activity

The ternary iron(II) complex [Fe(L')(L")](PF6)3(1) as a synthetic model for the bleomycins, where L' and L" are formed from metal-mediated cyclizations of N,N'-(2-hydroxypropane-1,3-diyl)bis(pyridine-2-aldimine)(L), is synthesized and structurally characterized by X-ray crystallography. In the six-coordinate iron(ii) complex, ligands L' and L" show tetradentate and bidentate chelating modes of bonding. Ligand L' is formed from an intramolecular attack of the alcoholic OH group of L to one imine moiety leading to the formation of a stereochemically constrained five-membered ring. Ligand L" which is formed from an intermolecular reaction involving one imine moiety of L and pyridine-2-carbaldehyde has an emissive cationic imidazopyridine pendant arm. The complex binds to double-stranded DNA in the minor groove giving a Kapp value of 4.1 x 10(5) M(-1) and displays oxidative cleavage of supercoiled DNA in the presence of H2O2 following a hydroxyl radical pathway. The complex also shows photo-induced DNA cleavage activity on UV light exposure involving formation of singlet oxygen as the reactive species.

Porphyrin?DNA cross-linking agent hybrids: chemical synthesis and biological studies

Three new porphyrin–DNA cross-linking conjugates 8, 9, and 10 have been synthesized. Their photoinduced DNA cleavage activity have been studied. The IC50 values to THP-1 cells in the presence of porphyrin derivatives 8, 9, and 10 with photoirradiation were 5.6, 88.4, and 61.8 nM, respectively.

Porphyrin–DNA cross-linking agent hybrids: chemical synthesis and biological studies

Three new porphyrin–DNA cross-linking conjugates 8, 9, and 10 have been synthesized. Their photoinduced DNA cleavage activity have been studied. The IC 50 values to THP-1 cells in the presence of porphyrin derivatives 8, 9, and 10 with photoirradiation were 5.6, 88.4, and 61.8 nM, respectively.

Synthesis, crystal structure and photo-induced DNA cleavage activity of ternary copper(II)-thiosemicarbazone complexes having heterocyclic bases

New ternary copper(II) complexes of formulations [Cu(Ph-tsc)B] (B=1,10-phenanthroline, phen ( 1); dipyridoquinoxaline, dpq ( 2); dipyridophenazine, dppz ( 3); Ph-H 2tsc, salicylaldehyde- N(4)-phenylthiosemicarbazone) and [Cu(Me-tsc)(phen)] ( 4, Me-H 2tsc, salicylaldehyde- N(4)-methylthiosemicarbazone) are prepared, and their DNA binding and cleavage properties studied. Complex 1 has been characterized by single crystal X-ray crystallography. The molecular structure shows a distorted square pyramidal (4 + 1) geometry of the complex with the dianionic NSO-donor N(4)-phenyl-substituted thiosemicarbazone binding at the basal plane and the NN-donor planar heterocyclic base (phen) displaying axial–equatorial coordination. The one-electron paramagnetic complexes exhibit axial EPR spectra and show a d–d band near 580 nm for the phen and near 720 nm for the dpq, dppz complexes in their electronic spectra in DMF. The complexes show quasireversible cyclic voltammetric response near 0.08 V vs. SCE in DMF–0.1 M TBAP assignable to the Cu(II)/Cu(I) couple. The Ph-tsc complexes display good binding propensity to calf thymus (CT) DNA. They also show oxidative cleavage of supercoiled (SC) pUC19 DNA in dark under aerobic condition in the presence of mercaptopropionic acid. The complexes exhibit light-induced DNA cleavage activity at 312 and 532 nm. Mechanistic investigations reveal DNA minor groove binding for the phen and dpq complexes, and major groove binding for the dppz species. The complexes are cleavage inactive under argon atmosphere. In the ternary structure, the thiosemicarbazones, dpq and dppz act as photosensitizers, while the planar heterocyclic bases are binder to DNA. The mechanistic pathways involved and the role of metal in the DNA cleavage reactions are discussed.