DNA binding and oxidative DNA cleavage activity of (μ-oxo)diiron(iii) complexes in visible light

Abstract

Four (mu-oxo)diiron(iii) complexes [Fe(2)(mu-O)(H(2)O)(2)B(4)](ClO(4))(4) ( and ) and [Fe(2)(mu-O)(mu-O(2)CMe)B(4)](ClO(4))(3) ( and ), where B = 1,10-phenanthroline (phen) and dipyrido[3,2-d:2',3'-f]quinoxaline (dpq), are prepared and their DNA binding and cleavage activity studied. The complexes show DNA binding propensity giving K(b) values of 3.6-9.3 x 10(4) M(-1). The viscosity and DNA melting data suggest a surface and/or groove binding nature of the complexes to calf thymus (CT) DNA. The DNA binding data obtained from isothermal calorimetric study indicate two binding modes involving surface aggregation and/or partial intercalation of the phenanthroline bases to CT DNA. All the complexes show chemical nuclease activity in the presence of 3-mercaptopropionic acid as a reducing agent following a mechanistic pathway that involves formation of superoxide and hydroxyl radicals. Photoirradiation of pUC19 DNA at 365 nm in the presence of 1-4 show that the complexes, barring 1 , are efficient photocleavers of supercoiled DNA to its nicked circular form. Complexes 2-4 display photocleavage activity in visible light of different wavelengths. Complexes 3 and 4 exhibit significant DNA cleavage activity in red light of 633 nm, the wavelength known for the activity of the photodynamic therapeutic drug Photofrin. The mechanistic study using various additives suggests a minor groove binding nature of the complexes with the formation of singlet oxygen from the quinoxaline moiety of dpq and hydroxyl radical from photodecarboxylation of the acetate ligand as the reactive oxygen species.

Synthesis, Crystal Structures and DNA-Cleaving Activities of [Cemp]₂[MCl₄] (Cemp=<i>N</i>-Carbethoxymethyl-1,10-phenanthrolinium, M=Cu^II, Zn^II, Co^II, Ni^II and Mn^II)

“…9b) gave the maximal first-order rate constant k max of (0.55± 0.028) h −1 and Michaelis constant K M of (47.6± 6.6) µm, respectively. Thus, complex 1 can catalyze the cleavage with a rate acceleration of about 1.5×10 7 -fold over uncatalyzed supercoiled DNA cleavage (k=3.6×10 −8 h −1 , 37°C). 39,40) Thirdly, to gain further insight into the cleaving activity of complex 1, its mechanism of action toward the cleavage of pBR322 DNA was investigated.…”

“…These species contain a photo or redox active center, which causes damage to the sugar and/or base. 7,8) Therefore, to distinguish the probable mechanism of action of complex 1, we conducted the cleavage reactions in the presence of hydroxyl radical scavengers dimethyl sulfoxide (DMSO) and MeOH, singlet oxygen scavenger NaN 3 , hydrogen peroxide scavenger KI and metal ion-chelating agent ethylenediamine tetraacetic acid …”

“…Such metal complexes can create open coordination positions for DNA binding, and generate reactive oxygencontaining species or other radicals that may cause damage to the sugar and/or base of DNA. 7,8) For example, Zn(II) and Cu(II) complexes that are derived from a wide range of ligands, such as Schiff bases, 9) macrocyclic polyamines 10,11) and terpyridine derivatives, [12][13][14][15] have been found to act as effective catalysts for phosphodiester cleavage. In addition, Co(III), Mn(II) and Ni(II) complexes have also been reported to show high catalytic activities.…”

Bioaktive lumineszierende Übergangsmetallkomplexe für biomedizinische Anwendungen

“…Den isoelektronischen Rhodium(II)-Analoga wurde außerdem die Fähigkeit zur Spaltung von DNA zugeschrieben. [106][107][108][109][110][111][112][113] Im Vergleich zu den 4d-Pendants der zweiten Übergangsmetallreihe werden diese 3d-Komplexe zur Photospaltung im Allgemeinen durch Licht längerer Wellenlängen photoaktiviert, was den Vorteil eines tieferen Eindringens in biologisches Gewebe bieten kann. [103][104][105] Kürzlich spielte die Gruppe von Chakravarty eine Schlüsselrolle bei den wegweisenden Entwicklungen von 3d-Übergangsmetallkomplexen für die Photospaltung (Abbildung 13).…”

“…[103][104][105] Kürzlich spielte die Gruppe von Chakravarty eine Schlüsselrolle bei den wegweisenden Entwicklungen von 3d-Übergangsmetallkomplexen für die Photospaltung (Abbildung 13). [106][107][108][109][110][111][112][113] Im Vergleich zu den 4d-Pendants der zweiten Übergangsmetallreihe werden diese 3d-Komplexe zur Photospaltung im Allgemeinen durch Licht längerer Wellenlängen photoaktiviert, was den Vorteil eines tieferen Eindringens in biologisches Gewebe bieten kann. Ein aktueller Übersichtsartikel zu photoaktivierten Metallopharmazeutika wurde von Schiller und Mitarbeitern verfasst.…”