Synthesis, DNA binding, photo-induced DNA cleavage and cytotoxicity studies of europium(iii) complexes

Abstract

Two Eu(III) complexes, [Eu(acac)(3)(dpq)] (1) and [Eu(acac)(3)(dppz)] CH(3)OH (2) {viz. acetylacetonate (acac), dipyrido[3,2-d:20,30-f]quinoxaline (dpq), dipyrido[3,2-a:20,30-c] phenazine (dppz)}, have been synthesized and their DNA binding, photo-induced DNA cleavage activity and cell cytotoxicity are studied. The complexes display significant binding propensity to the calf thymus DNA in the order: 2(dppz) >1(dpq). Cleavage experiments using pBR322 supercoiled DNA suggest major groove binding for 2 and minor groove binding for 1. The mechanistic aspects on natural light (natural light in room during the day) and UV-A (365 nm) irradiation are via a mechanistic pathway involving formation of singlet oxygen and hydroxyl radical as the reactive species. The photo-induced DNA cleavage activity of 2 is also stronger than 1. The cytotoxicity of 1 and 2 against HeLa (cervical) cancer cells show that the IC(50) value of 19.11 ± 3.56 μM and 17.95 ± 5.47 μM, respectively.

Photocytotoxic lanthanide complexes

“…Lanthanide complexes of non-macrocyclic ligands have recently been studied mainly by our group as photocytotoxic agents that show DNA photocleavage and photoactivated anticancer activity. [62][63][64][65][66] In contrast to the chemistry of macrocyclic texaphyrin complexes, the chemistry of photoactive non-macrocyclic lanthanide complexes is virtually unexplored. We have designed Ln(III) complexes to achieve efficient DNA cleavage activity and photocytotoxicity on exposure to light.…”

“…Similarly, Chen and co-workers studied two structurally characterized Eu(III) complexes of dpq and dppz, viz., [Eu(dpq)(acac) 3 ] and [Eu(dppz)(acac) 3 ] for their photoactivated DNA cleavage activity and cytotoxicity in UV-A and natural light. 66 The complexes were found to photocleave DNA in UV-A as well as natural light by dual mechanistic pathways involving the formation of both singlet oxygen and hydroxyl radicals as ROS. However, the complexes were found to be much less active in natural light compared to the UV-A light.…”

Synthesis, crystal structures, DNA binding and cleavage properties and protein binding activities of three mononuclear cobalt(II) complexes

“…The result indicates that the planar phenazine ring of the dppz ligand seems to have facilitated intercalation of the base through the DNA groove because of the presence of an extended aromatic moiety. The K b value of some rare earth metal and copper complexes in our previous study are also summarized in Table . From the data collected in Table2, it can be noted that the value of K b for 1 is more or less equal to the K b values of dppz complexes with the same auxiliary ligand (acac) having a rare earth metal and copper.…”

“…This result may be due to the dpq and dppz ligands, having a quinoxaline moiety with conjugated C═N bonds, generating photo‐excited 3 (n–π*) and/or 3 (π–π*) states induced by UV‐A of 365 nm light affecting DNA cleavage following an oxidative pathway . However, the dpq or dppz complexes, having a rare earth and copper, can cleave DNA with about 100% conversion of SC into NC at low concentration (less than 1 µ m ) under irradiation with UV‐A 365 nm . Thus the cleavage property is significantly influenced by the nature of the metal ion, and the ligands act as the unit of functional regulation.…”

“…Phenanthroline‐based ligands with extended planar quinoxaline moieties, like dipyrido[3,2‐d:2′,3′‐f]quinoxaline (dpq) or dipyrido[3,2‐a:2′,3′‐c]phenazine (dppz), could act as excellent bidentate ligands as well as good binders to DNA. Therefore, the dpq and dppz ligands with their respective quinoxaline and phenazine moieties have attracted the attention of many researchers, including our group …”