Photocytotoxicity and DNA photocleavage activity of La(III) and Gd(III) complexes of phenanthroline bases

Abstract

Lanthanide(III) complexes [La(B)(acac)₃] (<b style="">1</b>–<b style="">3</b>) and [Gd(B)(acac)₃] (<b style="">4</b>–<b style="">6</b>), whereB is a <i style="">N,N</i>-donor phenanthroline base, viz.,<i style=""> </i>1,10-phenanthroline (phen in <b style="">1</b>,<b style=""> 4</b>), dipyrido[3,2-<i>d</i>:2ʹ,3ʹ-<i>f</i>]quinoxaline (dpq in <b style="">2</b>,<b style=""> 5</b>) and dipyrido[3,2-<i>a</i>:2ʹ,3ʹ-<i>c</i>]phena­zine (dppz in <b style="">3</b>,<b style=""> 6</b>), have been prepared and characterized. The Gd(III) complexes <b style="">4</b> – <b style="">6</b> are structurally characterized by single crystal X-ray crystallography. The complexes display GdO₆N₂ coordination with the ligands showing bidentate chelating mode of bonding. The complexes are non-electrolytic in aqueous DMF and exhibit ligand-centered absorption bands in the UV region. The dppz complexes show a band at 380 nm in DMF. The La(III) complexes are diamagnetic. The Gd(III) complexes are paramagnetic with magnetic moment that corresponds to seven unpaired electrons. The complexes are avid binders to calf thymus DNA giving <i style="">K</i>_b values in the range of 4.7 x 10⁴- 6.1 x 10⁵ <i>M</i>^-1 with a relative binding order: <b style="">3</b>,<b style=""> 6</b> (dppz) > <b style="">2</b>,<b style=""> 5 </b>(dpq) > <b style="">1</b>,<b style=""> 4 </b>(phen). The binding data suggest DNA surface and/or groove binding nature of the complexes. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form in UV-A light of 365 nm via formation of both singlet oxygen (¹O₂) and hydroxyl radical (HO^●) species. The dppz complexes <b style="">3</b> and <b style="">6</b> exhibit significant PDT effect in HeLa cervical cancer cells giving respective IC₅₀ value of 460(±50) and 530(±30) n<i>M</i> in UV-A light of 365 nm, and are essentially non-toxic in dark with an IC₅₀ value of >100 <img src='/image/spc_char/micro.gif' border=0> <i>M</i>. The dppz ligand alone is cytotoxic in dark and UV-A light. A significant decrease in the dark toxicity of the dppz base is observed on binding to the Ln(III) ion while retaining its photocytotoxicity.