Pyrazolyl–Diamine Ligands That Bear Anthracenyl Moieties and Their Rhenium(I) Tricarbonyl Complexes: Synthesis, Characterisation and DNA‐Binding Properties

Abstract

Two novel families of pyrazolyl-diamine ligands that bear an anthracen-9-yl group as a DNA-binding fragment, pz*(CH2)2NH(CH2)2NHCH2-9-anthryl (pz*=pz (L(1)), 3,5-Me2pz (L2)) and pz*(CH2)2NH(CH2)2NH(2 (pz*=4-(9-anthrylmethyl)pz (L3), 3,5-Me2-4-(9-anthrylmethyl)pz (L4)), have been prepared and fully characterised. In the case of L2-L4, the evaluation of their coordination capability towards the fac-[Re(CO)3]+ core led to the synthesis of the organometallic complexes fac-[Re(CO)(3){3,5-Me(2)pz(CH2)2NH(CH2)2NHCH2-9-anthryl}]Br (7) and fac-[Re(CO)3{4-(9-anthrylmethyl)pz*(CH2)2NH(CH2)2NH2}]Br (pz*=pz (8), 3,5-Me2pz 9). The interaction of the novel pyrazole-diamine ligands and the rhenium(I) complexes with calf thymus (CT) DNA has been investigated with a variety of spectroscopic techniques (UV-visible, fluorescence, circular dichroism (CD) and linear dichroism (LD)). All of the evaluated compounds have a moderate affinity to CT DNA (3.46x10(3)<K(b)<1.95x10(4)), but the binding mode depends on the position of the chromophore in the framework of the pyrazolyl-diamine ligands. LD measurements have shown that L1 and L2 act as DNA intercalators, but complex 7 intercalates only partially. By contrast, the compounds with the anthracenyl group at the 4-position of the azolyl ring (L(3), L4 and 9) do not intercalate, and behave more like DNA groove binders. Fluorescence microscopy studies have demonstrated that complexes 7 and 9 can target the nucleus of murine B16-F1 melanoma cells, and appear to be promising platforms for the further design of radiopharmaceuticals for targeted radiotherapy.