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.

Synthesis and Biological Studies of Pyrazolyl‐Diamine PtII Complexes Containing Polyaromatic DNA‐Binding Groups

“…However, for the acridine orange ligand L 3 there was a change in the mobility of the plasmid DNA; this indicated that L 3 has a better ability than L 2 to interact with DNA. These findings are consistent with the results for L 2 Pt and L 3 Pt presented above: that is, a more probable contribution of the intercalation binding mode in the case of L 3 Pt reflecting a higher DNA affinity for the AO chromophore than for anthracene 8. 10…”

“…Moreover, we have also shown that 99m Tc I tricarbonyl complexes anchored by pyrazolyl‐diamine ligands functionalized with polyaromatic DNA intercalators have the ability to target the nuclei of tumor cells, with some complexes causing significant cell killing at low radioactivity levels, mainly through apoptotic pathways 8–10. These encouraging results prompted us to study Pt II complexes anchored by pyrazolyl‐diamine chelators bearing planar and aromatic DNA‐intercalating groups.…”

New heterobimetallic ferrocenyl derivatives are promising antitrypanosomal agents

“…73 Changes in the CD bands in this spectral range are useful to detect DNA conformational changes, damage and/or cleavage. 71,74,75 In addition, even if the complexes are not chiral and thus present no CD signal, their association with DNA may give rise to an induced circular dichroism spectra (ICD) in the range of the complexes´ absorption bands.…”

The Chemistry of Technetium–Water Complexes within the Manganese Triad: Challenges and Perspectives

“…Thereby, the Auger electrons emitted from the isomeric transition may become opportune for therapeutical purposes besides classical imaging. [92][93][94][95] In the context of combined fluorescence-radioimaging the metaldependent luminescence of rhenium amino-heterocycle complexes has been used to detect the localization of peptides on a cellular level. So-called single amino acid chelates (SAAC) were incorporated in the targeting fMLF sequence and then used for in vitro screening.…”