Bromo-substituted azadipyrromethene zinc(II), cobalt(II) and copper(II) complexes – Structural, spectroscopic, electrochemical properties and interaction with DNA G-quadruplexes

The development of new DNA-binding agents helps in understanding cellular functions and exploring potential treatment for cancer-related diseases. While azadipyrromethene (ADPM) ligands have been studied for these purposes, their metal ion complexes remain unexpectedly underdeveloped in this area. To address this, a small library of new azadipyrromethene complexes with zinc(II), cobalt(II) and copper(II) ions was prepared, with bromo-substituent located at the proximal terminus of the ADPM ligand. The chemical structure of synthesized ML2 isostructural species was confirmed by mass spectrometry and NMR spectroscopy. UV–Vis studies showedthat the CoL₂ and ZnL₂ complexes display a single long-wavelength absorption band in DCM, at 592 nm and 609 nm, respectively. In contrast, the CuL₂ analogue exhibits a split Q-band at 572 nm and 645 nm in DCM. Electrochemical studies suggest that oxidation processes are primarily ligand-centered, whereas metal ion affects theLUMO energy levels and reduction processes, especially for the CuL2 system. Binding ability of quadruple-helical DNA models implied in cancer (hTERT and Pu22) and dsDNA was also investigated. UV and circular dichroism (CD) spectroscopy revealed that, among the other complexes, the CoL2 complex primarily induces significantchanges of the structures of Pu22 and hTERT, while showing no interaction with dsDNA. Fluorescence indicator displacement (FID) assays with thiazole orange (TO) confirmed the interactions of CoL2 and CuL2 with G4 structures. The DC50 values for CuL2 where 88 μM and 80 μM, while for CoL2 59 μM and 40 μM towards hTERTand Pu22, respectively, whereas ZnL2 shows lower affinity towards both G4 structures. Such specificity towards cancer-related quadruplex models underscores its potential for further exploration in drug-based anticancer treatment, particularly when combined with photodynamic therapy, and the promise of other ADPM-based coordination compounds.