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 ML 2 isostructural species was confirmed by mass spectrometry and NMR spectroscopy. UV–Vis studies showed that 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 the LUMO energy levels and reduction processes, especially for the CuL 2 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 CoL 2 complex primarily induces significant changes 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 CoL 2 and CuL 2 with G4 structures. The DC 50 values for CuL 2 where 88 μM and 80 μM, while for CoL 2 59 μM and 40 μM towards hTERT and Pu22, respectively, whereas ZnL 2 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. • ADPM complexes of Zn(II), Co(II), and Cu(II) were successfully synthesized and fully characterized. • The Co(II) ADPM complex demonstrates selective binding to G-quadruplex structures. • The experimentally determined HOMO-LUMO gaps are in good agreement with the calculated values. • The absorption spectra of obtained complexes displayed intense bands with a maximum around 600 nm.