Synthesis and characterization of Cu(II)‑meso-HMPAO complex as a model for the development of potential 64Cu radiopharmaceutical

Abstract

In this work, Cu(II) complexes with meso‑HMPAO and d,l-HMPAO were synthesized. The structural characterisation of the isolated compounds has been done by single-crystal X-ray diffraction analysis, FTIR, and mass spectroscopy. Redox properties of complexes and binding to deoxyribonucleic acid (DNA) molecule have been analysed in detail by cyclic voltammetry and DFT calculations. The results of cyclic voltammetry fully agree with the data obtained by DFT calculations and indicate that the first electron removal takes place from the metal, while the second electron is removed from the ligand. The formation of the complex leads to the shift in oxidation peaks of the ligand from ‒0.29 V to 0,47 V and from 1.18 V to 1,24 V, indicating that ligand in the complex is much more difficult to oxidize. Electrochemical data confirmed the binding between the complex and DNA molecules through guanine. DFT calculations show that the complex is suitable not only for binding purine and pyrimidine bases through a coordination bond but also for additional hydrogen and CH-π interactions of the bases with the ligand. The fluorescence titration experiments revealed a moderate binding affinity of the [Cu-HMPAO]ClO4 complex to human serum albumin (HSA). Molecular docking revealed that this ligand preferentially binds to drug binding site 3 of HSA. Therefore, the novel compounds could be of great interest for further investigation, considering the potential anticancer activity, and as a model for the development of radiopharmaceutical with 64Cu.