Investigation of Cu(II)-HMPAO complex as a model for the development of a potential 64Cu radiopharmaceutical

Abstract

Taking into account the biological characteristics of Cu(II) complexes and the properties of hexamethylpropylene amine oxime (HMPAO) ligand used in nuclear medicine, we synthesized a Cu(II) complex featuring the meso-HMPAO ligand. This was done as a model to explore the potential development of a radiopharmaceutical utilizing 64Cu. The synthesis of the Cu(II)-HMPAO complex follows a procedure, wherein the metal precursor, copper(II) acetate monohydrate, is dissolved in MeOH and reacts with a hot MeOH ligand suspension in a 1:1 molar ratio. The complex's structure was analyzed using FTIR, cyclic voltammetry, and X-ray technique. Additionally, we explored the interactions of the synthesized metal complex with deoxyribonucleic acid (DNA) and human serum albumin (HSA). Isolated copper complex with meso-HMPAO ligand was air-stable, partially soluble in water and EtOH, soluble in polar (DMSO, MeOH, and CH3CN) but insoluble in nonpolar solvents (toluene and benzene). From the characterization methods, HMPAO has been shown to act as a tetradentate ligand that coordinates through the nitrogen atoms of the oxime and amine groups. The results of cyclic voltammetry of copper(II) acetate monohydrate, meso-HMPAO, and Cu(II)-HMPAO complex show that the formation of the complex strongly affects the redox behavior of the electroactive groups. The electrochemical analysis confirmed the binding between the complex and DNA molecule. The fluorescence titration experiments revealed a moderate binding affinity of the [Cu-HMPAO]ClO4 complex to HAS. Cu(II) complex with meso-HMPAO ligand was successfully synthesized and characterized. The binding affinity of the complexes was confirmed in their interaction with DNA and HAS. The experimental findings provide compelling reasons to explore this complex further, either for its potential as an anticancer agent or for its utility in nuclear medicine as a 64Cu radiopharmaceutical.