Structural and Functional Diversity in Rigid Thiosemicarbazones with Extended Aromatic Frameworks: Microwave-Assisted...

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Radiochemistry

Background:

• Thiosemicarbazones (TSCs) are of significant interest for theranostic applications, including cellular and multimodality imaging.
• Established bis(thiosemicarbazones) like copper(diacetyl-bis(N4-methylthiosemicarbazone)], [64Cu]Cu(ATSM), are utilized in preclinical and clinical cancer research for hypoxia imaging.

Purpose of the Study:

• To investigate the structural chemistry of rigid mono(thiosemicarbazone) ligands with extended aromatic backbones.
• To synthesize and characterize corresponding zinc(II) and copper(II) metal complexes.
• To explore the potential of these compounds as building blocks for theranostics and multimodality imaging probes.

Main Methods:

• Microwave-assisted synthesis for rapid preparation of ligands and Zn(II) complexes.
• Spectroscopic characterization (NMR, MS) and single crystal X-ray diffraction for structural analysis.
• DFT calculations to validate geometries.
• Radiolabeling with 64Cu under mild conditions.
• Cytotoxicity assays (IC50) against HeLa and PC-3 cancer cell lines.
• Cellular internalization studies using laser confocal fluorescent spectroscopy.

Main Results:

• Novel rigid mono(thiosemicarbazone) ligands and their Zn(II) complexes were synthesized efficiently using microwave irradiation.
• Characterization revealed diverse coordination geometries (distorted octahedral, tetrahedral) for Zn(II) complexes.
• Successful radiolabeling of thiosemicarbazones with 64Cu achieved high radiochemical incorporation (>80%).
• Cu(II) complexes formed in 1:1 and 1:2 metal:ligand ratios, with Cu(L)2 prevailing.
• Selected Zn(II) complexes exhibited cytotoxicity comparable to cisplatin.
• ZnL2-type compounds showed exclusive cytoplasmic localization in PC-3 cells.

Conclusions:

• The synthesized thiosemicarbazone ligands and their metal complexes are promising scaffolds for theranostic and multimodality imaging applications.
• The efficient microwave-assisted synthesis and mild radiolabeling protocols highlight their potential utility.
• The observed cytotoxicity and cellular uptake warrant further investigation for cancer therapy and diagnostics.