Functional, Aromatic, and Fluorinated Monothiosemicarbazones: Investigations into Their Structures and Activity toward the Gallium-68 Incorporation by Microwave Irradiation

Sophia Sarpaki, Fernando Cortezon Tamarit, Rudiger Maria Exner, Kexin Song, Sara M. M. de Aguiar, Haobo Ge, Charareh Pourzand, Stephen James Paisey, Gabriele Kociok-Kohn, Jonathan Robin Dilworth, Laurence Carroll, Sofia Pascu

Research output: Contribution to journalArticlepeer-review

Abstract

We report on the synthesis and spectroscopic characterization of a new series of coordinating monothiosemicarbazones incorporating aromatic backbones, featuring O/N/S donor centers monosubstituted with different aliphatic, aromatic, fluorinated, and amine-functionalized groups at their N centers. Their ability to bind metal ions such as Zn(II) and Ga(III) was explored, and the formation of two different coordination isomers of the Zn(II) complex was demonstrated by X-ray diffraction studies using synchrotron radiation. These studies showed the planar geometry for the coordinated mono(thiosemicarbazone) ligand and that the metal center can adopt either a heavily distorted tetrahedral Zn center (placed in an N/S/S/N environment, with CN = 4) or a pseudo-octahedral geometry, where the Zn(II) center is in the O/N/S/S/N/O environment, and CN = 6. Furthermore, 2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide (MTT) assays and cellular imaging in living cells were subsequently performed in two different cancer cell lines: PC-3 (a standard cell line derived from a bone metastasis of a stage IV prostate cancer) and EMT6 (a commercial murine mammary carcinoma cell line). The radiolabeling of new functional and aromatic monothiosemicarbazones with either gallium-68 (under pH control) or fluorine-18 is discussed. The potential of this class of compounds to act as synthetic scaffolds for molecular imaging agents of relevance to positron emission tomography was evaluated in vitro, and the cellular uptake of a simultaneously fluorinated and [68Ga]-labeled mono(thiosemicarbazone) was investigated and is reported here.
Original languageEnglish
Pages (from-to)13750-13777
Number of pages28
JournalACS OMEGA
Volume7
Issue number16
Early online date11 Apr 2022
DOIs
Publication statusPublished - 26 Apr 2022

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