Synthesis and Characterization of Water Soluble Thiosemicarbazone-Alkylthiocarbamate Ligands and Their Cu(II) Complexes

Authors

John J. Garvey IV, University of Louisville Department of ChemistryFollow
Sanjit Karki, University of Louisville Department of ChemistryFollow
Haixun Guo, University of Louisville Department of Radiology and UofL Center for Predictive MedicineFollow
Levi J. Beverly, University of Louisville Department of Medicine and James Graham Brown Cancer CenterFollow
Craig A. Grapperhaus, University of Louisville Department of ChemistryFollow
Robert M. Buchanan, University of Louisville Department of ChemistryFollow

Program/Event

Arts and Research Showcase 2024

Abstract

Thiosemicarbazone-alkylthiocarbamate N₂S₂ hybrid ligands are emerging as an important class of potential bioactive molecules that possess important pharmacokinetic properties. Resulting metal complexes have electronic properties that are composites of their homolog forms, bis-thiosemicarbazones and bis-alkylthiocarbamates, allowing for tuning redox potentials over a nearly 450 mV range. These versatile ligand frameworks possess remarkable antiproliferation activity against a broad range of solid tumors and low toxicity towards normal cells¹ indicating great promise for future drug development. Herein, we describe recent synthetic efforts to improve water solubility of thiosemicarbazone-alkylthiocarbamate hybrid ligand Cu(II) complexes. The parent 4-methyl-3-thiosemicarbazide half arm was modified by the addition of a pendant diamine to increase the hybrid ligand’s solubility in water. A charged ligand was also synthesized by addition of a pendant triamine to further increase the solubility in water.

Preliminary Log P measurements show an enhanced hydrophilicity associated with the addition of the free-amine pendant. The data also suggest retention of complex lipophilicity, which is important to passive diffusion across cell membranes and the blood-brain barrier, a result that is relevant to the development of future neurological therapeutics.

Recommended Citation

Garvey, John J. IV; Karki, Sanjit; Guo, Haixun; Beverly, Levi J.; Grapperhaus, Craig A.; and Buchanan, Robert M. (2024) "Synthesis and Characterization of Water Soluble Thiosemicarbazone-Alkylthiocarbamate Ligands and Their Cu(II) Complexes," The Cardinal Edge: Vol. 2: Iss. 2, Article 45.
Available at: https://ir.library.louisville.edu/tce/vol2/iss2/45