Laxmi Tiwari

Major: Chemistry

Faculty Advisor: Kristopher Waynant

Project Title:

Arylazothioformamide (ATF) Ligands: A Flexible Foundation for Coordination Complexes and Their Diverse Biological Activity

Abstract

Redox-active arylazothioformamide (ATF) ligands have gained recognition for their versatile properties in coordinating with late transition metals, particularly copper. ATF ligands swiftly form distinctive coordination complexes with copper(I) metal salts, all while maintaining their neutral charge (i.e., no redox event).

For this research study, various substitutions on the ATFs, both in aryl electronics and formamide sterics were performed. Coordination complexes were then prepared from mixing with copper(I) salts (specifically CuBr, CuI and [(CH3CN)4Cu](BF4)) resultant complexes were fully characterized, including X-ray crystallography for many. Electron-donating aryl substitutions (i.e., MeO) and locked steric groups (i.e., pyrrolidine) at the formamide produced stronger binding with copper(I) salts than other substitutions. Importantly, metal chelation plays a pivotal role in cellular proliferation, and compounds like ATF have displayed increased biological activity, encompassing antimicrobial, antineoplastic, and antifungal properties promoting this mechanism as a potential inhibition route. While the ATF ligands themselves exhibited no discernible activity against microbial agents and cancer cell lines, the metal complexes formed with these ligands significantly exhibited microbes and cytotoxic activity. Some of these metal complexes demonstrated very potent activity against certain cancer cell lines, with IC50 values less than 1 µM.

These activities were assessed against a range of cell lines, including human lung adenocarcinoma (A549), human fibrosarcoma (HT-1080), human breast cancer (MDA-MB-231), human myelogenous leukemia (K562), and normal human cell lines such as human fetal lung fibroblasts (MRC-5) and human foreskin fibroblasts (HFF). Additionally, the antibacterial activity was tested against Gram (+) bacteria like Staphylococcus aureus as well as against Gram (-) bacteria like Escherichia coli and the yeast Candida albicans.

The findings suggest the potential of these metal complexes in various biomedical applications.