Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C 6 H 8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Bajaj, Kritika; Andres, Sarah A.; Hofsommer, Dillon T.; Chekwube Michael, Okolocha; Mashuta, Mark S.; Bates, Paula J.; Buchanan, Robert M.; Grapperhaus, Craig A.

doi:10.1002/ejic.202300447

Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C ₆ H ₈ Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Journal Article · 29 September 2023 · European Journal of Inorganic Chemistry

DOI:https://doi.org/10.1002/ejic.202300447· OSTI ID:2419246

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Department of Chemistry University of Louisville 40292 Louisville KY United States; OSTI
Department of Medicine and Brown Cancer Center University of Louisville 40202 Louisville KY USA
Department of Chemistry University of Louisville 40292 Louisville KY United States

Abstract

A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3‐methylpentyl (H₂L²) and cyclohexyl (H₂L³) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL^2a/3ahave two imino N and two S donors resulting in three five‐member chelate rings (555 isomers). The kinetic isomers CuL^2b/3bhave one imino and one hydrazino N donor and two S donors resulting in four‐, six‐, and five‐member rings (465 isomers). The 555 isomers have more accessible Cu^II/Ipotentials (E_1/2=−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E_1/2=−923/‐854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR‐90) using the MTT assay. CuL^2awas potent (^A549EC₅₀=0.080 μM) and selective (^IMR‐90EC₅₀/^A549EC₅₀=25) for A549. Its linkage isomer CuL^2bhad equivalent A549 activity, but lower selectivity (^IMR‐90EC₅₀/^A549EC₅₀=12.5). The isomers CuL^3aand CuL^3bwere less potent with^A549EC₅₀ values of 1.9 and 0.19 M and less selective with^IMR‐90EC₅₀/^A549EC₅₀ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.

Research Organization:: Univ. of Louisville, KY (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

DOE Contract Number:: FG02-08CH11538

OSTI ID:: 2419246

Journal Information:: European Journal of Inorganic Chemistry, Journal Name: European Journal of Inorganic Chemistry Journal Issue: 34 Vol. 26; ISSN 1434-1948

Publisher:: ChemPubSoc Europe

Country of Publication:: United States

Language:: English

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