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 · Fri Sep 29 00:00:00 EDT 2023 · European Journal of Inorganic Chemistry

DOI:https://doi.org/10.1002/ejic.202300447· OSTI ID:2007124

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

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 (H ₂ L ² ) and cyclohexyl (H ₂ L ³ ) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL ^2a/3a have two imino N and two S donors resulting in three five‐member chelate rings (555 isomers). The kinetic isomers CuL ^2b/3b have 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/I potentials (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 ^2a was potent ( ^A549 EC ₅₀ =0.080 μM) and selective ( ^IMR‐90 EC ₅₀ / ^A549 EC ₅₀ =25) for A549. Its linkage isomer CuL ^2b had equivalent A549 activity, but lower selectivity ( ^IMR‐90 EC ₅₀ / ^A549 EC ₅₀ =12.5). The isomers CuL ^3a and CuL ^3b were less potent with ^A549 EC ₅₀ values of 1.9 and 0.19 M and less selective with ^IMR‐90 EC ₅₀ / ^A549 EC ₅₀ ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: FG02-08CH11538

OSTI ID:: 2007124

Alternate ID(s):: 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:: Wiley Blackwell (John Wiley & Sons)Copyright Statement

Country of Publication:: Germany

Language:: English

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