Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 1;26(34):e202300447.
doi: 10.1002/ejic.202300447. Epub 2023 Sep 14.

Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Kritika Bajaj  1 , Sarah A Andres  2 , Dillon T Hofsommer  1 , Okolocha Chekwube Michael  1 , Mark S Mashuta  1 , Paula J Bates  2 , Robert M Buchanan  1 , Craig A Grapperhaus  1
Affiliations

Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Kritika Bajaj et al. Eur J Inorg Chem. .

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 CuL2a/3a have two imino N and two S donors resulting in three five-member chelate rings (555 isomers). The kinetic isomers CuL2b/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 CuII/I potentials (E1/2 = -811/-768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E1/2 = -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. CuL2a was potent (A549EC50 = 0.080 μM) and selective (IMR-90EC50/A549EC50 = 25) for A549. Its linkage isomer CuL2b had equivalent A549 activity, but lower selectivity (IMR-90EC50/A549EC50 = 12.5). The isomers CuL3a and CuL3b were less potent with A549EC50 values of 1.9 and 0.19 μM and less selective with IMR-90EC50/A549EC50 ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.

Keywords: N2S2 ligands; antiproliferation activity; copper; ligand isomer; linkage isomer.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following competing financial interest(s): Complexes described in this manuscript are included in an issued US patent (US-11208379-B2) entitled “Compounds, Compositions, Methods for Treating Diseases, and Methods for Preparing Compounds.” A portion of the results described in this manuscript are included in the dissertation Alkylthiocarbamate metal complexes with antiproliferation activity by Kritika Bajaj, University of Louisville.[21]

Figures

Figure 1.
Figure 1.
General structures of bis(thiosemicarbazone) (BTSC), thiosemicarbazone-alkylthiocarbamate (TSTC), and bis(alkylthiocarbamate) (BATC) metal complexes with three five-membered chelate rings (555 isomers).
Figure 2.
Figure 2.
Previously reported linkage isomers CuL1a/b (ref. 11) and ligand constitutional and linkage isomers CuL2a-3b.
Figure 3.
Figure 3.
UV-visible spectra for the linkage isomer pair CuL2a/b in acetonitrile.
Figure 4.
Figure 4.
ORTEP representations of A) CuL2a; B) CuL2b; and C) CuL3a.
Figure 5.
Figure 5.
Comparison of CuII/I reduction potentials versus ferrocenium/ferrocene for CuL1a-3b. The end of the bar represents the E1/2 value for each complex. The bars are color coded by ligand with the 555 isomer in a darker shade with white lettering and the 465 isomer in the lighter shade with black lettering. Cyclic voltammograms were recorded in acetonitrile with 0.1 M NBu4PF6 as supporting electrolyte at a scan rate of 200 mV s−1.
Scheme 1.
Scheme 1.
Synthetic routes for the 555 linkage isomers CuL2a/3a and the 465 linkage isomers CuL2b/3b.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Werner A, Ber. Dtsch. Chem. Ges 1907, 40, 765–788.
    1. Balahura RJ, Lewis NA, Coord. Chem. Rev 1976, 20, 109–153.
    1. Appleton TG, Coord. Chem. Rev 1997, 166, 313–359.
    1. Hazari A, Ghosh A, J. Indian Chem. Soc 2018, 95, 1597–1606.
    1. Aly MM, Stephanos JJ, Spectrochim. Acta A 1994, 50, 835–840;
    2. Lacey MJ, Macdonald C, Shannon J, Aust. J. Chem 1973, 26, 263–268.

LinkOut - more resources