Copper, Nickel, and Zinc Cyclam−Amino Acid and Cyclam−Peptide Complexes May Be Synthesized with 'Click' Chemistry and Are Noncytotoxic

Yu, Mingfeng and Price, Jason R. and Jensen, Paul and Lovitt, Carrie J. and Shelper, Todd and Duffy, Sandra and Windus, Louisa C. and Avery, Vicky M. and Rutledge, Peter J. and Todd, Matthew H. (2011) Copper, Nickel, and Zinc Cyclam−Amino Acid and Cyclam−Peptide Complexes May Be Synthesized with 'Click' Chemistry and Are Noncytotoxic. Inorganic Chemistry, 50:24. pp. 12823-12835. ISSN 0002-7863


Abstract

We describe the synthesis of cyclam metal complexes derivatized with amino acids or a tripeptide using a copper(I)-catalyzed Huisgen “click” reaction. The linker triazole formed during the synthesis plays an active coordinating role in the complexes. The reaction conditions do not racemize the amino acid stereocenters. However, a methylene group adjacent to the triazole is susceptible to H/D exchange under ambient conditions, an observation which has potentially important implications for structures involving stereocenters adjacent to triazoles in click-derived structures. The successful incorporation of several amino acids is described, including reactive tryptophan and cysteine side chains. All complexes are formed rapidly upon introduction of the relevant metal salt, including synthetically convenient cases where trifluoroacetate salts of cyclam derivatives are used directly in the metalation. None of the metal complexes displayed any cytotoxicity to mammalian cells, suggesting that the attachment of such complexes to amino acids and peptides does not induce toxicity, further supporting their potential suitability for labeling/imaging studies. One Cu(II)–cyclam–triazole–cysteine disulfide complex displayed moderate activity against MCF-10A breast nontumorigenic epithelial cells.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Faculty/School / Institute/Centre: No Faculty
Faculty/School / Institute/Centre: No Faculty
Date Deposited: 27 Oct 2020 03:29
Last Modified: 27 Oct 2020 05:28
Uncontrolled Keywords: solid-phase synthesis; metal-complexes; biomedical applications; scorpionate complex; agents; cytotoxicity; stability; cells; probe
Fields of Research (2008): 03 Chemical Sciences > 0302 Inorganic Chemistry > 030205 Non-metal Chemistry
Socio-Economic Objectives (2008): E Expanding Knowledge > 97 Expanding Knowledge > 970103 Expanding Knowledge in the Chemical Sciences
Identification Number or DOI: https://doi.org/10.1021/ic2020012
URI: http://eprints.usq.edu.au/id/eprint/39990

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