Copper, Nickel, and Zinc Cyclam鈥揂mino Acid and Cyclam鈥揚eptide Complexes May Be Synthesized with 鈥淐lick鈥?Chemistry and Are Noncytotoxic

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• 作者：Mingfeng Yu ; Jason R. Price ; Paul Jensen ; Carrie J. Lovitt ; Todd Shelper ; Sandra Duffy ; Louisa C. Windus ; Vicky M. Avery ; Peter J. Rutledge ; Matthew H. Todd
• 刊名：Inorganic Chemistry
• 出版年：2011
• 出版时间：December 19, 2011
• 年：2011
• 卷：50
• 期：24
• 页码：12823-12835
• 全文大小：616K
• 年卷期：v.50,no.24(December 19, 2011)
• ISSN：1520-510X

文摘

We describe the synthesis of cyclam metal complexes derivatized with amino acids or a tripeptide using a copper(I)-catalyzed Huisgen 鈥渃lick鈥?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)鈥揷yclam鈥搕riazole鈥揷ysteine disulfide complex displayed moderate activity against MCF-10A breast nontumorigenic epithelial cells.