Optically pure, water-stable metallo-helical 'flexicate' assemblies with antibiotic activity

Suzanne E. Howson, Albert Bolhuis, Viktor Brabec, Guy J. Clarkson, Jaroslav Malina, Alison Rodger, Peter Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

157 Citations (Scopus)

Abstract

The helicates-chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands-may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) 'flexicate' system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).

Original languageEnglish
Pages (from-to)31-36
Number of pages6
JournalNature Chemistry
Volume4
Issue number1
Early online date27 Nov 2011
DOIs
Publication statusPublished - Jan 2012
Externally publishedYes

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