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


Reference:

Howson, S. E., Bolhuis, A., Brabec, V., Clarkson, G. J., Malina, J., Rodger, A. and Scott, P., 2012. Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity. Nature Chemistry, 4 (1), pp. 31-36.

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    Official URL:

    http://dx.doi.org/10.1038/nchem.1206

    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 alpha-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).

    Details

    Item Type Articles
    CreatorsHowson, S. E., Bolhuis, A., Brabec, V., Clarkson, G. J., Malina, J., Rodger, A. and Scott, P.
    DOI10.1038/nchem.1206
    DepartmentsFaculty of Science > Pharmacy & Pharmacology
    RefereedYes
    StatusPublished
    ID Code26611

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