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Sweetening ruthenium and osmium: organometallic arene complexes containing aspartame

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Abstract

The novel organometallic sandwich complexes [(η6-p-cymene)Ru(η6-aspartame)](OTf)2 (1) (OTf = trifluoromethanesulfonate) and [(η6-p-cymene)Os(η6-aspartame)](OTf)2 (2) incorporating the artificial sweetener aspartame have been synthesised and characterised. A number of properties of aspartame were found to be altered on binding to either metal. The pK a values of both the carboxyl and the amino groups of aspartame are lowered by between 0.35 and 0.57 pH units, causing partial deprotonation of the amino group at pH 7.4 (physiological pH). The rate of degradation of aspartame to 3,6-dioxo-5-phenylmethylpiperazine acetic acid (diketopiperazine) increased over threefold from 0.12 to 0.36 h−1 for 1, and to 0.43 h−1 for 2. Furthermore, the reduction potential of the ligand shifted from −1.133 to −0.619 V for 2. For the ruthenium complex 1 the process occurred in two steps, the first (at −0.38 V) within a biologically accessible range. This facilitates reactions with biological reductants such as ascorbate. Binding to and activation of the sweet taste receptor was not observed for these metal complexes up to concentrations of 1 mM. The factors which affect the ability of metal-bound aspartame to interact with the receptor site are discussed.

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Acknowledgments

We thank the EPSRC (studentship for J.C.G.) for support, Lesley Yellowlees for advice on cyclic voltammetry and Nicole Kratochwil for helpful discussion.

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Authors and Affiliations

  1. School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK

    Jennifer C. Gray

  2. Department of Chemistry, University of Warwick, Gibbet Hill Road, Coventry, CV4 7AL, UK

    Abraha Habtemariam & Peter J. Sadler

  3. The German Institute of Human Nutrition, Postdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany

    Marcel Winnig & Wolfgang Meyerhof

  4. Axxam, San Raffaele Biomedical Science Park, via Olgettina 58, 20132, Milan, Italy

    Marcel Winnig

Authors
  1. Jennifer C. Gray
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  2. Abraha Habtemariam
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  3. Marcel Winnig
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  4. Wolfgang Meyerhof
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  5. Peter J. Sadler
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Correspondence to Peter J. Sadler.

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Gray, J.C., Habtemariam, A., Winnig, M. et al. Sweetening ruthenium and osmium: organometallic arene complexes containing aspartame. J Biol Inorg Chem 13, 1111–1120 (2008). https://doi.org/10.1007/s00775-008-0396-1

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  • DOI: https://doi.org/10.1007/s00775-008-0396-1

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