Sweetening ruthenium and osmium: organometallic arene complexes containing aspartame.
The novel organometallic sandwich complexes [(eta(6)-p-cymene)Ru(eta(6)-aspartame)](OTf)(2) (1) (OTf = trifluoromethanesulfonate) and [(eta(6)-p-cymene)Os(eta(6)-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.
School of Chemistry, University of Edinburgh, West Mains Road, Edinburgh, EH9 3JJ, UK.
Jennifer C
JC
Gray
Abraha
A
Habtemariam
Marcel
M
Winnig
Wolfgang
W
Meyerhof
Peter J
PJ
Sadler
D001218:Aspartame / Q000737:chemistry*; D002460:Cell Line; D004563:Electrochemistry; D004583:Electrons; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009992:Osmium / Q000737:chemistry*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D012428:Ruthenium / Q000737:chemistry*; D013549:Sweetening Agents / Q000737:chemistry*
D009942:Organometallic Compounds; D043562:Receptors, G-Protein-Coupled; D013549:Sweetening Agents; D009992:Osmium; D012428:Ruthenium; D001218:Aspartame