Stability constant determinations of alitame with H(I) and Cu(II) under physiological conditions using potentiometric measurements

Stability constant determinations of the new artificial sweetener alitame (l-α-aspartyl-N-(2,2,4,4-tetramethyl-3-thietanyl)-d-alaninamide), an HL type ligand (L⁻=the deprotonated form of the ligand), was carried out with H(I) and Cu(II) under physiological conditions (I=0.15(NaCl) in water, 37°C) using potentiometric titration. The molar concentration stability constants of H(I) and Cu(II) complexes with alitame, together with a distribution diagram of the Cu(II)-alitame complex species as a function of pH, are obtained. Cu(II) is able to form binary complex species (CuL⁺, CuL₂) with alitame in solution. Those species are further deprotonated to form the corresponding CuLH₋₁, CuLH₋₂⁻ and CuL₂H₋₁⁻ species. The neutral Cu(II)-alitame complex, CuL₂, is the major species between pH=6.5 and 7.5 followed by CuLH₋₁. A comparison with the less-stable artificial sweetener, aspartame (N-l-α-aspartyl-l-phenylalanine 1-methyl ester), is considered. Preliminary stability tests for alitame and Cu(II)-alitame solutions, using pH and stability constant methods, are reported.