Rd. Skwierczynski et Ka. Connors, SOLVENT EFFECTS ON CHEMICAL PROCESSES .8. DEMETHYLATION KINETICS OF ASPARTAME IN BINARY AQUEOUS-ORGANIC SOLVENTS, Journal of pharmaceutical sciences, 83(12), 1994, pp. 1690-1696
The kinetics of demethylation of aspartame were studied in binary aque
ous-organic solvent mixtures at 25 degrees C under two solution condit
ions, namely 1.0 M HCl (pH 0.28 in water) and carbonate buffer (pH 10.
1 in water). Under these conditions solvent effects on the acid dissoc
iation constants of aspartame do not complicate the interpretation of
the kinetics. The organic cosolvents were acetone, acetonitrile, dimet
hyl sulfoxide, dioxane, tetrahydrofuran, and methanol. The observed ki
netic solvent effects were modest in magnitude, not exceeding a factor
of 3 in rate constant, relative to the fully aqueous solution. The ra
te changes included both increases and decreases, and in some solvent
mixtures extrema were observed. It is concluded that at least two cont
ributory factors, identified as an electrostatic (dielectric constant)
effect and a solvation effect, must be operating to produce the obser
ved kinetic solvent effects.