Solubility and Solvent Effect Analysis of N-Benzyloxycarbonyl-l-tryptophan in 12 Monosolvent Systems at Multiple Temperatures

Abstract

The solid–liquid equilibrium solubility and solvent effects of N-benzyloxycarbonyl-l-tryptophan in monosolvent systems (water, isopropanol, ethanol, n-propanol, isobutanol, n-butanol, acetonitrile, n-pentanol, 2-butanone, acetone, methyl acetate, and ethyl acetate) were reported in this work. All the solubility data were measured at 283.15–323.15 K (5 K interval) by the static gravimetric method. It was confirmed by powder X-ray diffraction that the crystal form of N-benzyloxycarbonyl-l-tryptophan did not change in the process of solubility determination. Among the 12 pure solvents, the solubility increased with the increase of absolute temperature. The solubility is the largest in acetone and the smallest in water. The solubility behavior and solvent effects in different monosolvents were first analyzed by taking the empirical solvent polarity parameter (ET(30)) as the main factor. Then the natural logarithm of solubility (lnx1) was linearly fitted to ET(30) for dipolar protic and aprotic solvents, respectively. Lastly, the special solubility behavior in isopropanol and water/acetonitrile was explained by the hydrogen bond acceptor tendencies and the cohesive energy density, respectively. The solvent effect analysis results illustrated that the solubility sequence of N-benzyloxycarbonyl-l-tryptophan in the test solvents resulted from the comprehensive effect of multiple factors. The Yaws model and the modified Apelblat model were employed to correlate the experimental solubility, and the fitting results of the two models were well. In addition, Akaike Information Criterion values and Akaike weights of the two models were calculated to evaluate the fitting level.