Entropy-enthalpy compensation in the methyl 5-thio-α-d-galactopyranoside–Jacalin interaction

Methyl 5-thio-α-d-galactopyranoside was synthesized and found to have a more favorable enthalpy of binding to Jacalin than methyl α-d-galactopyranoside, which is attributed to the greater magnitude of sulfur-π over oxygen-π interactions. This increase in enthalpy, however, was offset by a less favorable entropy of binding, arising from the need to constrain the more flexible thiosugar, thereby highlighting the complexities inherent in the design of effective sugar mimetics.