Statistical thermodynamics unveils the dissolution mechanism of cellobiose.

In the study of the cellulose dissolution mechanism opinion is still divided. Here, the solution interaction components of the most prominent hypotheses for the driving force of cellulose dissolution were evaluated quantitatively. Combining a rigorous statistical thermodynamic theory and cellobiose solubility data in the presence of chloride salts, whose cations progress in the Hofmeister series (KCl, NaCl, LiCl and ZnCl2), we have shown that cellobiose solubilization is driven by the preferential accumulation of salts around the solutes which is stronger than cellobiose hydration. Yet contrary to the classical chaotropy hypothesis, increasing salt concentration leads to cellobiose dehydration in the presence of the strongest solubilizer ZnCl2. However, thanks to cellobiose dehydration, cellobiose-salt interaction still remains preferential despite weakening salt accumulation. Based on such insights, the previous hypotheses based on hydrophobicity and polymer charging have also been evaluated quantitatively. Thus, our present study successfully paved a way towards identifying the basic driving forces for cellulose solubilization in a quantitative manner for the first time. When combined with unit additivity methods this quantitative information could lead to a full understanding of cellulose solubility.

Origin of non-linearity in phase solubility: solubilisation by cyclodextrin beyond stoichiometric complexation.

The low solubility of drugs, which poses a serious problem in drug development, can in part be overcome by the use of cyclodextrins (CDs) and their derivatives. Here, the key to solubilisation is identified as the formation of inclusion complexes with the drug molecule. If inclusion complexation were the only contribution to drug solubility, it would increase linearly with CD concentration (as per the Higuchi-Connors model); this is because inclusion complexation is a 1 : 1 stoichiometric process. However, solubility curves often deviate from this linearity, whose mechanism is yet to be understood. Here we aim to clarify the origin of such non-linearity, based on the Kirkwood-Buff and the McMillan-Mayer theories of solutions. The rigorous statistical thermodynamic theory shows that non-linearity of solubilisation can be rationalised by two contributions: CD-drug interaction and the drug-induced change of CD-CD interaction.