C-1004: Molecular modelling of the dynamic and thermodynamic characteristics associated with the glass transition of amorphous trehalose/water mixtures

Abstract

The glass transition temperature T g of biopreservative formulations is recognized as a significant parameter for predicting the long-term storage of biologics. As a complementary tool to thermal analysis techniques, molecular modelling has been successfully applied to predict the T g of several cryoprotectants and their mixtures with water. These molecular analyses, however, have rarely focused on the glass transition behavior of aqueous trehalose solutions. Information about the diffusivity, specific heat capacity, H-bonding dynamics in trehalose/water at sub-T g temperatures are largely still unavailable in the literature. And the self-association characteristics of sugar solutions in the glassy state are still relatively unknown. Using molecular modelling of several dynamic and thermodynamic properties, this study reproduced the supplemented phase diagram of trehalose/water mixtures, yielding good agreement with experimental values. The structure and dynamics of the H-bonding network in the mixtures were analyzed. The H-bonding lifetime was determined to be an order of magnitude higher in the glassy state than in the liquid state, while the constitution of the H-bonding network exhibited no noticeable change through the glass transition. It is speculated that the extended H-bond lifetime in the glassy state could reflect the slower secondary relaxation dynamics, both of which are primarily related to the local reorientation of –OH groups in the trehalose molecule. It was also found that trehalose molecules preferred to form small, scattered clusters above T g , but self-aggregation was substantially increased below T g . This aggregation phenomenon could help to shield preserved biologics from dynamically decoupled water in the vicinity of T g . Our findings demonstrated the feasibility of probing vitrification phenomena by molecular modelling based on multiple dynamic and thermodynamic properties and provided insights into the glass transition characteristics of aqueous trehalose, enabling a consideration of the implications for biopreservation.