Fast relaxation and elasticity-related properties of trehalose-glycerol mixtures

Abstract

Molecular dynamics simulations are used to investigate basic fast relaxation properties and thermo-physical properties of trehalose-glycerol mixtures over a wide composition range and for a temperature range from above to below the glass transition temperature, T_g. An important aspect of the present work is that we employ a revised force field that yields glycerol densities that agree much better with experiment than those formerly used in models of these mixtures. This optimized molecular model provides a platform for more refined simulation studies of this class of protein drug preservative matrix materials. For temperatures below T_g, the inverse of the Debye–Waller factor, <u²>⁻¹, exhibits a maximum near a 30% relative glycerol mass concentration. This local ‘stiffening’ effect, in conjunction with a reduction of T_g by glycerol, indicates that glycerol is an antiplastizer of trehalose at intermediate concentrations, a finding consistent with dielectric measurements on trehalose-glycerol mixtures in which moisture has been carefully excluded from the samples. We also find that the shear modulus of these materials C₁₁ increases progressively with glycerol concentration. The Boson peak, which provides one of the most experimentally accessible fast dynamics properties of glass-forming liquids, is also calculated for trehalose-glycerol glasses as a function of glycerol concentration. The change in the Boson peak intensity with glycerol concentration is found to be consistent with a reduction of fragility of glass formation with the addition of glycerol, an effect that previous simulation studies of coarse grain models have linked to antiplasticization. We also find general agreement with a recently proposed relation between the fast beta relaxation time τ_β and the local amplitude of atomic motion on picosecond timescales, <u²>. The implications of our simulations and their interpretation in terms of physics of glass formation are briefly discussed in the context of protein stabilization.