Glycerol is a major cryoprotective agent and is widely used to promote protein stabilization. Through a combined experimental and theoretical study, we show that global thermodynamic mixing properties of glycerol and water are dictated by local solvation motifs. We identify three water populations, i.e., bulk water, bound water (water hydrogen bonded to the hydrophilic groups of glycerol) and wrap water (water hydrating the hydrophobic moieties). Each population provides distinct spectroscopic fingerprints in the FIR/THz spectral range, which can be used to quantify their respective abundance and their partial contributions to the mixing enthalpy. We uncover a 1:1 connection between the number of bound waters and the mixing enthalpy, as deduced from experiments as well as from simulations. The balance between local hydrophobic wrap and hydrophilic bound contributions at the molecular level dictates macroscopic thermodynamics of mixing. This offers opportunities to rationally design polyol water mixtures to optimize technological applications by tuning mixing enthalpy and entropy based on spectroscopic screening.

中文翻译：

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局部溶剂化结构控制甘油-水溶液的混合热力学

甘油是一种主要的冷冻保护剂，广泛用于促进蛋白质稳定。通过实验和理论相结合的研究，我们表明甘油和水的整体热力学混合特性是由局部溶剂化基序决定的。我们确定了三种水群，即本体水、结合水（与甘油的亲水基团氢键合的水）和包裹水（与疏水部分水合的水）。每个群体在 FIR/THz 光谱范围内提供不同的光谱指纹，可用于量化它们各自的丰度及其对混合焓的部分贡献。根据实验和模拟推论，我们发现结合水的数量与混合焓之间存在 1:1 的关系。分子水平上局部疏水包裹和亲水结合贡献之间的平衡决定了混合的宏观热力学。这为合理设计多元醇水混合物提供了机会，通过基于光谱筛选调整混合焓和熵来优化技术应用。