Hydrogen-Bond Exchange Governs Opposite Vitrification Behaviors in Cryoprotectant Solutions

The glass transition is central to biomaterial vitrification, yet different cryoprotective agents (CPAs) exhibit markedly distinct effects on the glass-transition temperatures of aqueous solutions and their microscopic dynamical origins remain poorly understood. Here, we systematically investigate how two widely used CPAs, dimethyl sulfoxide (DMSO) and formamide (FA), regulate water vitrification, revealing that FA retards water dynamics at ambient temperature but exhibits faster dynamics relative to pure water upon cooling, in contrast to the monotonic slowing induced by DMSO. To rationalize this behavior, we quantitatively decompose both water reorientation times and diffusion coefficients into a jump contribution, driven by hydrogen-bond (HB) exchange, and a frame contribution, associated with molecular motions between successive HB exchanges. We demonstrate that the contrasting dynamic and vitrification behaviors of DMSO and FA solutions are governed by water-CPA HB exchange times. Furthermore, we propose two key indicators related to HB exchange time and HB number for an intuitive comparison of the glass-forming ability of the CPA solutions. These results elucidate the microscopic dynamic mechanisms underlying CPA-regulated vitrification and provide a quantitative framework for the rational design of highly efficient CPAs.