Noncovalent Cluster Packing Enables Ultrastable Glasses for Preservation and Delivery of Labile Biomolecules

Abstract

ABSTRACT The properties of molecular glasses are governed by a thermodynamic‐kinetic coupling described by the Adam–Gibbs theory. This relationship enforces a persistent trade‐off: glasses with low glass transition temperatures, essential for gentle processing, are inherently unstable and prone to rapid crystallization. Here, we report a noncovalent glass system that, defies this paradigm, achieving an exceptional crystallization barrier exceeding 653.2 kJ mol −1 , while maintaining a moderate glass transition temperature below 332.3 K. This anomalous decoupling originates from a “noncovalent cluster packing” architecture where internally rigid, hydrogen‐bonded nanoclusters are loosely interconnected by weak interactions. This distinct topology effectively isolates local structural rigidity from global relaxation, creating a landscape that, suppresses nucleation pathways. We demonstrate the practical utility of this principle through the robust room‐temperature preservation and delivery of labile biomolecules. By challenging conventional theoretical constraints, this work establishes a general design strategy for creating ultrastable yet functionally versatile amorphous materials.