Glass materials have long been integral to technological and cultural advancements due to their versatile properties. However, traditional glass materials often rely on strong ionic and covalent bonds, which pose challenges related to toxicity, resource depletion, and environmental persistence. In response to these challenges, researchers have been striving to develop next-generation glass materials that prioritize biodegradability, biorecyclability, and sustainability.

In this context, we pioneered the development of biodegradable and biorecyclable glasses based on amino acid and peptide components^1,2. The establishment of biomolecular non-covalent glass offers a sustainable alternative, promising both environmental and functional benefits³. However, creating stable non-covalent glass that can perform robustly under challenging physiological conditions while minimizing rejection remains a significant challenge. Cyclic peptides (CPs), characterized by a cyclic backbone connecting the amino and carboxyl ends, exhibit diverse biological activities, enhanced stability and resistance to enzymatic degradation compared to their linear counterparts, making CPs a promising platform for developing non-covalent glass for biomedical or other high-tech applications. However, their strong tendency to crystallize has limited their potential in glass technology^4,5.

To address this challenge, our research team has developed a novel methodology for achieving stable non-covalent glass based on CPs⁶. This innovative approach, termed high-entropy strategy, involves incorporating a diverse range of CPs components to create a high-entropy environment that effectively inhibited crystallization. The CPs were subjected to a melting-quenching process, where they were heated above their melting points and then rapidly cooled to preserve the disordered conformations in a supercooled liquid state, ultimately leading to the formation of glass (Figure 1). Notably, the main principles underlying this strategy are also general applicable to the preparation of high-entropy non-covalent glass consisting of other small organic molecules.

The resulting high-entropy non-covalent cyclic peptide (HECP) glass exhibits enhanced crystallization-resistance, improved mechanical properties, and greater enzyme tolerance compared to individual CPs glasses, due to the synergistic effect of sluggish diffusion and hyperconnected network architectures within the HECP glass (Figure 2). Furthermore, these properties can be feasibly tailored through compositional adjustments, making HECP glass a promising candidate for a wide range of applications, including biomedical devices, optoelectronic devices, environmentally friendly packaging materials, drug delivery systems and other medical applications where controlled release is essential.

The concept of HECP glass represents a milestone in the quest to develop non-covalent glasses derived from naturally prevalent components, surpassing their crystalline counterparts and paving the way for next-generation glassy biomaterials. Beyond pioneering a new class of functional glass, this study elucidates the fundamental molecular traits that characterize high-entropy non-covalent glasses, representing a landmark discovery in the landscape of amorphous material science. Moreover, the concept of HECP glass could be extended to incorporate other functional moieties, such as dyes and nanoparticles, offering a new paradigm for the design and development of multifunctional, sustainable, non-covalent glasses.

Looking ahead, further research is needed to explore the full potential of HECP glass in various applications. Key areas of interest include the development of HECP glasses with even higher thermal stability, the incorporation of additional functional groups to enhance their optoelectronic properties, and the exploration of alternative synthesis methods that avoid the use of organic solvents or high temperatures. Additionally, the scalability of HECP glass production and its integration into existing manufacturing processes will be critical to its commercial success.

More details on this study can be found in our recent article "high-entropy non-covalent cyclic peptide glass" published in Nature Nanotechnology (https://doi.org/10.1038/s41565-024-01766-3).

References:

1. Xing, R., Yuan, C., Fan, W., Ren, X. & Yan, X. Biomolecular glass with amino acid and peptide nanoarchitectonics. Sci. Adv. 9, eadd8105, (2023).
2. Cao, S., Fan, W., Chang, R., Yuan, C. & Yan, X. Metal Ion-Coordinated Biomolecular Noncovalent Glass with Ceramic-like Mechanics. CCS Chem., https://doi.org/10.31635/ccschem.31024.202303832, (2024).
3. Coleman, J. 3D-printable glass is made from proteins and biodegrades. Nature, https://doi.org/10.1038/d41586-023-00826-3, (2023)
4. Yuan, C. et al. Hierarchically oriented organization in supramolecular peptide crystals. Nat. Rev. Chem. 3, 567-588, (2019).
5. Chang, R., Yuan, C., Zhou, P., Xing, R. & Yan, X. Peptide Self-assembly: From Ordered to Disordered. Acc. Chem. Res. 57, 289-301, (2024).
6. Yuan, C. et al. High-entropy non-covalent cyclic peptide glass. Nat. Nanotechnol., https://doi.org/10.1038/s41565-41024-01766-3, (2024).