Supramolecular Peptide Crystals with Hydrophilic and Hydrophobic Pores for Chemo-Mechanical and Mechano-Chemical Actuation

Water-responsive (WR) materials generate mechanical energy by drastically changing their dimensions with respect to changes in relative humidity.¹Peptides are versatile building blocks for supramolecular materials with tunable properties and functionalities. We recently started to explore supramolecular peptide crystals with aqueous pores as candidates for systematic understanding of water-bonding triggered actuation, and recently demonstrated the first examples.²<br/>Based on these previous results, we hypothesized that, peptides self-assembling into hydrated crystals with flexible hydrophobic and hydrophilic pores can be developed as multifunctional chemo-mechanical actuators. We explore two main features: (i) development of addressable crystals that can access multiple phases with different porosity and mechanical properties through controlled environments; (ii) addressable porous crystals that control chemical reactions.<br/>First, we demonstrate that WR crystals of peptides with aliphatic and aromatic side-chains can be utilized to develop crystals with tunable mechanical properties. A number of di- and tri-peptides with aromatic and aliphatic side chains were studied, giving rise to crystals with water pores that are interspersed with hydrophobic (aromatic or aliphatic) pores. We will provide our progress in establishing systematic understanding of how peptide sequence dictates crystal packing and porosity.<br/>Second, we will discuss one example, dipeptide Leu-Ile, that shows remarkable multifunctional behavior. This peptide crystallizes from water at room temperature to form a 2.5 hydrate and under heating as 0.75 hydrate. Both the forms have hydrophilic and hydrophobic channels and are interconvertible, resulting in switchable porosity. Remarkably, we found that changes in heating and hydration allows us to access three additional polymorphs, with different properties and porosities. All five forms are interconverted reversibly by controlling relative humidity or temperature accordingly. The changes in the H-bonding pattern of water channel in each structure influenced the porosity, mechanical and solid-state fluorescence properties. Thus, a single crystal of the dipeptide can be tuned reversibly for different mechanical strengths with the aid of relative humidity and temperature.<br/>Due to the controlled mechanical actuation in response to water bonding, we reasoned that peptide crystals may be promising to control hydrolysis or condensation reactions. In order to study this aspect, WR crystals of the tripeptide His-Tyr-Phe, was investigated. These crystals have nanometer sized pores that allow for easy diffusion of various esters of <i>p</i>-nitrophenol. We observed that by applying changes in the relative humidity on these guest-included crystals, the crystals can be actuated (reversible pore closure) and esters can be hydrolyzed. LCMS measurements showed the presence of transesterification of ester-substrates with the tyrosyl -OH group of the peptide molecule, thus leaving the free nitrophenol. The mass corresponding to trans-esterified intermediate and <i>p</i>-nitrophenol were also observed in TOF-SIMS technique recorded in the solid-state. Thus, we show proof-of-concept of mechano-chemical actuation and reactivity of peptide crystals.<br/>In summary, we demonstrate that short peptide crystals are highly versatile materials with tunable porosity and responsiveness to humidity and temperature. These materials can be designed for multifunctional chemo-mechanical actuation by choosing suitable sequence of amino acid components. These structures are based on short peptides and are therefore scalable and hold much promise as sustainable and biodegradable materials.<br/>1. Y. Park, X. Chen, <i>J. Mater. Chem. A</i>, <b>2020</b>, <i>8</i>, 15227-15244.<br/>2. R. Piotrowska, T. Hesketh, H. Wang, A. R. G. Martin, D. Bowering, C. Zhang, C. T. Hu, S. A. McPhee, T. Wang, Y. Park, P. Singla, T. McGlone, A. Florence, T. Tuttle, R. V. Ulijn, X. Chen, <i>Nat. Mater. </i><b>2021</b>, <i>20</i>, 403-409.