Molecular Engineering of Piezoelectricity in L/L and L/D Amino Acid-Containing Dipeptide Assemblies

Biocompatible and flexible peptide assemblies have emerged as a promising class of piezoelectric materials for biomechanical energy harvesting, offering a viable pathway toward the self-powered operation of wearable and implantable electronic devices. However, despite substantial progress primarily driven by extensive investigations of homochiral l-diphenylalanine and its derivatives, the vast structural diversity of peptides, particularly that arising from heterochiral sequences, remains largely unexplored. Herein, we synthesized a series of L/D-containing dipeptides Boc-l-Ile-d-Phe-OMe (2) and Boc-l-Ile-d-Phg-OMe (4), along with their all-L counterparts Boc-l-Ile-l-Phe-OMe (1) and Boc-l-Ile-l-Phg-OMe (3). These peptides were successfully assembled into continuous, unidirectional, and densely packed supramolecular architectures through a dip-coating technique. Piezoresponse force microscopy results revealed effective d₃₃ coefficients of 2.15, 3.26, 4.63, and 6.31 pm V^-1 for peptides 1, 2, 3, and 4, respectively, exhibiting a clear ascending trend (1 < 2 < 3 < 4) that is consistent with the trends predicted by density functional theory calculations. Piezoelectric generators fabricated from the L/D-containing peptide 4 exhibited the highest open-circuit voltage of 3.30 V under an applied force of 35 N, while devices based on peptide 3 generated a short-circuit current of 80 nA under 43 N. Notably, these values outperform previously reported peptide-based piezoelectric generators, underscoring the considerable potential of these materials for efficient biomechanical energy conversion. These findings clearly demonstrate the coupled influence of a side-chain structure and residue chirality on crystal packing behavior and the resulting electromechanical properties, thereby broadening the design space for peptide-based piezoelectric materials and enabling performance optimization beyond conventional homochiral systems.