Hydrogen Network in a Tetrapeptide Crystal Characterized by X-Ray Diffraction and Raman Spectroscopy

In recent years, much attention has been paid to research aimed at elucidating the self-assembly mechanism of dipeptides, the smallest constituent unit of living organisms [1]. Attempts have been made to develop enzyme-inspired peptide-based supramolecular catalysts and to apply them to green piezoelectric materials that meet the requirements of biocompatible ultra-sensitivity, flexibility, and durability. In understanding their functionality, hydrogen bonds play should be investigated due to their important role in stabilizing the steric structure of proteins and in expressing their functions. The strength of hydrogen bonds has been investigated by single-crystal structural analysis and spectroscopic techniques. Nakamoto et al. found a linear relationship between the stretching vibrational modes of hydrogen bonds and the interatomic distance[2]. Elena et al. have combined angle-resolved Raman measurements and single-crystal structure analysis to investigate the thermal behavior of amino acid derivative crystals[3]. However, these studies were limited to relatively small molecular compounds such as amino acids. In this study, the hydrogen bonding network in peptide crystals was investigated using the tetrapeptide FEFE as a model system. Single-crystal X-ray structure analysis revealed that the crystal structure of FEFE has branched hydrogen bonds. Raman spectroscopy showed that the vibrational frequencies of the amide bonds correlate linearly with their interatomic distances. On the other hand, the lattice expansion-dependent vibrational frequency shift is significantly smaller than in previous studies. Our fragment molecular orbital (FMO) calculations revealed that branched hydrogen bonds affect the strength of hydrogen bonds differently from the Nakamoto diagram.<br/>Branched hydrogen bonds in proteins have been studied using both experimental approaches and computational analysis[4][5]. Our findings differ from previous works investigating amino acids or other small organic molecules and made a connection with natural proteins as a model system of peptides. We believe that this study opens a way for discussing the effects of branched-type hydrogen bonds in various peptide crystals.<br/>[reference]<br/>[1] C. Yuan, W. Ji, R. Xing, J. Li, E. Gazit, X. Yan, Nat. Rev. Chem. 2019, 3, 567–588.<br/>[2] K. Nakamoto, M. Margoshes, R. E. Rundle, J. Am. Chem. Soc. 1955, 77, 6480–6486.<br/>[3] B. A. Zakharov, B. A. Kolesov, E. V. Boldyreva, Phys. Chem. Chem. Phys. 2011, 13, 13106–13116.<br/>[4] E. S. Brielle, I. T. Arkin, J. Am. Chem. Soc. 2020, 142, 14150–14157.<br/>[5] E. S. Feldblum, I. T. Arkin, Proc. Natl. Acad. Sci. U. S. A. 2014, 111, 4085–4090.