Protonation and coordination ability of small peptides - theoretical and experimental approaches for elucidation

This review deals with modern theoretical and experimental approaches as well as structural elucidation of small peptides (SP), their protonated forms and metal complexes. Free peptide bond rotation in amino acids (AA) and peptides yielded various conformers, which may possess differing biological activities. Inter-and/or intramolecular stacking observed in aromatic SP is another phenomenon typical for both peptide salts and complexes. These phenomenological effects can be successfully studied, both theoretically and experimentally, using a combination of the theoretical approximations and physical methods, such as electronic absorption spectroscopy, vibrational spectroscopy (including IR and Raman), nuclear magnetic resonance, mass spectrometry, as well as single-crystal X-ray diffraction. The physical and chemical properties of these systems can be precisely calculated by ab initio and DFT methods, varying basis sets and the results obtained allow elucidation of their conformations as a function of the reaction conditions (pH, type of the solvent, temperature, metal to ligand molar ratio). Although the 3-D structures of many peptides have been determined over the past decades, peptide crystallization is still a major obstacle to crystallographic work and the presence of chiral center/s adds further difficulties. For this reason, a specific part of the review is focused on the study of the absolute structure of the peptides, their salts and metal complexes, discussing the conformational preferences of the peptides during these processes. The available crystallographic data for metal complexes are successfully used for the correlation between the structures and the spectroscopic properties.