Oxoanion Binding by Guanidiniocarbonylpyrrole Cations in Water: A Combined DFT and MD Investigation

Structures and properties of non-bonding interactions involving guanidinium functionalized hosts and carboxylate substrates were investigated by the combination of ab initio and molecular dynamic approaches. The systems under study are meant on one side to be a model of the arginine – anion bond, so often observed in proteins and nucleic acids, and on the other the occasion to investigate in detail the influence of molecular structure on the formation of supramolecular complexes. DFT calculations including extended basis sets and implicit water treatment allowed to determine minimum energy structures and binding enthalpies comparing well with experimental data. Intermolecular forces were found to be mostly due to electrostatic interactions by three hydrogen bonds, one of which bifurcate, and are sufficiently strong to induce a conformational change in the ligand consisting in the rotation of about 180° around the guanidiniocarbonyl-pyrrole axis. Free binding energies of the complexes were evaluated through MD simulations performed by explicit water molecules using the MM-PBSA and LIE approaches. LIE energies were in quantitative agreement with experimental data. A detailed analysis of the MD simulations revealed that the complexes can not be described in terms of a single binding structure, but that they are characterized by a significant internal mobility responsible of several low energy metastable structures.