Speciation of Copper–Peptide Complexes in Water Solution Using DFTB and DFT Approaches: Case of the [Cu(HGGG)(Py)] Complex

The DFTB and DFT methods are applied to the study of different forms of the [Cu(HGGG)(Py)] complex in water, with the aim of identifying the most stable isomer. The DFTB calculations were possible thanks to a careful parametrization of the atom–atom repulsive energy terms for Cu–H, Cu–C, Cu–N, and Cu–O. The speciation process is carried out by computing different DFTB-steered molecular dynamics (SMD) trajectories, each of which ends in a well-defined different form. The last frame of each trajectory is subjected to geometry optimization at both DFTB and DFT levels, leading to a different isomer. From the corresponding energy values, a rank of relative stability of the isomers can be established. The computational protocol developed here is of general applicability to other metal–peptide systems and represents a new powerful tool for the study of speciation of metal-containing systems in water solution, particularly useful when the full characterization of the compound cannot be carried out on the basis of experimental results only