Density functional study of Cu2+-phenylalanine complex under micro-solvation environment

• Mechanism of the micro-solvation processes (H2O, n = 1–4) for the Cu2+-Phe complexes is studied using combined DFT calculations as well as CPMD simulations.
• A minimum of two water molecules are required to assist the inter-conversion of the Phe moiety between its NT and ZW configurations in the Phe-Cu2+ complex.
• The maximum coordination of Cu2+ in the presence of the Phe ligand does not exceed four and any excess water molecules will migrate to the second solvation shell.
• The (N)H⋯O(3)⋯H2O–Cu2+ network plays a significant role in the stabilization of the micro-solvated Cu2+-Phe complexes.

We present an atomistic study carried out using density functional calculations including structural relaxations and Car–Parrinello Molecular Dynamics (CPMD) simulations, aiming to investigate the structures of phenylalanine-copper (II) ([Phe-Cu]2+) complexes and their micro-solvation processes. The structures of the [Phe-Cu]2+ complex with up to four water molecules are optimized using the B3LYP/6-311++G** model in gas phase to identify the lowest energy structures at each degree of solvation (n = 0–4). It is found that the phenylalanine appears to be in the neutral form in isolated and mono-hydrated complexes, but in the zwitterionic form in other hydrated complexes (with n ≥ 2). The most stable structures of the complexes suggest that the Cu2+–π interactions are not dominant in the [Phe-Cu]2+ complexes. The present CPMD simulations of the lowest energy micro-hydrated [Phe-Cu]2+ complexes also reveal that the maximum coordination of Cu2+ in the presence of the Phe ligand does not exceed four: the oxygen atoms from three water molecules and one carboxyl oxygen atom of Phe. Any excess water molecules will migrate to the second solvation shell. Moreover a unique structural motif, (N)H⋯O(3)⋯H2O–Cu2+ is present in the lowest energy complexes, which is recognized to be significant in stabilizing the structures of the complexes. Extensively rich information of the structures, energetics, hydrogen bonds and dynamics of the lowest energy complexes are discussed.

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