Hydrogen bonding interactions in cysteine–urea complexes: Theoretical studies of structures, properties and topologies

The hydrogen bonding interactions between cysteine and urea were studied with density functional theory (DFT) regarding their geometries, energies, vibrational frequencies, and topological features of the electron density. The quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analyses were employed to elucidate the interaction characteristics in the complexes. Multiple hydrogen bonds (H-bonds) are formed in one complex since both cysteine and urea have multiple sites as H-bond donor or acceptor. Most of intermolecular H-bonds involve O atom of cysteine/urea moiety as proton acceptors. The H-bond involving O atom of urea moiety as proton acceptor and hydroxyl of cysteine moiety as proton donor is the strongest one, which is attributed to a partial covalent character. The H-bonds involving the CH group of cysteine moiety as proton donor are very weak and show small blue shifts, while other H-bonds are red-shifting ones. Both hydrogen bonding interaction and structural deformation are responsible for the stability of Cys–Urea complexes, and the complexes involving either the strongest H-bond or the smallest deformation are not the stable ones. Analysis of various physically meaningful contributions arising from the energy decomposition procedures shows that the orbital interaction of H-bond is predominant during the formation of complex. The cooperative effects happened in complexes have also been discussed. Relationships between the topological properties (electron density ρ_b and its Laplacian ∇²ρ_b) at the bond critical point (BCP) of H-bond and structural parameter (δR) as well as the second-perturbation energies E(2) have also been discussed.