A combined experimental and modelling investigations on mixed bioligand complexes of divalent cobalt and copper in β‐cyclodextrin

Abstract

The biologically active divalent metal complexes [Co(II)(GluArg)(H2O)2] (1) and [Cu(II)(GluArg)] (2) (where Co = cobalt and Cu = copper) of mixed glutamic (Glu) and l‐arginine (Arg) amino acids form a stable 1:1 inclusion complex with β‐cyclodextrin (β‐CD) in water. The preferred orientation of guest molecules into the host is simulated by quantum chemical computations. Geometry‐optimized results using ONIOM technique identified the structure and show that the glutamic acid chelate moiety of both metal ions complexes is encapsulated within the β‐CD cavity while the l‐arginine chelate is partially located outside the cavity. The calculated inclusion binding energy (ΔEB, kJ mol−1) and other thermodynamic parameters reveal the noticeable thermal stability of 2‐(β‐CD) over the 1‐(β‐CD) capsulate. A reverse trend is experimentally found from the determined association constant values (K, m−1). The chemical reactivity and reactive site selectivity of these complexes were elucidated via conceptual density functional theory and an electrostatic potential surface map. Global electronic molecular descriptors [such as chemical potential (μ), hardness (η) and electrophilicity (ω)] validated the experimental findings. The reactivity of the encapsulated complexes is altered vis‐à‐vis the free complexes. The obtained results and contradictions are discussed and rationalized.