Results in Chemistry (Dec 2023)
Two adamantan-1-amine-based scaffolds: Synthesis, crystallographic synthons, TD/DFT calculations, in-depth molecular docking/ADME/T simulations, and shedding light on antibacterial/fungal activities
Abstract
This work synthesized and structurally characterized the two adamantan-1-amine-based compounds, C10H18N2O3 (1) and C21H23NO (2), reacting with adamantan-1-amine, copper nitrate and 2-hydroxy-1-napthaldehyde in methanol. 1 has a nitrate blue salt-like structure, while 2 has a yellow azomethine-bonded Schiff base. X-ray crystal structure divulges 1–2 crystallized orthorhombic (P212121) and monoclinic space groups (P21/c). In 1, the three nitrate O’s form H bonds with three amine H from three different adamantylamine (N-H∙∙∙O bonds), 2 adopts a keto-imine tautomeric form, shifting the -H from hydroxyl -O to imine -N. The crystal packing stability in 1 result from the coulombic energy between a cation (protonated amine) and an anion (nitrate), whereas in 2, dispersive energy dominates the crystal packing. Hirshfeld surfaces (HS) and 2D fingerprint plots visualize supramolecular contacts. DFT simulated IR/NMR spectrum and UV–vis in methanol were compared with experimental using TDDFT calculations. The AIM, NCI and HOMO-LUMO profiles substantiate the H-bonds classification. Espinosa's equation predicts that the H-bond strength for intra-molecular (2) and intermolecular (1) are −40.69 and −17.07 kJ/mol. The Fukui function, ESP, and NLO explore chemical reactivity locations and polarization characteristics. ADME/T prediction evaluates the drug-like properties. Molecular docking predicted antimicrobial potency against bacteria and fungus, confirmed further by experiments.
