Mechanistic Insights into the Antibacterial Activity of Self-Assembled Nickel(II)–Triethanolamine–Cinnamate Complexes

High Resolution Image Download MS PowerPoint Slide Herein, we report the room-temperature isolation of two new structurally similar mononuclear ionic nickel(II) complexes, [Ni(H 3 tea ) 2 ](2,3-DMCN) 2 ( 1 ) and [Ni(H 3 tea ) 2 ](2,4-DMCN) 2 (H 2 O) ( 2 ) (where H 3 tea = 2,2′,2″-nitrilotri(ethan-1-ol), 2,3-DMCN = 2,3-dimethoxycinnamate, and 2,4-DMCN = 2,4-dimethoxycinnamate). Both the crystalline complexes were structurally characterized by spectroscopic (FT-IR, UV–vis, and XPS) and single-crystal X-ray diffraction (SCXRD) methods. SCXRD unambiguously delineated the Ni(II) center octahedrally coordinated by strong chelating ligand H 3 tea, yielding complex cations with NiN 2 O 4 chromophore, which are counterbalanced by cinnamate anions in both cases. Crystal packing supported by Hirshfeld surface (HS) analysis revealed the role of various hydrogen-bonding interactions in crystal lattice stabilization. The outcomes of theoretical studies using DFT demonstrated notable concordance with the experimentally observed data. In vitro antibacterial studies indicated that both complexes exhibited remarkable selectivity for Gram-negative strains, specifically P. aeruginosa and K. pneumoniae, corroborated with in silico molecular docking results. Mechanistically, the [Ni(H 3 tea ) 2 ] 2+ core acts as an electronic shield, which, alongside lipophilic dimethoxycinnamate anions, promotes membrane translocation and subsequent structural disruption. This physical intrusion is complemented by a redox-active mechanism, viz., a high-lying HOMO facilitates interference with the bacterial respiratory chain, triggering intracellular reactive oxygen species generation and lethal oxidative damage to DNA and proteins. Detailed structural analysis of this self-assembled molecular framework─utilizing both experimental and theoretical tools─provides deeper mechanistic understanding of the antibacterial effect of Ni(II)-mixed-ligand complexes, advancing future metallodrug discovery.