Thermally driven isosymmetric phase transitions and structure-bioactivity relationships in a hybrid...

An isosymmetric hybrid material, 2-amino-5-ammoniopyridinium tetrachlorocuprate(II), has been synthesized and comprehensively investigated with respect to its structural, thermal, dielectric, biological, and theoretical properties. Single-crystal X-ray diffraction studies performed at four temperatures (293-393 K) reveal that the compound crystallizes in the orthorhombic space group Cmca and is composed of polymeric zig-zag [CuCl₄]^2- chains adopting a distorted square-pyramidal (4+1) coordination geometry, strongly influenced by Jahn-Teller effects and temperature-dependent chlorine disorder. Differential scanning calorimetry, thermogravimetric analysis, and dielectric measurements consistently evidence three reversible, weak first-order solid-solid phase transitions, associated with order-disorder phenomena within the inorganic sublattice. Infrared spectroscopy confirms the protonation state of the organic cation and the presence of extensive N-H⋯Cl hydrogen bonding, which, together with π⋯π stacking interactions, stabilizes a three-dimensional supramolecular framework. Biological investigations demonstrate that the copper(II) complex exhibits significantly enhanced antibacterial and anti-inflammatory activities compared to the free organic ligand, in agreement with chelation theory. Molecular docking studies reveal a multi-target biological profile, with preferential inhibition of iNOS and bacterial Cu-efflux ATPase (IS16), suggesting plausible mechanisms of action. Density functional theory calculations support the experimental findings by elucidating the optimized geometry, charge distribution, non-covalent interactions, and structure-property relationships. Overall, this study highlights the strong interplay between structural phase behavior, supramolecular organization, and bioactivity in copper-based hybrid materials, positioning this compound as a promising multifunctional system.