Supramolecular architecture and noncovalent interactions of a macrocyclic Zn(II) complex: implications for protein binding

The development of macrocyclic metal complexes capable of selective anion sensing and biologically relevant interactions is of significant interest in supramolecular and bioinorganic chemistry. Herein, we report a structural insight into a dual-anion Zn(II)-based macrocyclic Schiff base (48-membered ring) sensor. Structural elucidation reveals an unusual tetranuclear cationic assembly, [Zn₄(LH₃) (NO₃)₅]²⁺, stabilised by a [Zn(NO₃)₄]^2- counteranion. Owing to its large cavity size and macrocyclic framework, a detailed analysis of molecular packing and supramolecular organisation was carried out. Hirshfeld surface analysis highlights the contribution of secondary bonding and intrinsic noncovalent interactions in stabilising the crystal architecture. The biological relevance of the complex was further explored through molecular docking studies with bovine serum albumin (BSA), revealing strong binding affinity, with a maximum docking score of −74 kcal mol⁻¹ and a docking interaction energy of −13 kcal mol⁻¹. The binding is governed by a combination of hydrogen bonding, salt bridge formation, van der Waals forces and π-based interactions. These computational findings are supported by fluorescence quenching studies, where a comparatively low Stern–Volmer constant indicates stable protein–complex association. Overall, the results demonstrate that the macrocyclic Zn(II) complex possesses favourable supramolecular and biological interaction features, suggesting its potential applicability in sensing applications and as a prospective active pharmaceutical ingredient.