Crystallographic and computational insights into charge-assisted N/C–H···Br− hydrogen bonding in 2-Amino-1-alkylpyridinium bromide salts

Two aminopyridinium salts, 2-amino-1-butylpyridin-1-ium bromide, (1), C9H15N2+. Br− and 2-amino-1-octylpyridin-1-ium bromide, (2), C13H23N2+. Br−, differing in alkyl chain length, were synthesized and structurally characterized by single-crystal X-ray diffraction. Both salts crystallize in the monoclinic system, adopting the Cc (1) and P21/c (2) space groups. The asymmetric unit of each salt contains one 2-amino-1-aklylpyridin-1-ium cation and one bromide anion. In both structures, the pyridine nitrogen atom (N1) is quaternized by an n-butyl (1) or n-octyl (2) chain, resulting in a positively charged cation balanced by a bromide anion. Crystal packing is stabilized by a network of N–H···Br− and C–H···Br− hydrogen bonds, leading to distinct supramolecular architectures. Intermolecular interaction energies for selected dimers were evaluated using CLP-PIXEL and DFT methods, showing good agreement. The nature and strength of charge-assisted hydrogen bonds were further elucidated through topological parameters from the QTAIM framework and IQA approach. Hirshfeld surface (HS) analysis reveals that H···H, H···Br, and H···C contacts dominate the intermolecular interactions. Molecular electrostatic potential (MESP) maps highlight interacting sites and emphasizes the role of electrostatics in crystal stabilization. Molecular docking studies indicate that the pyridinium cations bind favorably to cyclin-dependent kinase 1 (CDK1) and Plasmodium falciparum dihydrofolate reductase-thymidylate synthase (DHFR-TS), with the longer alkyl spacer promoting enhanced hydrophobic interactions and overall binding stability. The combined experimental and computational insights provide comprehensive insights into the structural, energetic, and potential biological properties of aminopyridinium salts, offering a basis for their future biological and materials applications.