Substituent Effect in Histamine and Its Impact on Interactions with the G Protein-Coupled Human Receptor H₁ Modelled by Quantum-Chemical Methods.

ABSTRACT: Neutral and protonated histamine tautomers, mono-substituted with twelve functional groups, were studied theoretically as isolated molecules and complexes with the H₁ receptor. Geometry and energy of tautomers were optimized using the DFT method with the B3LYP functional and the aug-cc-pVTZ basis set. The approach was based on the charge of the substituent active region (cSAR) parameters and the Harmonic Oscillator Model of Aromaticity (HOMA) indices. The cSAR parameters characterized the electron density better than the conventional Hammett's constants σ. In general, the cSAR parameters correlate with other characteristics of the charge distribution, particularly those for substituents at the carbon atom in the ring adjacent to the side chain. Substituents at this atom a

SUBMITTER: Jezuita A 

PROVIDER: S-EPMC12472401 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature