Molecular Encapsulation of Histamine H₂-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational
Hang Yin1, Runmiao Wang2, Jianbo Wan3
1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. hyin531@outlook.com.
Abstract:
The histamine H₂-receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit[7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10³ M(-1), 1.30 (±0.27) × 10⁴ M(-1) and 1.05 (±0.33) × 10⁵ M(-1), respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by ¹H-NMR, UV-visible spectroscopic titrations (including Job plots), electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC), as well as theoretically by molecular dynamics (MD) computation. This study may provide important insights on the supramolecular formulation of H₂-receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes.
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