Molecular Encapsulation of Histamine H₂-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study.
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.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. hyin531@outlook.com.
Hang
H
Yin
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. kamileowang@gmail.com.
Runmiao
R
Wang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. jbwan@umac.mo.
Jianbo
J
Wan
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. yzheng@umac.mo.
Ying
Y
Zheng
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. defangouyang@umac.mo.
Defang
D
Ouyang
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau 999078, China. rwang@umac.mo.
Ruibing
R
Wang
D001952:Bridged-Ring Compounds / Q000737:chemistry*; D002927:Cimetidine / Q000737:chemistry*; D015738:Famotidine / Q000737:chemistry*; D006635:Histamine H2 Antagonists / Q000737:chemistry*; D007093:Imidazoles / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D016567:Nizatidine / Q000737:chemistry*; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
D001952:Bridged-Ring Compounds; D002927:Cimetidine; D015738:Famotidine; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D016567:Nizatidine; C456276:cucurbit(7)uril; D047028:Macrocyclic Compounds; D000099246:Cucurbit(n)urils
H2-receptor antagonists; complexation; cucurbit[7]uril; host-guest interaction; molecular modelling