Molecular Encapsulation of Histamine H2-Receptor Antagonists by Cucurbit[7]Uril: An Experimental and Computational Study

Abstract

Abstract:The histamine H 2 -receptor antagonists cimetidine, famotidine and nizatidine are individually encapsulated by macrocyclic cucurbit [7]uril (CB[7]), with binding affinities of 6.57 (±0.19) × 10 3 M −1 , 1.30 (±0.27) × 10 4 M −1 and 1.05 (±0.33) × 10 5 M −1 , respectively. These 1:1 host-guest inclusion complexes have been experimentally examined by 1 H-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 H 2 -receptor antagonist drugs for potentially enhanced stability and controlled release based on different binding strengths of these host-guest complexes.

Evaluating the Performance of Water Models with Host–Guest Force Fields in Binding Enthalpy Calculations for Cucurbit[7]uril–Guest Systems

“…We used 25 host–guest pairs obtained from various publications to calculate the binding enthalpy. − We selected isothermal titration calorimetry (ITC) experiments without salts or buffers since they may yield significant errors relative to experimental data when used to compute host–guest binding enthalpies . Structures are represented in Figure and are listed in Table .…”

Assessment of the Biocompatibility of Cucurbiturils in Blood Cells

“…These data assert and allow using cucurbiturils as a remarkable drug delivery system. Special cases of the encapsulation by cucurbiturils of serotonin [13] and histamine H2 antagonists such as cimetidine, famotidine and nizatidine [14] in the 1:1 inclusion complex allow to expand the possibility of cucurbituril's application for various nosologies. Recently, it was reported that complexation CB [7] with chloroquine permits reducing its nonspecific toxicity over several rounds and improves its antiviral activity against coronavirus, confirming the pronounced synergistic effect of cucurbiturils.…”

Toward Understanding CB[7]-Based Supramolecular Diels-Alder Catalysis

“…Computational studies can account for many aspects of the catalysis (Harvey et al, 2019 ) enhancing our understanding of the origins of these effects. Cucurbiturils are subject to many computational works, often in conjecture with experiments, contributing to interpretation of spectroscopy (Chio et al, 2019 ), electronic properties (Sin et al, 2020 ) and in particular binding free energies and structures (Yin et al, 2016 ; Senthilnathan et al, 2018 ; Olesińska et al, 2019 ; Wu et al, 2019 ). As hosts, CBs were featured in many blind prediction challenges (Muddana et al, 2012 , 2014 ; Lee et al, 2017 ; Rizzi et al, 2018 ).…”