Adamantane-bearing benzylamines and benzylamides: novel building blocks for supramolecular systems with finely tuned binding properties towards β-cyclodextrin

Rouchal, Michal; Matelová, Alena; Carvalho, Fabiana Pires de; Bernat, Robert; Grbic, Dragan; Kuřitka, Ivo; Babinský, Martin; Marek, Radek; Čmelík, Richard; Vícha, Robert

doi:10.1080/10610278.2013.783916

Cited by 5 publications

(11 citation statements)

References 55 publications

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“…In the solid state, X-ray crystallography reveals that 1-adamantanol forms both type I and type II complexes with a methylated βCD. 13 In contrast, most of the abovementioned studies of complexes in solution report the formation of a single type of complexes, most of them type I and only a few type II complexes 16,17,23 . It is possible, however, that many of the investigated complexes in solution form both type I and type II complexes.…”

Section: Introductionmentioning

confidence: 93%

Charge Determines Guest Orientation: A Combined NMR and Molecular Dynamics Study of β-Cyclodextrins and Adamantane Derivatives

Schönbeck

2018

J. Phys. Chem. B

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The strong binding of the adamantyl moiety to the cavity of β-cyclodextrin makes it a common binding motif in supramolecular chemistry and a common model system. Despite the attention, there are still unresolved questions regarding the orientation of the adamantane derivatives in the inclusion complexes-do they protrude from the wide or narrow opening of the cyclodextrin hosts? A combined analysis of ROESY NMR and molecular dynamics simulations allows the conclusion that positively charged adamantane derivatives are oriented with the hydrophilic group protruding from the wider opening of the cyclodextrin, while negatively charged adamantane derivatives form two coexisting types of complexes where the hydrophilic group respectively protrudes from the wide and narrow opening. Interestingly, structural modifications of the cyclodextrin host only have a slight impact on the guest orientation.

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Section: Introductionmentioning

confidence: 93%

Charge Determines Guest Orientation: A Combined NMR and Molecular Dynamics Study of β-Cyclodextrins and Adamantane Derivatives

Schönbeck

2018

J. Phys. Chem. B

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“…Subsequently, the previously prepared adamantylated aromatic amines [ 41 , 42 ], or benzylamine, were introduced to position 6 of the purine 2a . The nucleophilic aromatic substitution of chlorine at C6 led to the formation of compounds 3a – k ( Scheme 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…All starting compounds, reagents and solvents were purchased from commercial sources in analytical quality and were used without further purification. Adamantylated aromatic amines were prepared following previously published procedures [ 41 , 42 , 53 ]. Melting points were measured on a Kofler block and were not corrected.…”

Section: Methodsmentioning

confidence: 99%

Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity

Rouchal

Rudolfová

Kryštof

et al. 2021

IJMS

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Cyclin-dependent kinases (CDKs) play an important role in the cell-division cycle. Synthetic inhibitors of CDKs are based on 2,6,9-trisubstituted purines and are developed as potential anticancer drugs; however, they have low solubility in water. In this study, we proved that the pharmaco-chemical properties of purine-based inhibitors can be improved by appropriate substitution with the adamantane moiety. We prepared ten new purine derivatives with adamantane skeletons that were linked at position 6 using phenylene spacers of variable geometry and polarity. We demonstrated that the adamantane skeleton does not compromise the biological activity, and some of the new purines displayed even higher inhibition activity towards CDK2/cyclin E than the parental compounds. These findings were supported by a docking study, which showed an adamantane scaffold inside the binding pocket participating in the complex stabilisation with non-polar interactions. In addition, we demonstrated that β-cyclodextrin (CD) increases the drug’s solubility in water, although this is at the cost of reducing the biochemical and cellular effect. Most likely, the drug concentration, which is necessary for target engagement, was decreased by competitive drug binding within the complex with β-CD.

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“…This indicated the formation of another complex in a slow‐exchange mode. Note that the signals of the second set are split into pairs likely due to the inherently chiral β‐CD . Two observations should be stressed.…”

Section: Host‐guest Studiesmentioning

confidence: 99%

“…Upon the titration of ( Z )‐ 8 with γ‐CD, a significant downfield shift of H(a) and H(g–j) signals was observed, as can be seen in Figure S18. Assuming 1 : 1 binding stoichiometry, the chemical shifts of H(g) and H(j) plotted against the concentration of γ‐CD were analysed using the Hanna−Ashbaugh equation, as reported previously, to determine the K value to be (6.8±0.2)×10 3 M −1 . The most interesting results were obtained using β‐CD as a host (Figure , Figure S17).…”

Section: Host‐guest Studiesmentioning

confidence: 99%

A Photochemical/Thermal Switch Based on 4,4′‐Bis(benzimidazolio)stilbene: Synthesis and Supramolecular Properties.

et al. 2020

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Stilbene derivatives are well‐recognised substructures of molecular switches based on photochemically and/or thermally induced (E)/(Z) isomerisation. We combined a stilbene motif with two benzimidazolium arms to prepare new sorts of supramolecular building blocks and examined their binding properties towards cucurbit[n]urils (n=7, 8) and cyclodextrins (β‐CD, γ‐CD) in water. Based on the 1H NMR data and molecular dynamics simulations, we found that two distinct complexes with different stoichiometry, i. e., guest@β‐CD and guest@β‐CD2, coexist in equilibrium in a water solution of the (Z)‐stilbene‐based guests. We also demonstrated that the bis(benzimidazolio)stilbene guests can be transformed from the (E) into the (Z) form via UV irradiation and back via thermal treatment in DMSO.

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Adamantane-bearing benzylamines and benzylamides: novel building blocks for supramolecular systems with finely tuned binding properties towards β-cyclodextrin

Cited by 5 publications

References 55 publications

Charge Determines Guest Orientation: A Combined NMR and Molecular Dynamics Study of β-Cyclodextrins and Adamantane Derivatives

Charge Determines Guest Orientation: A Combined NMR and Molecular Dynamics Study of β-Cyclodextrins and Adamantane Derivatives

Adamantane-Substituted Purines and Their β-Cyclodextrin Complexes: Synthesis and Biological Activity

A Photochemical/Thermal Switch Based on 4,4′‐Bis(benzimidazolio)stilbene: Synthesis and Supramolecular Properties.

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