13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host-guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon signals in 13C NMR spectra. This signal split can be correlated to the distance of the guest atoms from the wall of the host cavity and to the spatial separation of binding sites preferred by pairs of prochiral carbon atoms. These measurements complement traditional solid-state analyses, which rely on the crystallization of host-guest complexes and their crystallographic analysis.

• Klíčová slova
• 13C NMR, anisotropy, cyclodextrin, host–guest complexes,
• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• 2,6,9-trisubstituted purine, adamantane, cyclin-dependent kinase, cytotoxicity, molecular docking, β-cyclodextrin,
• MeSH
• adamantan chemie   MeSH
• beta-cyklodextriny chemie   MeSH
• buňky K562 MeSH
• cyklin-dependentní kinasa 2 antagonisté a inhibitory   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• protinádorové látky chemie   farmakologie   MeSH
• puriny chemie   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adamantan MeSH
• beta-cyklodextriny MeSH
• CDK2 protein, human MeSH Prohlížeč
• cyklin-dependentní kinasa 2 MeSH
• inhibitory proteinkinas MeSH
• protinádorové látky MeSH
• puriny MeSH

Cyclodextrins are well known supramolecular hosts used in a wide range of applications. Monosubstitution of native cyclodextrins in the position C-6 of a glucose unit represents the simplest method how to achieve covalent binding of a well-defined host unit into the more complicated systems. These derivatives are relatively easy to prepare; that is why the number of publications describing their preparations exceeds 1400, and the reported synthetic methods are often very similar. Nevertheless, it might be very demanding to decide which of the published methods is the best one for the intended purpose. In the review, we aim to present only the most useful and well-described methods for preparing different types of mono-6-substituted derivatives. We also discuss the common problems encountered during their syntheses and suggest their optimal solutions.

• Klíčová slova
• applications, cyclodextrins, mono-6-substitution, synthesis,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The supramolecular recognition of closo,closo-[B21 H18 ]- by cyclodextrins (CDs) has been studied in aqueous solution by isothermal titration calorimetry and nuclear magnetic resonance spectroscopy. These solution studies follow up on previous mass-spectrometric measurements and computations, which indicated the formation and stability of CD ⋅ B21 H18- complexes in the gas phase. The thermodynamic signature of solution-phase binding is exceptional, the association constant for the γ-CD complex with B21 H18- reaches 1.8×106 M-1 , which is on the same order of magnitude as the so far highest observed value for the complex between γ-CD and a metallacarborane. The nature of the intermolecular interaction is also examined by quantum-mechanical computational protocols. These suggest that the desolvation penalty, which is particularly low for the B21 H18- anion, is the decisive factor for its high binding strength. The results further suggest that the elliptical macropolyhedral boron hydride is another example of a CD binder, whose extraordinary binding affinity is driven by the chaotropic effect, which describes the intrinsic affinity of large polarizable and weakly solvated chaotropic anions to hydrophobic cavities and surfaces in aqueous solution.

• Klíčová slova
• anion binding, boron clusters, desolvation, host-guest chemistry, intermolecular interactions,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A new hyaluronan derivative modified with β-cyclodextrin units (CD-HA) was prepared via the click reaction between propargylated hyaluronan and monoazido-cyclodextrin (CD) to achieve a degree of substitution of 4%. The modified hyaluronan was characterized by 1H-nuclear magnetic resonance spectroscopy (NMR) and size exclusion chromatography. Subsequent 1H-NMR and isothermal calorimetric titration experiments revealed that the CD units on CD-HA can form virtual 1:1, 1:2, and 1:3 complexes with one-, two-, and three-site adamantane-based guests, respectively. These results imply that the CD-HA chains used the multitopic guests to form a supramolecular cross-linked network. The free CD-HA polymer was readily restored by the addition of a competing macrocycle, which entrapped the cross-linking guests. Thus, we demonstrated that the new CD-HA polymer is a promising component for the construction of chemical stimuli-responsive supramolecular architectures.

• Klíčová slova
• click reaction, cyclodextrin, host-guest systems, sodium hyaluronan, supramolecular network,
• MeSH
• beta-cyklodextriny chemická syntéza   chemie   MeSH
• click chemie MeSH
• kalorimetrie MeSH
• kyselina hyaluronová chemická syntéza   chemie   MeSH
• magnetická rezonanční spektroskopie MeSH
• molekulární struktura * MeSH
• polymery chemická syntéza   chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• beta-cyklodextriny MeSH
• betadex MeSH Prohlížeč
• kyselina hyaluronová MeSH
• polymery MeSH

Monosubstituted derivatives of γ-cyclodextrin (γ-CD) are suitable building blocks for supramolecular polymers, and can also serve as precursors for the synthesis of other regioselectively monosubstituted γ-CD derivatives. We prepared a set of monosubstituted 2I-O-, 3I-O-, and 6I-O-(3-(naphthalen-2-yl)prop-2-en-1-yl) derivatives of γ-CD using two different methods. A key step of the first synthetic procedure is a cross-metathesis between previously described regioisomers of mono-O-allyl derivatives of γ-CD and 2-vinylnaphthalene which gives yields of about 16-25% (2-5% starting from γ-CD). To increase the overall yields, we have developed another method, based on a direct alkylation of γ-CD with 3-(naphthalen-2-yl)allyl chloride as the alkylating reagent. Highly regioselective reaction conditions, which differ for each regioisomer in a used base, gave the monosubstituted isomers in yields between 12-19%. Supramolecular properties of these derivatives were studied by DLS, ITC, NMR, and Cryo-TEM.

• Klíčová slova
• naphthylallyl derivatives, regioselective alkylation, supramolecular properties, synthesis, γ-cyclodextrin,
• Publikační typ
• časopisecké články MeSH

A general high-yielding method for the preparation of monosubstituted β-cyclodextrin derivatives which have attached a thiol group in position 6 is described. The thiol group is attached through linkers of different lengths and repeating units (ethylene glycol or methylene). The target compounds were characterized by IR, MS and NMR spectra. A simple method for their complete conversion to the corresponding disulfides as well as a method for the reduction of the disulfides back to the thiols is presented. Both, thiols and disulfides are derivatives usable for well-defined covalent attachment of cyclodextrin to gold or polydopamine-coated solid surfaces.

• Klíčová slova
• cyclodextrins, disulfides, monosubstituted derivatives, thiols,
• Publikační typ
• časopisecké články MeSH

We present the synthesis of a series of six new glycoluril derived molecular clips and acyclic CB[n]-type molecular containers (1–3) that all feature SO3(−) solubilizing groups but differ in the number of glycoluril rings between the two terminal dialkoxyaromatic sidewalls. We report the X-ray crystal structure of 3b which shows that its dialkoxynaphthalene sidewalls actively define a hydrophobic cavity with high potential to engage in π–π interactions with insoluble aromatic guests. Compounds 1–3 possess very good solubility characteristics (≥38 mM) and undergo only very weak self-association (Ks < 92 M(−1)) in water. The weak self-association is attributed to unfavorable SO3(−)···SO3(−) electrostatic interactions in the putative dimers 12–42. Accordingly, we created phase solubility diagrams to study their ability to act as solubilizing agents for four water insoluble drugs (PBS-1086, camptothecin, β-estradiol, and ziprasidone). We find that the containers 3a and 3b which feature three glycoluril rings between the terminal dialkoxy-o-xylylene and dialkoxynaphthalene sidewalls are less efficient solubilizing agents than 4a and 4b because of their smaller hydrophobic cavities. Containers 1 and 2 behave as molecular clip type receptors and therefore possess the ability to bind to and thereby solubilize aromatic drugs like camptothecin, ziprasidone, and PBS-1086.

• MeSH
• alkyny chemie   MeSH
• hydrofobní a hydrofilní interakce MeSH
• imidazoly chemie   MeSH
• krystalografie rentgenová MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• polymery chemie   MeSH
• rozpustnost MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• alkyny MeSH
• glycoluril MeSH Prohlížeč
• imidazoly MeSH
• polymery MeSH