10 research outputs found

    Cucurbiturils as fluorophilic receptors

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    <div><p>We report the formation of strong inclusion complexes between the macrocyclic host cucurbit[7]uril (CB7) and more than 20 perfluorinated compounds (PFCs) in aqueous solution. The binding constants and structures of the complexes were determined through a combination of dye displacement titrations, <sup>19</sup>F as well as <sup>1</sup>H NMR spectroscopy, and quantum chemical calculations. The high affinities, for example 1.2 × 10<sup>7</sup> M<sup>− 1</sup> for perfluorohexane and 1.1 × 10<sup>8</sup> M<sup>− 1</sup> for perfluoro(methylcylohexane), are driven, among others, by the low polarisability of the cucurbituril cavity, which favours the binding of non-polarisable guests such as PFCs. The complexation-induced chemical shifts of the <sup>19</sup>F resonances are downfield in cases where a conformational flexibility allows the (partial) interconversion of <i>gauche</i> conformations (favoured in water) to <i>anti</i> conformations (favoured inside the cavity of CB7). Only for conformationally rigid substrates, for example SF<sub>6</sub> and (CF<sub>3</sub>)<sub>3</sub>COH, upfield shifts prevail. These are attributed to the low polarisability of the inner cavity, similar to the upfield shifts observed for <sup>19</sup>F resonances upon going from highly polarisable to less polarisable solvents. Cucurbituril homologues (CB5, CB6 and CB8) were also studied and, among those, evidence for the formation of inclusion complexes was observed for CB6 as host and CF<sub>4</sub>, SF<sub>6</sub> and CF<sub>3</sub>CH<sub>2</sub>OH as guests. Besides contributing to the fundamental understanding of fluorophilic interactions, the results have implications for PFC separation and for the efficient removal of PFCs from and the sensing of PFCs in aqueous solution.</p></div

    Molecular dynamics simulation study of the structural features and inclusion capacities of cucurbit[6]uril derivatives in aqueous solutions

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    <div><p>Molecular dynamics (MD) simulations were performed for cucurbit[6]uril (CB6) methyl and cyclohexyl derivatives in aqueous solutions. Furthermore, MD simulations have been conducted to study the inclusion complexes between each CB6 derivative with α,ω-pentane diammonium ion (NH<sub>3</sub><sup>+</sup>(CH<sub>2</sub>)<sub>5</sub>NH<sub>3</sub><sup>+</sup>) to estimate the binding free energies, the complex geometries and the intermolecular forces responsible for complex formation. Results show a complete inclusion of the guest molecule in the cavity of the host for all complexes. Results also indicate that the guest dynamics inside the cavity of the substituted host is similar to that for the unsubstituted host. This demonstrates that the molecular recognition of the host is not affected by the alkyl substitution at the equator. Also, there is an insignificant conformational change of the macrocyclic structure upon inclusion of the guest. Molecular mechanics/Poisson Boltzmann surface area method was used to estimate the binding free energy of each complex. Results indicate that host–guest electrostatic interactions make the largest contribution to the complex binding free energy. Moreover, van der Waals interactions add significantly to the complex stability. The guest molecules show more or less similar binding free energies with the substituted CB6 that exhibits slightly more negative values than unsubstituted CB6 which is proved also by umbrella sampling.</p></div

    Coulomb Repulsion in Short Polypeptides

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    Coulomb repulsion between like-charged side chains is presently viewed as a major force that impacts the biological activity of intrinsically disordered polypeptides (IDPs) by determining their spatial dimensions. We investigated short synthetic models of IDPs, purely composed of ionizable amino acid residues and therefore expected to display an extreme structural and dynamic response to pH variation. Two synergistic, custom-made, time-resolved fluorescence methods were applied in tandem to study the structure and dynamics of the acidic and basic hexapeptides Asp<sub>6</sub>, Glu<sub>6</sub>, Arg<sub>6</sub>, Lys<sub>6</sub>, and His<sub>6</sub> between pH 1 and 12. (i) End-to-end distances were obtained from the short-distance Förster resonance energy transfer (sdFRET) from N-terminal 5-fluoro-l-tryptophan (FTrp) to C-terminal Dbo. (ii) End-to-end collision rates were obtained for the same peptides from the collision-induced fluorescence quenching (CIFQ) of Dbo by FTrp. Unexpectedly, the very high increase of charge density at elevated pH had no dynamical or conformational consequence in the anionic chains, neither in the absence nor in the presence of salt, in conflict with the common view and in partial conflict with accompanying molecular dynamics simulations. In contrast, the cationic peptides responded to ionization but with surprising patterns that mirrored the rich individual characteristics of each side chain type. The contrasting results had to be interpreted, by considering salt screening experiments, N-terminal acetylation, and simulations, in terms of an interplay of local dielectric constant and peptide-length dependent side chain charge–charge repulsion, side chain functional group solvation, N-terminal and side chain charge–charge repulsion, and side chain–side chain as well as side chain–backbone interactions. The common picture that emerged is that Coulomb repulsion between water-solvated side chains is efficiently quenched in short peptides as long as side chains are not in direct contact with each other or the main chain

    Nanomolar Binding of Steroids to Cucurbit[<i>n</i>]urils: Selectivity and Applications

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    Cucurbit­[<i>n</i>]­urils (CB<i>n</i>, <i>n</i> = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations. Notably, the CB<i>n</i>•steroid complexes are stable in water and buffers, in artificial gastric acid, and even in blood serum. Numerous applications have been demonstrated, which range from the solubility enhancement of the steroids in the presence of the macrocycles (up to 100 times, for drug delivery) and the principal component analysis of the fluorescence responses of different CB<i>n</i>•reporter dye combinations (for differential sensing of steroids) to the real-time monitoring of chemical conversions of steroids as substrates (for enzyme assays)

    Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils

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    <p>The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (<i>α</i>-, <i>β</i>-, and <i>γ</i>-), <i>p</i>-sulfonatocalix[<i>n</i>]arenes (<i>n</i> = 4–6) as well as cucurbit[<i>n</i>]urils (<i>n</i> = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by <i>β</i>-cyclodextrin and <i>p</i>-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (Δ<i>H</i>° < 0), accompanied by slightly unfavourable entropy changes (Δ<i>S</i>° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.</p

    Halogen Bonding inside a Molecular Container

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    The synthetic macrocycle cucurbit[6]­uril forms host–guest inclusion complexes with molecular dibromine and diiodine. As evidenced by their crystal structures, the encapsulated dihalogens adapt a tilted axial geometry and are held in place by two different types of halogen-bonding interactions, one with a water molecule (bond distances 2.83 Å for O···Br and 3.10 Å for O···I) and the other one with the ureido carbonyl groups of the molecular container itself (bond distances 3.33 Å for O···Br and 3.49 Å for O···I). While the former is of the conventional type, involving the lone electron pair of an oxygen donor, the latter is perpendicular, involving the π-system of the carbonyl oxygen (N–CO···X dihedrals ca. 90°). Such perpendicular interactions resemble those observed in protein complexes of halogenated ligands. A statistical analysis of small-molecule crystal structural data, as well as quantum-chemical calculations with urea as a model (MP2/aug-cc-pVDZ-PP), demonstrates that halogen bonding with the π-system of the carbonyl oxygen can become competitive with the commonly favored lone-pair interaction whenever the carbonyl group carries electron-donating substitutents, specifically for ureas, amides, and esters, and particularly when the lone pairs are engaged in orthogonal hydrogen bonding (<i>h</i>X bonds). The calculations further demonstrate that the perpendicular interactions remain significantly attractive also for nonlinear distortions of the O···X–X angle to ca. 140°, the angle observed in the two reported crystal structures. The structural and theoretical data jointly support the assignment of the observed dihalogen–carbonyl contacts as genuine halogen bonds

    Nanomolar Binding of Steroids to Cucurbit[<i>n</i>]urils: Selectivity and Applications

    No full text
    Cucurbit­[<i>n</i>]­urils (CB<i>n</i>, <i>n</i> = 7, 8) serve as artificial receptors for steroids (21 tested), including the hormones testosterone and estradiol as well as steroidal drugs. Fluorescence displacement titrations and isothermal titration calorimetry (ITC) provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors. Remarkable binding selectivities, even for homologous steroid pairs, were investigated in detail by NMR, X-ray crystal diffraction, ITC, and quantum chemical calculations. Notably, the CB<i>n</i>•steroid complexes are stable in water and buffers, in artificial gastric acid, and even in blood serum. Numerous applications have been demonstrated, which range from the solubility enhancement of the steroids in the presence of the macrocycles (up to 100 times, for drug delivery) and the principal component analysis of the fluorescence responses of different CB<i>n</i>•reporter dye combinations (for differential sensing of steroids) to the real-time monitoring of chemical conversions of steroids as substrates (for enzyme assays)

    Dodecaborate-Functionalized Anchor Dyes for Cyclodextrin-Based Indicator Displacement Applications

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    A new type of water-soluble anchor dyes, that is, dyes which carry an auxiliary unit for strong binding to macrocyclic host molecules, has been synthesized. It consists of 7-nitrobenzofurazan (NBD) as a dye and the dodecaborate cluster (B<sub>12</sub>H<sub>11</sub>R) as a dianionic, globular, and purely inorganic anchoring group for cyclodextrins (<i>K</i><sub>a</sub> > 10<sup>5</sup> M<sup>–1</sup>). The synthesized dodecaborate-substituted dyes show marked changes in their photophysical properties (UV–vis and fluorescence) upon complexation with cyclodextrins (β-CD and γ-CD), such that the resulting host·dye complexes (1:1 stoichiometry) present sensitive reporter pairs for indicator displacement applications

    Unconventional CO<sub>2</sub>‑Binding and Catalytic Activity of Urea-Derived Histidines

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    The development of an ideal sorbent/catalyst for CO2 capturing and fixation into cyclic carbonates under mild conditions is still ongoing. We report on furnishing l-histidine ester dihydrochloride (His-OMe) into a functionalized urea, 5,6,7,8-tetrahydro-7-(methoxycarbonyl)-5-oxoimidazo­[1,5-c]­pyrimidine (His-Urea, 2). The latter is prepared via a microwave and a modified sonochemical approach using propylene carbonate and N,N′-carbonyldiimidazole, which is further functionalized by different mono- or disubstituted alkyl halides with acceptable yields. Upon activation of 2 or its hydroxylated version 4b with NaH, the CO2 capturing in dimethyl sulfoxide is proven to be a dicarboxylated species (carbamide and alkyl carboxylates, 2·2CO2Na) or alkyl carbonate adduct in the case of 4b, as verified by 1H/13C NMR and ATR-FTIR spectroscopies. A first-time preparation of the dimeric ([DiHis-Urea-Pr]­Br, 6) is reported among the prepared bio-based materials. Density functional theory (DFT) calculations confirm the most active reaction site and verify the CO2-sequestrated adducts. Furthermore, the synthesized substrates (2, 4a–b, and 6) are tested for the cycloaddition reaction of epichlorohydrin with CO2 under mild reaction conditions, with good-to-excellent catalytic activity up to quantitative conversions under arbitrary conditions (3.0 mol% catalyst loading, 90 °C, 8 h, 1 atm CO2). The suggested reaction mechanism is verified via DFT calculations, in which the ring closure is the rate-determining step

    Pentaerythritol-Based Molecular Sorbent for CO<sub>2</sub> Capturing: A Highly Efficient Wet Scrubbing Agent Showing Proton Shuttling Phenomenon

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    Pentaerythritol (PE) is considered a biodegradable material that combines the ease of synthesis, nonvolatility, and extra stability under basic conditions (acidic gas sequestration, e.g., CO<sub>2</sub>), which makes it a useful candidate for postcombustion capture (PCC) application. To overcome corrosion problems associated with CO<sub>2</sub> binding organic liquids, a binary mixture comprised of PE/1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) (1:4 molar ratio) dissolved in dimethyl sulfoxide (DMSO) was exploited for CO<sub>2</sub> capturing. The formation of ionic alkyl organic carbonate (RCO<sub>3</sub><sup>–</sup> DBUH<sup>+</sup>) was confirmed using <sup>13</sup>C NMR (157.4 ppm) and ex situ attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR) (two peaks were identified, viz., 1670 and 1630 cm<sup>–1</sup>, which were ascribed to the symmetric and asymmetric stretching of both CO and O<sup><u>···</u></sup>C<sup><u>···</u></sup>O<sup>−</sup> within RCO<sub>3</sub>H and RCO<sub>3</sub><sup>–</sup>, respectively). The charged adduct was measured using a thermostated beaker coupled with conductivity and pH meter probes. The sorption capacity of a 5.0% PE (w/v) solution was measured volumetrically with high efficiencies as, ca. 16 and 18.5 wt %, for wet and dry conditions, respectively. In addition, density functional theory (DFT) was performed to understand the mechanism of action in the case of H<sub>2</sub>O, and simple alcohols, e.g., methanol and ethanol. Moreover, we reported on the newly discovered medium-dependent proton shuttling phenomenon that was verified experimentally and theoretically
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