| 1. |
- Brea, Oriana, et al.
(författare)
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Mechanism(s) of thermal decomposition of N-Nitrosoamides : A density functional theory study
- 2019
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Ingår i: Tetrahedron. - : Elsevier BV. - 0040-4020 .- 1464-5416. ; 75:8, s. 929-935
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Tidskriftsartikel (refereegranskat)abstract
- The thermal decomposition of N-nitrosoamides has experimentally been demonstrated to depend on several factors, such as temperature, solvent and the substituents on the substrate. Consequently, a number of reaction mechanisms have been proposed for this process in the literature. In this work, we present a comprehensive computational investigation in which we examine the detailed reaction mechanisms for two N-nitrosoamides (with aliphatic and aromatic substituents) in two different solvents (mesitylene and methanol). It is shown that the reaction mechanism can change dramatically with the nature of the substrate and the choice of solvent. Importantly, it is found that the polar solvent stabilizes ion-pairs that are unstable in the non-polar solvent, which can play a key role in the mechanism.
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| 2. |
- Brea, Oriana, et al.
(författare)
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Modeling Decomposition of N-Nitrosoamides in a Self-Assembled Capsule
- 2019
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Ingår i: Journal of Organic Chemistry. - : American Chemical Society (ACS). - 0022-3263 .- 1520-6904. ; 84:11, s. 7354-7361
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Tidskriftsartikel (refereegranskat)abstract
- Density functional theory calculations are employed to investigate the mechanism and energies of the decomposition of N-nitrosoamides in the presence of a resorcinarene-based self-assembled nanocapsule. From experiments, it is known that confinement in the capsule inhibits the thermal decomposition of these compounds. N-Nitrosoamides with both aromatic and aliphatic substituents are considered here and the calculations show that, for both kinds, binding to the capsule leads to a significant increase in the energy barrier of the rate-determining step, the 1,3 N -> O acyl transfer reaction. A distortion-interaction analysis is conducted to probe the reasons behind the inhibition of the reaction. In addition, we characterized hypothetical intermediates that might be involved in the formation of the decomposition products inside the capsule. Interestingly, it is found that the capsule stabilizes ion-pair species that are unstable in mesitylene solution. Finally, a possible explanation is proposed for the observed encapsulation of the decomposition product of only one of the substrates.
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| 3. |
- Daver, Henrik, et al.
(författare)
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Mixed Explicit-Implicit Solvation Approach for Modeling of Alkane Complexation in Water-Soluble Self-Assembled Capsules
- 2018
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 140:39, s. 12527-12537
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Tidskriftsartikel (refereegranskat)abstract
- The host-guest binding properties of a water-soluble resorcinarene-based cavitand are examined using density functional theory methodology. Experimentally, the cavitand has been observed to self-assemble in aqueous solution into both 1:1 and 2:1 host/guest complexes with hydrophobic guests such as n-alkanes. For n-decane, equilibrium was observed between the 1:1 and 2:1 complexes, while 1:1 complexes are formed with shorter n-alkanes and 2:1 complexes are formed with longer ones. These findings are used to assess the standard quantum chemical methodology. It is first shown that a rather advanced com- putational protocol (B3LYP-D3(BJ)/6-311+G(2d,2p) with COSMO-RS and quasi-rigid-rotor-harmonic-oscillator) gives very large errors. Systematic examination of the various elements of the methodology shows that the error stems from the implicit solvation model. A mixed explicit-implicit solvation protocol is developed that involves a parametrization of the hydration free energy of water such that water cluster formation in water is predicted to be thermoneutral. This new approach is demonstrated to lead to a major improvement in the calculated binding free energies of n-alkanes, reproducing very well the 1:1 versus 2:1 host/guest binding trends.
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| 4. |
- Daver, Henrik, et al.
(författare)
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Modeling the Reaction of Carboxylic Acids and Isonitriles in a Self-Assembled Capsule
- 2020
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 26:47, s. 10861-10870
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Tidskriftsartikel (refereegranskat)abstract
- Quantum chemical calculations were used to study the reaction of carboxylic acids with isonitriles inside a resorcinarene-based self-assembled capsule. Experimentally, it has been shown that the reactions betweenp-tolylacetic acid andn-butyl isonitrile or isopropyl isonitrile behave differently in the presence of the capsule compared both with each other and also with their solution counterparts. Herein, the reasons for these divergent behaviors are addressed by comparing the detailed energy profiles for the reactions of the two isonitriles inside and outside the capsule. An energy decomposition analysis was conducted to quantify the different factors affecting the reactivity. The calculations reproduce the experimental findings very well. Thus, encapsulation leads to lowering of the energy barrier for the first step of the reaction, the concerted alpha-addition and proton transfer, which in solution is rate-determining, and this explains the rate acceleration observed in the presence of the capsule. The barrier for the final step of the reaction, the 1,3 O -> N acyl transfer, is calculated to be higher with the isopropyl substituent inside the capsule compared withn-butyl. With the isopropyl substituent, the transition state and the product of this step are significantly shorter than the preceding intermediate, and this results in energetically unfavorable empty spaces inside the capsule, which cause a higher barrier. With then-butyl substituent, on the other hand, the carbon chain can untwine and hence uphold an appropriate guest length.
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| 5. |
- Daver, Henrik, et al.
(författare)
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Quantum Chemical Modeling of Cycloaddition Reaction in a Self-Assembled Capsule
- 2017
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 139:43, s. 15494-15503
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Tidskriftsartikel (refereegranskat)abstract
- Dispersion-corrected density functional theory is used to study the cycloaddition reaction between phenyl acetylene and phenyl azide inside a synthetic, self-assembled capsule. The capsule is first characterized computationally and a previously unrecognized structure is identified as being the most stable. Next, an examination of the free energies of host-guest complexes is conducted, considering all possible reagent, solvent and solvent impurity combinations as guests. The experimentally observed relative stabilities of host-guest complexes are quite well reproduced, when the experimental concentrations are taken into account. Experimentally, the presence of the host capsule has been shown to accelerate the cycloaddition reaction and to yield exclusively the 1,4-regioisomer product. Both these observations are reproduced by the calculations. A detailed energy decomposition analysis shows that reduction of the entropic cost of bringing together the reactants along with a geometric destabilization of the reactant supercomplex are the major contributors to the rate acceleration compared to the background reaction. Finally, a sensitivity analysis is conducted to assess the stability of the results with respect to the choice of methodology.
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| 6. |
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| 7. |
- Guan, Hua-Wei, et al.
(författare)
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Recognition of hydrophilic molecules in deep cavitand hosts with water-mediated hydrogen bonds
- 2021
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Ingår i: Chemical Communications. - : Royal Society of Chemistry (RSC). - 1359-7345 .- 1364-548X. ; 57:66, s. 8147-8150
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Tidskriftsartikel (refereegranskat)abstract
- We describe new container host molecules - deep cavitands with benzimidazole walls and ionic feet - to recognize highly hydrophilic guest molecules in water. The aromatic surfaces of the cavity recognize hydrophobic portions of the guest while bound water molecules mediate hydrogen bonding in the complex. Spectroscopic (NMR) evidence indicates slow in/out exchange on the chemical shift timescale and thermodynamic (ITC) methods show large association constants (Ka up to 6 x 10(4) M-1) for complexation of small, water-soluble molecules such as THF and dioxane. Quantum chemical calculations are employed to optimize the host-guest geometries and elucidate the hydrogen bonding patterns responsible for the binding.
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| 8. |
- Norjmaa, Gantulga, 1987-, et al.
(författare)
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Modeling Amine Methylation in Methyl Ester Cavitand
- 2024
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Ingår i: Chemistry - A European Journal. - 0947-6539 .- 1521-3765. ; 30:13
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Tidskriftsartikel (refereegranskat)abstract
- Methylation of amines inside an introverted resorcinarene-based deep methyl ester cavitand is investigated by means of molecular dynamics simulations and quantum chemical calculations. Experimentally, the cavitand has been shown to bind a number of amines and accelerate the methylation reaction by more than four orders of magnitude for some of them. Eight different amines are considered in the present study, and the geometries and energies of their binding to the cavitand are first characterized and analyzed. Next, the methyl transfer reactions are investigated and the calculated barriers are found to be in generally good agreement with experimental results. In particular, the experimentally-observed rate acceleration in the cavitand as compared to the solution reaction is well reproduced by the calculations. The origins of this rate acceleration are analyzed by computational modifications made to the structure of the cavitand, and the role of the solvent is discussed.
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| 9. |
- Rahman, Faiz-Ur, et al.
(författare)
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Binding and Assembly of a Benzotriazole Cavitand in Water
- 2022
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Ingår i: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 61:29
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Tidskriftsartikel (refereegranskat)abstract
- A water-soluble cavitand bearing a benzotriazole upper rim was prepared and characterized. It exists as a dimeric velcraplex in D2O, but forms host–guest complexes with hydrophobic and amphiphilic guests. Alkanes (C5 to C10), cyclic ketones (C6–C10), cyclic alcohols (C6–C8) and various amphiphilic guests form 1 : 1 cavitand complexes. A cyclic array of hydrogen bonds, bridged by solvent/water (D2O) molecules, stabilizes the vase conformation of the complexes. With longer alkanes (C12–C15), symmetrical dialkyl amine, urea and phosphate, 2 : 1 host:guest capsules are formed. Computations indicate that additional waters on the upper rim create a self-complementary hydrogen-bonding pattern for capsule formation.
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| 10. |
- Wahlström, Anna, et al.
(författare)
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Specific binding of a beta cyclodextrin dimer to the amyloid beta peptide modulates the peptide aggregation process
- 2012
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 51:21, s. 4280-4289
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease involves progressive neuronal loss. Linked to the disease is the amyloid beta (A beta) peptide, a 38-43-amino acid peptide found in extracellular amyloid plaques in the brain. Cyclodextrins are nontoxic, cone-shaped oligosaccharides with a hydrophilic exterior and a hydrophobic cavity making them suitable hosts for aromatic guest molecules in water. beta-Cyclodextrin consists of seven alpha-D-glucopyranoside units and has been shown to reduce the level of fibrillation and neurotoxicity of A beta. We have studied the interaction between A beta and a beta-cyclodextrin dimer, consisting of two beta-cyclodextrin monomers connected by a flexible linker. The beta-cyclodextrin monomer has been found to interact with A beta(1-40) at sites Y10, F19, and/or F20 with a dissociation constant (K-D) of 3.9 +/- 2.0 mM. Here H-1-N-15 and H-1-C-13 heteronuclear single-quantum correlation nuclear magnetic resonance (NMR) spectra show that in addition, the beta-cyclodextrin monomer and dimer bind to the histidines. NMR translational diffusion experiments reveal the increased affinity of the beta-cyclodextrin dimer (apparent K-D of 1.1 +/- .5 mM) for A beta(1-40) compared to that of the beta-cyclodextrin monomer. Kinetic aggregation experiments based on thioflavin T fluorescence indicate that the dimer at 0.05-5 mM decreases the lag time of A beta aggregation, while a concentration of 10 mM increases the lag time. The beta-cyclodextrin monomer at a high concentration decreases the lag time of the aggregation. We conclude that cyclodextrin monomers and dimers have specific, modulating effects on the A beta(1-40) aggregation process. Transmission electron microscopy shows that the regular fibrillar aggregates formed by A beta(1-40) alone are replaced by a major fraction of amorphous aggregates in the presence of the beta-cyclodextrin dimer.
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