| 1. |
- Bunrit, Anon, et al.
(författare)
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Brønsted Acid-Catalyzed Intramolecular Nucleophilic Substitution of the Hydroxyl Group in Stereogenic Alcohols with Chirality Transfer
- 2015
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 137:14, s. 4646-4649
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Tidskriftsartikel (refereegranskat)abstract
- The hydroxyl group of enantioenriched benzyl, propargyl, allyl, and alkyl alcohols has been intramolecularly displaced by uncharged O-, N-, and S-centered nucleophiles to yield enantioenriched tetrahydrofuran, pyrrolidine, and tetrahydrothiophene derivatives with phosphinic acid catalysis. The five-membered heterocyclic products are generated in good to excellent yields, with high degree of chirality transfer, and water as the only side-product. Racemization experiments show that phosphinic acid does not promote S(N)1 reactivity. Density functional theory calculations corroborate a reaction pathway where the phosphinic acid operates as a bifunctional catalyst in the intramolecular substitution reaction. In this mechanism, the acidic proton of the phosphinic acid protonates the hydroxyl group, enhancing the leaving group ability. Simultaneously, the oxo group of phosphinic acid operates as a base abstracting the nucleophilic proton and thus enhancing the nucleophilicity. This reaction will open up new atom efficient techniques that enable alcohols to be used as nucleofuges in substitution reactions in the future.
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| 2. |
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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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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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| 5. |
- Hayashi, Yukiko, et al.
(författare)
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Enzyme-Like Catalysis via Ternary Complex Mechanism : Alkoxy-Bridged Dinuclear Cobalt Complex Mediates Chemoselective O-Esterification over N-Amidation
- 2013
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 135:16, s. 6192-6199
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxy group-selective acylation in the presence of more nucleophilic amines was achieved using acetates of first-row late transition metals, such as Mn, Fe, Co, Cu, and Zn. Among them, cobalt(II) acetate was the best catalyst in terms of reactivity and selectivity. The combination of an octanuclear cobalt carboxylate cluster [Co-4(OCOR)(6)O](2) (2a: R = CF3, 2b: R = CH3, 2c: R = Bu-t) with nitrogen-containing ligands, such as 2,2'-bipyridine, provided an efficient catalytic system for transesterification, in which an alkoxide-bridged dinuclear complex, Co-2((OCOBu)-Bu-t)(2)-(bpy)(2)(mu(2)-OCH2-C6H4-4-CH3)(2) (10), was successfully isolated as a key intermediate. Kinetic studies and density functional theory calculations revealed Michaelis-Menten behavior of the complex 10 through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting the formation of alkoxides followed by coordination of the ester.
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| 6. |
- Himo, Fahmi, et al.
(författare)
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Catalytic mechanism of galactose oxidase : A theoretical study
- 2000
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 122:33, s. 8031-8036
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Tidskriftsartikel (refereegranskat)abstract
- Density functional methods, alone and together with molecular mechanics, are used to study the catalytic mechanism of galactose oxidase. This enzyme catalyzes the conversion of primary alcohols to the corresponding aldehydes, coupled with reduction of dioxygen to hydrogen peroxide. It is shown that the proposed mechanism for this enzyme is energetically feasible. In particular the barrier for the postulated rate-limiting hydrogen atom, transfer between the substrate and the tyrosyl radical, located at equatorial Tyr272, is very plausible. We propose that the radical site, prior to the initial proton transfer step, is located at the axial tyrosine (Tyr495). The radical is transferred to the equatorial tyrosine (Tyr272) simultaneously with the proton transfer. It is, furthermore, argued that the electron transfer from the ketyl radical intermediate to Cu(II) cannot be very exothermic, because this would render the oxygen reduction steps rate-limiting. Finally, the cysteine cross-link on the active site tyrosine is shown to have very minor effects on the energetics of the reaction.
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| 7. |
- Himo, Fahmi, et al.
(författare)
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Catalytic mechanism of glyoxalase I : A theoretical study
- 2001
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 123:42, s. 10280-10289
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Tidskriftsartikel (refereegranskat)abstract
- Hybrid density functional theory is used to study the catalytic mechanism of human glyoxalase I (GlxI). This zinc enzyme catalyzes the conversion of the hemithioacetal of toxic methylglyoxal and glutathione to nontoxic (S)-D-lactoylglutathione. GlxI can process both diastereomeric forms of the substrate, yielding the same form of the product. As a starting point for the calculations, we use a recent crystal structure of the enzyme in complex with a transition-state analogue, where it was found that the inhibitor is bound directly to the zinc by its hydroxycarbamoyl functions. It is shown that the Zn ligand Glu172 can abstract the substrate Cl proton from the S enantiomer of the substrate, without being displaced from the Zn ion. The calculated activation barrier is in excellent agreement with experimental rates. Analogously, the Zn ligand Glu99 can abstract the proton from the R form of the substrate. To account for the stereochemical findings, it is argued that the S and R reactions cannot be fully symmetric. A detailed mechanistic scheme is proposed.
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| 8. |
- Himo, Fahmi, et al.
(författare)
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Copper(I)-catalyzed synthesis of azoles. DFT study predicts unprecedented reactivity and intermediates
- 2005
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 127:1, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- Huisgen's 1,3-dipolar cycloadditions become nonconcerted when copper(l) acetylides react with azides and nitrile oxides, providing ready access to 1,4-disubstituted 1,2,3-triazoles and 3,4-disubstituted isoxazoles, respectively. The process is highly reliable and exhibits an unusually wide scope with respect to both components. Computational studies revealed a stepwise mechanism involving unprecedented metallacycle intermediates, which appear to be common for a variety of dipoles.
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| 9. |
- Himo, Fahmi, et al.
(författare)
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Mechanisms of tetrazole formation by addition of azide to nitriles
- 2002
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 124:41, s. 12210-12216
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Tidskriftsartikel (refereegranskat)abstract
- It is well-known that azide salts can engage nitriles at elevated temperatures to yield tetrazoles; however, there is continued debate as to the mechanism of the reaction. Density functional theory calculations with the hybrid functional B3LYP have been performed to study different mechanisms of tetrazole formation, including concerted cycloaddition and stepwise addition of neutral or anionic azide species. The calculations presented here suggest a previously unsuspected nitrile activation step en route to an imidoyl azide, which then cyclizes to give the tetrazole. The activation barriers are found to correlate strongly with the electron-withdrawing potential of the substituent on the nitrile.
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| 10. |
- Himo, Fahmi
(författare)
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Recent Trends in Quantum Chemical Modeling of Enzymatic Reactions
- 2017
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 139:20, s. 6780-6786
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Forskningsöversikt (refereegranskat)abstract
- The quantum chemical cluster approach is a powerful method for investigating enzymatic reactions. Over the past two decades, a large number of highly diverse systems have been studied and a great wealth of mechanistic insight has been developed using this technique. This Perspective reviews the current status of the methodology. The latest technical developments are highlighted, and challenges are discussed. Some recent applications are presented to illustrate the capabilities and progress of this approach, and likely future directions are outlined.
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