6 research outputs found
Unraveling the Reaction Mechanism on Nitrile Hydration Catalyzed by [Pd(OH<sub>2</sub>)<sub>4</sub>]<sup>2+</sup>: Insights from Theory
Density
functional theory methodologies combined with continuum
and discrete-continuum descriptions of solvent effects were used to
investigate the [PdĀ(OH<sub>2</sub>)<sub>4</sub>]<sup>2+</sup>-catalyzed
acrylonitrile hydration to yield acrylamide. According to our results,
the intramolecular hydroxide attack mechanism and the external addition
mechanism of a water molecule with rate-determining Gibbs energy barriers
in water solution of 27.6 and 28.3 kcal/mol, respectively, are the
most favored. The experimental kinetic constants of the hydration
started by hydroxide, <i>k</i>(OH), and water, <i>k</i>(H<sub>2</sub>O), attacks for the <i>cis</i>-[PdĀ(en)Ā(OH<sub>2</sub>)<sub>2</sub>]<sup>2+</sup>-catalyzed dichloroacetonitrile
hydration rendered Gibbs energy barriers whose energy difference,
0.7 kcal/mol, is the same as that obtained in the present study. Our
investigation reveals the nonexistence of the internal attack of a
water ligand for Pd-catalyzed nitrile hydration. At the low pHs used
experimentally, the equilibrium between [PdĀ(OH<sub>2</sub>)<sub>3</sub>(nitrile)]<sup>2+</sup> and [PdĀ(OH<sub>2</sub>)<sub>2</sub>(OH)Ā(nitrile)]<sup>+</sup> is completely displaced to [PdĀ(OH<sub>2</sub>)<sub>3</sub>(nitrile)]<sup>2+</sup>. Experimental studies in these conditions
stated that water acts as a nucleophile, but they could not distinguish
whether it was a water ligand, an external water molecule, or a combination
of both possibilities. Our theoretical explorations clearly indicate
that the external water mechanism becomes the only operative one at
low pHs. On the basis of this mechanistic proposal it is also possible
to ascribe an <sup>1</sup>H NMR signal experimentally detected to
the presence of a unidentate iminol intermediate and to explain the
influence of nitrile concentration reported experimentally for nitriles
other than acrylonitrile in the presence of aquaāPdĀ(II) complexes.
Therefore, our theoretical point of view on the mechanism of nitrile
hydration catalyzed by aquaāPdĀ(II) complexes can shed light
on these relevant processes at a molecular level as well as afford
valuable information that can help in designing new catalysts in milder
and more efficient conditions
Taste for Chiral Guests: Investigating the Stereoselective Binding of Peptides to Ī²āCyclodextrins
Obtaining compounds of diastereomeric
purity is extremely important
in the field of biological and pharmaceutical industry, where amino
acids and peptides are widely employed. In this work, we theoretically
investigate the possibility of chiral separation of peptides by Ī²-cyclodextrins
(Ī²-CDs), providing a description of the associated interaction
mechanisms by means of molecular dynamics (MD) simulations. The formation
of host/guest complexes by including a model peptide in the macrocycle
cavity is analyzed and discussed. We consider the terminally blocked
phenylalanine dipeptide (Ace-Phe-Nme), in the l- and d-configurations, to be involved in the host/guest recognition
process. The CDāpeptide free energies of binding for the two
enantiomers are evaluated through a combined approach that assumes:
(1) extracting a set of independent molecular structures from the
MD simulation, (2) evaluating the interaction energies for the host/guest
complexes by hybrid quantum mechanics/molecular mechanics (QM/MM)
calculations carried out on each structure, for which we also compute,
(3) the solvation energies through the PoissonāBoltzmann surface
area method. We find that chiral discrimination by the CD macrocycle
is of the order of 1 kcal/mol, which is comparable to experimental
data for similar systems. According to our results, the Ace-(d)ĀPhe-Nme isomer leads to a more stable complex with a Ī²-CD
compared to the Ace-(l)ĀPhe-Nme isomer. Nevertheless, we show
that the chiral selectivity of Ī²-CDs may strongly depend on
the secondary structure of larger peptides. Although the free energy
differences are relatively small, the predicted selectivities can
be rationalized in terms of host/guest hydrogen bonds and hydration
effects. Indeed, the two enantiomers display different interaction
modes with the cyclodextrin macrocavity and different mobility within
the cavity. This finding suggests a new interpretation for the interactions
that play a key role in chiral recognition, which may be exploited
to design more efficient and selective chiral separations of peptides
Understanding the Hydrolysis Mechanism of Ethyl Acetate Catalyzed by an Aqueous Molybdocene: A Computational Chemistry Investigation
A thoroughly mechanistic investigation
on the [Cp<sub>2</sub>MoĀ(OH)Ā(OH<sub>2</sub>)]<sup>+</sup>-catalyzed
hydrolysis of ethyl acetate has been performed using density functional
theory methodology together with continuum and discreteācontinuum
solvation models. The use of explicit water molecules in the PCM-B3LYP/aug-cc-pVTZ
(aug-cc-pVTZ-PP for Mo)//PCM-B3LYP/aug-cc-pVDZ (aug-cc-pVDZ-PP for
Mo) computations is crucial to show that the intramolecular hydroxo
ligand attack is the preferred mechanism in agreement with experimental
suggestions. Besides, the most stable intermediate located along this
mechanism is analogous to that experimentally reported for the norbornenyl
acetate hydrolysis catalyzed by molybdocenes. The three most relevant
steps are the formation and cleavage of the tetrahedral intermediate
immediately formed after the hydroxo ligand attack and the acetic
acid formation, with the second one being the rate-determining step
with a Gibbs energy barrier of 36.7 kcal/mol. Among several functionals
checked, B3LYP-D3 and M06 give the best agreement with experiment
as the rate-determining Gibbs energy barrier obtained only differs
0.2 and 0.7 kcal/mol, respectively, from that derived from the experimental
kinetic constant measured at 296.15 K. In both cases, the acetic acid
elimination becomes now the rate-determining step of the overall process
as it is 0.4 kcal/mol less stable than the tetrahedral intermediate
cleavage. Apart from clarifying the identity of the cyclic intermediate
and discarding the tetrahedral intermediate formation as the rate-determining
step for the mechanism of the acetyl acetate hydrolysis catalyzed
by molybdocenes, the small difference in the Gibbs energy barrier
found between the acetic acid formation and the tetrahedral intermediate
cleavage also uncovers that the rate-determining step could change
when studying the reactivity of carboxylic esters other than ethyl
acetate substrate specific toward molybdocenes or other transition
metal complexes. Therefore, in general, the information reported here
could be of interest in designing new catalysts and understanding
the reaction mechanism of these and other metal-catalyzed hydrolysis
reactions
Influence of the NāN Coligand: CāC Coupling Instead of Formation of Imidazol-2-yl Complexes at {Mo(Ī·<sup>3</sup>āallyl)(CO)<sub>2</sub>} Fragments. Theoretical and Experimental Studies
New <i>N</i>-methylimidazole (N-MeIm) complexes of the {MoĀ(Ī·<sup>3</sup>-allyl)Ā(CO)<sub>2</sub>(NāN)} fragment have been prepared,
in which the N,N-bidentate chelate ligand is a 2-pyridylimine. The
addition of a strong base to the new compounds deprotonates the central
CH group of the imidazole ligand and subsequently forms the CāC
coupling product that results from the nucleophilic attack to the
imine C atom. This reactivity contrasts with that previously found
for the analogous 2,2ā²-bipyridine compounds [MoĀ(Ī·<sup>3</sup>-allyl)Ā(CO)<sub>2</sub>Ā(bipy)Ā(N-RIm)]ĀOTf [N-RIm = N-MeIm, <i>N</i>-mesitylimidazole (N-MesIm, Mes= 2,4,6-trimethylphenyl);
OTf = trifluoromethanesulfonate) which afforded imidazol-2-yl complexes
upon deprotonation. Density Functional Theory (DFT) computations uncover
that the reactivity of the imine C atom along with its ability to
delocalize electron density are responsible for the new reactivity
pattern found for the kind of molybdenum complexes reported herein
Unveiling the Reactivity of Propargylic Hydroperoxides under Gold Catalysis
Controlled gold-catalyzed reactions of primary and secondary
propargylic hydroperoxides with a variety of nucleophiles including
alcohols, phenols, 2-hydroxynaphthalene-1,4-dione, and indoles allow
the direct and efficient synthesis of Ī²-functionalized ketones.
Moreover, the utility of some of the resulting products for the selective
preparation of fused polycycles has been demonstrated. In addition,
density functional theory (DFT) calculations and <sup>18</sup>O-labeling
experiments were performed to obtain an insight into various aspects
of the controlled reactivity of propargylic hydroperoxides with external
nucleophiles under gold catalysis
Insights on the Reactivity of Terminal Phosphanido Metal Complexes toward Activated Alkynes from Theoretical Computations
Herein we present a theoretical study
on the reaction of [ReĀ(PPh<sub>2</sub>) (CO)<sub>3</sub>(phen)] (phen
= 1,10-phenanthroline) and
[ReĀ(PPh<sub>2</sub>) (CO)<sub>3</sub>(bipy)] (bipy = 2,2ā²-bipyridine)
toward methyl propiolate. In agreement with experimental results for
the phen ligand, the coupling of the substituted acetylenic carbon
with the nonsubstituted <i>ortho</i> carbon of the phen
ligand is the preferred route from both kinetic and thermodynamic
viewpoints with a Gibbs energy barrier of 18.8 kcal/mol and an exoergicity
of 11.1 kcal/mol. There are other two routes, the insertion of the
acetylenic fragment into the PāRe bond and the coupling between
the substituted acetylenic carbon and a carbonyl ligand in <i>cis</i> disposition, which are kinetically less favorable than
the preferred route (by 2.8 and 1.9 kcal/mol, respectively). Compared
with phen, the bipy ligand shows less electrophilic character and
also less Ļ electron delocalization due to the absence of the
fused ring between the two pyridine rings. As a consequence, the route
involving the coupling with a carbonyl ligand starts to be kinetically
competitive, whereas the product of the attack to bipy is still the
most stable and would be the one mainly obtained after spending enough
time to reach thermal equilibrium