DFT Studies on Copper-Catalyzed Hydrocarboxylation of Alkynes Using CO₂ and Hydrosilanes

In this paper, DFT calculations have been carried out to study the reaction mechanism of copper-catalyzed hydrocarboxylation of alkynes using CO₂ and hydrosilanes. In addition to hydrocarboxylation of alkynes, possible competitive reactions such as hydrosilylation of alkynes, hydrosilylation of CO₂, and silacarboxylation of alkynes have also been investigated and compared. Through these DFT calculations, we are able to understand the reason only hydrocarboxylation of alkynes has been observed experimentally

An [Au₁₃]⁵⁺ Approach to the Study of Gold Nanoclusters

Recently, many examples of gold nanoclusters have been synthesized due to their exceptional spectroscopic properties and potential applications in nanotechnology. In this work we put forward an approach based on the icosahedral [Au₁₃]⁵⁺ unit and summarize three possible extensions of the unit: wrapping, bonding, and vertex sharing. We show that the electronic structure of such clusters can be treated in a more localized manner and show how the approach could be applied to understand the structure and bonding of a large variety of gold nanoclusters

Automatic State Partitioning for Multibody Systems (APM): An Efficient Algorithm for Constructing Markov State Models To Elucidate Conformational Dynamics of Multibody Systems

The conformational dynamics of multibody systems plays crucial roles in many important problems. Markov state models (MSMs) are powerful kinetic network models that can predict long-time-scale dynamics using many short molecular dynamics simulations. Although MSMs have been successfully applied to conformational changes of individual proteins, the analysis of multibody systems is still a challenge because of the complexity of the dynamics that occur on a mixture of drastically different time scales. In this work, we have developed a new algorithm, automatic state partitioning for multibody systems (APM), for constructing MSMs to elucidate the conformational dynamics of multibody systems. The APM algorithm effectively addresses different time scales in the multibody systems by directly incorporating dynamics into geometric clustering when identifying the metastable conformational states. We have applied the APM algorithm to a 2D potential that can mimic a protein–ligand binding system and the aggregation of two hydrophobic particles in water and have shown that it can yield tremendous enhancements in the computational efficiency of MSM construction and the accuracy of the models

Binary docking models undergo substantial structural re-arrangement towards binary crystal during MD simulations.

<p>(A) Projections of MD trajectories of three representative successful docking models. The rationale behind the choice of representative docked conformations is simply to select conformations that contain different fractions of native contacts (i.e. the lowest: 27.1%; median: 35.4%, and highest: 50.0%). (B) Upper panel: interface-RMSD (iRMSD) of models against binary crystal structure. Lower panel: fraction of native contacts (f_nat) between hAgo2 and miRNA of the models. (C) Structural comparison between the binary crystal structure (left) and a representative model from MD (right) with hAgo2 colored in grey and miRNA in red.</p

Mutations in PIWI loops destabilize the closed conformation and accelerate the closed-to-open transitions.

<p>Three mutants were generated: D823A (green), E821A-D823A-E826A (red) and ∆602–605∆819–833 (a deletion mutant where both PIWI loops are truncated, cyan). MD simulations of WT hAgo2 (blue) and the mutants were initiated from three conformations: (A) a closed conformation, (B) a partially open conformation extracted from the binary hAgo2-miRNA crystal structure (PDB ID: 4F3T) and (C) an open conformation. Time traces of the c.o.m. distance between the PAZ domain and PIWI loops of the WT hAgo2 and the three mutants are displayed. Error bars were computed from five independent MD simulations.</p

The proposed two-step model of miRNA loading into hAgo2: Selective binding followed by structural re-arrangement (highlighted by the cyan arrow).

<p>The induced fit mechanism (marked by the upper right grey arrow) and the conformational selection mechanism (marked by the lower left grey arrow) are also presented to compare with the two-step model. Average transition times between the closed states, the open state and the partially open states are computed from ten independent 10-ms synthetic trajectories generated by sampling the transition probability matrix of the 480-microstate MSM (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004404#pcbi.1004404.s010" target="_blank">S10 Fig</a> for additional details). The detailed transition pathways from the closed states to the open state can be found in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004404#pcbi.1004404.s011" target="_blank">S11 Fig</a>.</p

Visualization of the seven metastable macrostates obtained from MSM of apo hAgo2.

<p>(A) Distribution of the PAZ-PIWI loops center-of-mass (c.o.m.) distances for each macrostate. A large distance implies an open conformation. The equilibrium population of each macrostate is presented. (B) Projections of the open and partially open states onto PAZ-PIWI loops c.o.m. distance and the major PIWI loop angle (see <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004404#pcbi.1004404.s003" target="_blank">S3 Fig</a> for the angle definition). The green cross corresponds to the binary partially open crystal structure (missing residues modeled). (C) Representative structures of closed, partially open and open states. Enlarged view of the inter-domain region between PAZ (red) and PIWI (green) of each structure is presented in the inset panel (see representative structure for each macrostate in <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1004404#pcbi.1004404.s004" target="_blank">S4 Fig</a>).</p

Projection of hAgo2-miRNA docking models built from the selected structures of open microstates.

<p>Red dots mark the successful docking models and black dots mark the unsuccessful ones. A successful docking model is a hAgo2-miRNA docking pose where at least two native contacts are preserved at each miRNA terminus.</p

Exoselective 1,3-Dipolar [3 + 6] Cycloaddition of Azomethine Ylides with 2‑Acylcycloheptatrienes: Stereoselectivity and Mechanistic Insight

A highly <i>exo</i>-selective 1,3-dipolar [3 + 6] cycloaddition of azomethine ylides with 2-acylcycloheptatrienes was realized with a Cu­(I)/(<i>S</i>,<i>R</i>_p)-PPF-NHMe complex as the catalyst, leading to a diverse range of bridged piperidines with multiple functionalities in good yield with excellent stereoselectivity control. Theoretical calculations indicated a stepwise mechanism for this <i>exo</i>-selective [3 + 6] annulation, which accounts for the remarkable feature of this annulation: all of the larger substituent groups occupy the axial positions in the six-membered chairlike conformation of the piperidine ring

Catalytic Enantioselective Intermolecular Desymmetrization of Azetidines

The first catalytic asymmetric desymmetrization of azetidines is disclosed. Despite the low propensity of azetidine ring opening and challenging stereocontrol, smooth intermolecular reactions were realized with excellent efficiency and enantioselectivity. These were enabled by the suitable combination of catalyst, nucleophile, protective group, and reaction conditions. The highly enantioenriched densely functionalized products are versatile precursors to other useful chiral molecules. Mechanistic studies, including DFT calculations, revealed that only one catalyst molecule is involved in the key transition state, though both reactants can be activated. Also, the Curtin–Hammett principle dictates the reaction proceeds via amide nitrogen activation