Mechanistic investigation of the copper-catalyzed reactions of diphenyliodonium salts

Restructuring of interface plays a crucial role in materials science and heterogeneous catalysis. Bimetallic systems, in particular, often adopt very different composition and morphology at surfaces compared to the bulk. For the first time, we reveal a detailed atomistic picture of the long-timescale restructuring of Pd deposited on Ag, using microscopy, spectroscopy, and novel simulation methods. Encapsulation of Pd by Ag always precedes layer-by-layer dissolution of Pd, resulting in significant Ag migration out of the surface and extensive vacancy pits. These metastable structures are of vital catalytic importance, as Ag-encapsulated Pd remains much more accessible to reactants than bulk-dissolved Pd. The underlying mechanisms are uncovered by performing fast and large-scale machine-learning molecular dynamics, followed by our newly developed method for complete characterization of atomic surface restructuring events. Our approach is broadly applicable to other multimetallic systems of interest and enables the previously impractical mechanistic investigation of restructuring dynamics.

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Theoretical and experimental studies of palladium-catalyzed site-selective C(sp3)−H bond functionalization enabled by transient ligands

10.26434/chemrxiv.5717950 ◽

2017 ◽

Author(s):

Haibo Ge ◽

Lei Pan ◽

Piaoping Tang ◽

Ke Yang ◽

Mian Wang ◽

...

Keyword(s):

Bond Activation ◽

Theoretical Calculations ◽

Experimental Studies ◽

Bond Functionalization ◽

Aliphatic Ketones ◽

Site Selectivity ◽

Mechanistic Investigation ◽

Palladium Catalyzed ◽

Metal Catalyzed ◽

Site Selective

Transition metal-catalyzed selective C–H bond functionalization enabled by transient ligands has become an extremely attractive topic due to its economical and greener characteristics. However, catalytic pathways of this reaction process on unactivated sp<sup>3</sup> carbons of reactants have not been well studied yet. Herein, detailed mechanistic investigation on Pd-catalyzed C(sp<sup>3</sup>)–H bond activation with amino acids as transient ligands has been systematically conducted. The theoretical calculations showed that higher angle distortion of C(sp2)-H bond over C(sp3)-H bond and stronger nucleophilicity of benzylic anion over its aromatic counterpart, leading to higher reactivity of corresponding C(sp<sup>3</sup>)–H bonds; the angle strain of the directing rings of key intermediates determines the site-selectivity of aliphatic ketone substrates; replacement of glycine with β-alanine as the transient ligand can decrease the angle tension of the directing rings. Synthetic experiments have confirmed that β-alanine is indeed a more efficient transient ligand for arylation of β-secondary carbons of linear aliphatic ketones than its glycine counterpart.<br><br>

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A kinetic analysis of coupled sequential enzyme reactions

10.26434/chemrxiv.5746065.v2 ◽

2018 ◽

Author(s):

Justin Eilertsen ◽

Santiago Schnell

Keyword(s):

Enzyme Assay ◽

Sequential Reaction ◽

Enzyme Reactions ◽

Indicator Reaction ◽

Single Substrate ◽

Complex Sequences ◽

Catalyzed Reactions ◽

Enzyme Catalyzed Reactions ◽

Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis--Menten reaction mechanism. The sequential reaction consists of a single-substrate, single-enzyme non-observable reaction followed by another single-substrate, single-enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis--Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis--Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

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A kinetic analysis of coupled sequential enzyme reactions

10.26434/chemrxiv.5746065.v1 ◽

2018 ◽

Author(s):

Justin Eilertsen ◽

Santiago Schnell

Keyword(s):

Enzyme Assay ◽

Sequential Reaction ◽

Enzyme Reactions ◽

Indicator Reaction ◽

Single Substrate ◽

Complex Sequences ◽

Catalyzed Reactions ◽

Enzyme Catalyzed Reactions ◽

Single Enzyme

<div>As a case study, we consider a coupled enzyme assay of sequential enzyme reactions obeying the Michaelis-Menten reaction mechanism. The sequential reaction consists of a single-substrate, single enzyme non-observable reaction followed by another single-substrate, single enzyme observable reaction (indicator reaction). In this assay, the product of the non-observable reaction becomes the substrate of the indicator reaction. A mathematical analysis of the reaction kinetics is performed, and it is found that after an initial fast transient, the sequential reaction is described by a pair of interacting Michaelis-Menten equations. Timescales that approximate the respective lengths of the indicator and non-observable reactions, as well as conditions for the validity of the Michaelis-Menten equations are derived. The theory can be extended to deal with more complex sequences of enzyme catalyzed reactions.</div>

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Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

10.26434/chemrxiv.7322330.v1 ◽

2018 ◽

Author(s):

Timothy Newhouse ◽

Daria E. Kim ◽

Joshua E. Zweig

Keyword(s):

Chemical Synthesis ◽

Total Synthesis ◽

Small Molecules ◽

First Principles ◽

Quantum Chemical ◽

Computational Analysis ◽

Empirical Evaluation ◽

Synthetic Strategy ◽

Catalyzed Reactions ◽

Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

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