scholarly journals A Computational Investigation of the Uncatalysed and Water-Catalysed Acyl Rearrangements in Ingenol Esters

2018 ◽  
Vol 71 (4) ◽  
pp. 212 ◽  
Author(s):  
Asja A. Kroeger ◽  
Amir Karton
Keyword(s):  
Ring Opening ◽  
Density Functional ◽  
Skin Lesions ◽  
Functional Theory ◽  
Reaction Barrier ◽  
Barrier Heights ◽  
Rate Determining Step ◽  
Proton Transfers ◽  
Biological Potency ◽  
Hybrid Density Functional

Ingenol esters have been identified as potent anticancer and HIV latency reversing agents. Ingenol-3-angelate was recently approved as a topical treatment for precancerous actinic keratosis skin lesions. It was found, however, that ingenol esters can undergo a series of acyl rearrangements, which may affect their biological potency and the shelf-life of drug formulations. We use double-hybrid density functional theory to explore the mechanisms for the uncatalysed and water-catalysed acyl migrations in a model ingenol ester. The uncatalysed reaction may proceed either via a concerted mechanism or via a stepwise mechanism that involves a chiral orthoester intermediate. We find that the stepwise pathway is kinetically preferred by a significant amount of ΔΔH‡298 = 44.5 kJ mol−1. The uncatalysed 3-O-acyl to 5-O-acyl and 5-O-acyl to 20-O-acyl stepwise rearrangements involve cyclisation and ring-opening steps, both concomitant with a proton transfer. We find that the ring-opening step is the rate-determining step for both rearrangements, with reaction barrier heights of ΔH‡298 = 251.6 and 177.1 kJ mol−1 respectively. The proton transfers in the cyclisation and ring-opening steps may be catalysed by a water molecule. The water catalyst reduces the reaction barrier heights of these steps by over 90 kJ mol−1.

DENSITY FUNCTIONAL THEORY STUDY ON THE MECHANISM OF TRIMETHYLAMINE-CATALYZED BAYLIS–HILLMAN REACTION

2010 ◽  
Vol 09 (supp01) ◽  
pp. 65-75 ◽  
Author(s):  
JING LI ◽  
WAN-YI JIANG
Keyword(s):  
Density Functional Theory ◽  
Density Functional ◽  
Dft Method ◽  
Polarizable Continuum Model ◽  
Functional Theory ◽  
Reaction Barrier ◽  
Hydrogen Shift ◽  
Rate Determining Step ◽  
The Density Functional Theory ◽  
Polarizable Continuum

The trimethylamine-catalyzed Baylis–Hillman reaction of formaldehyde and vinylaldehyde has been studied with the density functional theory (DFT) method of B3LYP/6-31+G(d,p). In the gas phase, the reaction involves an amine–formaldehyde–vinylaldehyde trimolecular addition transition structure followed by rate-determining intramolecular 1,3-hydrogen shift. When a bulk solvent effect of water was considered with conductor-like polarizable continuum model (CPCM), the reaction was found to follow the sequence of Michael-addition of amine to vinylaldehyde (step 1), addition of formaldehyde (step 2), and 1,3-hydrogen shift (step 3), with the 1,3-hydrogen shift as rate-determining. The overall reaction barrier is significantly reduced. When a molecule of water is involved in the reaction, the 1,3-hydrogen shift is significantly promoted so that the rate-determining step becomes the C–C bond formation. The calculated overall reaction barrier is in agreement with experimental observations.

scholarly journals The Gas-Phase Formation Mechanism of Dibenzofuran (DBF), Dibenzothiophene (DBT), and Carbazole (CA) from Benzofuran (BF), Benzothiophene (BT), and Indole (IN) with Cyclopentadienyl Radical

2019 ◽  
Vol 20 (21) ◽  
pp. 5420
Author(s):  
Xuan Li ◽  
Yixiang Gao ◽  
Chenpeng Zuo ◽  
Siyuan Zheng ◽  
Fei Xu ◽  
...  
Keyword(s):  
Density Functional ◽  
State Theory ◽  
Ring Closure ◽  
Functional Theory ◽  
Elementary Steps ◽  
Rate Determining Step ◽  
Polycyclic Aromatic ◽  
Cyclopentadienyl Radical ◽  
Hybrid Density Functional ◽  
Phase Formation Mechanism

Benzofuran (BF), benzothiophene (BT), indole (IN), dibenzofuran (DBF), dibenzothiophene (DBT), and carbazole (CA) are typical heterocyclic aromatic compounds (NSO-HETs), which can coexist with polycyclic aromatic hydrocarbons (PAHs) in combustion and pyrolysis conditions. In this work, quantum chemical calculations were carried out to investigate the formation of DBF, DBT, and CA from the reactions of BF, BT, and IN with a cyclopentadienyl radical (CPDyl) by using the hybrid density functional theory (DFT) at the MPWB1K/6-311+G(3df,2p)//MPWB1K/6-31+G(d,p) level. The rate constants of crucial elementary steps were deduced over 600−1200 K, using canonical variational transition state theory with a small-curvature tunneling contribution (CVT/SCT). This paper showed that the production of DBF, DBT, and CA from the reactions of BF, BT, and IN with CPDyl involved six elementary steps: the addition reaction, ring closure, the first H shift, C–C cleavage, the second H shift, and elimination of CH3 or H. The cleavage of the C–C bond was regarded as the rate-determining step for each pathway due to the extremely high barrier. The 1-methyl substituted products were more easily formed than the 4-methyl substituted products. The main products were DBF and 1-methyl-DBF, DBT and 1-methyl-DBT, and CA and 1-methyl-CA for reactions of BF, BT, and IN with CPDyl, respectively. The ranking of DBF, DBT, and CA formation potential was as follows: DBT and methyl-DBT formation > DBF and methyl-DBF formation > CA, and methyl-CA formation. Comparison with the reaction of naphthalene with CPDyl indicated that the reactions of CPDyl attacking a benzene ring and a furan/thiophene/pyrrole ring could be inferred to be comparable under high temperature conditions.

Evaluating Transition Metal Barrier Heights with the Latest DFT Exchange–Correlation Functionals – the MOBH35 Benchmark Dataset

2019 ◽  
Author(s):  
Mark Iron ◽  
Trevor Janes
Keyword(s):  
Transition Metal ◽  
Density Functional ◽  
Computational Cost ◽  
Basis Set ◽  
Functional Theory ◽  
Exchange Correlation ◽  
Barrier Heights ◽  
Complete Basis Set ◽  
Complete Basis Set Limit ◽  
Hybrid Functionals

A new database of transition metal reaction barrier heights – MOBH35 – is presented. Benchmark energies (forward and reverse barriers and reaction energy) are calculated using DLPNO-CCSD(T) extrapolated to the complete basis set limit using a Weizmann1-like scheme. Using these benchmark energies, the performance of a wide selection of density functional theory (DFT) exchange–correlation functionals, including the latest from the Truhlar and Head-Gordon groups, is evaluated. It was found, using the def2-TZVPP basis set, that the ωB97M-V (MAD 1.8 kcal/mol), ωB97X-V (MAD 2.1 kcal/mol) and SCAN0 (MAD 2.1 kcal/mol) hybrid functionals are recommended. The double-hybrid functionals PWPB95 (MAD 1.6 kcal/mol) and B2K-PLYP (MAD 1.8 kcal/mol) did perform slightly better but this has to be balanced by their increased computational cost.

scholarly journals Efficient charge separation and visible-light response in bilayer HfS2-based van der Waals heterostructures

RSC Advances ◽  
2018 ◽  
Vol 8 (34) ◽  
pp. 18889-18895 ◽  
Author(s):  
Biao Wang ◽  
Xukai Luo ◽  
Junli Chang ◽  
Xiaorui Chen ◽  
Hongkuan Yuan ◽  
...  
Keyword(s):  
Charge Separation ◽  
Density Functional ◽  
Van Der Waals ◽  
Light Response ◽  
Hybrid Density Functional Theory ◽  
Functional Theory ◽  
Visible Light Response ◽  
Efficient Charge ◽  
Hybrid Density Functional ◽  
Photocatalytic Applications

In this work, we employ hybrid density functional theory to investigate HfS2-based van der Waals (vdW) heterojunctions for highly efficient photovoltaic and photocatalytic applications.

Activity of faujasite supported gold monomer towards water gas shift reaction: hybrid density functional theory/molecular mechanics approach

RSC Advances ◽  
2015 ◽  
Vol 5 (96) ◽  
pp. 78864-78873 ◽  
Author(s):  
Subhi Baishya ◽  
Ramesh Ch. Deka
Keyword(s):  
Density Functional ◽  
Water Gas Shift ◽  
Hybrid Density Functional Theory ◽  
Water Gas Shift Reaction ◽  
Functional Theory ◽  
Cationic Monomer ◽  
Shift Reaction ◽  
Supported Gold ◽  
Water Gas ◽  
Hybrid Density Functional

Neutral gold monomer supported on faujasite (Au0/FAU) exhibits superior catalytic activity towards water gas shift reaction compared to cationic monomer.

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