scholarly journals Catalyst design in C–H activation: a case study in the use of binding free energies to rationalise intramolecular directing group selectivity in iridium catalysis

2021 ◽  
Author(s):  
William J. Kerr ◽  
Gary J. Knox ◽  
Marc Reid ◽  
Tell Tuttle
Keyword(s):  
In Silico ◽  
Catalyst Design ◽  
Free Energies ◽  
Iridium Catalysis ◽  
Bifunctional Molecule ◽  
Directing Group ◽  
Binding Free Energies

In C–H activation chemistries, the interpretation of the influence of remote directing groups in a bifunctional molecule depends on the in silico method used to inform catalyst design.

scholarly journals Catalyst Design in C–H Activation: A Case Study in the Use of Binding Free Energies to Rationalise Intramolecular Directing Group Selectivity in Iridium Catalysis

2021 ◽  
Author(s):  
William Kerr ◽  
Gary J. Knox ◽  
Marc Reid ◽  
Tell Tuttle
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Catalyst Design ◽  
Binding Energies ◽  
Mechanistic Study ◽  
Iridium Catalysis ◽  
The Face ◽  
Directing Group ◽  
Limiting Case

<div>Remote directing groups in a bifunctional molecule do not always behave independently of one another in C–H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C–H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity. Rational catalyst design, guided solely by qualitative substrate-catalyst binding free energy predictions, enabled intramolecular discrimination between competing ortho directing groups in C–H activation and delivered improved catalysts for sulfonamide-selective C–H deuteration. As a result, chemoselective binding of the primary sulfonamide moiety was achieved in the face of an intrinsically more powerful pyrazole directing group present in the same molecule. Detailed DFT calcualtions and mechanistic experiments revealed a breakdown in the applied binding free energy model, illustrating the important interconnectivity of ligand design, substrate geometry, directing group cooperativity, and solvation in supporting DFT calculations. This work has important implications around attempts to predict intramolecular C–H activation directing group chemoselectivity using simplified monofunctional fragment molecules. More generally, these studies provide insights for catalyst design methods for late-stage C–H functionalisation.</div>

scholarly journals Catalyst Design in C–H Activation: A Case Study in the Use of Binding Free Energies to Rationalise Intramolecular Directing Group Selectivity in Iridium Catalysis

2021 ◽  
Author(s):  
William Kerr ◽  
Gary J. Knox ◽  
Marc Reid ◽  
Tell Tuttle
Keyword(s):  
Free Energy ◽  
Dft Calculations ◽  
Binding Free Energy ◽  
Catalyst Design ◽  
Binding Energies ◽  
Mechanistic Study ◽  
The Face ◽  
Directing Group ◽  
Limiting Case

<div>Remote directing groups in a bifunctional molecule do not always behave independently of one another in C–H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C–H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity. Rational catalyst design, guided solely by qualitative substrate-catalyst binding free energy predictions, enabled intramolecular discrimination between competing ortho directing groups in C–H activation and delivered improved catalysts for sulfonamide-selective C–H deuteration. As a result, chemoselective binding of the primary sulfonamide moiety was achieved in the face of an intrinsically more powerful pyrazole directing group present in the same molecule. Detailed DFT calculations and mechanistic experiments revealed a breakdown in the applied binding free energy model, illustrating the important interconnectivity of ligand design, substrate geometry, directing group cooperativity, and solvation in supporting DFT calculations. This work has important implications around attempts to predict intramolecular C–H activation directing group chemoselectivity using simplified monofunctional fragment molecules. More generally, these studies provide insights for catalyst design methods for late-stage C–H functionalisation.</div>

scholarly journals In silico studies of ASEM analogues targeting α7-nAChR and experimental verification

RSC Advances ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 3942-3951
Author(s):  
Yang Zhou ◽  
Guanglin Kuang ◽  
Junhao Li ◽  
Christer Halldin ◽  
Agneta Nordberg ◽  
...  
Keyword(s):  
Experimental Verification ◽  
In Silico ◽  
Free Energies ◽  
Binding Assays ◽  
Α7 Nachr ◽  
In Silico Studies ◽  
Binding Free Energies

The in silico binding free energies of the ASEM analogues targeting α7-nAChR are in line with the inhibition obtained from in vitro binding assays.

scholarly journals Effect of Composition and Surface Type on Activity of Transition Metal Oxides and Sulfides for CO2 Electrochemical Reduction

2020 ◽  
Author(s):  
Sahithi Ananthaneni ◽  
Rees Rankin
Keyword(s):  
Transition Metal ◽  
Metal Oxides ◽  
Transition Metal Oxides ◽  
Catalyst Activity ◽  
Catalyst Design ◽  
Product Selectivity ◽  
Free Energies ◽  
Intermediate Species ◽  
Catalyst Composition ◽  
Binding Free Energies

Transition metal oxides (TMO) and transition metal sulfides (TMS) are proven to be promising electrocatalysts for CO2RR but there is no clear understanding on catalyst activity or product selectivity based on trends in binding free energies. Therefore, a broader array of TMO and TMS are studied as electrocatalysts for CO2RR thus addressing the gap in this field. This work shows how different types of surface facets with same catalyst composition can fine-tune the binding free energies of intermediate species by modifying the active binding site. Here, catalyst activity for CO2RR towards formation of 4 different products is computed and compared for different materials with (100), (110) and (111) crystal facets and based on this, product selectivity is determined. Optimal catalyst design strategies for this family of materials are developed using the binding free energies of 4 key intermediate species COOH*, CO*, HCO* and H*. In this study, among the materials studied, ZnO zincblende (100) is the material that showed highest catalyst activity towards CO2RR to CH3OH and CH4 while minimizing HER<br>

An In Silico Approach of Coumarin-Derived Inhibitors for Human DNA Topoisomerase I

2016 ◽  
Vol 69 (9) ◽  
pp. 1005 ◽  
Author(s):  
Amali G. Guruge ◽  
Chandani Udawatte ◽  
Samantha Weerasinghe
Keyword(s):  
In Silico ◽  
Topoisomerase I ◽  
Docking Studies ◽  
The Other ◽  
Planar Geometry ◽  
Free Energies ◽  
Anti Cancer ◽  
Poisson Boltzmann ◽  
Binding Free Energies

Human topoisomerase I (Htopo I) is a vital target for anti-cancer agents; however, available anti-cancer agents are linked with several limitations. Therefore, designing novel inhibitors for Htopo I is significant. The rationale behind the current study is to identify novel coumarin inhibitors for Htopo I using in silico approaches and predict drug leads for in vitro studies. Using molecular docking and molecular dynamics, the binding affinities of 75 coumarins were compared with a known Htopo I inhibitor, topotecan. Docking studies predict three coumarins T1L25, T2L25, and T3L25 as most potent inhibitors for Htopo I. T2L25 gives the best grid score (–295 kJ mol–1), which is very comparable with that of topotecan (–302 kJ mol–1). The binding of these coumarins occurs preferentially via a planar geometry, and ligands bind at the binding site parallel to the axis of base pairing. NHCOCH3-substituted ligands are more favourable for binding when compared with the other substitute groups considered. The binding free energies calculated from molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) method imply that T3L25 possesses the highest binding affinity when compared with the other two ligands. However, T1L25 and T2L25 have comparable binding free energies according to MM-PBSA calculations. Additionally, other calculated properties also support the suitability of these three derivatives as inhibitors for Htopo I. Therefore, the current study theoretically predicts three coumarin derivatives T1L25, T2L25, and T3L25 as potent inhibitors for Htopo I. These findings could lead to exploring novel non-camptothecin inhibitors for Htopo I.

scholarly journals Effect of Composition and Surface Type on Activity of Transition Metal Oxides and Sulfides for CO2 Electrochemical Reduction

2020 ◽  
Author(s):  
Sahithi Ananthaneni ◽  
Rees Rankin
Keyword(s):  
Transition Metal ◽  
Metal Oxides ◽  
Transition Metal Oxides ◽  
Catalyst Activity ◽  
Catalyst Design ◽  
Product Selectivity ◽  
Free Energies ◽  
Intermediate Species ◽  
Catalyst Composition ◽  
Binding Free Energies

Transition metal oxides (TMO) and transition metal sulfides (TMS) are proven to be promising electrocatalysts for CO2RR but there is no clear understanding on catalyst activity or product selectivity based on trends in binding free energies. Therefore, a broader array of TMO and TMS are studied as electrocatalysts for CO2RR thus addressing the gap in this field. This work shows how different types of surface facets with same catalyst composition can fine-tune the binding free energies of intermediate species by modifying the active binding site. Here, catalyst activity for CO2RR towards formation of 4 different products is computed and compared for different materials with (100), (110) and (111) crystal facets and based on this, product selectivity is determined. Optimal catalyst design strategies for this family of materials are developed using the binding free energies of 4 key intermediate species COOH*, CO*, HCO* and H*. In this study, among the materials studied, ZnO zincblende (100) is the material that showed highest catalyst activity towards CO2RR to CH3OH and CH4 while minimizing HER<br>

scholarly journals Catalyst Design in C–H Activation: A Case Study in the Use of Binding Free Energies to Rationalise Intramolecular Directing Group Selectivity in Iridium Catalysis

2021 ◽  
Author(s):  
William Kerr ◽  
Gary J. Knox ◽  
Marc Reid ◽  
Tell Tuttle
Keyword(s):  
Free Energy ◽  
Dft Calculations ◽  
Binding Free Energy ◽  
Catalyst Design ◽  
Binding Energies ◽  
Mechanistic Study ◽  
The Face ◽  
Directing Group ◽  
Limiting Case

<div>Remote directing groups in a bifunctional molecule do not always behave independently of one another in C–H activation chemistries. A combined DFT and experimental mechanistic study to provide enhanced Ir catalysts for chemoselective C–H deuteration of bifunctional aryl primary sulfonamides is described. This provides a pharmaceutically relevant and limiting case study in using binding energies to predict intramolecular directing group chemoselectivity. Rational catalyst design, guided solely by qualitative substrate-catalyst binding free energy predictions, enabled intramolecular discrimination between competing ortho directing groups in C–H activation and delivered improved catalysts for sulfonamide-selective C–H deuteration. As a result, chemoselective binding of the primary sulfonamide moiety was achieved in the face of an intrinsically more powerful pyrazole directing group present in the same molecule. Detailed DFT calculations and mechanistic experiments revealed a breakdown in the applied binding free energy model, illustrating the important interconnectivity of ligand design, substrate geometry, directing group cooperativity, and solvation in supporting DFT calculations. This work has important implications around attempts to predict intramolecular C–H activation directing group chemoselectivity using simplified monofunctional fragment molecules. More generally, these studies provide insights for catalyst design methods for late-stage C–H functionalisation.</div>

scholarly journals Purification and identification of metabolites produced by Bacillus cereus and B. subtilis active against Meloidogyne exigua, and their in silico interaction with a putative phosphoribosyltransferase fromM. incognita

2014 ◽  
Vol 86 (2) ◽  
pp. 525-538 ◽  
Author(s):  
DENILSON F. OLIVEIRA ◽  
HELVÉCIO M. DOS SANTOS JÚNIOR ◽  
ALEXANDRO S. NUNES ◽  
VICENTE P. CAMPOS ◽  
RENATA S.C. DE PINHO ◽  
...  
Keyword(s):  
Bacillus Cereus ◽  
Active Site ◽  
In Silico ◽  
Parasitic Nematode ◽  
Free Energies ◽  
Similar Sequence ◽  
Dynamics Simulations ◽  
Plant Parasitic ◽  
Selection Of ◽  
Binding Free Energies

To contribute to the development of products to controlMeloidogyne exigua, the bacteria Bacillus cereus and B. subtilis were cultivated in liquid medium to produce metabolites active against this plant-parasitic nematode. Fractionation of the crude dichloromethane extracts obtained from the cultures afforded uracil, 9H-purine and dihydrouracil. All compounds were active against M. exigua, the latter being the most efficient. This substance presented a LC50 of 204 µg/mL against the nematode, while a LC50 of 260 µg/mL was observed for the commercial nematicide carbofuran. A search for protein-ligand complexes in which the ligands were structurally similar to dihydrouracil resulted in the selection of phosphoribosyltransferases, the sequences of which were used in an in silico search in the genome of M. incognita for a similar sequence of amino acids. The resulting sequence was modelled and dihydrouracil and 9H-purine were inserted in the active site of this putative phosphoribosyltransferase resulting in protein-ligand complexes that underwent molecular dynamics simulations. Calculation of the binding free-energies of these complexes revealed that the dissociation constant of dihydrouracil and 9H-purine to this protein is around 8.3 x 10-7 and 1.6 x 10-6 M, respectively. Consequently, these substances and the putative phosphoribosyltransferase are promising for the development of new products to control M. exigua.

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