scholarly journals Near-Stoichiometric Conversion of H2O2to FeIV=O at a Nonheme Iron(II) Center. Insights into the O−O Bond Cleavage Step

2010 ◽  
Vol 132 (7) ◽  
pp. 2134-2135 ◽  
Author(s):  
Feifei Li ◽  
Jason England ◽  
Lawrence Que
Keyword(s):  
Bond Cleavage ◽  
Nonheme Iron ◽  
Cleavage Step

scholarly journals Mechanistic Insight into the Ring-Opening Polymerization of ɛ-Caprolactone and L-Lactide Using Ketiminate-Ligated Aluminum Catalysts

Polymers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1530 ◽  
Author(s):  
Lin ◽  
Jheng
Keyword(s):  
Thermal Effects ◽  
Ring Opening ◽  
Density Functional ◽  
Bond Cleavage ◽  
Ring Opening Polymerization ◽  
Catalyst Design ◽  
Reaction Conditions ◽  
Functional Theory ◽  
Cleavage Step ◽  
Insight Into

The reactivity and the reaction conditions of the ring-opening polymerization of ɛ-caprolactone (ɛ-CL) and L-lactide (LA) initiated by aluminum ketiminate complexes have been shown differently. Herein, we account for the observation by studying the mechanisms on the basis of density functional theory (DFT) calculations. The calculations show that the ring-opening polymerization of ɛ-CL and LA are rate-determined by the benzoxide insertion and the C–O bond cleavage step, respectively. Theoretical computations suggest that the reaction temperature of L–LA polymerization should be higher than that of ɛ-CL one, in agreement with the experimental data. To provide a reasonable interpretation of the experimental results and to give an insight into the catalyst design, the influence of the electronic, steric, and thermal effects on the polymerization behaviors will be also discussed in this study.

Rhodium(I)-Catalysed Aryl C–H Carboxylation of 2-Arylanilines with CO2

2019 ◽  
Author(s):  
yuzhen gao ◽  
Zhihua Cai ◽  
Shangda Li ◽  
Gang Li
Keyword(s):  
General Type ◽  
Bond Cleavage ◽  
Bond Formation ◽  
Direct Conversion ◽  
Activation Process ◽  
Amino Group ◽  
Mechanistic Studies ◽  
Organometallic Reagent ◽  
Cleavage Step ◽  
Neutral Conditions

<b>An unprecedented amino-group assisted C–H carboxylation of 2-arylanilines with CO<sub>2</sub> under redox-neutral conditions using a Rhodium(I)-catalyst has been developed. This reaction was promoted by a phosphine ligand with <i>t</i>-BuOK as the base and did not require the use of an extra strong organometallic reagent. Notably, this protocol may involve an oxidative addition in the C–H bond cleavage step and is distinct from previous Rh(I) or Rh(II)-catalysed methods for C–H carboxylation with </b><b>CO<sub>2</sub> </b><b>mechanistically. It enabled an efficient direct conversion of a broad range of 2-(hetero)arylanilines including electron-deficient heteroarenes to various phenanthridinones, which could be further transformed to other synthetically useful compounds readily. Preliminary mechanistic studies were carried out and possible intermediates of the reaction were evaluated, which revealed that the Rh(I)-catalyst is essential for the C–H activation process, providing a promising general type of method for utilization of </b><b>CO<sub>2</sub></b><b> for C–C bond formation.</b><br>

Gold(III)/Sodium Diphenylphosphinobenzene-3-sulfonate (TPPMS) Catalyzed Dehydrative N-Benzylation of Electron-Deficient Anilines in Water

Synthesis ◽  
2019 ◽  
Vol 51 (13) ◽  
pp. 2729-2736 ◽  
Author(s):  
Hidemasa Hikawa ◽  
Mika Matsumoto ◽  
Sayoko Tawara ◽  
Shoko Kikkawa ◽  
Isao Azumaya
Keyword(s):  
Lewis Acid ◽  
Acid Catalysis ◽  
Bond Cleavage ◽  
Solvent Isotope Effect ◽  
Mild Conditions ◽  
Simple Protocol ◽  
Economic Process ◽  
Cleavage Step ◽  
Activation Of Alcohols ◽  
Solvent Isotope

A strategy for the dehydrative N-benzylation of electron-deficient anilines in water has been developed. The gold(III)/sodium diphenylphosphinobenzene-3-sulfonate (TPPMS) catalyst is highly effective as a Lewis acid for the activation of alcohols and tolerates aerobic conditions. A Hammett study in the reaction of para-substituted benzhydryl alcohols shows negative σ values, indicating a build-up of cationic charge during the rate-determining sp3 C–O bond-cleavage step. The inverse kinetic solvent isotope effect (KSIE = 0.6) is consistent with a specific acid catalysis mechanism. This simple protocol can be performed under mild conditions in an atom-economic process without the need for base or other additives, furnishing the electron-deficient N-benzylic anilines in moderate to excellent yields along with water as a sole coproduct.

scholarly journals Mechanistic studies on C-19 demethylation in oestrogen biosynthesis

1982 ◽  
Vol 201 (3) ◽  
pp. 569-580 ◽  
Author(s):  
Muhammad Akhtar ◽  
Michael R. Calder ◽  
David L. Corina ◽  
J. Neville Wright
Keyword(s):  
Formic Acid ◽  
Bond Cleavage ◽  
Mechanistic Studies ◽  
Hydroxy Compound ◽  
Microsomal Preparation ◽  
Methyl Group ◽  
Cleavage Step ◽  
Compound Ii ◽  
Cumulative Evidence ◽  
Oxygen Atoms

Mechanistic aspects of the biosynthesis of oestrogen have been studied with a microsomal preparation from full-term human placenta. The overall transformation, termed the aromatization process, involves three steps using O2 and NADPH, in which the C-19 methyl group of an androgen is oxidised to formic acid with concomitant production of the aromatic ring of oestrogen: [Formula: see text] To study the mechanism of this process in terms of the involvement of the oxygen atoms, a number of labelled precursors were synthesized. Notable amongst these were 19-hydroxy-4-androstene-3,17-dione (II) and 19-oxo-4-androstene-3,17-dione (IV) in which the C-19 was labelled with2H in addition to18O. In order to follow the fate of the labelled atoms at C-19 of (II) and (IV) during the aromatization, the formic acid released from C-19 was benzylated and analysed by mass spectrometry. Experimental procedures were devised to minimize the exchange of oxygen atoms in substrates and product with oxygens of the medium. In the conversion of the 19-[18O] compounds of types (II) and (IV) into 3-hydroxy-1,3,5-(10)-oestratriene-17-one (V, oestrone), it was found that the formic acid from C-19 retained the original substrate oxygen. When the equivalent16O substrates were aromatized under18O2, the formic acid from both substrates contained one atom of18O. It is argued that in the conversion of the 19-hydroxy compound (II) into the 19-oxo compound (IV), the C-19 oxygen of the former remains intact and that one atom of oxygen from O2 is incorporated into formic acid during the conversion of the 19-oxo compound (IV) into oestrogen. This conclusion was further substantiated by demonstrating that in the aromatization of 4-androstene-3,17-dione (I), both the oxygen atoms in the formic acid originated from molecular oxygen. 10β-Hydroxy-4-oestrene-3,17-dione formate, a possible intermediate in the aromatization, was synthesized and shown not to be converted into oestrogen. In the light of the cumulative evidence available to date, stereochemical aspects of the conversion of the 19-hydroxy compound (II) into the 19-oxo compound (IV), and mechanistic features of the C-10–C-19 bond cleavage step during the conversion of the 19-oxo compound (IV) into oestrogen are discussed.

Remdesivir: Mechanism of Metabolic Conversion from Prodrug to Drug

2021 ◽  
Vol 23 ◽  
Author(s):  
Saumya Kapoor ◽  
Gurudutt Dubey ◽  
Samima Khatun ◽  
Prasad V. Bharatam
Keyword(s):  
Potential Energy ◽  
Potential Energy Surface ◽  
Density Functional ◽  
Energy Surface ◽  
Bond Cleavage ◽  
Catalytic Triad ◽  
Model System ◽  
Metabolic Reaction ◽  
Additional Water ◽  
Cleavage Step

Background: Remdesivir (GS-5734) has emerged as a promising drug during the challenging times of COVID-19 pandemic. Being a prodrug, it undergoes several metabolic reactions before converting to its active triphosphate metabolite. It is important to establish the atomic level details and explore the energy profile of the prodrug to drug conversion process. Methods: In this work, Density Functional Theory (DFT) calculations were performed to explore the entire metabolic path. Further, the potential energy surface (PES) diagram for the conversion of prodrug remdesivir to its active metabolite was established. The role of catalytic triad of Hint1 phosphoramidase enzyme in P-N bond hydrolysis was also studied on a model system using combined molecular docking and quantum mechanics approach. Results: The overall energy of reaction is 11.47 kcal/mol exergonic and the reaction proceeds through many steps requiring high activation energies. In the absence of a catalyst, the P-N bond breaking step requires 41.78 kcal/mol, which is reduced to 14.26 kcal/mol in a catalytic environment. Conclusion: The metabolic pathways of model system of remdesivir (MSR) were completely explored completely and potential energy surface diagrams at two levels of theory, B3LYP/6-311++G(d, p) and B3LYP/6-31+G(d), were established and compared. The results highlight the importance of an additional water molecule in the metabolic reaction. The P-N bond cleavage step of the metabolic process requires the presence of an enzymatic environment.

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