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Wonwoo Nam - One of the best experts on this subject based on the ideXlab platform.
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tunneling controls the reaction pathway in the Deformylation of aldehydes by a nonheme iron iii hydroperoxo complex hydrogen atom abstraction versus nucleophilic addition
Journal of the American Chemical Society, 2019Co-Authors: Seong Hee Bae, Mi Sook Seo, Wonwoo Nam, Shunichi Fukuzumi, Yongmin LeeAbstract:Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)-hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the Deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde Deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde Deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C-H bonds by a mononuclear nonheme iron(III)-hydroperoxo complex.
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Tunneling Controls the Reaction Pathway in the Deformylation of Aldehydes by a Nonheme Iron(III)–Hydroperoxo Complex: Hydrogen Atom Abstraction versus Nucleophilic Addition
2019Co-Authors: Seong Hee Bae, Mi Sook Seo, Shunichi Fukuzumi, Yongmin Lee, Wonwoo NamAbstract:Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)–hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the Deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde Deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde Deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C–H bonds by a mononuclear nonheme iron(III)–hydroperoxo complex
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Reactivity of a cobalt(III)-peroxo complex in oxidative nucleophilic reactions
Journal of inorganic biochemistry, 2008Co-Authors: Jamespandi Annaraj, Mi Sook Seo, Jaeheung Cho, Yongmin Lee, Sung Yeon Kim, Wonwoo NamAbstract:Abstract A mononuclear cobalt(III)-peroxo complex bearing a macrocyclic tetradentate N 4 ligand, [Co III (TMC)(O 2 )] + (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), was generated in the reaction of [Co II (TMC)] 2+ and H 2 O 2 in the presence of triethylamine in CH 3 CN. The reactivity of the cobalt(III)-peroxo complex was investigated in aldehyde Deformylation with various aldehydes and compared with that of iron(III)- and manganese(III)-peroxo complexes, such as [Fe III (TMC)(O 2 )] + and [Mn III (TMC)(O 2 )] + . In this reactivity comparison, the reactivities of metal-peroxo species were found to be in the order of [Mn III (TMC)(O 2 )] + > [Co III (TMC)(O 2 )] + > [Fe III (TMC)(O 2 )] + . A positive Hammett ρ value of 1.8, obtained in the reactions of [Co III (TMC)(O 2 )] + and para -substituted benzaldehydes, demonstrates that the aldehyde Deformylation by the cobalt(III)-peroxo species occurs via a nucleophilic reaction.
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Reactivities of mononuclear non-heme iron intermediates including evidence that iron(III)-hydroperoxo species is a sluggish oxidant.
Journal of the American Chemical Society, 2006Co-Authors: Mi Joo Park, Yumi Suh, Jimin Lee, Jinheung Kim, Wonwoo NamAbstract:There is an intriguing, current controversy on the involvement of iron(III)−hydroperoxo species as a “second electrophilic oxidant” in oxygenation reactions by heme and non-heme iron enzymes and their model compounds. In the present work, we have performed reactivity studies of the iron−hydroperoxo species in nucleophilic and electrophilic reactions, with in situ-generated mononuclear non-heme iron(III)−hydroperoxo complexes that have been well characterized with various spectroscopic techniques. The intermediates did not show any reactivities in the nucleophilic (e.g., aldehyde Deformylation) and electrophilic (e.g., oxidation of sulfide and olefin) reactions. These results demonstrate that non-heme iron(III)−hydroperoxo species are sluggish oxidants and that the oxidizing power of the intermediates cannot compete with that of high-valent iron(IV)−oxo complexes. We have also reported reactivities of mononuclear non-heme iron(III)−peroxo and iron(IV)−oxo complexes in the aldehyde Deformylation and the oxi...
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Mononuclear nonheme ferric-peroxo complex in aldehyde Deformylation
Chemical communications (Cambridge England), 2005Co-Authors: Jamespandi Annaraj, Yumi Suh, Mi Sook Seo, Sun Ok Kim, Wonwoo NamAbstract:A mononuclear nonheme ferric-peroxo complex bearing a macrocyclic tetradentate N4 ligand, [(TMC)FeIII–O2]+, was prepared and used in mechanistic studies of aldehyde Deformylation; a catalytic aldehyde Deformylation by a nonheme iron(II) complex, [FeII(TMC)]2+, and molecular oxygen is reported as well.
John C. Hackett - One of the best experts on this subject based on the ideXlab platform.
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Peroxo−Iron Mediated Deformylation in Sterol 14α-Demethylase Catalysis
Journal of the American Chemical Society, 2010Co-Authors: Kakali Sen, John C. HackettAbstract:The mechanisms of cytochrome P450 (CYP) catalyzed C−C bond cleavage have been strongly debated and difficult to unravel. Herein, Deformylation mechanisms of the sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis are elucidated using molecular dynamics simulation, density functional theory, and hybrid quantum mechanics/molecular mechanics methods. These results provide strong theoretical support for the operation of the peroxo intermediate in CYP-catalyzed Deformylation. Molecular dynamics simulations support the lanosterol carboxaldehyde intermediate diverts the hydrogen-bonded network of water putatively involved in proton delivery to peroxo and compound 0 (Cmpd 0) away from the O2 ligand. In the presence of the aldehyde substrate, the peroxo intermediate is trapped as the peroxohemiacetal without an apparent barrier, which may then be protonated in the active site. The unprotonated peroxohemiacetal provides a branch point for a concerted Deformylation mechanism; however, a stepwise mechanism...
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peroxo iron mediated Deformylation in sterol 14α demethylase catalysis
Journal of the American Chemical Society, 2010Co-Authors: Kakali Sen, John C. HackettAbstract:The mechanisms of cytochrome P450 (CYP) catalyzed C−C bond cleavage have been strongly debated and difficult to unravel. Herein, Deformylation mechanisms of the sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis are elucidated using molecular dynamics simulation, density functional theory, and hybrid quantum mechanics/molecular mechanics methods. These results provide strong theoretical support for the operation of the peroxo intermediate in CYP-catalyzed Deformylation. Molecular dynamics simulations support the lanosterol carboxaldehyde intermediate diverts the hydrogen-bonded network of water putatively involved in proton delivery to peroxo and compound 0 (Cmpd 0) away from the O2 ligand. In the presence of the aldehyde substrate, the peroxo intermediate is trapped as the peroxohemiacetal without an apparent barrier, which may then be protonated in the active site. The unprotonated peroxohemiacetal provides a branch point for a concerted Deformylation mechanism; however, a stepwise mechanism...
Debabrata Maiti - One of the best experts on this subject based on the ideXlab platform.
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palladium catalyzed Deformylation reactions with detailed experimental and in silico mechanistic studies
European Journal of Organic Chemistry, 2017Co-Authors: Atanu Modak, Sujoy Rana, Ashwini K. Phukan, Debabrata MaitiAbstract:A facile, efficient and general Deformylation reaction has been developed using palladium acetate as precatalyst under exogenous ligand-free conditions with a wide range of functional group compatibility. Mechanistic details of the palladium catalyzed Deformylation reaction have been outlined based on the combination of experimental and computational studies. The heterogeneous pathway is predominant for the Deformylation along with the existence of lesser extent of homogeneous catalysis. This ligand-free catalytic cycle is proposed to undergo oxidative addition, migratory extrusion and reductive elimination as key steps. Kinetic studies reveal the 1st order rate dependency with respect to aldehyde. Furthermore, kinetic isotope effect, competition experiment and Hammett study suggest that the migratory extrusion step is the rate determining step which has also been supported by DFT studies.
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Palladium‐Catalyzed Deformylation Reactions with Detailed Experimental and in Silico Mechanistic Studies
European Journal of Organic Chemistry, 2017Co-Authors: Atanu Modak, Sujoy Rana, Ashwini K. Phukan, Debabrata MaitiAbstract:A facile, efficient and general Deformylation reaction has been developed using palladium acetate as precatalyst under exogenous ligand-free conditions with a wide range of functional group compatibility. Mechanistic details of the palladium catalyzed Deformylation reaction have been outlined based on the combination of experimental and computational studies. The heterogeneous pathway is predominant for the Deformylation along with the existence of lesser extent of homogeneous catalysis. This ligand-free catalytic cycle is proposed to undergo oxidative addition, migratory extrusion and reductive elimination as key steps. Kinetic studies reveal the 1st order rate dependency with respect to aldehyde. Furthermore, kinetic isotope effect, competition experiment and Hammett study suggest that the migratory extrusion step is the rate determining step which has also been supported by DFT studies.
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Metal-mediated Deformylation reactions: synthetic and biological avenues.
Angewandte Chemie (International ed. in English), 2011Co-Authors: Tuhin Patra, Srimanta Manna, Debabrata MaitiAbstract:Methods for the removal of functional groups from organic molecules are immensely important in synthesis and biology. Synthetically, the utility of functional groups is mainly due to their ability to act as directing groups as well as their high reactivity and selectivity in a wide variety of transformations. In this regard, metal-mediated Deformylation reactions have attracted the attention of chemists for decades since such processes enable temporary use of the beneficial features of the CHO functionality. Also the majority of C!C bondcleavage reactions catalyzed by cytochrome P450 (CYP) in nature are Deformylation reactions. Interestingly, the biosynthesis of alkanes and alkenes from cyanobacteria has been recently suggested to occur through Deformylation as one of the key steps. In 2008, Madsen and co-workers reported detailed mechanistic studies on the decarbonylation of aldehydes catalyzed by a bidentate phosphine ligated rhodium complex (Scheme 1). Linear Hammett plots having positive slopes of+ 0.79 and+ 0.43 were obtained for both the benzaldehyde derivatives and the phenyl acetaldehyde derivatives, respectively. These values suggest that there is a build up of a negative charge in the selectivity determining steps in both cases. The observed kinetic isotope effect values of 1.73 for benzaldehyde and 1.77 for phenyl acetaldehyde indicate a similarity in their reaction mechanisms. A detailed density functional theory (DFT; B3LYP) study of the catalytic cycle suggested a rapid oxidative addition into the C(O)!H bond followed by the rate-limiting elimination of CO and product formation. Furthermore, the theoretical kinetic isotope effects matched well with the observed experimental values for both benzaldehyde and phenyl acetaldehyde, provided removal of carbon monoxide was selected as the ratedetermining step. Based on this information, the Deformylation mechanism by rhodium complexes are suggested to be as follows: 1) coordination of the aldehyde substrate to the metal complex, 2) oxidative addition of the aldehydic C!H bond to form a metal acyl complex (Rh!Rh), 3) migratory extrusion of carbon monoxide, 4) reductive elimination of the product (Rh!Rh). For the case of cytochrome-P450-catalyzed Deformylation, methyl group hydroxylation occurs first to generate an alcohol and then a geminal diol. The diol intermediate then dehydrates to the aldehyde, which is removed by the enzyme. Sen and Hackett demonstrated the Deformylation mechanism of the sterol 14a-demethylase (CYP51) from Mycobacterium tuberculosis by using a molecular dynamics simulation, DFT, and hybrid quantum mechanics/molecular mechanics methods. A heme/peroxo intermediate has been established as the key active species in CYP-catalyzed Deformylation (Scheme 2). Molecular dynamics simulations indicate that the hydrogen-bonded proton shuttle in this enzyme is diverted to the aldehyde oxygen atom from the peroxo intermediate, thus allowing the peroxo species to accumulate. In turn, the peroxo intermediate is trapped by the preorganized aldehyde substrate, thus resulting in a peroxohemiacetal without an apparent barrier. A transition state for the concerted rearrangement to produce the formate and the triene steroid was found; however, a stepwise mechanism involving heterolytic C!C bond cleavage is favored as a result of its lower energy, and thus a carbanion at C14 is generated along the way. The researchers also show that a homolytic C! C cleavage is favorable in the absence of the protein electrostatic background. According to them, this fact clearly Scheme 1. Catalytic cycle for the rhodium-catalyzed decarbonylation of aldehydes.
Shunichi Fukuzumi - One of the best experts on this subject based on the ideXlab platform.
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tunneling controls the reaction pathway in the Deformylation of aldehydes by a nonheme iron iii hydroperoxo complex hydrogen atom abstraction versus nucleophilic addition
Journal of the American Chemical Society, 2019Co-Authors: Xiaoxi Li, Shunichi FukuzumiAbstract:Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)–hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the Deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde Deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde Deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde pr...
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tunneling controls the reaction pathway in the Deformylation of aldehydes by a nonheme iron iii hydroperoxo complex hydrogen atom abstraction versus nucleophilic addition
Journal of the American Chemical Society, 2019Co-Authors: Seong Hee Bae, Mi Sook Seo, Wonwoo Nam, Shunichi Fukuzumi, Yongmin LeeAbstract:Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)-hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the Deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde Deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde Deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C-H bonds by a mononuclear nonheme iron(III)-hydroperoxo complex.
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Tunneling Controls the Reaction Pathway in the Deformylation of Aldehydes by a Nonheme Iron(III)–Hydroperoxo Complex: Hydrogen Atom Abstraction versus Nucleophilic Addition
2019Co-Authors: Seong Hee Bae, Mi Sook Seo, Shunichi Fukuzumi, Yongmin Lee, Wonwoo NamAbstract:Mononuclear nonheme iron(III)-hydroperoxo intermediates play key roles in biological oxidation reactions. In the present study, we report the highly intriguing reactivity of a nonheme iron(III)–hydroperoxo complex, [(TMC)FeIII(OOH)]2+ (1), in the Deformylation of aldehydes, such as 2-phenylpropionaldehyde (2-PPA) and its derivatives; that is, the reaction pathway of the aldehyde Deformylation by 1 varies depending on reaction conditions, such as temperature and substrate. At temperature above 248 K, the aldehyde Deformylation occurs predominantly via a nucleophilic addition (NA) pathway. However, as the reaction temperature is lowered, the reaction pathway changes to a hydrogen atom transfer (HAT) pathway. Interestingly, the reaction rate becomes independent of temperature below 233 K with a huge kinetic isotope effect (KIE) value of 93 at 203 K, suggesting that the HAT reaction results from tunneling. In contrast, reactions with a deuterated 2-PPA at the α-position and 2-methyl-2-phenylpropionaldehyde proceed exclusively via a NA pathway irrespective of the reaction temperature. We conclude that the bifurcation pathways between NA and HAT result from the tunneling effect in the HAT reaction by 1. To the best of our knowledge, this study reports the first example showing that tunneling plays a significant role in the activation of substrate C–H bonds by a mononuclear nonheme iron(III)–hydroperoxo complex
Kakali Sen - One of the best experts on this subject based on the ideXlab platform.
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Peroxo−Iron Mediated Deformylation in Sterol 14α-Demethylase Catalysis
Journal of the American Chemical Society, 2010Co-Authors: Kakali Sen, John C. HackettAbstract:The mechanisms of cytochrome P450 (CYP) catalyzed C−C bond cleavage have been strongly debated and difficult to unravel. Herein, Deformylation mechanisms of the sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis are elucidated using molecular dynamics simulation, density functional theory, and hybrid quantum mechanics/molecular mechanics methods. These results provide strong theoretical support for the operation of the peroxo intermediate in CYP-catalyzed Deformylation. Molecular dynamics simulations support the lanosterol carboxaldehyde intermediate diverts the hydrogen-bonded network of water putatively involved in proton delivery to peroxo and compound 0 (Cmpd 0) away from the O2 ligand. In the presence of the aldehyde substrate, the peroxo intermediate is trapped as the peroxohemiacetal without an apparent barrier, which may then be protonated in the active site. The unprotonated peroxohemiacetal provides a branch point for a concerted Deformylation mechanism; however, a stepwise mechanism...
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peroxo iron mediated Deformylation in sterol 14α demethylase catalysis
Journal of the American Chemical Society, 2010Co-Authors: Kakali Sen, John C. HackettAbstract:The mechanisms of cytochrome P450 (CYP) catalyzed C−C bond cleavage have been strongly debated and difficult to unravel. Herein, Deformylation mechanisms of the sterol 14α-demethylase (CYP51) from Mycobacterium tuberculosis are elucidated using molecular dynamics simulation, density functional theory, and hybrid quantum mechanics/molecular mechanics methods. These results provide strong theoretical support for the operation of the peroxo intermediate in CYP-catalyzed Deformylation. Molecular dynamics simulations support the lanosterol carboxaldehyde intermediate diverts the hydrogen-bonded network of water putatively involved in proton delivery to peroxo and compound 0 (Cmpd 0) away from the O2 ligand. In the presence of the aldehyde substrate, the peroxo intermediate is trapped as the peroxohemiacetal without an apparent barrier, which may then be protonated in the active site. The unprotonated peroxohemiacetal provides a branch point for a concerted Deformylation mechanism; however, a stepwise mechanism...