The reaction of nitroxyl radicals TEMPO (2,2′,6,6′‐tetramethylpiperidinyloxyl) and AZADO (2‐azaadamantane‐N‐oxyl) with an iron(I) synthon affords iron(II)‐nitroxido complexes (ArL)Fe(κ1‐TEMPO) and (ArL)Fe(κ2‐N,O‐AZADO) (ArL=1,9‐(2,4,6‐Ph3C6H2)2‐5‐mesityldipyrromethene). Both high‐spin iron(II)‐nitroxido species are stable in the absence of weak C−H bonds, but decay via N−O bond homolysis to ferrous or ferric iron hydroxides in the presence of 1,4‐cyclohexadiene. Whereas (ArL)Fe(κ1‐TEMPO) reacts to give a diferrous hydroxide [(ArL)Fe]2(μ‐OH)2, the reaction of four‐coordinate (ArL)Fe(κ2‐N,O‐AZADO) with hydrogen atom donors yields ferric hydroxide (ArL)Fe(OH)(AZAD). Mechanistic experiments reveal saturation behavior in C−H substrate and are consistent with rate‐determining hydrogen atom transfer.
Lytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of monocopper enzymes broadly distributed across the tree of life. Recent reports indicate that LPMOs can use H2O2as an oxidant and thus carry out a novel type of peroxygenase reaction involving unprecedented copper chemistry. Here, we present a combined computational and experimental analysis of the H2O2-mediated reaction mechanism. In silico studies, based on a model of the enzyme in complex with a crystalline substrate, suggest that a network of hydrogen bonds, involving both the enzyme and the substrate, brings H2O2into a strained reactive conformation and guides a derived hydroxyl radical toward formation of a copper–oxyl intermediate. The initial cleavage of H2O2and subsequent hydrogen atom abstraction from chitin by the copper–oxyl intermediate are the main energy barriers. Stopped-flow fluorimetry experiments demonstrated that the priming reduction of LPMO–Cu(II) to LPMO–Cu(I) is a fast process compared to the reoxidation reactions. Using conditions resulting in single oxidative events, we found that reoxidation of LPMO–Cu(I) is 2,000-fold faster with H2O2than with O2, the latter being several orders of magnitude slower than rates reported for other monooxygenases. The presence of substrate accelerated reoxidation by H2O2, whereas reoxidation by O2became slower, supporting the peroxygenase paradigm. These insights into the peroxygenase nature of LPMOs will aid in the development and application of enzymatic and synthetic copper catalysts and contribute to a further understanding of the roles of LPMOs in nature, varying from biomass conversion to chitinolytic pathogenesis-defense mechanisms.
more » « less- Award ID(s):
- 1715176
- NSF-PAR ID:
- 10129857
- Publisher / Repository:
- Proceedings of the National Academy of Sciences
- Date Published:
- Journal Name:
- Proceedings of the National Academy of Sciences
- Volume:
- 117
- Issue:
- 3
- ISSN:
- 0027-8424
- Page Range / eLocation ID:
- p. 1504-1513
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract -
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Abstract The reaction of nitroxyl radicals TEMPO (2,2′,6,6′‐tetramethylpiperidinyloxyl) and AZADO (2‐azaadamantane‐N‐oxyl) with an iron(I) synthon affords iron(II)‐nitroxido complexes (ArL)Fe(κ1‐TEMPO) and (ArL)Fe(κ2‐N,O‐AZADO) (ArL=1,9‐(2,4,6‐Ph3C6H2)2‐5‐mesityldipyrromethene). Both high‐spin iron(II)‐nitroxido species are stable in the absence of weak C−H bonds, but decay via N−O bond homolysis to ferrous or ferric iron hydroxides in the presence of 1,4‐cyclohexadiene. Whereas (ArL)Fe(κ1‐TEMPO) reacts to give a diferrous hydroxide [(ArL)Fe]2(μ‐OH)2, the reaction of four‐coordinate (ArL)Fe(κ2‐N,O‐AZADO) with hydrogen atom donors yields ferric hydroxide (ArL)Fe(OH)(AZAD). Mechanistic experiments reveal saturation behavior in C−H substrate and are consistent with rate‐determining hydrogen atom transfer.
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Abstract The synthesis and characterization of (tBuPBP)Ni(OAc) (
5 ) by insertion of carbon dioxide into the Ni−C bond of (tBuPBP)NiMe (1 ) is presented. An unexpected CO2cleavage process involving the formation of new B−O and Ni−CO bonds leads to the generation of a butterfly‐structured tetra‐nickel cluster (tBuPBOP)2Ni4(μ‐CO)2(6 ). Mechanistic investigation of this reaction indicates a reductive scission of CO2by O‐atom transfer to the boron atom via a cooperative nickel‐boron mechanism. The CO2activation reaction produces a three‐coordinate (tBuP2BO)Ni‐acyl intermediate (A ) that leads to a (tBuP2BO)−NiIcomplex (B ) via a likely radical pathway. The NiIspecies is trapped by treatment with the radical trap (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) to give (tBuP2BO)NiII(η2‐TEMPO) (7 ). Additionally,13C and1H NMR spectroscopy analysis using13C‐enriched CO2provides information about the species involved in the CO2activation process. -
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Abstract The synthesis and characterization of (tBuPBP)Ni(OAc) (
5 ) by insertion of carbon dioxide into the Ni−C bond of (tBuPBP)NiMe (1 ) is presented. An unexpected CO2cleavage process involving the formation of new B−O and Ni−CO bonds leads to the generation of a butterfly‐structured tetra‐nickel cluster (tBuPBOP)2Ni4(μ‐CO)2(6 ). Mechanistic investigation of this reaction indicates a reductive scission of CO2by O‐atom transfer to the boron atom via a cooperative nickel‐boron mechanism. The CO2activation reaction produces a three‐coordinate (tBuP2BO)Ni‐acyl intermediate (A ) that leads to a (tBuP2BO)−NiIcomplex (B ) via a likely radical pathway. The NiIspecies is trapped by treatment with the radical trap (2,2,6,6‐tetramethylpiperidin‐1‐yl)oxyl (TEMPO) to give (tBuP2BO)NiII(η2‐TEMPO) (7 ). Additionally,13C and1H NMR spectroscopy analysis using13C‐enriched CO2provides information about the species involved in the CO2activation process. -
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