How Axial Coordination Regulates the Electronic Structure and C–H Amination Reactivity of Fe–Porphyrin–Nitrene?

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1. 1

   Dunham, N. P.; Arnold, F. H. Nature’s Machinery, Repurposed: Expanding the Repertoire of Iron-Dependent Oxygenases. ACS Catal. 2020, 10, 12239– 12255,  DOI: 10.1021/acscatal.0c03606

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   1

   Nature's machinery, repurposed: Expanding the repertoire of iron-dependent oxygenases

   Dunham, Noah P.; Arnold, Frances H.

   ACS Catalysis (2020), 10 (20), 12239-12255CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

   A review. Iron is an esp. important redox-active cofactor in biol. because of its ability to mediate reactions with atm. O2. Iron-dependent oxygenases exploit this earth-abundant transition metal for the insertion of oxygen atoms into org. compds. Throughout the astounding diversity of transformations catalyzed by these enzymes, the protein framework directs reactive intermediates toward the precise formation of products, which, in many cases, necessitates the cleavage of strong C-H bonds. In recent years, members of several iron-dependent oxygenase families have been engineered for new-to-nature transformations that offer advantages over conventional synthetic methods. In this Perspective, we first explore what is known about the reactivity of heme-dependent cytochrome P 450 oxygenases and nonheme iron-dependent oxygenases bearing the 2-His-1-carboxylate facial triad by reviewing mechanistic studies with an emphasis on how the protein scaffold maximizes the catalytic potential of the iron-heme and iron cofactors. We then review how these cofactors have been repurposed for abiol. transformations by engineering the protein frameworks of these enzymes. Finally, we discuss contemporary challenges assocd. with engineering these platforms and comment on their roles in biocatalysis moving forward.

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2. 2

   Yang, Y.; Arnold, F. H. Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer. Acc. Chem. Res. 2021, 54, 1209– 1225,  DOI: 10.1021/acs.accounts.0c00591

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   2

   Navigating the Unnatural Reaction Space: Directed Evolution of Heme Proteins for Selective Carbene and Nitrene Transfer

   Yang, Yang; Arnold, Frances H.

   Accounts of Chemical Research (2021), 54 (5), 1209-1225CODEN: ACHRE4; ISSN:0001-4842. (American Chemical Society)

   A review. Conspectus: Despite the astonishing diversity of naturally occurring biocatalytic processes, enzymes do not catalyze many of the transformations favored by synthetic chemists. Either nature does not care about the specific products, or if she does, she has adopted a different synthetic strategy. In many cases, the appropriate reagents used by synthetic chemists are not readily accessible to biol. systems. Here, the authors' efforts to expand the catalytic repertoire of enzymes to encompass powerful reactions previously known only in small-mol. catalysis: formation and transfer of reactive carbene and nitrene intermediates leading to a broad range of products, including products with bonds not known in biol. are discussed. In light of the structural similarity of iron carbene (Fe:C(R1)(R2)) and iron nitrene (Fe = NR) to the iron oxo (Fe = O) intermediate involved in cytochrome P 450-catalyzed oxidn., the authors used synthetic carbene and nitrene precursors that biol. systems have not encountered and repurposed P450s to catalyze reactions that are not known in the natural world. The resulting protein catalysts are fully genetically encoded and function in intact microbial cells or cell-free lysates, where their performance can be improved and optimized by directed evolution. By leveraging the catalytic promiscuity of P 450 enzymes, the authors evolved a range of carbene and nitrene transferases exhibiting excellent activity toward these new-to-nature reactions. Since the authors' initial report in 2012, a no. of other heme proteins including myoglobins, protoglobins, and cytochromes c also were found and engineered to promote unnatural carbene and nitrene transfer. Due to the altered active-site environments, these heme proteins often displayed complementary activities and selectivities to P450s. Using wild-type and engineered heme proteins, the authors and others have described a range of selective carbene transfer reactions, including cyclopropanation, cyclopropenation, Si-H insertion, B-H insertion, and C-H insertion. Similarly, a variety of asym. nitrene transfer processes including aziridination, sulfide imidation, C-H amidation, and, most recently, C-H amination were demonstrated. The scopes of these biocatalytic carbene and nitrene transfer reactions are often complementary to the state-of-the-art processes based on small-mol. transition-metal catalysts, making engineered biocatalysts a valuable addn. to the synthetic chemist's toolbox. Moreover, enabled by the exquisite regio- and stereocontrol imposed by the enzyme catalyst, this biocatalytic platform provides an exciting opportunity to address challenging problems in modern synthetic chem. and selective catalysis, including ones that have eluded synthetic chemists for decades.

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3. 3

   Chen, K.; Arnold, F. H. Engineering New Catalytic Activities in Enzymes. Nat. Catal. 2020, 3, 203– 213,  DOI: 10.1038/s41929-019-0385-5

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   3

   Engineering new catalytic activities in enzymes

   Chen, Kai; Arnold, Frances H.

   Nature Catalysis (2020), 3 (3), 203-213CODEN: NCAACP; ISSN:2520-1158. (Nature Research)

   A review. Abstr.: The efficiency, selectivity and sustainability benefits offered by enzymes are enticing chemists to consider biocatalytic transformations to complement or even supplant more traditional synthetic routes. Increasing demands for efficient and versatile synthetic methods, combined with powerful new discovery and engineering tools, has prompted innovations in biocatalysis, esp. the development of new enzymes for precise transformations or 'mol. editing'. As a result, the past decade has witnessed an impressive expansion of the catalytic repertoire of enzymes to include new and useful transformations not known (or relevant) in the biol. world. In this Review we illustrate various ways in which researchers have approached using the catalytic machineries of enzymes for new-to-nature transformations. These efforts have identified genetically encoded catalysts that can be tuned and diversified by engineering the protein sequence, particularly by directed evolution. Discovery and improvement of these new enzyme activities is opening a floodgate that connects the chem. of the biol. world to that invented by humans over the past 100 years.

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4. 4

   Singh, R.; Mukherjee, A. Metalloporphyrin Catalyzed C-H Amination. ACS Catal. 2019, 9, 3604– 3617,  DOI: 10.1021/acscatal.9b00009

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   4

   Metalloporphyrin Catalyzed C-H Amination

   Singh, Ritesh; Mukherjee, Anirban

   ACS Catalysis (2019), 9 (4), 3604-3617CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

   A review discusses the use of metalloporphyrins in org. synthesis for the amination, azidation, and imination of C-H bonds to yield amines, azides, and imines; the use of metalloporphyrin-contg. enzymes for regioselective or enantioselective amination reactions and the mechanisms of selected reactions are also discussed.

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5. 5

   Hyster, T. K.; Farwell, C. C.; Buller, A. R.; McIntosh, J. A.; Arnold, F. H. Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C-H Amination. J. Am. Chem. Soc. 2014, 136, 15505– 15508,  DOI: 10.1021/ja509308v

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   5

   Enzyme-Controlled Nitrogen-Atom Transfer Enables Regiodivergent C-H Amination

   Hyster, Todd K.; Farwell, Christopher C.; Buller, Andrew R.; McIntosh, John A.; Arnold, Frances H.

   Journal of the American Chemical Society (2014), 136 (44), 15505-15508CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

   We recently demonstrated that variants of cytochrome P 450BM3 (CYP102A1) catalyze the insertion of nitrogen species into benzylic C-H bonds to form new C-N bonds. An outstanding challenge in the field of C-H amination is catalyst-controlled regioselectivity. Here, we report two engineered variants of P 450BM3 that provide divergent regioselectivity for C-H amination - one favoring amination of benzylic C-H bonds and the other favoring homo-benzylic C-H bonds. The two variants provide nearly identical kinetic isotope effect values (2.8-3.0), suggesting that C-H abstraction is rate-limiting. The 2.66-Å crystal structure of the most active enzyme suggests that the engineered active site can preorganize the substrate for reactivity. We hypothesize that the enzyme controls regioselectivity through localization of a single C-H bond close to the iron nitrenoid.

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6. 6

   Singh, R.; Bordeaux, M.; Fasan, R. P450-Catalyzed Intramolecular Sp3 C–H Amination with Arylsulfonyl Azide Substrates. ACS Catal. 2014, 4, 546– 552,  DOI: 10.1021/cs400893n

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   6

   P450-Catalyzed Intramolecular sp3 C-H Amination with Arylsulfonyl Azide Substrates

   Singh, Ritesh; Bordeaux, Melanie; Fasan, Rudi

   ACS Catalysis (2014), 4 (2), 546-552CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

   The direct amination of aliph. C-H bonds represents a most valuable transformation in org. chem. While a no. of transition-metal-based catalysts have been developed and investigated for this purpose, the possibility to execute this transformation with biol. catalysts has remained largely unexplored. Here, we report that cytochrome P 450 enzymes can serve as efficient catalysts for mediating intramol. benzylic C-H amination reactions in a variety of arylsulfonyl azide compds. Under optimized conditions, the P 450 catalysts were found to support up to 390 total turnovers leading to the formation of the desired sultam products with excellent regioselectivity. In addn., the chiral environment provided by the enzyme active site allowed for the reaction to proceed in a stereo- and enantioselective manner. The C-H amination activity, substrate profile, and enantio/stereoselectivity of these catalysts could be modulated by utilizing enzyme variants with engineered active sites.

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7. 7

   Steck, V.; Kolev, J. N.; Ren, X.; Fasan, R. Mechanism-Guided Design and Discovery of Efficient Cytochrome P450-Derived C-H Amination Biocatalysts. J. Am. Chem. Soc. 2020, 142, 10343– 10357,  DOI: 10.1021/jacs.9b12859

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   7

   Mechanism-Guided Design and Discovery of Efficient Cytochrome P450-Derived C-H Amination Biocatalysts

   Steck, Viktoria; Kolev, Joshua N.; Ren, Xinkun; Fasan, Rudi

   Journal of the American Chemical Society (2020), 142 (23), 10343-10357CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

   Cytochromes P 450 have been recently identified as a promising class of biocatalysts for mediating C-H aminations via nitrene transfer, a valuable transformation for forging new C-N bonds. The catalytic efficiency of P450s in these non-native transformations is however significantly inferior to that exhibited by these enzymes in their native monooxygenase function. Using a mechanism-guided strategy, we report here the rational design of a series of P 450BM3-based variants with dramatically enhanced C-H amination activity acquired through disruption of the native proton relay network and other highly conserved structural elements within this class of enzymes. This approach further guided the identification of XplA and BezE, two "atypical" natural P450s implicated in the degrdn. of a man-made explosive and in benzastatins biosynthesis, resp., as very efficient C-H aminases. Both XplA and BezE could be engineered to further improve their C-H amination reactivity, which demonstrates their evolvability for abiol. reactions. These engineered and natural P 450 catalysts can promote the intramol. C-H amination of arylsulfonyl azides with over 10 000-14 000 catalytic turnovers, ranking among the most efficient nitrene transfer biocatalysts reported to date. Mechanistic and structure-reactivity studies provide insights into the origin of the C-H amination reactivity enhancement and highlight the divergent structural requirements inherent to supporting C-H amination vs. C-H monooxygenation reactivity within this class of enzymes. Overall, this work provides new promising scaffolds for the development of nitrene transferases and demonstrates the value of mechanism-driven rational design as a strategy for improving the catalytic efficiency of metalloenzymes in the context of abiol. transformations.

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8. 8

   Conradie, J.; Ghosh, A. Electronic Structure of an Iron-Porphyrin–Nitrene Complex. Inorg. Chem. 2010, 49, 243– 248,  DOI: 10.1021/ic901897w

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   8

   Electronic Structure of an Iron-Porphyrin-Nitrene Complex

   Conradie, Jeanet; Ghosh, Abhik

   Inorganic Chemistry (2010), 49 (1), 243-248CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)

   Middle and late transition metal imido complexes (which may also be viewed as metal-nitrene adducts) are rather rare, esp. for square-pyramidal and octahedral coordination geometries. However, an iron(II) porphyrin aminonitrene adduct, denoted here as Fe(Por)(NN), has been known for almost a quarter of a century. Unlike the corresponding S = 1 oxene and S = 0 carbene adducts, Fe(Por)(NN) exhibits an S = 2 ground state. DFT-GGA calcns. reported herein provide a MO description of this unusual species as well as a rationale for its S = 2 ground state. The electronic configuration of Fe(Por)(NN) may be described as dπ2dxy1dz21dx2-y21dπ'1, where the z direction corresponds to the Fe-NN axis. The stability and double occupancy of one of the dπ orbitals may be attributed to a π-backbonding interaction with the N-N π* orbital. The weak σ-donor ability of the aminonitrene ligand results in a relatively low-energy dz2 orbital and an overall d orbital splitting pattern that engenders a high-spin ground state.

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9. 9

   Li, X.; Dong, L.; Liu, Y. Theoretical Study of Iron Porphyrin Nitrene: Formation Mechanism, Electronic Nature, and Intermolecular C-H Amination. Inorg. Chem. 2020, 59, 1622– 1632,  DOI: 10.1021/acs.inorgchem.9b02216

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   9

   Theoretical Study of Iron Porphyrin Nitrene: Formation Mechanism, Electronic Nature, and Intermolecular C-H Amination

   Li, Xinyi; Dong, Lihua; Liu, Yongjun

   Inorganic Chemistry (2020), 59 (3), 1622-1632CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)

   The formation mechanism and electronic structures of iron porphyrin nitrene intermediates, as well as the nitrene-mediated intermol. C-H amination have been studied by performing DFT and ab initio complete active space SCF (CASSCF) calcns. Compared with that of cobalt porphyrin nitrene and iron porphyrin carbene, the formation of iron porphyrin nitrene shows similar but different characteristics. The common feature is that all their formation requires to undergo the "far" or "close" complexes, but these complexes correspond to different energies relative to their resp. reactants (isolated metalloporphyrins and azides), which is considered as one main reason to det. the reaction barriers. The overall free energy barrier for the formation of iron porphyrin nitrene was calcd. to be 10.6 kcal/mol on triplet state surface, which is lower than those of cobalt porphyrin nitrene and iron porphyrin carbene. The departure of N2 from the "close complexes" formed by iron porphyrin and tosyl azide is nearly barrierless. For iron porphyrin nitrene, both CASSCF and unrestricted DFT calcns. revealed that the triplet and open-shell singlet complexes correspond to very similar energies, and the triplet nitrene complex can be described as [(por)(-OCH3)FeII = NTs]- ↔ [(por)(-OCH3)FeIII = N•-Ts]- ↔ [(por)(-OCH3)FeIV = N2-Ts]-. While the oss nitrene complex can be described as [(por)(-OCH3)FeIII-N•-Ts]-. Since the N atom bears similar spin d. as in cobalt porphyrin nitrene, the iron porphyrin nitrene exhibits similar activity in hydrogen abstraction. In addn., the intermol. C-H amination catalyzed by iron porphyrin nitrene follows the hydrogen atom abstraction/radical recombination mechanism with a free energy barrier of 7.1 kcal/mol on the triplet state surface. In general, the medium reactivity and easily prepd. characteristic of iron porphyrin nitrene make it a potential catalyst for C-H amination. DFT calcns. revealed that iron porphyrin nitrene shows similar activity as cobalt porphyrin nitrene and iron porphyrin carbene toward H-abstraction and C-H amination.

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10. 10

    Kuijpers, P. F.; van der Vlugt, J. I.; Schneider, S.; de Bruin, B. Nitrene Radical Intermediates in Catalytic Synthesis. Chem. Eur. J. 2017, 23, 13819– 13829,  DOI: 10.1002/chem.201702537

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    10

    Nitrene Radical Intermediates in Catalytic Synthesis

    Kuijpers, Petrus F.; van der Vlugt, Jarl Ivar; Schneider, Sven; de Bruin, Bas

    Chemistry - A European Journal (2017), 23 (56), 13819-13829CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Nitrene radical complexes are reactive intermediates with discrete spin d. at the nitrogen-atom of the nitrene moiety. These species have become important intermediates for org. synthesis, being invoked in a broad range of C-H functionalization and aziridination reactions. Nitrene radical complexes have intriguing electronic structures, and are best described as one-electron reduced Fischer type nitrenes. They can be generated by intramol. single electron transfer to the "redox non-innocent" nitrene moiety at the metal. Nitrene radicals generated at open-shell cobalt(II) have thus far received most attention in terms of spectroscopic characterization, reactivity screening, catalytic nitrene-transfer reactions and (computational and exptl.) mechanistic studies, but some interesting iron and precious metal catalysts have also been employed in related reactions involving nitrene radicals. In some cases, redox-active ligands are used to facilitate intramol. single electron transfer from the complex to the nitrene moiety. Org. azides are among the most attractive nitrene precursors in this field, typically requiring pre-activated org. azides (e.g. RSO2N3, (RO)2P(=O)N3, ROC(=O)N3 and alike) to achieve efficient and selective catalysis. Challenging, non-activated aliph. org. azides were recently added to the palette of reagents useful in synthetically relevant reactions proceeding via nitrene radical intermediates. This concept article describes the electronic structure of nitrene radical complexes, emphasizes on their usefulness in the catalytic synthesis of various org. products, and highlights the important developments in the field.

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11. 11

    Mahajan, M.; Mondal, B. Origin of the Distinctive Electronic Structure of Co- and Fe-Porphyrin-Nitrene and Its Effect on Their Nitrene Transfer Reactivity. Inorg. Chem. 2023, 62, 5810– 5821,  DOI: 10.1021/acs.inorgchem.3c00463

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    11

    Origin of the Distinctive Electronic Structure of Co- and Fe-Porphyrin-Nitrene and Its Effect on Their Nitrene Transfer Reactivity

    Mahajan, Mayank; Mondal, Bhaskar

    Inorganic Chemistry (2023), 62 (14), 5810-5821CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)

    Metal-bound nitrene species are the crucial intermediate in catalytic nitrene transfer reactions exhibited by engineered enzymes and mol. catalysts. The electronic structure of such species and its correlation with nitrene transfer reactivity have not been fully understood yet. This work presents an in-depth electronic structure anal. and nitrene transfer reactivity of two prototypical metal-nitrene species derived from CoII(TPP) and FeII(TPP) (TPP = meso-tetraphenylporphyrin) complexes and tosyl azide nitrene precursor. Parallel to the well-known "cobalt(III)-imidyl" electronic structure of the Co-porphyrin-nitrene species, the formation mechanism and electronic structure of the elusive Fe-porphyrin-nitrene have been established using d. functional theory (DFT) and multiconfigurational complete active-space SCF (CASSCF) calcns. Electronic structure evolution anal. for the metal-nitrene formation step and CASSCF-derived natural orbitals advocates that the electronic nature of the metal-nitrene (M-N) core of Fe(TPP) is strikingly different from that of the Co(TPP). Specifically, the "imidyl" nature of the Co-porphyrin-nitrene [(TPP)CoIII-•NTos] (Tos = tosyl) (I1Co) is contrasted by the "imido-like" character of the Fe-porphyrin-nitrene [(TPP)FeIV[Formula Omitted]NTos] (I1Fe). This difference between Co- and Fe-nitrene has been attributed to the addnl. interactions between Fe-dπ and N-pπ orbitals in Fe-nitrene, which is further complemented by the shortened Fe-N bond length of 1.71 Å. This stronger M-N bond in Fe-nitrene compared to the Co-nitrene is also reflected in the higher exothermicity (ΔΔH = 16 kcal/mol) of the Fe-nitrene formation step. The "imido-like" character renders a relatively lower spin population on the nitrene nitrogen (+0.42) in the Fe-nitrene complex I1Fe, which undergoes the nitrene transfer to the C=C bond of styrene with a considerably higher enthalpy barrier (ΔH‡ = 10.0 kcal/mol) compared to the Co congener I1Co (ΔH‡ = 5.6 kcal/mol) possessing a higher nitrogen spin population (+0.88) and a relatively weaker M-N bond (Co-N = 1.80 Å).

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12. 12

    Svastits, E. W.; Dawson, J. H.; Breslow, R.; Gellman, S. H. Functionalized Nitrogen Atom Transfer Catalyzed by Cytochrome P-450. J. Am. Chem. Soc. 1985, 107, 6427– 6428,  DOI: 10.1021/ja00308a064

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    12

    Functionalized nitrogen atom transfer catalyzed by cytochrome P-450

    Svastits, Edmund W.; Dawson, John H.; Breslow, Ronald; Gellman, Samuel H.

    Journal of the American Chemical Society (1985), 107 (22), 6427-8CODEN: JACSAT; ISSN:0002-7863.

    Purified rabbit liver microsomal cytochrome P 450 (I) catalyzed the inter- and intramol. transfer and insertion of a functionalized N atom into a C-H bond. Although metalloporphyrins and metal complexes have previously been found to catalyze this reaction, this is the 1st report of N atom transfer by I. The intramol. reaction rate was linear with time, I concn., and substrate concn., having a lower limit (because of substrate soly.) of 1.0 nmol product/nmol I/min for the LM3,4 form mixt. The reaction was dependent on the integrity of I; neither partially denatured (P-420) nor extensively denatured I was able to catalyze the reaction. Both the intra- and intermol. transfer reactions were I form-dependent, with the LM2 form exhibiting essentially no activity in contrast to either crude liver microsomes or a mixt. of the LM3 and LM4 purified forms.

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13. 13

    Singh, R.; Bordeaux, M.; Fasan, R. P450-Catalyzed Intramolecular sp3 C–H Amination with Arylsulfonyl Azide Substrates. ACS Catal. 2014, 4, 546– 552,  DOI: 10.1021/cs400893n

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    13

    P450-Catalyzed Intramolecular sp3 C-H Amination with Arylsulfonyl Azide Substrates

    Singh, Ritesh; Bordeaux, Melanie; Fasan, Rudi

    ACS Catalysis (2014), 4 (2), 546-552CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

    The direct amination of aliph. C-H bonds represents a most valuable transformation in org. chem. While a no. of transition-metal-based catalysts have been developed and investigated for this purpose, the possibility to execute this transformation with biol. catalysts has remained largely unexplored. Here, we report that cytochrome P 450 enzymes can serve as efficient catalysts for mediating intramol. benzylic C-H amination reactions in a variety of arylsulfonyl azide compds. Under optimized conditions, the P 450 catalysts were found to support up to 390 total turnovers leading to the formation of the desired sultam products with excellent regioselectivity. In addn., the chiral environment provided by the enzyme active site allowed for the reaction to proceed in a stereo- and enantioselective manner. The C-H amination activity, substrate profile, and enantio/stereoselectivity of these catalysts could be modulated by utilizing enzyme variants with engineered active sites.

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14. 14

    Bordeaux, M.; Singh, R.; Fasan, R. Intramolecular C(sp3)–H Amination of Arylsulfonyl Azides with Engineered and Artificial Myoglobin-Based Catalysts. Bioorg. Med. Chem. 2014, 22, 5697– 5704,  DOI: 10.1016/j.bmc.2014.05.015

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    14

    Intramolecular C(sp3)-H amination of arylsulfonyl azides with engineered and artificial myoglobin-based catalysts

    Bordeaux, Melanie; Singh, Ritesh; Fasan, Rudi

    Bioorganic & Medicinal Chemistry (2014), 22 (20), 5697-5704CODEN: BMECEP; ISSN:0968-0896. (Elsevier B.V.)

    The direct conversion of aliph. C-H bonds into C-N bonds provides an attractive approach to the introduction of nitrogen-contg. functionalities in org. mols. Following the recent discovery that cytochrome P 450 enzymes can catalyze the cyclization of arylsulfonyl azide compds. via an intramol. C(sp3)-H amination reaction, we have explored here the C-H amination reactivity of other hemoproteins. Various heme-contg. proteins, and in particular myoglobin and horseradish peroxidase, were found to be capable of catalyzing this transformation. Based on this finding, a series of engineered and artificial myoglobin variants contg. active site mutations and non-native Mn- and Co-protoporphyrin IX cofactors, resp., were prepd. to investigate the effect of these structural changes on the catalytic activity and selectivity of these catalysts. Our studies showed that metallo-substituted myoglobins constitute viable C-H amination catalysts, revealing a distinctive reactivity trend as compared to synthetic metalloporphyrin counterparts. On the other hand, amino acid substitutions at the level of the heme pocket were found to be beneficial toward improving the stereo- and enantioselectivity of these Mb-catalyzed reactions. Mechanistic studies involving kinetic isotope effect expts. indicate that C-H bond cleavage is implicated in the rate-limiting step of myoglobin-catalyzed amination of arylsulfonyl azides. Altogether, these studies indicate that myoglobin constitutes a promising scaffold for the design and development of C-H amination catalysts.

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15. 15

    McIntosh, J. A.; Coelho, P. S.; Farwell, C. C.; Wang, Z. J.; Lewis, J. C.; Brown, T. R.; Arnold, F. H. Enantioselective Intramolecular C-H Amination Catalyzed by Engineered Cytochrome P450 Enzymes in Vitro and in Vivo. Angew. Chem., Int. Ed. 2013, 52, 9309– 9312,  DOI: 10.1002/anie.201304401

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    15

    Enantioselective Intramolecular C-H Amination Catalyzed by Engineered Cytochrome P450 Enzymes In Vitro and In Vivo

    McIntosh, John A.; Coelho, Pedro S.; Farwell, Christopher C.; Wang, Z. Jane; Lewis, Jared C.; Brown, Tristan R.; Arnold, Frances H.

    Angewandte Chemie, International Edition (2013), 52 (35), 9309-9312CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Though P 450 enzymes are masters of oxygen activation and insertion into C-H bonds, their ability to use nitrogen for the same purpose has so far not been explored. Engineered variants of cytochrome P 450BM3 have now been found to catalyze intramol. C-H aminations in azide substrates. Mutations to two highly conserved residues significantly increased this activity.

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16. 16

    Cho, I.; Prier, C. K.; Jia, Z. J.; Zhang, R. K.; Görbe, T.; Arnold, F. H. Enantioselective Aminohydroxylation of Styrenyl Olefins Catalyzed by an Engineered Hemoprotein. Angew. Chem., Int. Ed. 2019, 58, 3138– 3142,  DOI: 10.1002/anie.201812968

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    16

    Enantioselective aminohydroxylation of styrenyl olefins catalyzed by an engineered hemoprotein

    Cho, Inha; Prier, Christopher K.; Jia, Zhi-Jun; Zhang, Ruijie K.; Goerbe, Tamas; Arnold, Frances H.

    Angewandte Chemie, International Edition (2019), 58 (10), 3138-3142CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Chiral 1,2-amino alcs. are widely represented in biol. active compds. from neurotransmitters to antivirals. While many synthetic methods have been developed for accessing amino alcs., the direct aminohydroxylation of alkenes to unprotected, enantio-enriched amino alcs. remains a challenge. Using directed evolution, we have engineered a hemoprotein biocatalyst based on a thermostable cytochrome c that directly transforms alkenes to amino alcs. with high enantioselectivity (up to 2500 TTN and 90 % ee) under anaerobic conditions with O-pivaloylhydroxylamine as an aminating reagent. The reaction is proposed to proceed via a reactive iron-nitrogen species generated in the enzyme active site, enabling tuning of the catalyst's activity and selectivity by protein engineering.

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17. 17

    Moore, E. J.; Fasan, R. Effect of Proximal Ligand Substitutions on the Carbene and Nitrene Transferase Activity of Myoglobin. Tetrahedron 2019, 75, 2357– 2363,  DOI: 10.1016/j.tet.2019.03.009

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    17

    Effect of proximal ligand substitutions on the carbene and nitrene transferase activity of myoglobin

    Moore, Eric J.; Fasan, Rudi

    Tetrahedron (2019), 75 (16), 2357-2363CODEN: TETRAB; ISSN:0040-4020. (Elsevier Ltd.)

    Engineered myoglobins (Mbs) were recently shown to be effective catalysts for abiol. carbene and nitrene transfer reactions. Here, we investigated the impact of substituting the conserved heme-coordinating histidine residue with both proteinogenic (Cys, Ser, Tyr, Asp) and non-proteinogenic Lewis basic amino acids (3-(3'-pyridyl)-alanine, p-aminophenylalanine, and β-(3-thienyl)-alanine), on the reactivity of this metalloprotein toward these abiotic transformations. These studies showed that mutation of the proximal histidine residue with both natural and non-natural amino acids result in stable myoglobin variants that can function as both carbene and nitrene transferases. In addn., substitution of the proximal histidine with an aspartate residue led to a myoglobin-based catalyst capable of promoting stereoselective olefin cyclopropanation under nonreducing conditions. Overall, these studies demonstrate that proximal ligand substitution provides a promising strategy to tune the reactivity of myoglobin-based carbene and nitrene transfer catalysts and provide a first, proof-of-principle demonstration of the viability of pyridine-, thiophene-, and aniline-based unnatural amino acids for metalloprotein engineering.

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18. 18

    Kalita, S.; Shaik, S.; Dubey, K. D. MD Simulations and QM/MM Calculations Reveal the Key Mechanistic Elements Which Are Responsible for the Efficient C-H Amination Reaction Performed by a Bioengineered P450 Enzyme. Chem. Sci. 2021, 12, 14507– 14518,  DOI: 10.1039/D1SC03489H

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    18

    MD simulations and QM/MM calculations reveal the key mechanistic elements which are responsible for the efficient C-H amination reaction performed by a bioengineered P450 enzyme

    Kalita, Surajit; Shaik, Sason; Dubey, Kshatresh Dutta

    Chemical Science (2021), 12 (43), 14507-14518CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)

    An enzyme which is capable of catalyzing C-H amination reactions is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calcns. The study shows that the efficient C-H amination by the engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of the axial cysteine ligand to serine relays electron d. to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. In comparison, the native cysteine-ligated P 450 cannot bind the tosyl azide. Addnl., the A78V and A82L mutations in P411 provide 'bulk' to the active site which increases the enantioselectivity via a steric effect. At the same time, the QM/MM calcns. elucidate the C-H amination by the iron nitrenoid, revealing a mechanism analogous to Compd. I in the native C-H hydroxylation by P 450.

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19. 19

    Wei, Y.; Conklin, M.; Zhang, Y. Biocatalytic Intramolecular C–H Aminations via Engineered Heme Proteins: Full Reaction Pathways and “axial” Ligand Effects. Chem. Eur. J. 2022, 28, e202202006  DOI: 10.1002/chem.202202006

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    19

    Biocatalytic Intramolecular C-H aminations via Engineered Heme Proteins: Full Reaction Pathways and Axial Ligand Effects

    Wei, Yang; Conklin, Melissa; Zhang, Yong

    Chemistry - A European Journal (2022), 28 (59), e202202006CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Engineered heme protein biocatalysts provide an efficient and sustainable approach to develop amine-contg. compds. through C-H amination. A quantum chem. study to reveal the complete heme catalyzed intramol. C-H amination pathway and protein axial ligand effect is reported, using reactions of an exptl. used arylsulfonylazide with hemes contg. L = none, SH-, MeO-, and MeOH to simulate no axial ligand, neg. charged Cys and Ser ligands, and a neutral ligand for comparison. Nitrene formation is the overall rate-detg. step (RDS) and the catalyst with Ser ligand has the best reactivity, consistent with exptl. reports. Both RDS and non-RDS (nitrene transfer) transition states follow the barrier trend of MeO-<SH-<MeOH<None due to the charge donation capability of the axial ligand to influence the key charge transfer process as the electronic driving forces. Results also provide new ideas for future biocatalyst design with enhanced reactivities.

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20. 20

    Yang, Y.; Cho, I.; Qi, X.; Liu, P.; Arnold, F. H. An Enzymatic Platform for the Asymmetric Amination of Primary, Secondary and Tertiary C(sp3)–H Bonds. Nat. Chem. 2019, 11, 987– 993,  DOI: 10.1038/s41557-019-0343-5

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    20

    An enzymatic platform for the asymmetric amination of primary, secondary and tertiary C(sp3)-H bonds

    Yang, Yang; Cho, Inha; Qi, Xiaotian; Liu, Peng; Arnold, Frances H.

    Nature Chemistry (2019), 11 (11), 987-993CODEN: NCAHBB; ISSN:1755-4330. (Nature Research)

    The ability to selectively functionalize ubiquitous C-H bonds streamlines the construction of complex mol. architectures from easily available precursors. Here we report enzyme catalysts derived from a cytochrome P 450 that use a nitrene transfer mechanism for the enantioselective amination of primary, secondary and tertiary C(sp3)-H bonds. These fully genetically encoded enzymes are produced and function in bacteria, where they can be optimized by directed evolution for a broad spectrum of enantioselective C(sp3)-H amination reactions. These catalysts can aminate a variety of benzylic, allylic and aliph. C-H bonds in excellent enantioselectivity with access to either antipode of product. Enantioselective amination of primary C(sp3)-H bonds in substrates that bear geminal di-Me substituents furnished chiral amines that feature a quaternary stereocenter. Moreover, these enzymes enabled the enantioconvergent transformation of racemic substrates that possess a tertiary C(sp3)-H bond to afford products that bear a tetrasubstituted stereocenter, a process that has eluded small-mol. catalysts. Further engineering allowed for the enantioselective construction of methyl-Et stereocenters, which is notoriously challenging in asym. catalysis.

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21. 21

    Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Petersson, G. A.; Nakatsuji, H.; Li, X.; Caricato, M.; Marenich, A. V.; Bloino, J.; Janesko, B. G.; Gomperts, R.; Mennucci, B.; Hratchian, H. P.; Ortiz, J. V.; Izmaylov, A. F.; Sonnenberg, J. L.; Williams-Young, D.; Ding, F.; Lipparini, F.; Egidi, F.; Goings, J.; Peng, B.; Petrone, A.; Henderson, T.; Ranasinghe, D.; Zakrzewski, V. G.; Gao, J.; Rega, N.; Zheng, G.; Liang, W.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Throssell, K.; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M. J.; Heyd, J. J.; Brothers, E. N.; Kudin, K. N.; Staroverov, V. N.; Keith, T. A.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A. P.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Millam, J. M.; Klene, M.; Adamo, C.; Cammi, R.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Farkas, O.; Foresman, J. B.; Fox, D. J. Gaussian 16, Revision C.01; Gaussian, Inc.: Wallingford CT, 2016.

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    There is no corresponding record for this reference.
22. 22

    Lee, C.; Yang, W.; Parr, R. G. Development of the Colle-Salvetti Correlation-Energy Formula into a Functional of the Electron Density. Phys. Rev. B 1988, 37, 785– 789,  DOI: 10.1103/PhysRevB.37.785

    Google Scholar

    22

    Development of the Colle-Salvetti correlation-energy formula into a functional of the electron density

    Lee, Chengteh; Yang, Weitao; Parr, Robert G.

    Physical Review B: Condensed Matter and Materials Physics (1988), 37 (2), 785-9CODEN: PRBMDO; ISSN:0163-1829.

    A correlation-energy formula due to R. Colle and D. Salvetti (1975), in which the correlation energy d. is expressed in terms of the electron d. and a Laplacian of the 2nd-order Hartree-Fock d. matrix, is restated as a formula involving the d. and local kinetic-energy d. On insertion of gradient expansions for the local kinetic-energy d., d.-functional formulas for the correlation energy and correlation potential are then obtained. Through numerical calcns. on a no. of atoms, pos. ions, and mols., of both open- and closed-shell type, it is demonstrated that these formulas, like the original Colle-Salvetti formulas, give correlation energies within a few percent.

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23. 23

    Becke, A. D. Density-Functional Thermochemistry. III. The Role of Exact Exchange. J. Chem. Phys. 1993, 98, 5648– 5652,  DOI: 10.1063/1.464913

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    23

    Density-functional thermochemistry. III. The role of exact exchange

    Becke, Axel D.

    Journal of Chemical Physics (1993), 98 (7), 5648-52CODEN: JCPSA6; ISSN:0021-9606.

    Despite the remarkable thermochem. accuracy of Kohn-Sham d.-functional theories with gradient corrections for exchange-correlation, the author believes that further improvements are unlikely unless exact-exchange information is considered. Arguments to support this view are presented, and a semiempirical exchange-correlation functional (contg. local-spin-d., gradient, and exact-exchange terms) is tested for 56 atomization energies, 42 ionization potentials, 8 proton affinities, and 10 total at. energies of first- and second-row systems. This functional performs better than previous functionals with gradient corrections only, and fits expt. atomization energies with an impressively small av. abs. deviation of 2.4 kcal/mol.

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24. 24

    Moreau, Y.; Chen, H.; Derat, E.; Hirao, H.; Bolm, C.; Shaik, S. NR Transfer Reactivity of Azo-Compound I of P450. How Does the Nitrogen Substituent Tune the Reactivity of the Species toward C-H and C = C Activation?. J. Phys. Chem. B 2007, 111, 10288– 10299,  DOI: 10.1021/jp0743065

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    24

    NR Transfer Reactivity of Azo-Compound I of P450. How Does the Nitrogen Substituent Tune the Reactivity of the Species toward C-H and C:C Activation?

    Moreau, Yohann; Chen, Hui; Derat, Etienne; Hirao, Hajime; Bolm, Carsten; Shaik, Sason

    Journal of Physical Chemistry B (2007), 111 (34), 10288-10299CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)

    The authors studied electronic structures and reactivity patterns of azo-compd. I species (RN-Cpd I) by comparison to O-Cpd I of, e.g., cytochrome P 450. The RN-Cpd I species are capable of C=C aziridination and C-H amidation, in a two-state mechanism similar to that of O-Cpd I. However, unlike O-Cpd I, here the nitrogen substituent (R) exerts a major impact on structure and reactivity. Thus, Fe = NR bonds of RN-Cpd I will generally be substantially longer than Fe = O bonds; electron-withdrawing R groups will generate a very long Fe = N bond, whereas electron-releasing R groups should have the opposite effect and hence a shorter Fe = N bond. The R substituent controls also the reactivity of RN-Cpd I toward C=C and C-H bonds by exerting steric and electronic effects. Anal. shows that an electron-releasing substituent will lower the barriers for both bond activation reactions, since the electronic factor makes the reactions highly exothermic, while an electron-withdrawing one should raise both barriers. The steric bulk of the substituent is predicted to inhibit more strongly the aziridination reactions. It is predicted that electron-releasing substituents with small bulk will create powerful aziridination reagents, whereas electron-withdrawing substituents like MeSO2 will prefer C-H bond activation with preference that increases with steric bulk. Finally, the study predicts (i) that the reactions of RN-Cpd I will be less stereospecific than those of O-Cpd I and (ii) that aziridination will be more stereoselective than amidation.

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25. 25

    Sharon, D. A.; Mallick, D.; Wang, B.; Shaik, S. Computation Sheds Insight into Iron Porphyrin Carbenes’ Electronic Structure, Formation, and N-H Insertion Reactivity. J. Am. Chem. Soc. 2016, 138, 9597– 9610,  DOI: 10.1021/jacs.6b04636

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    25

    Computation Sheds Insight into Iron Porphyrin Carbenes' Electronic Structure, Formation, and N-H Insertion Reactivity

    Sharon, Dina A.; Mallick, Dibyendu; Wang, Binju; Shaik, Sason

    Journal of the American Chemical Society (2016), 138 (30), 9597-9610CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Iron porphyrin carbenes constitute a new frontier of species with considerable synthetic potential. Exquisitely engineered myoglobin and cytochrome P 450 enzymes can generate these complexes and facilitate the transformations they mediate. The current work harnesses d. functional theor. methods to provide insight into the electronic structure, formation, and N-H insertion reactivity of an iron porphyrin carbene, [Fe(Por)(SCH3)(CHCO2Et)]-, a model of a complex believed to exist in an exptl. studied artificial metalloenzyme. The ground state electronic structure of the terminal form of this complex is an open-shell singlet, with two antiferromagnetically coupled electrons residing on the iron center and carbene ligand. As the authors shall reveal, the bonding properties of [Fe(Por)(SCH3)(CHCO2Et)]-are remarkably analogous to those of ferric heme superoxide complexes. The carbene forms by dinitrogen loss from Et diazoacetate. This reaction occurs preferentially through an open-shell singlet transition state: iron donates electron d. to weaken the C-N bond undergoing cleavage. Once formed, the iron porphyrin carbene accomplishes N-H insertion via nucleophilic attack. The resulting ylide then rearranges, using an internal carbonyl base, to form an enol that leads to the product. The findings rationalize exptl. obsd. reactivity trends reported in artificial metalloenzymes employing iron porphyrin carbenes. Also, these results suggest a possible expansion of enzymic substrate scope, to include aliph. amines. Thus, this work, among the first several computational explorations of these species, contributes insights and predictions to the surging interest in iron porphyrin carbenes and their synthetic potential.

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26. 26

    Schäfer, A.; Horn, H.; Ahlrichs, R. Fully Optimized Contracted Gaussian Basis Sets for Atoms Li to Kr. J. Chem. Phys. 1992, 97, 2571– 2577,  DOI: 10.1063/1.463096

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    There is no corresponding record for this reference.
27. 27

    Schäfer, A.; Huber, C.; Ahlrichs, R. Fully Optimized Contracted Gaussian Basis Sets of Triple Zeta Valence Quality for Atoms Li to Kr. J. Chem. Phys. 1994, 100, 5829– 5835,  DOI: 10.1063/1.467146

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    There is no corresponding record for this reference.
28. 28

    Grimme, S.; Ehrlich, S.; Goerigk, L. Effect of the Damping Function in Dispersion Corrected Density Functional Theory. J. Comput. Chem. 2011, 32, 1456– 1465,  DOI: 10.1002/jcc.21759

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    28

    Effect of the damping function in dispersion corrected density functional theory

    Grimme, Stefan; Ehrlich, Stephan; Goerigk, Lars

    Journal of Computational Chemistry (2011), 32 (7), 1456-1465CODEN: JCCHDD; ISSN:0192-8651. (John Wiley & Sons, Inc.)

    It is shown by an extensive benchmark on mol. energy data that the math. form of the damping function in DFT-D methods has only a minor impact on the quality of the results. For 12 different functionals, a std. "zero-damping" formula and rational damping to finite values for small interat. distances according to Becke and Johnson (BJ-damping) has been tested. The same (DFT-D3) scheme for the computation of the dispersion coeffs. is used. The BJ-damping requires one fit parameter more for each functional (three instead of two) but has the advantage of avoiding repulsive interat. forces at shorter distances. With BJ-damping better results for nonbonded distances and more clear effects of intramol. dispersion in four representative mol. structures are found. For the noncovalently-bonded structures in the S22 set, both schemes lead to very similar intermol. distances. For noncovalent interaction energies BJ-damping performs slightly better but both variants can be recommended in general. The exception to this is Hartree-Fock that can be recommended only in the BJ-variant and which is then close to the accuracy of cor. GGAs for non-covalent interactions. According to the thermodn. benchmarks BJ-damping is more accurate esp. for medium-range electron correlation problems and only small and practically insignificant double-counting effects are obsd. It seems to provide a phys. correct short-range behavior of correlation/dispersion even with unmodified std. functionals. In any case, the differences between the two methods are much smaller than the overall dispersion effect and often also smaller than the influence of the underlying d. functional. © 2011 Wiley Periodicals, Inc.; J. Comput. Chem., 2011.

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29. 29

    Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions. J. Phys. Chem. B 2009, 113, 6378– 6396,  DOI: 10.1021/jp810292n

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    29

    Universal Solvation Model Based on Solute Electron Density and on a Continuum Model of the Solvent Defined by the Bulk Dielectric Constant and Atomic Surface Tensions

    Marenich, Aleksandr V.; Cramer, Christopher J.; Truhlar, Donald G.

    Journal of Physical Chemistry B (2009), 113 (18), 6378-6396CODEN: JPCBFK; ISSN:1520-6106. (American Chemical Society)

    We present a new continuum solvation model based on the quantum mech. charge d. of a solute mol. interacting with a continuum description of the solvent. The model is called SMD, where the "D" stands for "d." to denote that the full solute electron d. is used without defining partial at. charges. "Continuum" denotes that the solvent is not represented explicitly but rather as a dielec. medium with surface tension at the solute-solvent boundary. SMD is a universal solvation model, where "universal" denotes its applicability to any charged or uncharged solute in any solvent or liq. medium for which a few key descriptors are known (in particular, dielec. const., refractive index, bulk surface tension, and acidity and basicity parameters). The model separates the observable solvation free energy into two main components. The first component is the bulk electrostatic contribution arising from a self-consistent reaction field treatment that involves the soln. of the nonhomogeneous Poisson equation for electrostatics in terms of the integral-equation-formalism polarizable continuum model (IEF-PCM). The cavities for the bulk electrostatic calcn. are defined by superpositions of nuclear-centered spheres. The second component is called the cavity-dispersion-solvent-structure term and is the contribution arising from short-range interactions between the solute and solvent mols. in the first solvation shell. This contribution is a sum of terms that are proportional (with geometry-dependent proportionality consts. called at. surface tensions) to the solvent-accessible surface areas of the individual atoms of the solute. The SMD model has been parametrized with a training set of 2821 solvation data including 112 aq. ionic solvation free energies, 220 solvation free energies for 166 ions in acetonitrile, methanol, and DMSO, 2346 solvation free energies for 318 neutral solutes in 91 solvents (90 nonaq. org. solvents and water), and 143 transfer free energies for 93 neutral solutes between water and 15 org. solvents. The elements present in the solutes are H, C, N, O, F, Si, P, S, Cl, and Br. The SMD model employs a single set of parameters (intrinsic at. Coulomb radii and at. surface tension coeffs.) optimized over six electronic structure methods: M05-2X/MIDI!6D, M05-2X/6-31G*, M05-2X/6-31+G**, M05-2X/cc-pVTZ, B3LYP/6-31G*, and HF/6-31G*. Although the SMD model has been parametrized using the IEF-PCM protocol for bulk electrostatics, it may also be employed with other algorithms for solving the nonhomogeneous Poisson equation for continuum solvation calcns. in which the solute is represented by its electron d. in real space. This includes, for example, the conductor-like screening algorithm. With the 6-31G* basis set, the SMD model achieves mean unsigned errors of 0.6-1.0 kcal/mol in the solvation free energies of tested neutrals and mean unsigned errors of 4 kcal/mol on av. for ions with either Gaussian03 or GAMESS.

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    Li, C.; Wu, W.; Cho, K.; Shaik, S. Oxidation of Tertiary Amines by Cytochrome P450─Kinetic Isotope Effect as a Spin-State Reactivity Probe. Chem. Eur. J. 2009, 15, 8492– 8503,  DOI: 10.1002/chem.200802215

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    30

    Oxidation of Tertiary Amines by Cytochrome P450-Kinetic Isotope Effect as a Spin-State Reactivity Probe

    Li, Chunsen; Wu, Wei; Cho, Kyung-Bin; Shaik, Sason

    Chemistry - A European Journal (2009), 15 (34), 8492-8503, S8492/1-S8492/37CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)

    Two types of tertiary amine oxidn. processes, namely, N-dealkylation and N-oxygenation, by compd. I (Cpd I) of cytochrome P 450 are studied theor. using hybrid DFT calcns. All the calcns. show that both N-dealkylation and N-oxygenation of trimethylamine (TMA) proceed preferentially from the low-spin (LS) state of Cpd I. Indeed, the computed kinetic isotope effects (KIEs) for the rate-controlling hydrogen abstraction step of dealkylation show that only the KIELS fits the exptl. datum, whereas the corresponding value for the high-spin (HS) process is much higher. These results second those published before for N,N-dimethylaniline (DMA), and as such, they further confirm the conclusion drawn then that KIEs can be a sensitive probe of spin state reactivity. The ferric-carbinolamine of TMA decomps. most likely in a non-enzymic reaction since the Fe-O bond dissocn. energy (BDE) is neg. The computational results reveal that in the reverse reaction of N-oxygenation, the N-oxide of arom. amine can serve as a better oxygen donor than that of aliph. amine to generate Cpd I. This capability of the N-oxo derivs. of arom. amines to transfer oxygen to the heme, and thereby generate Cpd I, is in good accord with exptl. data previously reported.

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    Harvey, J. N.; Aschi, M.; Schwarz, H.; Koch, W. The Singlet and Triplet States of Phenyl Cation. A Hybrid Approach for Locating Minimum Energy Crossing Points between Non-Interacting Potential Energy Surfaces. Theor. Chem. Acc. 1998, 99, 95– 99,  DOI: 10.1007/s002140050309

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    31

    The singlet and triplet states of phenyl cation. A hybrid approach for locating minimum energy crossing points between non-interacting potential energy surfaces

    Harvey, Jeremy N.; Aschi, Massimiliano; Schwarz, Helmut; Koch, Wolfram

    Theoretical Chemistry Accounts (1998), 99 (2), 95-99CODEN: TCACFW; ISSN:1432-881X. (Springer-Verlag)

    The Ph cation is known to have 2 low-energy min., corresponding to 1A1 and 3B1 states, the first of which is more stable by ∼25 kcal/mol. The min. energy crossing point between these 2 surfaces, located at various levels including a hybrid method first described here, lies just above the min. of the triplet, 0.12 kcal/mol at the CCSD(T)/cc-pVDZ// B3LYP/SV level, and there is significant spin-orbit coupling between the surfaces at this point. On the basis of these results, the lifetime of the triplet is expected to be very short.

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32. 32

    Rodríguez-Guerra, J. Jaimergp/easymecp: V0.3.2. Zenodo November 27, 2020.

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    There is no corresponding record for this reference.
33. 33

    Roos, B. O. The Complete Active Space Self-Consistent Field Method and Its Applications in Electronic Structure Calculations. Adv. Chem. Phys. 1987, 69, 399– 445,  DOI: 10.1002/9780470142943.ch7

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    33

    The complete active space self-consistent field method and its applications in electronic structure calculations

    Roos, Bjoern

    Advances in Chemical Physics (1987), 69 (Ab Initio Methods Quantum Chem.--2), 399-445CODEN: ADCPAA; ISSN:0065-2385.

    A review with 121 refs.

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34. 34

    Kupper, C.; Mondal, B.; Serrano-Plana, J.; Klawitter, I.; Neese, F.; Costas, M.; Ye, S.; Meyer, F. Nonclassical Single-State Reactivity of an Oxo-Iron(IV) Complex Confined to Triplet Pathways. J. Am. Chem. Soc. 2017, 139, 8939– 8949,  DOI: 10.1021/jacs.7b03255

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    34

    Nonclassical Single-State Reactivity of an Oxo-Iron(IV) Complex Confined to Triplet Pathways

    Kupper, Claudia; Mondal, Bhaskar; Serrano-Plana, Joan; Klawitter, Iris; Neese, Frank; Costas, Miquel; Ye, Shengfa; Meyer, Franc

    Journal of the American Chemical Society (2017), 139 (26), 8939-8949CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    C-H bond activation mediated by oxo-iron (IV) species represents the key step of many heme and nonheme O2-activating enzymes. Of crucial interest is the effect of spin state of the FeIV(O) unit. Here we report the C-H activation kinetics and corresponding theor. investigations of an exclusive tetracarbene ligated oxo-iron(IV) complex, [LNHCFeIV(O)(MeCN)]2+ (1). Kinetic traces using substrates with bond dissocn. energies (BDEs) up to 80 kcal mol-1 show pseudo-first-order behavior and large but temp.-dependent kinetic isotope effects (KIE 32 at -40 °C). When compared with a topol. related oxo-iron(IV) complex bearing an equatorial N-donor ligand, [LTMCFeIV(O) (MeCN)]2+ (A), the tetracarbene complex 1 is significantly more reactive with second order rate consts. k'2 that are 2-3 orders of magnitude higher. UV-vis expts. in tandem with cryospray mass spectrometry evidence that the reaction occurs via formation of a hydroxo-iron(III) complex (4) after the initial H atom transfer (HAT). An extensive computational study using a wave function based multireference approach, viz. complete active space SCF (CASSCF) followed by N-electron valence perturbation theory up to second order (NEVPT2), provided insight into the HAT trajectories of 1 and A. Calcd. free energy barriers for 1 reasonably agree with exptl. values. Because the strongly donating equatorial tetracarbene pushes the Fe-dx2-y2 orbital above dz2, 1 features a dramatically large quintet-triplet gap of ∼18 kcal/mol compared to ∼2-3 kcal/mol computed for A. Consequently, the HAT process performed by 1 occurs on the triplet surface only, in contrast to complex A reported to feature two-state-reactivity with contributions from both triplet and quintet states. Despite this, the reactive FeIV(O) units in 1 and A undergo the same electronic-structure changes during HAT. Thus, the unique complex 1 represents a pure "triplet-only" ferryl model.

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35. 35

    Mondal, B.; Neese, F.; Bill, E.; Ye, S. Electronic Structure Contributions of Non-Heme Oxo-Iron(V) Complexes to the Reactivity. J. Am. Chem. Soc. 2018, 140, 9531– 9544,  DOI: 10.1021/jacs.8b04275

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    35

    Electronic Structure Contributions of Non-Heme Oxo-Iron(V) Complexes to the Reactivity

    Mondal, Bhaskar; Neese, Frank; Bill, Eckhard; Ye, Shengfa

    Journal of the American Chemical Society (2018), 140 (30), 9531-9544CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Oxo-iron(V) species have been implicated in the catalytic cycle of the Rieske dioxygenase. Its synthetic analog, [FeV(O)(OC(O)CH3)(PyNMe3)]2+ (1, PyNMe3 = 3,6,9,15-tetraazabicyclo[9.3.1]pentadeca-1(15),11,13-triene-3,6,9- trimethyl), derived from the O-O bond cleavage of its acetylperoxo iron(III) precursor, has been shown exptl. to perform regio- and stereo-selective C-H and C=C bond functionalization. However, its structure-activity relation is poorly understood. Herein we present a detailed electronic-structure and spectroscopic anal. of complex 1 along with well-characterized oxo-iron(V) complexes, [FeV(O)(TAML)]- (2, TAML = tetraamido macrocyclic ligand), [FeV(O)(TMC)(NC(O)CH3)]+ (4, TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane) and [FeV(O)(TMC)(NC(OH)CH3)]2+ (4-H+) using wavefunction-based multireference complete active-space SCF calcns. Our results reveal that the x/y anisotropy of the 57Fe A-matrix is not a reliable spectroscopic marker to identify oxo-iron(V) species, and that the drastically different Ax and Ay values detd. for complexes 1, 4 and 4-H+ have distinctive origins compared to complex 2, a genuine oxo-iron(V) species. Complex 1, in fact, has a dominant character of [FeIV(O•••OC(O)CH3)2-•]2+, i.e. an SFe = 1 iron(IV) center antiferromagnetically coupled to an O-O σ* radical, where the O-O bond has not been completely broken. Complex 4 is best described as a triplet ferryl unit that strongly interacts with the trans acetylimidyl radical in an antiferromagnetic fashion, [FeIV(O)(•N=C(O-)CH3)]+. Complex 4-H+ features a similar electronic structure, [FeIV(O)(•N=C(OH)CH3)]2+. Owing to the remaining approx. half σ-bond in the O-O moiety, complex 1 can arrange two electron-accepting orbitals (α σ* O-O and β Fe-dxz) in such a way that both orbitals can simultaneously interact with the doubly occupied electron-donating orbitals (σC-H or πC-C). Hence, complex 1 can promote a concerted yet asynchronous two-electron oxidn. of the C-H and C=C bonds, which nicely explains the stereospecificity obsd. for complex 1 and the related species.

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36. 36

    Angeli, C.; Cimiraglia, R.; Evangelisti, S.; Leininger, T.; Malrieu, J.-P. Introduction of n -Electron Valence States for Multireference Perturbation Theory. J. Chem. Phys. 2001, 114, 10252– 10264,  DOI: 10.1063/1.1361246

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    36

    Introduction of n-electron valence states for multireference perturbation theory

    Angeli, C.; Cimiraglia, R.; Evangelisti, S.; Leininger, T.; Malrieu, J.-P.

    Journal of Chemical Physics (2001), 114 (23), 10252-10264CODEN: JCPSA6; ISSN:0021-9606. (American Institute of Physics)

    The present work presents three second-order perturbative developments from a complete active space (CAS) zero-order wave function, which are strictly additive with respect to mol. dissocn. and intruder state free. They differ by the degree of contraction of the outer-space perturbers. Two types of zero-order Hamiltonians are proposed, both are bielectronic, incorporating the interactions between electrons in the active orbitals, therefore introducing a rational balance between the zero-order wave function and the outer-space. The use of Dyall's Hamiltonian, which puts the active electrons in a fixed core field, and of a partially contracted formalism seems a promising compromise. The formalism is generalizable to multireference spaces which are parts of a CAS. A few test applications of the simplest variant developed in this paper illustrate its potentialities.

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37. 37

    Neese, F. The ORCA Program System. WIREs Comput. Mol. Sci. 2012, 2, 73– 78,  DOI: 10.1002/wcms.81

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    37

    The ORCA program system

    Neese, Frank

    Wiley Interdisciplinary Reviews: Computational Molecular Science (2012), 2 (1), 73-78CODEN: WIRCAH; ISSN:1759-0884. (Wiley-Blackwell)

    A review. ORCA is a general-purpose quantum chem. program package that features virtually all modern electronic structure methods (d. functional theory, many-body perturbation and coupled cluster theories, and multireference and semiempirical methods). It is designed with the aim of generality, extendibility, efficiency, and user friendliness. Its main field of application is larger mols., transition metal complexes, and their spectroscopic properties. ORCA uses std. Gaussian basis functions and is fully parallelized. The article provides an overview of its current possibilities and documents its efficiency.

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38. 38

    Wang, J.; Gao, H.; Yang, L.; Gao, Y. Q. Role of Engineered Iron-Haem Enzyme in Reactivity and Stereoselectivity of Intermolecular Benzylic C–H Bond Amination. ACS Catal. 2020, 10, 5318– 5327,  DOI: 10.1021/acscatal.0c00248

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    38

    Role of Engineered Iron-haem Enzyme in Reactivity and Stereoselectivity of Intermolecular Benzylic C-H Bond Amination

    Wang, Juping; Gao, Hui; Yang, Lijiang; Gao, Yi Qin

    ACS Catalysis (2020), 10 (9), 5318-5327CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

    A recent success in which the engineered iron-haem enzymes P411CHA' aminate the intermol. benzylic C-H bond with both high efficiency and stereoselectivity solves a long-standing challenge in synthetic chem. (). The mechanism, reactivity, and stereoselectivity of this reaction were studied by quantum mech. (QM)/mol. mech. (MM) calcns. in this work. To understand better the origin of such an excellent catalytic performance of biocatalyst P411CHA', iron-cofactor FePIX alone for the intermol. C-H bond amination was also theor. investigated as a comparison. The catalytic cycle includes two processes: N2 dissocn. and nitrene transfer. The calcn. results show that P411CHA' enzyme can catalyze intermol. C-H amination with high reactivity and stereoselectivity, whereas the FePIX-catalyzed reaction has much higher barriers for both N2 dissocn. and nitrene transfer compared to P411CHA'. The reason for this dramatic difference in catalytic reactivity between P411CHA' and FePIX is that the former but not the latter allows the formation of precursors B-5PR1 and B-3PR2, which are structurally close to transition states B-3TS1 and B-3TS2 and accelerate N2 dissocn. and nitrene transfer, resp. The mutated residues (A82L A78V F263L) assist the formations of B-5PR1 and B-3PR2 via reducing effectively the size of the haem distal pocket. High stereoselectivity of P411CHA' stems from the steric effect in H-abstraction. A theor. anal. on how para substituent R affects reactivity was also carried out. A strong π-type electron-donating group on the substrate enhances significantly the reactivity of P411CHA'-catalyzed intermol. C-H amination. These results provide valuable information for designing and constructing environmentally friendly biocatalytic C-H amination systems with high reactivity and stereoselectivity.

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39. 39

    Huang, H.; Zhao, D.-X.; Yang, Z.-Z. Theoretical Study of Enantioenriched Aminohydroxylation of Styrene Catalyzed by an Engineered Hemoprotein. J. Phys. Org. Chem. 2022, 35, e4280  DOI: 10.1002/poc.4280

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    39

    Theoretical study of enantioenriched aminohydroxylation of styrene catalyzed by an engineered hemoprotein

    Huang, Hong; Zhao, Dong-Xia; Yang, Zhong-Zhi

    Journal of Physical Organic Chemistry (2022), 35 (1), e4280CODEN: JPOCEE; ISSN:0894-3230. (John Wiley & Sons Ltd.)

    Transforming olefins to chiral amino alcs. is a useful approach to synthesize biol. active natural products and numerous drugs. A recent study has demonstrated a promising and synthetic value of an engineered hemoprotein for catalyzing olefins to chiral amino alcs. with 2500 total turnover nos. and 90% ee. D. functional theory (DFT) calcn. has been used to systematically investigate the detailed mechanisms of the aforementioned process. One electron transfers from Fe atom to HN-nitrene in the iron-nitrene intermediate formation. Subsequently, styrene aziridination, singlet state is characterized by a nonradical, concerted nonsynchronous mechanism, while a radical and stepwise mechanism for triplet. Through hydrolysis reaction forming amino alc. enantiomers, radical intermediate in triplet state without ring-opening process is obviously more feasible than singlet aziridine, where the energy barrier difference between triplet and singlet approaches to 20.00 kcal/mol. Moreover, due to the hydrogen bond effect, the water dimer-assisted hydrolysis reaction is effective to reduce the energy barrier by about 7.00 kcal/mol compared with one water assisted in triplet; however, the energy barrier difference in singlet is unapparent with only 0.18 kcal/mol accompanied with ring-opening process. Further, homol. modeling shows that the reactivity and enantioselectivity can be attributed to the structure of the enzyme active pocket. This study sheds light on the mechanism of engineered hemoprotein-mediated amino alcs. synthesis and shows the development of biol. catalysts.

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40. 40

    Das, S. K.; Das, S.; Ghosh, S.; Roy, S.; Pareek, M.; Roy, B.; Sunoj, R. B.; Chattopadhyay, B. An Iron(II)-Based Metalloradical System for Intramolecular Amination of C(sp2)-H and C(sp3)-H Bonds: Synthetic Applications and Mechanistic Studies. Chem. Sci. 2022, 13, 11817– 11828,  DOI: 10.1039/D2SC03505G

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    40

    An iron(II)-based metalloradical system for intramolecular amination of C(sp2)-H and C(sp3)-H bonds: synthetic applications and mechanistic studies

    Das, Sandip Kumar; Das, Subrata; Ghosh, Supratim; Roy, Satyajit; Pareek, Monika; Roy, Brindaban; Sunoj, Raghavan B.; Chattopadhyay, Buddhadeb

    Chemical Science (2022), 13 (40), 11817-11828CODEN: CSHCCN; ISSN:2041-6520. (Royal Society of Chemistry)

    A catalytic system for intramol. C(sp2)-H and C(sp3)-H amination of substituted tetrazolopyridines was successfully developed. The amination reactions were developed using an iron-porphyrin based catalytic system. It was demonstrated that the same iron-porphyrin based catalytic system efficiently activates both the C(sp2)-H and C(sp3)-H bonds of the tetrazole as well as azide-featuring substrates with a high level of regioselectivity. The method exhibited an excellent functional group tolerance. The method afforded three different classes of high-value N-heterocyclic scaffolds. A no. of important late-stage C-H aminations were performed to access important classes of mols. Detailed studies (exptl. and computational) showed that both the C(sp2)-H and C(sp3)-H amination reactions involve a metalloradical activation mechanism, which is different from the previously reported electro-cyclization mechanism. Collectively, this study reports the discovery of a new class of metalloradical activation modes using a base metal catalyst that should find wide application in the context of medicinal chem., drug discovery and industrial applications.

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41. 41

    Liu, Z.; Qin, Z. Y.; Zhu, L.; Athavale, S. V.; Sengupta, A.; Jia, Z. J.; Garcia-Borràs, M.; Houk, K. N.; Arnold, F. H. An Enzymatic Platform for Primary Amination of 1-Aryl-2-Alkyl Alkynes. J. Am. Chem. Soc. 2022, 144, 80– 85,  DOI: 10.1021/jacs.1c11340

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    41

    An enzymic platform for primary amination of 1-aryl-2-alkyl alkynes

    Liu, Zhen; Qin, Zi-Yang; Zhu, Ledong; Athavale, Soumitra V.; Sengupta, Arkajyoti; Jia, Zhi-Jun; Garcia-Borras, Marc; Houk, K. N.; Arnold, Frances H.

    Journal of the American Chemical Society (2022), 144 (1), 80-85CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Propargyl amines are versatile synthetic intermediates with numerous applications in the pharmaceutical industry. An attractive strategy for efficient prepn. of these compds. is nitrene propargylic C(sp3)-H insertion. However, achieving this reaction with good chemo-, regio-, and enantioselective control has proven to be challenging. Here, we report an enzymic platform for the enantioselective propargylic amination of alkynes using a hydroxylamine deriv. as the nitrene precursor. Cytochrome P 450 variant PA-G8 catalyzing this transformation was identified after eight rounds of directed evolution. A variety of 1-aryl-2-alkyl alkynes are accepted by PA-G8, including those bearing heteroarom. rings. This biocatalytic process is efficient and selective (up to 2610 total turnover no. (TTN) and 96% ee) and can be performed on preparative scale.

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42. 42

    Mai, B. K.; Neris, N. M.; Yang, Y.; Liu, P. C-N Bond Forming Radical Rebound Is the Enantioselectivity-Determining Step in P411-Catalyzed Enantioselective C(sp3)-H Amination: A Combined Computational and Experimental Investigation. J. Am. Chem. Soc. 2022, 144, 11215– 11225,  DOI: 10.1021/jacs.2c02283

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    42

    C-N Bond forming radical rebound is the enantioselectivity-determining step in P411-catalyzed enantioselective C(sp3)-H amination: A combined computational and experimental investigation

    Mai, Binh Khanh; Neris, Natalia M.; Yang, Yang; Liu, Peng

    Journal of the American Chemical Society (2022), 144 (25), 11215-11225CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    Engineered metalloenzymes represent promising catalysts for stereoselective C-H functionalization reactions. Recently, P 450 enzymes have been evolved to allow for new-to-nature intramol. C(sp3)-H amination reactions via a nitrene transfer mechanism, giving rise to diamine derivs. with excellent enantiocontrol. To shed light on the origin of enantioselectivity, a combined computational and exptl. study was carried out. Hybrid quantum mechanics/mol. mechanics calcns. were performed to investigate the activation energies and enantioselectivities of both the hydrogen atom transfer (HAT) and the subsequent C-N bond forming radical rebound steps. Contrary to previously hypothesized enantioinduction mechanisms, our calcns. show that the radical rebound step is enantioselectivity-detg., whereas the preceding HAT step is only moderately stereoselective. Furthermore, the selectivity in the initial HAT is ablated by rapid conformational change of the radical intermediate prior to C-N bond formation. This finding is corroborated by our exptl. study using a set of enantiomerically pure, monodeuterated substrates. Furthermore, classical and ab initio mol. dynamics simulations were carried out to investigate the conformational flexibility of the carbon-centered radical intermediate. This key radical species undergoes a facile conformational change in the enzyme active site from the pro-(R) to the pro-(S) configuration, whereas the radical rebound is slower due to the spin-state change and ring strain of the cyclization process, thereby allowing stereoablative C-N bond formation. Together, these studies revealed an underappreciated enantioinduction mechanism in biocatalytic C(sp3)-H functionalizations involving radical intermediates, opening up new avenues for the development of other challenging asym. C(sp3)-H functionalizations.

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43. 43

    Goswami, M.; Lyaskovskyy, V.; Domingos, S. R.; Buma, W. J.; Woutersen, S.; Troeppner, O.; Ivanović-Burmazović, I.; Lu, H.; Cui, X.; Zhang, X. P.; Reijerse, E. J.; DeBeer, S.; van Schooneveld, M. M.; Pfaff, F. F.; Ray, K.; de Bruin, B. Characterization of Porphyrin-Co(III)-‘Nitrene Radical’ Species Relevant in Catalytic Nitrene Transfer Reactions. J. Am. Chem. Soc. 2015, 137, 5468– 5479,  DOI: 10.1021/jacs.5b01197

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    43

    Characterization of Porphyrin-Co(III)-'Nitrene Radical' Species Relevant in Catalytic Nitrene Transfer Reactions

    Goswami, Monalisa; Lyaskovskyy, Volodymyr; Domingos, Sergio R.; Buma, Wybren Jan; Woutersen, Sander; Troeppner, Oliver; Ivanovic-Burmazovic, Ivana; Lu, Hongjian; Cui, Xin; Zhang, X. Peter; Reijerse, Edward J.; DeBeer, Serena; van Schooneveld, Matti M.; Pfaff, Florian Felix; Ray, Kallol; de Bruin, Bas

    Journal of the American Chemical Society (2015), 137 (16), 5468-5479CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    To fully characterize the CoIII-'nitrene radical' species that are proposed as intermediates in nitrene transfer reactions mediated by Co(II) porphyrins, different combinations of Co(II) complexes of porphyrins and nitrene transfer reagents were combined, and the generated species were studied using EPR, UV-visible, IR, VCD, UHR-ESI-MS, and XANES/XAFS measurements. Reactions of Co(II) porphyrins 1P1 (P1 = meso-tetraphenylporphyrin (TPP)) and 1P2 (P2 = 3,5-DitBu-ChenPhyrin) with org. azides 2Ns (NsN3), 2Ts (TsN3), and 2Troc (TrocN3) gave mono-nitrene species 3P1Ns, 3P2Ts, and 3P2Troc, resp., which are best described as [CoIII(por)(NR''•-)] nitrene radicals (imidyl radicals) resulting from single electron transfer from the Co(II) porphyrin to the 'nitrene' moiety (Ns: R'' = -SO2-p-C6H5NO2; Ts: R'' = -SO2C6H6; Troc: R'' = -C(O)OCH2CCl3). Remarkably, the reaction of 1P1 with N-nosyl iminoiodane (PhI = NNs) 4Ns gave a bis-nitrene species 5P1Ns. This species is best described as a triple-radical complex [(por•-)CoIII(NR''•-)2] contg. three ligand-centered unpaired electrons: two nitrene radicals (NR''•-) and one oxidized porphyrin radical (por•-). Thus, the formation of the 2nd nitrene radical involves another intramol. 1-electron transfer to the nitrene moiety, but now from the porphyrin ring instead of the metal center. This bis-nitrene species is obsd. only on reacting 4Ns with 1P1. Reaction of the more bulky 1P2 with 4Ns results again in formation of mainly mono-nitrene species 3P2Ns according to EPR and ESI-MS spectroscopic studies. The mono- and bis-nitrene species were initially expected to be five- and six-coordinate species, resp., but XANES data revealed that both mono- and bis-nitrene species are six-coordinate Oh species. The nature of the 6th ligand bound to Co(III) in the mono-nitrene case remains elusive, but some plausible candidates are NH3, NH2-, NsNH-, and OH-; NsNH- being the most plausible. Conversion of mono-nitrene species 3P1Ns into bis-nitrene species 5P1Ns upon reaction with 4Ns was demonstrated. Solns. contg. 3P1Ns and 5P1Ns proved to be still active in catalytic aziridination of styrene, consistent with their proposed key involvement in nitrene transfer reactions mediated by Co(II) porphyrins.

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44. 44

    van Leest, N. P.; de Bruin, B. Revisiting the Electronic Structure of Cobalt Porphyrin Nitrene and Carbene Radicals with NEVPT2-CASSCF Calculations: Doublet versus Quartet Ground States. Inorg. Chem. 2021, 60, 8380– 8387,  DOI: 10.1021/acs.inorgchem.1c00910

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    44

    Revisiting the Electronic Structure of Cobalt Porphyrin Nitrene and Carbene Radicals with NEVPT2-CASSCF Calculations: Doublet versus Quartet Ground States

    van Leest, Nicolaas P.; de Bruin, Bas

    Inorganic Chemistry (2021), 60 (12), 8380-8387CODEN: INOCAJ; ISSN:0020-1669. (American Chemical Society)

    Cobalt porphyrin complexes are established catalysts for carbene and nitrene radical group-transfer reactions. The key carbene and mono- and bisnitrene radical complexes coordinated to [Co(TPP)] (TPP = tetraphenylporphyrin) have previously been investigated with a variety of exptl. techniques and supporting (single-ref.) d. functional theory (DFT) calcns. that indicated doublet (S = 1/2) ground states for all three species. In this contribution, we revisit their electronic structures with multireference N-electron valence state perturbation theory (NEVPT2)-complete-active-space self-consistent-field (CASSCF) calcns. to investigate possible multireference contributions to the ground-state wave functions. The carbene ([CoIII(TPP)(•CHCO2Et)]) and mononitrene ([CoIII(TPP)(•NNs)]) radical complexes were confirmed to have uncomplicated doublet ground states, although a higher carbene or nitrene radical character and a lower Co-C/N bond order was found in the NEVPT2-CASSCF calcns. Supported by ESR anal. and spin counting, paramagnetic molar susceptibility detn., and NEVPT2-CASSCF calcns., we report that the cobalt porphyrin bisnitrene complex ([CoIII(TPP•)(•NNs)2]) has a quartet (S = 3/2) spin ground state, with a thermally accessible multireference and multideterminant "broken-symmetry" doublet spin excited state. A spin flip on the porphyrin-centered unpaired electron allows for interconversion between the quartet and broken-symmetry doublet spin states, with an approx. 10-fold higher Boltzmann population of the quartet at room temp.

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45. 45

    Vardhaman, A. K.; Barman, P.; Kumar, S.; Sastri, C. V.; Kumar, D.; de Visser, S. P. Comparison of the Reactivity of Nonheme Iron(IV)-Oxo versus Iron(IV)-Imido Complexes: Which Is the Better Oxidant?. Angew. Chem., Int. Ed. 2013, 52, 12288– 12292,  DOI: 10.1002/anie.201305370

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    45

    Comparison of the Reactivity of Nonheme Iron(IV)-Oxo versus Iron(IV)-Imido Complexes: Which is the Better Oxidant?

    Vardhaman, Anil Kumar; Barman, Prasenjit; Kumar, Suresh; Sastri, Chivukula V.; Kumar, Devesh; de Visser, Sam P.

    Angewandte Chemie, International Edition (2013), 52 (47), 12288-12292CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    A comparative study on the reactivity patterns of nonheme iron(IV)-oxo vs. iron(IV)-imido is reported. Owing to the larger electron affinity of the oxidant, iron(IV)-imido is a better oxidant of sulfoxidn. reactions than iron(IV)-oxo. By contrast, these trends are reversed for stepwise one-electron transfer reactions, such as hydrogen atom abstraction reactions where stereochem. interactions upon substrate approach det. the relative rate consts.

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46. 46

    Mukherjee, G.; Reinhard, F. G. C.; Bagha, U. K.; Sastri, C. V.; de Visser, S. P. Sluggish Reactivity by a Nonheme Iron(IV)-Tosylimido Complex as Compared to Its Oxo Analogue. Dalt. Trans. 2020, 49, 5921– 5931,  DOI: 10.1039/D0DT00018C

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47. 47

    Coin, G.; Patra, R.; Rana, S.; Biswas, J. P.; Dubourdeaux, P.; Clémancey, M.; De Visser, S. P.; Maiti, D.; Maldivi, P.; Latour, J. M. Fe-Catalyzed Aziridination Is Governed by the Electron Affinity of the Active Imido-Iron Species. ACS Catal. 2020, 10, 10010– 10020,  DOI: 10.1021/acscatal.0c01427

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    47

    Fe-Catalyzed Aziridination Is Governed by the Electron Affinity of the Active Imido-Iron Species

    Coin, Guillaume; Patra, Ranjan; Rana, Sujoy; Biswas, Jyoti Prasad; Dubourdeaux, Patrick; Clemancey, Martin; de Visser, Sam P.; Maiti, Debabrata; Maldivi, Pascale; Latour, Jean-Marc

    ACS Catalysis (2020), 10 (17), 10010-10020CODEN: ACCACS; ISSN:2155-5435. (American Chemical Society)

    Aziridination has very recently been found to be catalyzed by heme and nonheme Fe enzymes, opening the way to biotechnol. developments. However, its mechanism is not fully understood owing to the contrasting behaviors exhibited by several Fe catalysts. Indeed, whereas a few Fe catalysts exhibit an activity dominated by inductive effects, the activity of others reveal significant and even dominant radical delocalization. Therefore, no clear and general rationale of aziridination has yet emerged. Elaborating on our previous studies, we anticipated that replacing two pyridines of a pentanitrogen ligand by two quinolines would enhance the electron affinity of the corresponding imido FeIV active species and hence its aziridination activity. This proved to be the case, and Hammett correlations indicate an electrophilic active species and dominant inductive effects. The calcd. reaction profile points to a two-step mechanism with the formation of the first C-N bond being rate-detg. and involving a strong charge transfer in the transition state. The aziridine ring closure in the second step is almost barrierless. A clear correlation of aziridination yields with calcd. EA for Fe-catalysts indicate that the dependence of aziridination efficacy on EA of active species is a quite general feature. To generalize this anal., we reinvestigated a catalyst exhibiting a radical delocalization dominance. Indeed, a similar two-step mechanism was found, which involves a partial charge transfer in the C-N bond formation as all other cases. The interesting point is that owing to the strong steric hindrance of the catalyst substitution, the aziridine ring closure of the intermediate benzylic radical (second step) becomes rate-detg., thus explaining the dominance of the radical delocalization effect. Eventually, a general aziridination two-step mechanism has been rationalized, and EA thus appears as the key descriptor for Fe-based catalytic aziridination that can be used in a predictable way.

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48. 48

    Shaik, S.; Chen, H.; Janardanan, D. Exchange-Enhanced Reactivity in Bond Activation by Metal–Oxo Enzymes and Synthetic Reagents. Nat. Chem. 2011, 3, 19– 27,  DOI: 10.1038/nchem.943

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    48

    Exchange-enhanced reactivity in bond activation by metal-oxo enzymes and synthetic reagents

    Shaik Sason; Chen Hui; Janardanan Deepa

    Nature chemistry (2011), 3 (1), 19-27 ISSN:.

    Reactivity principles based on orbital overlap and bonding/antibonding interactions are well established to describe the reactivity of organic species, and atomic structures are typically predicted by Hund's rules to have maximum single-electron occupancy of degenerate orbitals in the ground state. Here, we extend the role of exchange to transition states and discuss how, for reactions and kinetics of bioinorganic species, the analogue of Hund's rules is exchange-controlled reactivity. Pathways that increase the number of unpaired and spin-identical electrons on a metal centre will be favoured by exchange stabilization. Such exchange-enhanced reactivity endows transition states with a stereochemistry different from that observed in cases that are not exchange-enhanced, and is in good agreement with the reactivity observed for iron-based enzymes and synthetic analogues. We discuss the interplay between orbital- and exchange-controlled principles, and how this depends on the identity of the transition metal, its oxidation number and its coordination sphere.

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49. 49

    Wong, S. D.; Bell, C. B.; Liu, L. V.; Kwak, Y.; England, J.; Alp, E. E.; Zhao, J.; Que, L.; Solomon, E. I. Nuclear Resonance Vibrational Spectroscopy on the FeIV = O S = 2 Non-Heme Site in TMG 3 Tren: Experimentally Calibrated Insights into Reactivity. Angew. Chem., Int. Ed. 2011, 50, 3215– 3218,  DOI: 10.1002/anie.201007692

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    49

    Nuclear Resonance Vibrational Spectroscopy on FeIV=O S=2 non-heme site in TMG3tren: experimentally calibrated insights into reactivity

    Wong, Shaun D.; Bell, Caleb B., III; Liu, Lei V.; Kwak, Yeonju; England, Jason; Alp, E. Ercan; Zhao, Jiyong; Que, Lawrence, Jr.; Solomon, Edward I.

    Angewandte Chemie, International Edition (2011), 50 (14), 3215-3218, S3215/1-S3215/8CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    [(TMG3tren)FeIV=O] (1) has an FeV=O unit ligated by TMG3tren in a C3, trigonal bipyramidal geometry, and an S = 2 ground state replicating that of enzyme intermediates.TMG3tren = 1,1,1-tris{2-[N2-(1,1,3,3-tetramethylguanidino)]ethyl}amine. We utilize nuclear resonance vibrational spectroscopy (NRVS) to obtain ground-state vibrational data on 1. DFT optimizations of 1 using both the BP86 and B3LYP functionals gave structures in good agreement with X-ray crystallog. and EXAFS results.

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50. 50

    Hirao, H.; Kumar, D.; Que, L.; Shaik, S. Two-State Reactivity in Alkane Hydroxylation by Non-Heme Iron–Oxo Complexes. J. Am. Chem. Soc. 2006, 128, 8590– 8606,  DOI: 10.1021/ja061609o

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    50

    Two-State Reactivity in Alkane Hydroxylation by Non-Heme Iron-Oxo Complexes

    Hirao, Hajime; Kumar, Devesh; Que, Lawrence, Jr.; Shaik, Sason

    Journal of the American Chemical Society (2006), 128 (26), 8590-8606CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)

    D. functional theory is used to explore the mechanisms of alkane hydroxylation for four synthetic non-heme iron(IV)-oxo complexes with three target substrates (Kaizer, J.; Klinker, E. J.; Oh, N. Y.; Rohde; J.-U.; Song, W. J.; Stubna, A.; Kim, J.; Muenck, E.; Nam, W.; Que, L. Jr. J. Am. Chem. Soc. 2004, 126, 472-473; Rohde, J.-U.; Que, L. Jr. Angew. Chem. Int. Ed. 2005, 44, 2255-2258.). The iron-oxo reagents possess triplet ground states and low-lying quintet excited states. The set of exptl. and theor. reactivity trends can be understood if the reactions proceed on the two spin states, namely two-state reactivity (TSR); an appropriate new model is presented. The TSR model makes testable predictions: (a) If crossing to the quintet state occurs, the hydroxylation will be effectively concerted; however, if the process transpires only on the triplet surface, stepwise hydroxylation will occur, and side products derived from radical intermediates would be obsd. (e.g., loss of stereochem.). (b) In cases of crossing en route to the quintet transition state, one expects kinetic isotope effects (KIEs) typical of tunneling. (c) In situations where the two surfaces contribute to the rate, one expects intermediate KIEs and radical scrambling patterns that reflect the two processes. (d) Solvent effects on these reactions are expected to be very large.

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    Louwerse, M. J.; Jan Baerends, E. Oxidative Properties of FeO2+: Electronic Structure and Solvation Effects. Phys. Chem. Chem. Phys. 2007, 9, 156– 166,  DOI: 10.1039/B613182D

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    51

    Oxidative properties of FeO2+: electronic structure and solvation effects

    Louwerse, Manuel J.; Baerends, Evert Jan

    Physical Chemistry Chemical Physics (2007), 9 (1), 156-166CODEN: PPCPFQ; ISSN:1463-9076. (Royal Society of Chemistry)

    An electronic structure anal. is provided of the action of solvated FeO2+, [FeO(H2O)5]2+, as a hydroxylation catalyst. It is emphasized that the oxo end of FeO2+ does not form hydrogen bonds (as electron donor and H-bond acceptor) with H-bond donors nor with aliph. C-H bonds, but it activates C-H bonds as an electron acceptor. It is extremely electrophilic, to the extent that it can activate even such poor electron donors as aliph. C-H bonds, the C-H bond orbital acting as electron donor in a charge transfer type of interaction. Lower lying O-H bonding orbitals are less easily activated. The primary electron accepting orbital in a water environment is the 3σ*α orbital, an antibonding combination of Fe-3dz2 and O-2pz, which is very low-lying relative to the π*α compared with, for example, the σ* orbital in O2 relative to its π*. This is ascribed to relatively small Fe-3dz2 with O-2pz overlap, due to the nodal structure of the 3dz2.The H-abstraction barrier is very low in the gas phase, but it is considerably enhanced in water solvent. This is shown to be due to strong screening effects of the dielec. medium, leading to relative destabilization of the levels of the charged [FeO(H2O)5]2+ species compared to those of the neutral substrate mols., making it a less effective electron acceptor. The solvent directly affects the orbital interactions responsible for the catalytic reaction.

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52. 52

    Hirao, H.; Que, L.; Nam, W.; Shaik, S. A Two-State Reactivity Rationale for Counterintuitive Axial Ligand Effects on the C-H Activation Reactivity of Nonheme FeIV = O Oxidants. Chem. Eur. J. 2008, 14, 1740– 1756,  DOI: 10.1002/chem.200701739

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    52

    A two-state reactivity rationale for counterintuitive axial ligand effects on the C-H activation reactivity of nonheme FeIV=O oxidants

    Hirao, Hajime; Que, Lawrence, Jr.; Nam, Wonwoo; Shaik, Sason

    Chemistry - A European Journal (2008), 14 (6), 1740-1756CODEN: CEUJED; ISSN:0947-6539. (Wiley-VCH Verlag GmbH & Co. KGaA)

    This paper addresses the observation of counterintuitive reactivity patterns of iron-oxo reagents, TMC(L)FeO2+.1+; L = CH3CN, CF3CO2-, N3-, and SR-, in O-transfer to phosphines vs. H-abstraction from, for example, 1,4-cyclohexadiene. Expts. show that O-transfer reactivity correlates with the electrophilicity of the oxidant, but H-abstraction reactivity follows an opposite trend. DFT/B3LYP calcns. reveal that two-state reactivity (TSR) serves as a compelling rationale for these trends, whereby all reactions involve two adjacent spin-states of the iron(IV)-oxo species, triplet and quintet. The ground state triplet surface has high barriers, whereas the excited state quintet surface features lower ones. The barriers, on any single surface, are found to increase as the electrophilicity of TMC(L)FeO2+.1+ decreases. Thus, the counterintuitive behavior of the H-abstraction reactions cannot be explained by considering the reactivity of only a single spin state but can be rationalized by a TSR model in which the reactions proceed on the two surfaces. Two TSR models are outlined: one is traditional involving a variable transmission coeff. for crossover from triplet to quintet, followed by quintet-state reactions; the other considers the net barrier as a blend of the triplet and quintet barriers. The blending coeff. (x), which ests. the triplet participation, increases as the quintet-triplet energy gap of the TMC(L)FeO2+.1+ reagent increases, in the following order of L: CH3CN > CF3CO2- > N3- > SR-. The calcd. barriers predict the dichotomic exptl. trends and the counterintuitive behavior of the H-abstraction series. The TSR approaches make a variety of testable predictions.

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53. 53

    Janardanan, D.; Wang, Y.; Schyman, P.; Que, L.; Shaik, S. The Fundamental Role of Exchange-Enhanced Reactivity in C-H Activation by S = 2 Oxo Iron(IV) Complexes. Angew. Chem., Int. Ed. 2010, 49, 3342– 3345,  DOI: 10.1002/anie.201000004

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    53

    The fundamental role of exchange-enhanced reactivity in C-H activation by S = 2 oxo iron(IV) complexes

    Janardanan, Deepa; Wang, Yong; Schyman, Patric; Que, Lawrence, Jr.; Shaik, Sason

    Angewandte Chemie, International Edition (2010), 49 (19), 3342-3345, S3342/1-S3342/51CODEN: ACIEF5; ISSN:1433-7851. (Wiley-VCH Verlag GmbH & Co. KGaA)

    C-H-Activation of 1,4-cyclohexadiene by nitrogen tri- and tetradentate iron(IV) oxo complexes was explored by DFT calcn. of potential energy surface of allylic hydrogen cleavage to form cyclohexadienyl radical and hydroxyiron(III) complex. 1,4-Cyclohexadiene undergoes hydrogen abstraction in reaction with triimine complex [(L1-N4)FeO]2+ [1-t, L1-N4 = tris(N-methyleneaminoethyl)amine], triguanidine complex [(L2-N4)FeO]2+ [1, L2-N4 = tris[N-bis(dimethylamino)methyleneaminoethyl]amine], tetrapyridine complex [(L3-N5)FeO]2+ [2, L3-N5 = bis(2-pyridinylmethyl)(di-2-pyridinylmethyl)amine], macrocyclic [(L4-N4)(MeCN)FeO]2+ [3, L4-N4 = 1,5,8,12-tetramethyl-1,5,8,12-tetraazatetradecane] and neutral scorpionate [(TpPh)FeO(O2CPh)] [4, TpPh = hydrotris(3,5-diphenylpyrazolyl)borate], giving 2,5-cyclohexadienyl radical and corresponding iron(III) complexes [(Ln-Nm)(L)Fe(OH)]k+ (L absent or MeCN, K = 2, 0). The reaction rate strongly depends on the spin state of Fe(IV), having favorable activation barriers for quintet complexes (S = 2). Whereas the quintet state is the ground state for 1-t, 1 and 4, complexes 2 and 3 exist in triplet ground state. For 2 and 3, hydrogen abstraction from the quintet state is almost barrier-free; the low reactivity of these species is accounted for low probability of the spin crossover and entropic effects of assocn. Low reactivity of 1 is a result of high activation barriers both for triplet and quintet states. Triplet and quintet states for 4 are very near in energy, the quintet state features monodentate benzoate, which facilitates the reaction. The overall reactivity is changed in a series of 4»2≥1>3.

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