Benchmarking Density Functional Theory Methods for Metalloenzyme Reactions: The Introduction of the MME55 Set

Journal of Chemical Theory and Computation, Год журнала: 2023, Номер 19(22), С. 8365 - 8383

Опубликована: Ноя. 9, 2023

We present a new benchmark set of metalloenzyme model reaction energies and barrier heights that we call MME55. The contains 10 different enzymes, representing eight transition metals, both open closed shell systems, system sizes up to 116 atoms. use four DLPNO-CCSD(T)-based approaches calculate reference values against which then the performance range density functional approximations with without dispersion corrections. Dispersion corrections improve results across board, triple-ζ basis sets provide best balance efficiency accuracy. Jacob's ladder is reproduced for whole based on averaged mean absolute (percent) deviations, double hybrids SOS0-PBE0-2-D3(BJ) revDOD-PBEP86-D4 standing out as most accurate methods MME55 set. range-separated ωB97M-V ωB97X-V also perform well here can be recommended reliable compromise between accuracy efficiency; they have already been shown robust many other types chemical problems, well. Despite popularity B3LYP in computational enzymology, it not strong performer our set, discourage its enzyme energetics.

Язык: Английский

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Role of Noncovalent Interactions in Inducing High Enantioselectivity in an Alcohol Reductive Deoxygenation Reaction Involving a Planar Carbocationic Intermediate

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(5), С. 2884 - 2900

Опубликована: Янв. 25, 2023

The involvement of planar carbocation intermediates is generally considered undesirable in asymmetric catalysis due to the difficulty gaining facial control and their intrinsic stability issues. Recently, suitably designed chiral catalyst(s) have enabled a guided approach nucleophiles one prochiral faces carbocations affording high enantiocontrol. Herein, we present vital mechanistic insights from our comprehensive density functional theory (B3LYP-D3) study on Ir-phosphoramidite-catalyzed reductive deoxygenation racemic tertiary α-substituted allenylic alcohols. catalytic transformation relies synergistic action phosphoramidite-modified Ir catalyst Bi(OTf)3, first leading formation an Ir-π-allenyl intermediate through turn-over-determining SN1 ionization, followed by face-selective hydride transfer Hantzsch ester analogue yield enantioenriched product. Bi(OTf)3 was found promote significant number ionic interactions as well noncovalent (NCIs) with substrates (allenylic alcohol ester), thus providing access lower energy route compared pathways devoid Bi(OTf)3. In nucleophilic addition, induction depend efficacy such key NCIs. curious case reversal enantioselectivity, when α-substituent allenyl changed methyl cyclopropyl, identified originate change mechanism enantioconvergent pathway (α-methyl) dynamic kinetic (α-cyclopropyl). These molecular could lead newer strategies tame enantioselective reactions using suitable combinations catalysts additives.

Язык: Английский

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Spectroscopic, structural, and intermolecular interactions of 4-(2-hydroxy-3-methoxybenzylideneamino)-N-(5-methylisoxazol-3-yl)benzenesulfonamide enol-imine and keto-amine isomers

Journal of Molecular Structure, Год журнала: 2023, Номер 1279, С. 134978 - 134978

Опубликована: Янв. 15, 2023

Язык: Английский

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Seven-Membered Ring Formation in Triterpene Biosynthesis: A Key Cyclopropane Rearrangement in Ilelic Acid Biosynthesis

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Фев. 17, 2025

Triterpenes represent a crucial class of natural compounds with diverse biological activities and structural complexity. Among the various skeletal modifications in triterpene biosynthesis, formation seven-membered rings through ring expansion reactions significantly contributes to their diversity and, consequently, functional versatility. This study elucidates detailed reaction mechanism key via cyclopropane rearrangement biosynthesis ilelic acid. Using density theory (DFT) calculations, we thoroughly investigated biosynthetic pathway acid, focusing on critical step. Our computational analysis reveals that proceeds cationic rather than radical-mediated process. Notably, found inherent instability secondary carbocation intermediate drives concerted pathway, avoiding high-energy intermediates. mechanistic understanding not only sheds light acid but also offers broader implications for comprehending similar transformations other pathways. findings contribute fundamental pave way potential biomimetic approaches synthesis complex ring-containing terpenes. Furthermore, this work underscores power methods unraveling intricate mechanisms.

Язык: Английский

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QM/MM Modeling Aided Enzyme Engineering in Natural Products Biosynthesis

Journal of Chemical Information and Modeling, Год журнала: 2023, Номер 63(16), С. 5018 - 5034

Опубликована: Авг. 9, 2023

Natural products and their derivatives are widely used across various industries, particularly pharmaceuticals. Modern engineered biosynthesis provides an alternative way of producing meeting the growing need for diverse natural products. enzymes, on other hand, often exhibit unsatisfactory catalytic characteristics necessitate further enzyme engineering modifications. QM/MM, as a powerful extensively computational tool in field catalysis, has been increasingly applied rational over past decade. In this review, we summarize recent advances QM/MM investigation catalysis product biosynthesis. The challenges perspectives future applications aided will also be discussed.

Язык: Английский

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Experimental and mechanism exploration on the separation of methanol-containing azeotropic compounds from biodiesel by phosphate esters ionic liquids

Fuel, Год журнала: 2023, Номер 355, С. 129450 - 129450

Опубликована: Авг. 11, 2023

Язык: Английский

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Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(28), С. 18967 - 18978

Опубликована: Июль 8, 2024

Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl-acyl carrier protein synthase (FabF) in the bacterial mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables unified these three natural FabF their skeletally diverse analogs, all stemming from common

Язык: Английский

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A comprehensive benchmark investigation of quantum chemical methods for carbocations

Physical Chemistry Chemical Physics, Год журнала: 2022, Номер 25(3), С. 1903 - 1922

Опубликована: Дек. 8, 2022

The application of various density functional approximations (DFAs) and an emphasis on popular methods without any consensus have prevailed in computational studies dedicated to carbocations. More importantly, extensive rigorous benchmark investigation functionals for the class is still lacking. To close this gap, we present a comprehensive study quantum chemical series classical nonclassical carbocations, CARBO33 dataset. We evaluate total 107 DFT from all rungs giving particular attention double hybrid as potential has been largely undermined context support our findings, DLPNO-CCSD(T) at complete basis set (CBS) limit W1-F12 are used reference methods. Our results indicate that composite CBS-QB3 method performs poorly should not be adopted target energies. Oftentimes, tested DFAs lower rung perform better than several higher Perdew's "Jacob's ladder". Nonetheless, hybrids DSD-PBEP86-NL ωB97X-2-D3(BJ) stand out by showing overall best performance. Among evaluated, about half them show mean absolute deviation (MAD) below 1.1 kcal mol-1, including M06-2X mPW1PW91. In family, MN15-D3(BJ) particularly well (MAD = 0.77 mol-1) displaying reliable across tests. Highly B3LYP exhibited one worst performances 4.74 mol-1), do recommend its also assess 24 general-purpose sets single- up quadruple-ζ quality. compromise between accuracy cost achieved with cc-pVTZ followed def2-TZVP. Computations larger structures general interest, terpene presented selected confirming trends results.

Язык: Английский

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Tryptophan Stabilization of a Biochemical Carbocation Evaluated by Analysis of π Complexes of 3-Ethylindole with the t-Butyl Cation

ACS Omega, Год журнала: 2023, Номер 8(29), С. 26497 - 26507

Опубликована: Июль 12, 2023

Understanding how the highly unstable carbocation intermediates in terpenoid biosynthesis are stabilized and protected during their transient existence enzyme active sites is an intriguing challenge which has to be addressed computationally. Our efforts have focused on evaluating stabilization afforded via carbocation-π complexation between a biochemical aromatic amino acid residue. This involved making measurements X-ray structure of site that shows π donor proximate putative using these build models analyzed computationally provide estimated energy (SE). Previously, we reported SEs for several such complexes involving phenylalanine. Herein, report first estimate tryptophan as donor. Because there was almost no published information about indole π-complexation donor, located equilibrium σ 3-ethylindole with t-butyl cation relevant background information. Then, CotB2 complexed geranylgeranyl thiodiphosphate (GGSPP), specifically geometric relationship at C15 GGSPP W186, were used model computed SE -15.3 kcal/mol.

Язык: Английский

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Docking carbocations into terpene synthase active sites using chemically meaningful constraints—The TerDockin approach

Methods in enzymology on CD-ROM/Methods in enzymology, Год журнала: 2024, Номер unknown, С. 231 - 263

Опубликована: Янв. 1, 2024

Язык: Английский

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