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1. Formic acid catalyzed isomerization and adduct formation of an isoprene-derived Criegee intermediate: experiment and theory

   https://doi.org/10.1039/d0cp05018k  

   Vansco, Michael F.; Caravan, Rebecca L.; Pandit, Shubhrangshu; Zuraski, Kristen; Winiberg, Frank A.; Au, Kendrew; Bhagde, Trisha; Trongsiriwat, Nisalak; Walsh, Patrick J.; Osborn, David L.; et al (December 2020, Physical Chemistry Chemical Physics)

   null (Ed.)

   Isoprene is the most abundant non-methane hydrocarbon emitted into the Earth's atmosphere. Ozonolysis is an important atmospheric sink for isoprene, which generates reactive carbonyl oxide species (R 1 R 2 CO + O − ) known as Criegee intermediates. This study focuses on characterizing the catalyzed isomerization and adduct formation pathways for the reaction between formic acid and methyl vinyl ketone oxide (MVK-oxide), a four-carbon unsaturated Criegee intermediate generated from isoprene ozonolysis. syn -MVK-oxide undergoes intramolecular 1,4 H-atom transfer to form a substituted vinyl hydroperoxide intermediate, 2-hydroperoxybuta-1,3-diene (HPBD), which subsequently decomposes to hydroxyl and vinoxylic radical products. Here, we report direct observation of HPBD generated by formic acid catalyzed isomerization of MVK-oxide under thermal conditions (298 K, 10 torr) using multiplexed photoionization mass spectrometry. The acid catalyzed isomerization of MVK-oxide proceeds by a double hydrogen-bonded interaction followed by a concerted H-atom transfer via submerged barriers to produce HPBD and regenerate formic acid. The analogous isomerization pathway catalyzed with deuterated formic acid (D 2 -formic acid) enables migration of a D atom to yield partially deuterated HPBD (DPBD), which is identified by its distinct mass ( m / z 87) and photoionization threshold. In addition, bimolecular reaction of MVK-oxide with D 2 -formic acid forms a functionalized hydroperoxide adduct, which is the dominant product channel, and is compared to a previous bimolecular reaction study with normal formic acid. Complementary high-level theoretical calculations are performed to further investigate the reaction pathways and kinetics. 

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2. Fast predictions of liquid-phase acid-catalyzed reaction rates using molecular dynamics simulations and convolutional neural networks

   https://doi.org/10.1039/d0sc03261a  

   Chew, Alex K.; Jiang, Shengli; Zhang, Weiqi; Zavala, Victor M.; Van Lehn, Reid C. (December 2020, Chemical Science)

   null (Ed.)

   The rates of liquid-phase, acid-catalyzed reactions relevant to the upgrading of biomass into high-value chemicals are highly sensitive to solvent composition and identifying suitable solvent mixtures is theoretically and experimentally challenging. We show that the complex atomistic configurations of reactant–solvent environments generated by classical molecular dynamics simulations can be exploited by 3D convolutional neural networks to enable accurate predictions of Brønsted acid-catalyzed reaction rates for model biomass compounds. We develop a 3D convolutional neural network, which we call SolventNet, and train it to predict acid-catalyzed reaction rates using experimental reaction data and corresponding molecular dynamics simulation data for seven biomass-derived oxygenates in water–cosolvent mixtures. We show that SolventNet can predict reaction rates for additional reactants and solvent systems an order of magnitude faster than prior simulation methods. This combination of machine learning with molecular dynamics enables the rapid, high-throughput screening of solvent systems and identification of improved biomass conversion conditions. 

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3. Lewis Acid-Catalyzed 2,3-Dihydrofuran Acetal Ring-Opening Benzannulations toward Functionalized 1-Hydroxycarbazoles

   https://doi.org/10.3390/molecules27238344  

   Yuan, Shaoren; Guerra Faura, Gabriel; Areheart, Hailey E.; Peulen, Natalie E.; France, Stefan (December 2022, Molecules)

   The development of a Lewis acid-catalyzed, intramolecular ring-opening benzannulation of 5-(indolyl)2,3-dihydrofuran acetals is described. The resulting 1-hydroxycarbazole-2-carboxylates are formed in up to 90% yield in 1 h. The dihydrofuran acetals are readily accessed from the reactions of enol ethers and α-diazo-β-indolyl-β-ketoesters. To highlight the method’s synthetic utility, a formal total synthesis of murrayafoline A, a bioactive carbazole-containing natural product, was undertaken. 

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4. The inhibitor of κB kinase β (IKKβ) phosphorylates IκBα twice in a single binding event through a sequential mechanism

   https://doi.org/10.1016/j.jbc.2022.102796  

   Stephenson, Anthony A.; Taggart, David J.; Xu, Guozhou; Fowler, Jason D.; Wu, Hao; Suo, Zucai (January 2023, Journal of Biological Chemistry)

   Phosphorylation of Inhibitor of κB (IκB) proteins by IκB Kinase β (IKKβ) leads to IκB degradation and subsequent activation of nuclear factor κB transcription factors. Of particular interest is the IKKβ-catalyzed phosphorylation of IκBα residues Ser32 and Ser36 within a conserved destruction box motif. To investigate the catalytic mechanism of IKKβ,we performed pre–steady-state kinetic analysis of the phosphorylation of IκBα protein substrates catalyzed by constitutively active, human IKKβ. Phosphorylation of full-length IκBα catalyzed by IKKβ was characterized by a fast exponential phase followed by a slower linear phase. The maximum observed rate (kp) of IKKβ-catalyzed phosphorylation of IκBα was 0.32 s−1 and the binding affinity of ATP for the IKKβ IκBα complex (Kd) was 12 μM. Substitution of either Ser32 or Ser36 with Ala, Asp, or Cys reduced the amplitude of the exponential phase by approximately 2-fold. Thus, the exponential phase was attributed to phosphorylation of IκBα at Ser32 and Ser36, whereas the slower linear phase was attributed to phosphorylation of other residues. Interestingly, the exponential rate of phosphorylation of the IκBα(S32D) phosphomimetic amino acid substitution mutant was nearly twice that of WT IκBα and 4-fold faster than any of the other IκBα amino acid substitution mutants, suggesting that phosphorylation of Ser32 increases the phosphorylation rate of Ser36. These conclusions were supported by parallel experiments using GST-IκBα(1–54) fusion protein substrates bearing the first 54 residues of IκBα. Our data suggest a model wherein, IKKβ phosphorylates IκBα at Ser32 followed by Ser36 within a single binding event. 

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5. Palladium-Catalyzed β-C(sp3)–H Bond Arylation of Tertiary Aldehydes Facilitated by 2-Pyridone Ligands

   https://doi.org/10.3390/molecules29010259  

   Xu, Ziting; Li, Zhi; Liu, Chong; Yang, Ke; Ge, Haibo (January 2024, Molecules)

   2-Pyridone ligand-facilitated palladium-catalyzed direct C–H bond functionalization via the transient directing group strategy has become an attractive topic. Here, we report a Pd-catalyzed direct β-C(sp3)–H arylation reaction of tertiary aliphatic aldehydes by using an α-amino acid as a transient directing group in combination with a 2-pyridone ligand. 

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