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1. Ethylene oligomerization into linear olefins over cobalt oxide on carbon catalyst

   https://doi.org/10.1039/d1cy00207d  

   Jonathan, Alvin; Eagan, Nathaniel M.; Bruns, David L.; Stahl, Shannon S.; Lanci, Michael P.; Dumesic, James A.; Huber, George W. (May 2021, Catalysis Science & Technology)

   null (Ed.)

   Here, we show that C 4 –C 12 linear olefins, including linear alpha olefins, can be selectively produced from ethylene over a stable cobalt oxide on carbon catalyst. Both bulk and surface cobalt phases are CoO when the catalyst is stable, suggesting CoO is the stable cobalt phase for oligomerization. During the reaction, polyethylene forms in the catalyst pores which influences the product selectivity. The catalyst is more stable at higher temperatures (∼200 °C) likely due to reduction of Co 3 O 4 to CoO while rapid deactivation is observed at lower temperatures ( e.g. , 80–140 °C). The product selectivity can be fit to two different Schulz Flory distributions, one from C 4 to C 10 olefins and one above C 10 olefins, suggesting that transport restrictions influence product selectivity. At 48.3% conversion, product linearities up to C 12 olefins are above 90%, making it the most selective heterogeneous catalyst to linear olefins to date in the absence of activators and/or solvents. 

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2. Plant “helper” immune receptors are Ca ²⁺ -permeable nonselective cation channels

   https://doi.org/10.1126/science.abg7917  

   Jacob, Pierre; Kim, Nak Hyun; Wu, Feihua; El-Kasmi, Farid; Chi, Yuan; Walton, William G.; Furzer, Oliver J.; Lietzan, Adam D.; Sunil, Sruthi; Kempthorn, Korina; et al (June 2021, Science)

   Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. InArabidopsis, a subfamily of “helper” NLRs is required by many “sensor” NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta, and conferred cytoplasmic calcium ion (Ca²⁺) influx in plant and human cells. NRG1.1-dependent Ca²⁺influx and cell death were sensitive to Ca²⁺channel blockers and were suppressed by mutations affecting oligomerization or plasma membrane enrichment. Ca²⁺influx and cell death mediated by NRG1.1 and ACTIVATED DISEASE RESISTANCE 1 (ADR1), another helper NLR, required conserved negatively charged N-terminal residues. Whole-cell voltage-clamp recordings demonstrated thatArabidopsishelper NLRs form Ca²⁺-permeable cation channels to directly regulate cytoplasmic Ca²⁺levels and consequent cell death. Thus, helper NLRs transduce cell death signals directly. 

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3. Anti-Markovnikov terminal and gem -olefin hydrosilylation using a κ ⁴ -diimine nickel catalyst: selectivity for alkene hydrosilylation over ether C–O bond cleavage

   https://doi.org/10.1039/C8DT04608E  

   Rock, Christopher L.; Trovitch, Ryan J. (January 2019, Dalton Transactions)

   The phosphine-substituted α-diimine Ni precursor, ( Ph2PPr DI)Ni , has been found to catalyze alkene hydrosilylation in the presence of Ph 2 SiH 2 with turnover frequencies of up to 124 h −1 at 25 °C (990 h −1 at 60 °C). Moreover, the selective hydrosilylation of allylic and vinylic ethers has been demonstrated, even though ( Ph2PPr DI)Ni is known to catalyze allyl ester C–O bond hydrosilylation. At 70 °C, this catalyst has been found to mediate the hydrosilylation of ten different gem -olefins, with turnover numbers of up to 740 under neat conditions. Prior and current mechanistic observations suggest that alkene hydrosilylation takes place though a Chalk–Harrod mechanism following phosphine donor dissociation. 

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4. Homo-oligomerization of the human adenosine A2A receptor is driven by the intrinsically disordered C-terminus

   https://doi.org/10.7554/eLife.66662  

   Nguyen, Khanh Dinh; Vigers, Michael; Sefah, Eric; Seppälä, Susanna; Hoover, Jennifer Paige; Schonenbach, Nicole Star; Mertz, Blake; O'Malley, Michelle Ann; Han, Songi (July 2021, eLife)

   null (Ed.)

   G protein-coupled receptors (GPCRs) have long been shown to exist as oligomers with functional properties distinct from those of the monomeric counterparts, but the driving factors of oligomerization remain relatively unexplored. Herein, we focus on the human adenosine A 2A receptor (A 2A R), a model GPCR that forms oligomers both in vitro and in vivo. Combining experimental and computational approaches, we discover that the intrinsically disordered C-terminus of A 2A R drives receptor homo-oligomerization. The formation of A 2A R oligomers declines progressively with the shortening of the C-terminus. Multiple interaction types are responsible for A 2A R oligomerization, including disulfide linkages, hydrogen bonds, electrostatic interactions, and hydrophobic interactions. These interactions are enhanced by depletion interactions, giving rise to a tunable network of bonds that allow A 2A R oligomers to adopt multiple interfaces. This study uncovers the disordered C-terminus as a prominent driving factor for the oligomerization of a GPCR, offering important insight into the effect of C-terminus modification on receptor oligomerization of A 2A R and other GPCRs reconstituted in vitro for biophysical studies. 

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5. Joint Computational/Cell-Based Approach for Screening Inhibitors of Tau Oligomerization: A Proof-of-Concept Study

   https://doi.org/10.3233/JAD-220450  

   Man, Viet Hoang; Lin, Da; He, Xibing; Gao, Jie; Wang, Junmei (August 2022, Journal of Alzheimer's Disease)

   Background: Tau assembly produces soluble oligomers and insoluble neurofibrillary tangles, which are neurotoxic to the brain and associated with Alzheimer’s and Parkinson’s diseases. Therefore, preventing tau aggregation is a promising therapy for those neurodegenerative disorders. Objective: The aim of this study was to develop a joint computational/cell-based oligomerization protocol for screening inhibitors of tau assembly. Methods: Virtual oligomerization inhibition (VOI) experiment using molecular dynamics simulation was performed to screen potential oligomerization inhibitors of PHF6 hexapeptide. Tau seeding assay, which is directly related to the outcome of therapeutic intervention, was carried out to confirm a ligand’s ability in inhibiting tau assembly formation. Results: Our protocol was tested on two known compounds, EGCG and Blarcamesine. EGCG inhibited both the aggregation of PHF6 peptide in VOI and tau assembly in tau seeding assay, while Blarcamesine was not a good inhibitor at the two tasks. We also pointed out that good binding affinity to tau aggregates is needed, but not sufficient for a ligand to become a good inhibitor of tau oligomerization. Conclusion: VOI goes beyond traditional computational inhibitor screening of amyloid aggregation by directly examining the inhibitory ability of a ligand to tau oligomerization. Comparing with the traditional biochemical assays, tau seeding activities in cells is a better indicator for the outcome of a therapeutic intervention. Our hybrid protocol has been successfully validated. It can effectively and efficiently identify the inhibitors of amyloid oligomerization/aggregation processes, thus, facilitate to the drug development of tau-related neurodegenerative diseases. 

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