Insertion Barrier Research Articles

Vastly different energy landscapes of the membrane insertions of monomeric gasdermin D and A3

Gasdermin D and gasdermin A3 belong to the same family of pore-forming proteins and executors of pyroptosis, a form of programmed cell death. To unveil the process of their pore formation, we examine the energy landscapes upon insertion of the gasdermin D and A3 monomers into a lipid bilayer by extensive atomistic molecular dynamics simulations. We reveal a lower free energy barrier of membrane insertion for gasdermin D than for gasdermin A3 and a preference of gasdermin D for the membrane-inserted and of gasdermin A3 for the membrane-adsorbed state, suggesting that gasdermin D first inserts and then oligomerizes while gasdermin A3 oligomerizes and then inserts. Gasdermin D stabilizes itself in the membrane by forming more salt bridges and pulling phosphatidylethanolamine lipids and more water into the membrane. Gasdermin-lipid interactions support the pore formation. Our findings suggest that both the gasdermin species and the lipid composition modulate gasdermin pore formation.

Designing of imine thiophene-ligated metal-complexes and implication in ethylene polymerization

Polyethylene is the single largest volume polymer produced globally using Ziegler-type catalysts. Numerous modifications have been reported in search of a better catalyst that can control molecular weight, polydispersity, and branching. In our attempts to identify a suitable imine thiophene-ligated chromium complex, we examined 9 different titanium complexes computationally. The DFT investigations considered barriers for insertion, propagation, and termination by β-H elimination or chain transfer, and identified N-(4-methoxyphenyl)-2-phenyl-1-(thiophen-2-yl)ethan-1-imine(L9) as the most suitable ligand. Subsequently, L9 was prepared in good yield (70%) by condensing 2-phenyl-1-(thiophen-2-yl)ethan-1-one with 4-methoxyaniline. Ligand L9 was treated with early transition metal precursors (Ti, Cr, Zr) to generate a homogenous catalyst. The identity of these catalysts was unambiguously ascertained using a combination of NMR, ICP, FT-IR, UV-Vis spectroscopy, and ESI-MS. The performance of L9-ligated titanium complex [Cat.1] was examined in ethylene polymerization using MMAO as a co-catalyst. Insertion of ethylene was tracked using high-pressure NMR experiments and Cat.1 was found to be active in the polymerization. Ethylene polymerization conditions were optimized to obtain high activity and molecular weight polyethylene. The chromium complex [Cat.2] outperformed the Ti and Zr-derived catalysts with the highest TOF of 6294 mol of PE/mol of Cr/h. Cat.2 produced high molecular weight, high-density polyethylene.

Palladium-catalyzed dicarbonylation of 1,3-butadiene with bidentate phosphine ligands: A density functional theory study

Palladium-catalyzed dicarbonylation of 1,3-butadiene with bidentate phosphine ligands: A density functional theory study

Facet and dual vacancy engineering-boosting BiOBr for enhanced CO2 and epoxide cycloaddition reaction under mild and cocatalyst-free conditions: Double substrate active sites and activated surface bromine ions synergy

Facet and dual vacancy engineering-boosting BiOBr for enhanced CO2 and epoxide cycloaddition reaction under mild and cocatalyst-free conditions: Double substrate active sites and activated surface bromine ions synergy

Copolymerization of norbornene with 1-hexene catalyzed by sulfur-containing Schiff base titanium complex and density functional theory analysis

Copolymerization of norbornene with 1-hexene catalyzed by sulfur-containing Schiff base titanium complex and density functional theory analysis

Heterogeneous Rhodium Single-Atom-Site Catalyst Enables Chemoselective Carbene N-H Bond Insertion.

Transition-metal-catalyzed carbene insertion reactions of a nitrogen-hydrogen bond have emerged as robust and versatile methods for the construction of C-N bonds. While significant progress of homogeneous catalytic metal carbene N-H insertions has been achieved, the control of chemoselectivity in the field remains challenging due to the high electrophilicity of the metal carbene intermediates. Herein, we present an efficient strategy for the synthesis of a rhodium single-atom-site catalyst (Rh-SA) that incorporates a Rh atom surrounded by three nitrogen atoms and one phosphorus atom doped in a carbon support. This Rh-SA catalyst, with a catalyst loading of only 0.15 mol %, exhibited exceptional catalytic performance for heterogeneous carbene insertion with various anilines and heteroaryl amines in combination with diazo esters. Importantly, the heterogeneous catalyst selectively transformed aniline derivatives bearing multiple nucleophilic moieties into single N-H insertion isomers, while the popular homogeneous Rh2(OAc)4 catalyst produced a mixture of overfunctionalized side products. Additionally, similar selectivities for N-H bond insertion with a set of stereoelectronically diverse diazo esters were obtained, highlighting the general applicability of this heterogeneous catalysis approach. On the basis of density functional theory calculations, the observed selectivity of the Rh-SA catalyst was attributed to the insertion barriers and the accelerated proton transfer assisted by the phosphorus atom in the support. Overall, this investigation of heterogeneous metal-catalyzed carbene insertion underscores the potential of single-atom-site catalysis as a powerful and complementary tool in organic synthesis.

Effect of ligand structure and metal center on ethylene oligomerization with N, N′ Schiff base late transition complexes: experiments and calculations

A series of N, N’ bis(pyridine-imine) Schiff base late transition metal (Fe, Co, and Ni) complexes with different ligand structures and catalytic active sites were synthesized. Ethylene oligomerization results showed that bis(pyridine-imine) iron complex had the highest catalytic activity (10.8 × 105 g/mol Fe h), and the catalytic activity of cobalt complex was the lowest (2.5 × 105 g/mol Co h); nickel complex had the highest selectivity toward high carbon olefins (28.6%), while the iron complex had the lowest (0.2%). The structure-activity relationship between the catalyst structure and catalytic properties for ethylene oligomerization was further studied by density functional theory (DFT) calculations. The bis(pyridine-imine) iron complex had the highest energy gap value and the most stable catalyst structure, which was more conducive to oligomerization; and the N–M–N bond of the nickel complex had the smallest bond angle, which was beneficial for chain growth. Based on the Cossee mechanism, a mechanism for ethylene oligomerization catalyzed by bis(pyridine-imine) metal complexes was proposed. To further study the micro reaction process of ethylene oligomerization, a molecular model of pyridine imine nickel complex and its catalytic ethylene oligomerization reaction path were proposed. The structure and energy of the reaction intermediate and transition state were calculated using DFT. The molecular model of the nickel complex had a lower ethylene insertion barrier and β-H elimination of energy barriers, indicating that the molecular model of the pyridine imine nickel complex had ethylene oligomerization active centers.

Machine Learning Models for Predicting Zirconocene Properties and Barriers.

Zr metallocenes have significant potential to be highly tunable polyethylene catalysts through modification of the aromatic ligand framework. Here we report the development of multiple machine learning models using a large library (>700 systems) of DFT-calculated zirconocene properties and barriers for ethylene polymerization. We show that very accurate machine learning models are possible for HOMO-LUMO gaps of precatalysts but the performance significantly depends on the machine learning algorithm and type of featurization, such as fingerprints, Coulomb matrices, smooth overlap of atomic positions, or persistence images. Surprisingly, the description of the bonding hapticity, the number of direct connections between Zr and the ligand aromatic carbons, only has a moderate influence on the performance of most models. Despite robust models for HOMO-LUMO gaps, these types of machine learning models based on structure connectivity type features perform poorly in predicting ethylene migratory insertion barrier heights. Therefore, we developed several relatively robust and accurate machine learning models for barrier heights that are based on quantum-chemical descriptors (QCDs). The quantitative accuracy of these models depends on which potential energy surface structure QCDs were harvested from. This revealed a Hammett-type principle to naturally emerge showing that QCDs from the π-coordination complexes provide much better descriptions of the transition states than other potential-energy structures. Feature importance analysis of the QCDs provides several fundamental principles that influence zirconocene catalyst reactivity.

Ir/Zn-cocatalyzed chemo- and atroposelective [2+2+2] cycloaddition for construction of C─N axially chiral indoles and pyrroles.

Here, an Ir/Zn-cocatalyzed atroposelective [2+2+2] cycloaddition of 1,6-diynes and ynamines was developed, forging various functionalized C─N axially chiral indoles and pyrroles in generally good to excellent yields (up to 99%), excellent chemoselectivities, and high enantioselectivities (up to 98% enantiomeric excess) with wide substrate scope. This cocatalyzed strategy not only provided an alternative promising and reliable way for asymmetric alkyne [2+2+2] cyclotrimerization in an easy handle but also settled the issues of previous [Rh(COD)2]BF4-catalyzed system on the construction of C─N axial chirality such as complex operations, limited substrate scope, and low efficiency. In addition, control experiments and theoretical calculations disclosed that Zn(OTf)2 markedly reduced the barrier of migration insertion to significantly increase reaction efficiency, which was distinctly different from previous work on the Lewis acid for improving reaction yield through accelerating oxidative addition and reductive elimination.

Atomistic study on the origins of the anisotropic lithiation behaviors of the silicon anode using the reactive force field based molecular dynamics simulations

Atomistic study on the origins of the anisotropic lithiation behaviors of the silicon anode using the reactive force field based molecular dynamics simulations

The GET insertase exhibits conformational plasticity and induces membrane thinning

The eukaryotic guided entry of tail-anchored proteins (GET) pathway mediates the biogenesis of tail-anchored (TA) membrane proteins at the endoplasmic reticulum. In the cytosol, the Get3 chaperone captures the TA protein substrate and delivers it to the Get1/Get2 membrane protein complex (GET insertase), which then inserts the substrate via a membrane-embedded hydrophilic groove. Here, we present structures, atomistic simulations and functional data of human and Chaetomium thermophilum Get1/Get2/Get3. The core fold of the GET insertase is conserved throughout eukaryotes, whilst thinning of the lipid bilayer occurs in the vicinity of the hydrophilic groove to presumably lower the energetic barrier of membrane insertion. We show that the gating interaction between Get2 helix α3’ and Get3 drives conformational changes in both Get3 and the Get1/Get2 membrane heterotetramer. Thus, we provide a framework to understand the conformational plasticity of the GET insertase and how it remodels its membrane environment to promote substrate insertion.

A stereoselective nontraditional Heck reaction mechanism: Origins of enantioselectivity and diastereoselectivity

A stereoselective nontraditional Heck reaction mechanism: Origins of enantioselectivity and diastereoselectivity

Remote Steric and Electronic Effects of N-Heterocyclic Carbene Ligands on Alkene Reactivity and Regioselectivity toward Hydrocupration Reactions: The Role of Expanded-Ring N-Heterocyclic Carbenes.

The remote groups in N-heterocyclic carbene (NHC) ligands have a significant influence on metal-catalyzed reactions. We examine how remote bulkiness, electronic groups, and expanded-ring NHCs (ER-NHCs) influence alkene reactivity and regioselectivity toward hydrocupration using density functional theory calculations. The impact of remote steric bulkiness on the Cu-H insertion rate is analyzed, revealing a strong correlation between the steric substituent constant and rate ratio, where a bulky group increases the rate due to reduced steric effects in the transition state (TS). The steric properties of the examined catalysts (with a remote group R2 = CPh3, CHPh2, CH2Ph, CH3, and H) and their corresponding TSs are found to be modulated greatly by the remote steric substitution group and the ring size of the NHC ligand. Enhanced bulkiness enhances the nucleophilic Cu-H moiety. The remote electronic groups have a smaller impact on insertion barrier compared to that of steric hindrance. Furthermore, ER-NHC exploration indicates that NHCs with over five-membered rings have a significantly negative influence on the reaction rate. Finally, with a highly bulky group (R2 = CPh3), anti-Markovnikov insertion preference is attributed to high interaction energy and improved steric properties. Overall, our findings here provide valuable insights for the development of a more effective catalyst in metal-catalyzed reactions.

Metal Effect on Cationic [Cp2MH]+ (M = Group 4 and 5)-Mediated CO2 Hydrogenation in the Gas Phase.

Effective CO2 hydrogenation has recently attracted quite some attention for producing more valuable chemical oxygenates (such as methanol, formate) in mild conditions. However, the influence of the metal center on the CO2 activation remains unclear. First, electrospray ionization mass spectrometry (ESI-MS) was employed to explore the direct CO2 hydrogenation to formic acid mediated by [Cp2MH]+ (M = Zr, Hf) in the gas phase at room temperature. The key formate intermediate [Cp2M(O2CH)]+ (M = Zr, Hf) was confirmed by traveling wave ion mobility spectrometry (TWIMS). Second, to gain insights into the metal effect, the CO2 hydrogenation process involving Group 4 (i.e., Ti, Zr, Hf) transition metals was calculated along with Group 5 (i.e., V, Nb, Ta) by density functional theory (DFT) methods. The CO2 insertion process was found to be the rate-limiting step. For [Cp2TiH]+, [Cp2ZrH]+, [Cp2HfH]+, [Cp2VH]+, [Cp2NbH]+, and [Cp2TaH]+, the barriers are +7.7, +6.5, +5.9, +9.2, +8.0, and +6.3 kcal/mol, respectively. [Cp2HfH]+-mediated CO2 hydrogenation occurs the most rapidly, as revealed by MS. According to the orbital analysis on the CO2 insertion transition state, the electron-deficient metal center resulting in a low-lying lowest unoccupied molecular orbital (LUMO) could interact more favorably with the π bond of deformed CO2, which was also consistent with the natural bond orbital (NBO) results. Last but not the least, NBO charges on the metal centers were found to correlate linearly well with the CO2 insertion barriers rather than hydride affinity. Thus, the reactivity of different metal hydride complexes with CO2 to produce a formate could be estimated by the NBO charge on metals. Our findings might provide a series of candidates for the catalyst as well as guidance for catalyst design in mild CO2 hydrogenation.

POSS@TiCl4 nanoparticles: A minimalism styled Ziegler-Natta catalytic system

POSS@TiCl4 nanoparticles: A minimalism styled Ziegler-Natta catalytic system

Ion Size-Dependent Electrochromism in Air-Stable Napthalenediimide-Based Conjugated Polymers.

Conjugated polymers (CPs) that show stable and reversible cation insertion/deinsertion under ambient conditions hold great potential for optoelectronic and energy storage devices. However, n-doped CPs are prone to parasitic reactions upon exposure to moisture or oxygen. This study reports a new family of napthalenediimide (NDI) based conjugated polymers capable of undergoing electrochemical n-type doping in ambient air. By functionalizing the NDI-NDI repeating unit with alternating triethylene glycol and octadecyl side chains, the polymer backbone shows stable electrochemical doping at ambient conditions. We systematically investigate the extent of volumetric doping involving monovalent cations of varying size (Li+, Na+, tetraethylammonium (TEA+)) with electrochemical methods, including cyclic voltammetry, differential pulse voltammetry, spectroelectrochemistry, and electrochemical impedance spectroscopy. We observed that introducing hydrophilic side chains on the polymer backbone improves the local dielectric environment of the backbones and lowers the energetic barrier for ion insertion. Surprisingly, when using Na+ electrolyte, the polymer films exhibit higher volumetric doping efficiency, faster-switching kinetics, higher optical contrast, and selective multielectrochromism when compared to Li+ or TEA+ electrolytes. Using well-tempered metadynamics, we characterize the free energetics of side chain-ion interactions to find that Li+ binds more tightly to the glycolated NDI moieties than Na+, hindering Li+ ion transport, switching kinetics, and limiting the films' doping efficiency.

A Density Functional Study on Ethylene Trimerization and Tetramerization Using Real Sasol Cr-PNP Catalysts.

To gain molecular-level insight into the intricate features of the catalytic behavior of chromium-diphosphine complexes regarding ethylene tri- and tetramerizations, we performed density functional theory (DFT) calculations. The selective formation of 1-hexene and 1-octene by the tri- and tetramerizations of ethylene are generally accepted to follow the metallacycle mechanism. To explore the mechanism of ethylene tri- and tetramerizations, we used a real Sasol chromium complex with a nitrogen-bridged diphosphine ligand with ortho- and para-methoxyaryl substituents. We explore the trimerization mechanism for ethylene first and, later on for comparison, we extend the potential energy surfaces (PES) for the tetramerization of ethylene with both catalysts. The calculated results reveal that the formation of 1-hexene and 1-octene with the ortho-methoxyaryl and para-methoxyaryl Cr-PNP catalysts have nearly similar potential energy surfaces (PES). From the calculated results important insights are gained into the tri- and tetramerizations. The tetramerization of ethylene with the para-methoxyaryl Cr-PNP catalyst lowers the barrier height by ~2.6 kcal/mol compared to that of ethylene with the ortho-methoxyaryl Cr-PNP catalyst. The selectivity toward trimerization or tetramerization comes from whether the energy barrier for ethylene insertion to metallacycloheptane is higher than β-hydride transfer to make 1-hexene. The metallacycle mechanism with Cr (I)-Cr (III) intermediates is found to be the most favored, with the oxidative coupling of the two coordinated ethylenes to form chromacyclopentane being the rate-determining step.

Small, Electron-Donating Substituents Give CO2 Activation by Permethylpentalene Zirconium Amido Complexes the Upper Hand: A DFT Study of Distortion and Interaction

An insight into factors controlling CO2 activation is necessary to develop molecular systems that utilize CO2 as a chemical feedstock. Two permethylpentalene zirconium cyclopentadienyl (mono)amido complexes, Pn*ZrCp(NR2), were previously assessed for CO2 activation, and a strong dependence on the amido substituent was observed. The R = Me analogue reacted rapidly and quantitatively at room temperature to form the carbamato complex, while the R = Ph species was inert. Here, we investigate the origin of this reactivity difference using DFT and the distortion-interaction model to characterize steric and electronic contributions to the activation barrier. We find that the barrier for CO2 insertion with R = Me (19.1 kcal/mol) is lower than with R = Ph (36.6 kcal/mol), explaining the inertness of the Ph-substituted analogue. The distortion energy trend follows the steric bulk of the amido substituents, and the bulkier Ph-substituted complex has a consistently higher distortion energy along its potential energy surface than that of the Me-substituted complex. The interaction energy trend follows the electronics, and a more electron-donating Me-substituted complex shows a consistently lower interaction energy. The balance of these effects at the corresponding TS gives a reduced activation barrier. Small, electron-donating substituents therefore facilitate CO2 activation in these complexes.

3D ordered amorphous and porous TiO2 framework anode with low insertion barrier and fast kinetics for K-ion hybrid capacitors

TiO2 is considered as a low cost, long-term stable, and safe anode for high power K-ion hybrid capacitors (KICs) due to its abundant reserve, small volume expansion rate, and sloping voltage plateau that avoids K-ion plating at high voltage polarization. However, the enhancement of its low capacity and sluggish kinetics caused by poor electroconductivity and high insertion barrier is still challenging to further develop high-performance KICs. Herein, the reduced graphene oxide (rGO) is embedded in the walls of 3D ordered macro-/mesoporous TiO2 (termed as TiO2@rGO framework) to create intimate TiO2/rGO interfaces, ensuring the effectively electron transportation during potassiation/depotassiation of TiO2 while maintaining rapid ions/electrolyte diffusion. Furthermore, the controlled amorphous TiO2 framework can further lower the lattice insertion energies, contributing to a fast accommodation of K-ion. As expected, the amorphous TiO2@rGO framework (TiO2@rGO-1) exhibits a superior rate capability (148.8 mAh g-1 at 5 A g-1) and cycling stability (171.2 mAh g-1 at 1 A g-1 after 800 cycles). The assembled KICs can reach a high energy/power density of 125.2 Wh kg-1/4267.4Wkg-1 as well as a long-term lifespan. This tactic provides a reliable and general way to design a TiO2-based anode with fast kinetics toward high-performance KICs.

Solution-Phase Conformational/Vibrational Anharmonicity in Comonomer Incorporation Polyolefin Catalysis.

The prediction of comonomer incorporation statistics in polyolefin catalysis necessitates an accurate calculation of free energies corresponding to monomer binding and insertion, often requiring sub-kcal/mol resolution to resolve experimental free energies. Batch reactor experiments are used to probe incorporation statistics of ethene and larger α-olefins for three constrained geometry complexes which are employed as model systems. Herein, over 6 ns of quantum mechanics/molecular mechanics (QM/MM) molecular dynamics is performed in combination with the zero-temperature string method to characterize the solution-phase insertion barrier and to analyze the contributions from conformational and vibrational anharmonicity arising both in vacuum and in solution. Conformational sampling in the solution-phase results in 0-2 kcal/mol corrections to the insertion barrier which are on the same scale necessary to resolve experimental free energies. Anharmonic contributions from conformational sampling in the solution phase are crucial energy contributions missing from static density functional theory calculations and implicit solvation models, and the accurate calculation of these contributions is a key step toward the quantitative prediction of comonomer incorporation statistics.