Full Atom Research Articles

Water as a Reactant: DABCO-Catalyzed Hydration of Activated Alkynes for the Synthesis of Divinyl Ethers.

A practical and efficient addition of water to readily available activated alkynes delivering divinyl ethers is reported. The reaction proceeds with full atom economy in a very straightforward experimental procedure. Additionally, of all the tertiary amines studied to catalyze the reaction, the best and most efficient is clearly DABCO (1,4-diazabicyclo[2.2.2]octane). Finally, the solvent choice is crucial for the efficiency of this process and we have found that the reaction is best performed in wet dichloromethane for propiolic esters and alkynones, and in wet acetonitrile for propiolamides.

Visible-light-enabled stereoselective synthesis of functionalized cyclohexylamine derivatives via [4 + 2] cycloadditions.

An unprecedented intermolecular [4 + 2] cycloaddition of benzocyclobutylamines with α-substituted vinylketones, enabled by photoredox catalysis, has been developed. The current method enables facile access to highly functionalized cyclohexylamine derivatives that were otherwise inaccessible, in moderate to good yields with excellent diastereoselectivities. This protocol has some excellent features, such as full atom economy, good functional-group compatibility, mild reaction conditions, and an overall redox-neutral process. Additionally, an asymmetric version of this cycloaddition was preliminarily investigated via the incorporation of a chiral phosphoric acid (CPA), and moderate to good enantioselectivity could be effectively realized with excellent diastereoselectivity. Synthetic applications were demonstrated via a scale-up experiment and elaborations to access amino alcohol and cyclobutene derivatives. Based on the results of control experiments, a reasonable reaction mechanism was proposed to elucidate the reaction pathway.

Unlocking metal-ligand cooperative catalytic photochemical benzene carbonylation: a mechanistic approach.

A key challenge in green synthesis is the catalytic transformation of renewable substrates at high atom and energy efficiency, with minimal energy input (ΔG ≈ 0). Non-thermal pathways, i.e., electrochemical and photochemical, can be used to leverage renewable energy resources to drive chemical processes at well-defined energy input and efficiency. Within this context, photochemical benzene carbonylation to produce benzaldehyde is a particularly interesting, albeit challenging, process that combines unfavorable thermodynamics (ΔG° = 1.7 kcal mol-1) and the breaking of strong C-H bonds (113.5 kcal mol-1) with full atom efficiency and the use of renewable starting materials. Herein, we present a mechanistic study of photochemical benzene carbonylation catalyzed by a rhodium-based pincer complex that is capable of metal-ligand cooperation. The catalytic cycle, comprising both thermal and non-thermal steps, was probed by NMR spectroscopy, UV-visible spectroscopy and spectrophotochemistry, and density functional theory calculations. This investigation provided us with a detailed understanding of the reaction mechanism, allowing us to unlock the catalytic reactivity of the Rh-pincer complex, which represents the first example of a metal-ligand cooperative system for benzene carbonylation, exhibiting excellent selectivity.

Distribution function and atomization parameters of petroleum fuels sprays: An experimental and numerical study

Heavy fuels are difficult to spray. To investigate the burning of this fuel and create an appropriate combustion chamber, one must first understand the atomization process and spray properties of petroleum fuels. The Diesel spray behavior compared to Mazut fuel spray gives us an understanding of the atomization phenomenon of fuels. The most crucial fuel atomization characteristics include droplet diameter, spray angle, breakdown length, and droplet distribution. The shadowgraphy technique is used to capture images of fuel spray, which are then processed using image analysis software. The size and speed of the fuel spray droplets are predicted using the maximum entropy method. From a pressure difference of 15 bar onwards, the rate of mass flow remains almost constant. The fuels spray cone angle initially increases, and after the flow approaches full atomization, it reaches approximately a constant value. The breakup length and droplets diameter decrease with increasing fuel temperature and pressure, and with the full development of the flow, they tend to almost zero. By raising the fluid's viscosity, the diameter size distribution of the droplets becomes more uniform and smooth (unlike velocity distribution). In this research, an attempt has been made to develop experimental and numerical methods to measure the powdering parameters of a heavy non-Newtonian oil fuel called Mazut and a light petroleum fuel called diesel, as well as to investigate the spray behavior of these fuels.

Ab Initio Prediction of 3-D Conformations for Protein Long Loops with High Accuracy and Applications to Antibody CDRH3 Modeling.

Residue-level potentials of mean force were widely used for protein backbone refinements to avoid simultaneous sampling of side-chain conformations. The interaction energy between the reduced side chains and backbone atoms was not considered explicitly. In this study, we developed novel methods to calculate the residue-atom interaction energy in combination with atomic and residue-level terms. The parameters were optimized step by step to remove the overcounting or overlap problem between different energy terms. The mixing energy functions were then used to evaluate the generated backbone conformations at the initial sampling stage of protein loop modeling (OSCAR-loop), including the interaction energy between the reduced loop residues and full atoms of the protein framework. The accuracies of top-ranked decoys were 1.18 and 2.81 Å for 8-residue and 12-residue loops, respectively. We then selected diverse decoys for side-chain modeling, backbone refinement, and energy minimization. The procedure was repeated multiple times to select one prediction with the lowest energy. Consequently, we obtained an accuracy of 0.74 Å for a prevailing test set of 12-residue loops, compared with >1.4 Å reported by other researchers. The OSCAR-loop was also effective for modeling the H3 loops of antibody complementary determining regions (CDRs) in the crystal environment. The prediction accuracy of OSCAR-loop (1.74 Å) was better than the accuracy of the Rosetta NGK method (3.11 Å) or those achieved by deep learning methods (>2.2 Å) for the CDRH3 loops of 49 targets in the Rosetta antibody benchmark. The performance of OSCAR-loop in a model environment was also discussed.

Ultrasensitive electrochemical sensing of catechol and hydroquinone via single-atom nanozyme anchored on MOF-derived porous carbon

Single-atom nanozymes (SANs) can significantly enhance the sensitivity and selectivity of electrochemical sensing platforms due to the homogeneity of their active sites, full atom utilization, and high catalytic activity. In this study, we demonstrate the synthesis and characterization of a high-density Co-based single-atom nanozyme anchored on activated MOF-derived porous carbon (Co-AcNC-3) via a cascade anchoring strategy for ultrasensitive, simultaneous electrochemical detection of catechol (CC) and hydroquinone (HQ). The Co-AcNC-3 displays a large specific surface area, high defectivity, and abundant oxygen-containing groups, with Co atoms being atomically dispersed throughout the carbon support via Co–N bonds. The Co-AcNC-3 biosensor exhibits superior electrochemical signals for CC and HQ, with linear ranges of 4.0 μM–300.0 μM. and detection limits of 0.072 μM and 0.034 μM, respectively. Moreover, the Co-AcNC-3 biosensor has shown excellent performance in accurately detecting CC and HQ in actual samples. Our findings highlight the potential of the proposed Co-AcNC-3 biosensor as a reliable and promising sensing platform for determining CC and HQ.

The increased Diels–Alder reactivity of umpolung tropone: analysis of individual atoms and bonds using QTAIM and IQA along complete IRC paths

AbstractA fruitful debate took place recently in literature, discussing the enhanced Diels–Alder reactivity of tropone derivatives for which the carbonyl polarity was reversed by means of umpolung. Karas et al. sustained that the umpolung increases the antiaromatic character of the ring, affecting the highest occupied molecular orbital (HOMO)/least unoccupied molecular orbital (LUMO) energies, speeding up the reaction. Tiekink et al. challenged this interpretation by sustaining that the asynchronicity of the reaction mechanisms, rather than orbital energy perturbation, was the main responsible for the smaller reaction barriers. We shed light on this dispute by computing full interaction quantum atom (IQA) and quantum theory of atoms in molecules (QTAIM) analyses over complete intrinsic reaction coordinate (IRC) paths for the Diels–Alder reaction of tropone and its umpolung derivatives, using the same systems studied by Karas et al. and Tiekink et al. Our results confirm that the asynchronicity is indeed very high for those reactions with smaller reaction barriers and offer an atom‐by‐atom and bond‐by‐bond analysis of the entire IRC pathways. Even though asynchronicity and lower reactions barriers seem to be related, antiaromaticity and lower barriers are related as well, but discussing both these interpretations does not necessarily require arguments on HOMO/LUMO energies to be invoked.

Parallel Implementation of Nonadditive Gaussian Process Potentials for Monte Carlo Simulations.

A strategy is presented to implement Gaussian process potentials in molecular simulations through parallel programming. Attention is focused on the three-body nonadditive energy, though all algorithms extend straightforwardly to the additive energy. The method to distribute pairs and triplets between processes is general to all potentials. Results are presented for a simulation box of argon, including full box and atom displacement calculations, which are relevant to Monte Carlo simulation. Data on speed-up are presented for up to 120 processes across four nodes. A 4-fold speed-up is observed over five processes, extending to 20-fold over 40 processes and 30-fold over 120 processes.

Detection of sulfur mustard simulants using the microwave atmospheric pressure plasma optical emission spectroscopy method.

Sulfur mustard (SM) is one kind of highly toxic chemical warfare agent and easy to spread, while existing detection methods cannot fulfill the requirement of rapid response, good portability, and cost competitiveness at the same time. In this work, the microwave atmospheric pressure plasma optical emission spectroscopy (MW-APP-OES) method, taking the advantage of non-thermal equilibrium, high reactivity, and high purity of MW plasma, is developed to detect three kinds of SM simulants, i.e., 2-chloroethyl ethyl sulfide, dipropyl disulfide, and ethanethiol. Characteristic OES from both atom lines (C I and Cl I) and radical bands (CS, CH, and C2) is identified, confirming MW-APP-OES can preserve more information about target agents without full atomization. Gas flow rate and MW power are optimized to achieve the best analytical results. Good linearity is obtained from the calibration curve for the CS band (linear coefficients R 2 > 0.995) over a wide range of concentrations, and a limit of detection down to sub-ppm is achieved with response time on the order of second. With SM simulants as examples, the analytical results in this work indicate that MW-APP-OES is a promising method for real-time and in-site detection of chemical warfare agents.

Ultra-high vacuum compatible full metal atom beam shutter for optical lattice clocks.

We developed a shutter driven by a solenoid to switch on/off the atomic beam of optical lattice clocks developed at KRISS [C. Y. Park etal., Metrologia 50, 119 (2013), S. Lee etal., New J. Phys. 18, 033030 (2016), H. Kim etal., Jpn. J. Appl. Phys. 56, 050302 (2017), and H. Kim etal., Metrologia 58, 055007 (2021)]. The shutter design was focused on long lifetime and compatibility with an ultra-high vacuum (UHV) environment. Thus, the solenoid was designed to be easily installed and removed from the air-side of a CF flange of the shutter. The flag in the vacuum-side moves only with the simple spring action of a sheet of a metal plate without any frictional movement of mechanical parts. All parts in the vacuum-side were made of metals (stainless steel and pure iron) to be baked over the temperature of 200 °C for UHV. The flag head of the shutter displaces up to 10mm (5mm) with a response time of 50 (30ms) and 80ms (10ms) for the opening-action and the closing-action, respectively. The lifetime was tested up to 6 × 106 cycles with no performance degradation. We expect the actual lifetime to be much longer than this by virtue of its friction-free design.

Phase Transition between Crystalline Variants of Ordinary Ice.

Water is one of the most abundant molecules on Earth. However, this common and "simple" material has more than 18 different phases, which poses a great challenge to theoretically study the nature of water and ice. We designed two reaction coordinates that can distinguish between water and various ice states and used them to efficiently sample all possible states of the system in all-atom molecular dynamics simulation at ambient temperature and pressure. Various structural and thermodynamics properties, including the water-ice phase diagrams, can thus be calculated. We also present a simple model that successfully explains the thermodynamic stability of different ice states. Our work provides effective methods and data for theoretical studies of different phases of water and ice.

Molecular basis of the anchoring and stabilization of human islet amyloid polypeptide in lipid hydroperoxidized bilayers

The molecular structure of membrane lipids is formed by mono- or polyunsaturations on their aliphatic tails that make them susceptible to oxidation, facilitating the incorporation of hydroperoxide (R-OOH) functional groups. Such groups promote changes in both composition and complexity of the membrane significantly modifying its physicochemical properties. Human Langerhans islets amyloid polypeptide (hIAPP) is the main component of amyloid deposits found in the pancreas of patients with type-2 diabetes (T2D). hIAPP in the presence of membranes with oxidized lipid species accelerates the formation of amyloid fibrils or the formation of intermediate oligomeric structures. However, the molecular bases at the initial stage of the anchoring and stabilization of the hIAPP in a hydroperoxidized membrane are not yet well understood. To shed some light on this matter, in this contribution, three bilayer models were modeled: neutral (POPC), anionic (POPS), and oxidized (POPCOOH), and full atom Molecular Dynamics (MD) simulations were performed. Our results show that the POPCOOH bilayer increases the helicity in hIAPP when compared to POPC or POPS bilayer. The modification in the secondary structure covers the residues of the so-called amyloidogenic core of the hIAPP. Overall, the hydroperoxidation of the neutral lipids modifies both the anchoring and the stabilization of the peptide hIAPP by reducing the random conformations of the peptide and increasing of hydrogen bond population with the hydroperoxidized lipids.

Synthesis of Unnatural α-Amino Acid Derivatives via Photoredox Activation of Inert C(sp3)-H Bonds.

The synthesis of unnatural, tertiary amino acids is a challenging task. While decarboxylation-radical addition has been an important strategy for their formation, the use of alkyl radicals from C(sp3)-H bonds has not been fully explored. Herein, we report a photocatalytic protocol for the synthesis of unnatural α-amino esters employing abundant alkanes and imines retaining full atom economy. When this method is applied, several amino acid derivatives are synthesized in moderate to good yields.

Drug Repurposing of the Unithiol: Inhibition of Metallo-β-Lactamases for the Treatment of Carbapenem-Resistant Gram-Negative Bacterial Infections.

The increasing antibiotic resistance is a clinical problem worldwide. Numerous Gram-negative bacteria have already become resistant to the most widely used class of antibacterial drugs, β-lactams. One of the main mechanisms is inactivation of β-lactam antibiotics by bacterial β-lactamases. Appearance and spread of these enzymes represent a continuous challenge for the clinical treatment of infections and for the design of new antibiotics and inhibitors. Drug repurposing is a prospective approach for finding new targets for drugs already approved for use. We describe here the inhibitory potency of known detoxifying antidote 2,3-dimercaptopropane-1-sulfonate (unithiol) against metallo-β-lactamases. Unithiol acts as a competitive inhibitor of meropenem hydrolysis by recombinant metallo-β-lactamase NDM-1 with the KI of 16.7 µM. It is an order of magnitude lower than the KI for l-captopril, the inhibitor of angiotensin-converting enzyme approved as a drug for the treatment of hypertension. Phenotypic methods demonstrate that the unithiol inhibits natural metallo-β-lactamases NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains. The 3D full atom structures of unithiol complexes with NDM-1 and VIM-2 are obtained using QM/MM modeling. The thiol group is located between zinc cations of the active site occupying the same place as the catalytic hydroxide anion in the enzyme–substrate complex. The sulfate group forms both a coordination bond with a zinc cation and hydrogen bonds with the positively charged residue, lysine or arginine, responsible for proper orientation of antibiotics upon binding to the active site prior to hydrolysis. Thus, we demonstrate both experimentally and theoretically that the unithiol is a prospective competitive inhibitor of metallo-β-lactamases and it can be utilized in complex therapy together with the known β-lactam antibiotics.

Developing a stable full atom molecular dynamics model starting from a cyro-EM structure of a K+ channel bound to regulatory protein and varying PIP2 concentrations to understand regulation

Small conductance Ca2+-activated K+ (SK) channels are unique since they are gated solely by changes in intracellular Ca2+ and are known to be upregulated in heart failure and cardiac arrhythmias. SK channels are regulated via the ubiquitous Ca2+ sensing protein, calmodulin (CaM). New evidence suggests that the anionic lipid phosphatidylinositol 4,5-bisphosphate (PIP2) is also essential for the activation for SK channels. Recent cryo-EM structures with a nearly complete tetrameric SK4-CaM complex (PDB: 6CNM, 6CNN, 6CNO) allowed us to generate nearly full-length SK2-CaM homology models (SK2-CaM).

An End-to-End Deep Learning Pipeline for Assigning Secondary Structure in Proteins

Protein secondary structure assignment, a subdiscipline of computational chemistry, is yet to be explored using deep learning techniques. Protein secondary structure elements are assigned to support structural analysis and prediction. Algorithms like DSSP, generally regarded as the gold standard for assigning the secondary structure of proteins, need full atom information to label protein coordinates. The PDB database has been the major repository for data on the 3D structures of proteins, nucleic acids, and other complex assemblies since 1971. However, a significant fraction of protein structures contains missing atoms. As a result, new approaches to reliably and consistently assigning secondary structures based on coarse-grained atomic coordinates are needed. While deep learning architectures have an unparalleled track record in applications such as protein structure prediction, there are only a few known deep learning solutions for structure assignment problems. While the gold standard methods are based on bonding information and other geometric characteristics, deep learning methods extract features themselves without human intervention. The benefit that standardised datasets provide to the effectiveness of deep learning systems in multiple domains motivated us to create a labeled dataset for protein structure assignment tasks. Additionally, a deep learning model, named PSSADL, solely based on [Formula: see text] coordinates was trained on the generated dataset to validate its potency. The proposed method, which combines Convolutional Neural Networks (CNN) and Long Short Term Memory (LSTM)/Bidirectional LSTM networks, has been compared to the established standards and more recent techniques. The model achieved an accuracy of [Formula: see text] on the benchmark and individual test sets. The results show that deep learning techniques have a promising future in protein structure analysis, implying that the dataset developed as part of our work will be a valuable resource for further protein structure research.

Rhodium catalysts with superbulky NHC ligands for the selective α-hydrothiolation of alkynes.

Eight rhodium complexes-including four new compounds-with the generic formula [RhCl(cod)(NHC)] (cod is 1,3-cyclooctadiene) differing by the size of their N-heterocyclic carbene (NHC) ligand were prepared, characterized, and found to be catalytically active in the hydrothiolation of terminal alkynes with aliphatic or aromatic thiols. The steric bulk of the carbene was found to markedly influence the reaction rate and selectivity. In particular, superbulky NHCs led to the almost quantitative formation of the sole α-vinyl sulfide products. The experimental conditions were optimized to allow the straightforward synthesis of a broad range of mono- and disubstituted α-adducts starting from terminal alkynes (18 examples) and thiols (5 examples). Altogether, the procedure devised in this study provides an easy access to α-vinyl sulfides with full atom economy and a low catalyst loading.

An attempt to predict spray characteristics at early stage of the atomization process by using surface density and curvature distribution

Nowadays, numerical simulations of atomization has reached a mature state through interface capturing approaches. With these approaches, the liquid–gas flow with its complex interface morphology can be precisely described but at the price of high mesh resolution, that makes these simulations very intensive in terms of computational cost. Practically, for most of the injection system, it is not possible to achieve a simulation up to a point where the spray formation is completed. Thus, there are several attempts based on the transformation of liquid elements such as ligaments, liquid sheet or other non-spherical to equivalent droplets. Overall, these approaches assumed that before the complete finalization of the atomization process the spray under formation carries enough information to be representative of the final spray. In this work, we have pushed this idea a step further by using global variables such as the liquid volume fraction and the surface density available in ELSA models to ensure the transports and the conservation of the main features of the spray. Then, the surface curvature distribution is analysed assuming that a part of the interface carries already curvatures that are relevant with respect to the final spray. A well-known academic test case representative of an aeronautical injection system and based on a planar prefilmer atomizer with a gas co-flow has been selected to evaluate our proposal. This configuration was studied both experimentally and numerically thanks to high-fidelity simulations. Our purpose has been to follow the already validated numerical approaches but with less computationally intensive simulations. Then, new analysis based on surface density and surface curvature distribution have been tested to recover spray characteristics and even the spray diameter distribution. It appears that these variables are meaningful even when there is no droplet yet formed, and thus they allow the description of the full atomization process from the early stage even on the liquid film. Finally, a procedure has been proposed where the spray is sufficiently atomized to reconstruct the diameter distribution from the curvature distribution. At our best knowledge, this last step is a first attempt on practical injection system. We have proposed a very simple method to detect which part of the interface carries the relevant curvature, thus obtaining a reconstructed diameter distribution that fit well with available experimental data. Although the proposed approach cannot be still considered universally applicable to any case, this preliminary assessment clearly shows its potential.

Fully Exposed Cluster Catalyst (FECC): Toward Rich Surface Sites and Full Atom Utilization Efficiency.

Increasing attention has been paid to single-atom catalysts (SACs) in heterogeneous catalysis because of their unique electronic properties, maximized atomic utilization efficiency, and potential to serve as a bridge between the heterogeneous and homogeneous catalysis. However, SACs can have limited advantages or even constrained applications for the reactions that require designated metallic states with multiple atoms or surface sites with metal–metal bonds. As a cross-dimensional extension to the concept of SACs, fully exposed cluster catalysts (FECCs) offer diverse surface sites formed by an ensemble of metal atoms, for the adsorption and transformation of reactants/intermediates. More importantly, FECCs have the advantage of maximized atom utilization efficiency. Thus, FECCs provide a novel platform to design effective and efficient catalysts for certain chemical processes. This outlook summarizes recent advances and proposes prospective research directions in the design of catalysts and characterizations of FECCs, together with potential challenges.

Observing the emergence of a quantum phase transition shell by shell.

Many-body physics describes phenomena that cannot be understood by looking only at the constituents of a system1. Striking examples are broken symmetry, phase transitions and collective excitations2. To understand how such collective behaviour emerges as a system is gradually assembled from individual particles has been a goal in atomic, nuclear and solid-state physics for decades3-6. Here we observe the few-body precursor of a quantum phase transition from a normal to a superfluid phase. The transition is signalled by the softening of the mode associated with amplitude vibrations of the order parameter, usually referred to as a Higgs mode7. We achieve fine control over ultracold fermions confined to two-dimensional harmonic potentials and prepare closed-shell configurations of 2, 6 and 12 fermionic atoms in the ground state with high fidelity. Spectroscopy is then performed on our mesoscopic system while tuning the pair energy from zero to a value larger than the shell spacing. Using full atom counting statistics, we find the lowest resonance to consist of coherently excited pairs only. The distinct non-monotonic interaction dependence of this many-body excitation, combined with comparison with numerical calculations allows us to identify it as the precursor of the Higgs mode. Our atomic simulator provides a way to study the emergence of collective phenomena and the thermodynamic limit, particle by particle.