bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of Multicore Colloidosomes: Nanoparticle-Assembled Capsules with Adjustable Size, Internal Structure, and Functionalities for Oil Encapsulation
Authors: Brossault David F.F. , McCoy Thomas M. , Routh Alexander F.
Published: February 2022

Colloidosomes, also known as Pickering emulsion capsules, have attracted considerable attention for encapsulation of both hydrophilic and hydrophobic actives. However, current preparation methods are limited to single core structures and require modified/engineered nanoparticles for forming the capsules. Here, a simple, safe, and highly versatile approach for producing multicore colloidosomes from non-modified nanoparticles is reported. Multi-oil core silica colloidosomes are prepared at room temperature via salt-driven assembly of cheap hydrophilic nanoparticles dispersed within a double (O/W/O) emulsion template. The internal structure and overall diameter of the final capsules can be adjusted by altering the primary and secondary emulsification conditions. With this approach, 7 to 35 µm diameter capsules containing 0.9 to 4.2 µm diameter multiple oil cores are produced. Nanoparticles such as Fe3O4, TiO2 and ZnO can easily be incorporated within the structure, conferring magnetic and photocatalytic properties to the capsules, enabling degradation of Rhodamine B under UV-light irradiation as well as magnetic capture. These capsules can also be used to entrain hydrophobic dye (Nile red), with ultrasound rupturing serving as a facile method for accessing the internal core environments. This work offers a promising approach for producing tunable multifunctional microcapsules for oil encapsulation.
Molecular Dynamics and Network Analysis Reveal the Contrasting Roles of Polar Solutes Within Organic Phase Amphiphile Aggregation
Authors: Sadhu Biswajit , Clark Aurora E.
Published: February 2022

Amphiphile self-assembly in non-polar media is often enhanced by polar co-solutes. This is observed within many biphasic separations processes, where amphiphiles mediate transport of water and acid into organic solution. A myriad of competitive intermolecular interactions have thus far prevented a fundamental understanding of the individual and dual role of these polar solutes upon amphiphile self-assembly in non-polar media. Toward this end, the current work employs classical molecular dynamics and intermolecular network analyses to deconstruct the individual affects of water and nitric acid upon the self-assembly of N,N,N\textsuperscript{$'$},N{$'$}-tetraoctyl-3-oxapentanediamide (TODGA), a prevalent amphiphile extractant used in metal ion separations. In the absence of acid, and at low water concentration, H$_2$O is found to promote local dimer and trimer formation of TODGA, however as [H$_2$O]$_{org}$ increases, preferential self-solvation leads to large (H$_2$O)$_n$ clusters that cause TODGA clusters to sorb to the (H$_2$O)$_n$ periphery and supports extended aggregation. Addition of HNO$_3$ to the humid solutions disrupts the water hydrogen bond network and inhibits the formation of large water clusters - thus preventing extended aggregation behavior and encouraging local aggregation. Prior experimental observations of enhanced TODGA self-assembly under these conditions are attributed primarily to the role of water rather than co-extracted HNO$_3$, thus providing valuable new insight into the means by which extractant aggregation can be tuned within separations processes. The different roles of polar co-solutes, that derive from their individual hydrogen bonding capabilities and competitive interactions in the context of preferred solvation environments, is of fundamental importance amphiphile behavior in non-polar media.
A New Formula Assignment Algorithm for the Deuterium Labeled Ultrahigh-Resolution Mass Spectrometry: Implications to the Formation Mechanism of Halogenated Disinfection Byproducts
Authors: Fu Qing-Long , Fujii Manabu , Watanabe Akari , Kwon Eunsang
Published: February 2022

The ultrahigh-resolution mass spectrometry (UHR-MS) coupled with isotope labeling is of increasing attentions in elucidating the transform mechanisms of dissolved organic matter (DOM). However, there is a paucity of automated formula assignment algorithm applicable to halogenated disinfection byproducts (Xn-DBPs), particurally for iodinated organic compounds, and deuterated DOM . Herein, for the first time, we have developed a novel formula assignment algorithm based on deuterium-labeled UHR-MS, namely FTMSDeu, and the algorithm was applied to determine precursor molecules of Xn-DBPs and evaluate the relative contribution of electrophilic addition and electrophilic substitution reactions in Xn-DBPs formation according to the hydrogen/deuterium exchange of DOM molecules. Furthermore, tandem mass spectrometry with homologous-based network analysis was employed to validate the formula assignment accuracy (41%) of FTMSDeu for iodinated disinfection byproducts (In-DBPs). And the remaining In-DBPs compounds were assigned with the empirical rule of minimum number of non-oxygen heteratoms. The electrophilic substitution accounted for 82%-98%, 71%-89%, and 43%-45% of Xn-DBPs formation for Xn-DBPs containing chlorine, bromine, and iodine, respectively, manifesting the dominant role of electrophilic substitution in chlorine disinfection under conditions of low bromine and iodine concentrations. The absence of presumed Xn-DBPs precursors in some treatments in this study also suggests that Xn-DBPs formation include secondary reactions (e.g., oxidation, hydrolysis) in addition to electrophilic addition and/or substitution of halogens. These findings highlight the significance of isotopically labeled UHR-MS techniques in revealing the transformation of DOM in natural and engineered systems.
Supervised Machine Learning Classification Algorithms for Detection of Fracture Location in Dissimilar Friction Stir Welded Joints
Authors: Mishra Akshansh
Published: February 2022

Machine Learning focuses on the study of algorithms that are mathematical or statistical in nature in order to extract the required information pattern from the available data. Supervised Machine Learning algorithms are further sub-divided into two types i.e. regression algorithms and classification algorithms. In the present study, four supervised machine learning-based classification models i.e. Decision Trees algorithm, K- Nearest Neighbors (KNN) algorithm, Support Vector Machines (SVM) algorithm, and Ada Boost algorithm were subjected to the given dataset for the determination of fracture location in dissimilar Friction Stir Welded AA6061-T651 and AA7075-T651 alloy. In the given dataset, rotational speed (RPM), welding speed (mm/min), pin profile, and axial force (kN) were the input parameters while Fracture location is the output parameter. The obtained results showed that the Support Vector Machine (SVM) algorithm classified the fracture location with a good accuracy score of 0.889 in comparison to the other algorithms.
Photoswitchable Serotonins for Optical Control of the 5-HT2A Receptor
Authors: Morstein Johannes , Romano Giovanna , Hetzler Belinda , Plante Ambrose , Haake Caleb , Levitz Joshua , Trauner Dirk
Published: February 2022

The serotonin receptor family of G protein-coupled receptors (GPCRs) and ligand-gated ion channels play central roles in neuromodulation and are critical drug targets for the treatment of psychiatric disorders. Optical control of serotonin receptor subtypes has the potential to greatly enhance our understanding of the spatiotemporal dynamics of receptor function both at the cellular level and within neural circuits. While other neuromodulatory receptors have been successfully rendered photoswitchable, reversible photocontrol of serotonin receptors has not been achieved, representing a major gap in GPCR photopharmacology. Herein, by designing and screening a family of azobenzene-conjugated serotonin analogues, we developed the first photopharmacological tools that allow for such control. Azo5HT-2 shows light-dependent 5-HT2AR agonism, inducing receptor-mediated calcium signaling in the light-activated cis-form. Based on computational docking and test compound analysis, we also synthesize and test photoswitchable orthogonal, remotely-tethered ligands (PORTLs). BG-Azo5HTn PORTLs provide rapid, reversible and repeatable optical control following conjugation to SNAP-tagged 5-HT2AR. Overall, this study both introduces new tools for the optical control of 5-HT2ARs and provides a foundation for the broad extension of photopharmacology to the serotonin receptor family.
Crystal Phase Mediated Restructuring of Pt on TiO2 with Tunable Re-activity: Redispersion versus Reshaping
Authors: Zhang Xiaoben , Li Zhimin , Pei Wei , Li Gao , Liu Wei , Du Pengfei , Wang Zhen , Qin Zhaoxian , Zhou Si , Zhao Jijun , Yang Bing , Shen Wenjie
Published: February 2022

Restructuring of supported metal nanoparticles (NPs) e.g., reshaping and redispersion are of tremendous interest for the rational design of high-efficiency catalyst materials with precise particle sizes, shapes, and reactivities. Here we show a crystal phase mediated restructuring of Pt NPs on TiO2, as a simple approach for fabricating either atomically dispersed single atoms (SAs) or reshaped planar NPs of Pt catalysts with tunable reactivities. Utilizing a variety of state-of-the-art characterizations, we showed that rutile TiO2 favors the reshaping of 2D planar Pt NPs, whereas the anatase surface facilitates the redispersion of Pt NPs to SAs upon calcination in the air up to 400 ºC. Environmental transmission electron microscopy (ETEM) and density function theory (DFT) calculations were employed to directly visualize the dynamic transformation of Pt NPs and reveal the specific role that TiO2 supports play in promoting the stability and diffusion of Pt SAs. As a result, the reverse reactivity was achieved by tunning their distinct restructuring behaviors. Thus, the Pt SAs on anatase TiO2 preferentially activated selective hydrogenation of phenylacetylene (21.22 x 10-2 s-1 at 50 ºC), while planar Pt NPs on rutile significantly enhanced the combustion of methane (3.11 x 10-2 s-1 at 310 ºC). Our results therefore open up new routes for tuning the restructuring behavior of supported metal catalysts and designing catalysts with controlled catalytic structures and reactivities.
Tuning the excited state properties of [2.2]paracyclophane-based antennas to ensure efficient sensitization of lanthanide ions or singlet oxygen generation.
Authors: Wu Shiqi , Abad Galan Laura , Roux Margaux , Riobé François , Le Guennic Boris , Guyot Yannick , Le Bahers Tangui , Micouin Laurent , Maury Olivier , Benedetti Erica
Published: February 2022

The multi-step synthesis of original antennas incorporating substituted [2.2]paracyclophane (pCp) moieties in the -conjugated skeleton is described. These antennas, functionalized with electron an donor alkoxy fragment (A1) or with a fused coumarin derivative (A2) are incorporated in a triazacyclonane macrocyclic ligand L1 or L2, respectively for the design of Eu(III), Yb(III) and Gd(III) complexes. A combined photophysical/theoretical study reveals that A1 presents a charge transfer character via the through-space paracyclophane conjugation, whereas A2 presents only local excited states centered on the coumarin-paracyclophane moiety, strongly favoring triplet state population via intersystem crossing. The resulting complexes EuL1 and YbL2 are fully emissive in the red and near infrared, respectively whereas the GdL2 complex acts as photosensitizer for the generation of singlet oxygen.
A Potential–dependent Thiele Modulus to Quantify the Effectiveness of Porous Electrocatalysts
Authors: Wan Charles , Greco Katharine , Alazmi Amira , Darling Robert , Chiang Yet- Ming , Brushett Fikile
Published: February 2022

Electrochemical reactors often employ high surface area electrocatalysts to accelerate volumetric reaction rates and increase productivity. While electrocatalysts can alleviate kinetic overpotentials, diffusional resistances at the pore-scale often prevent full catalyst utilization. The effect of intraparticle diffusion on the overall reaction rate can be quantified through an effectiveness factor expression governed by the Thiele modulus parameter. This analytical approach is integral to the development of catalytic structures for thermochemical processes and has previously been extended to electrochemical processes by accounting for the relationship between reaction kinetics and electrode overpotential. In this paper, we illustrate the method by deriving the expression for the potential-dependent Thiele modulus and using it to quantify the effectiveness factor for porous electrocatalytic structures. Specifically, we demonstrate the application of this mathematical framework to spherical microparticles as a function of applied overpotential across catalyst properties and reactant characteristics. The relative effects of kinetics and mass transport are related to overall reaction rates, revealing markedly lower catalyst utilization at increasing overpotential. Subsequently, we generalize the analysis to different catalyst shapes and provide guidance on the design of porous catalytic materials for use in electrochemical reactors.
The Preservation of English Oak in Marine Environments
Authors: Montgomery Wren , Schofield Eleanor , Watson Jonathan S. , Sephton Mark A.
Published: February 2022

This study compares the chemical integrity of English Oak (Quercus robur) samples with an age range of four centuries by analysing the lignin degradation. The samples were collected from four historic British vessels and thus represent samples of diverse ages which have nonetheless experienced similar non-arboreal environments. We conclude that the Mary Rose, the oldest vessel studied and the recipient of the most intensive conservation efforts, has been well-preserved through treatment with PEG, and we present a baseline for assessing whether a ship hasbeen biologically degraded. The work combines quantitative analytic chemistry techniques (e.g., THM-GC-MS) with the conservation of large historic artifacts.
Mass difference matching crystallizes hidden molecular structures of dissolved organic matter from ultrahigh-resolution tandem mass spectra
Authors: Simon Carsten , Petras Daniel , Roth Vanessa-Nina , Dührkop Kai , Böcker Sebastian , Dorrestein Pieter , Gleixner Gerd
Published: February 2022

Ultrahigh-resolution mass spectrometry has revealed unprecedented detail of natural complex mixtures such as dissolved organic matter (DOM) on a molecular formula level but we lack information on the underlying structural complexity for full-scale identification. We applied a novel approach to decipher DOM’s characteristic chimeric tandem mass (MS2) spectra that represent multiple precursors of the same nominal mass. We calculated mass difference (Δm) matrices from precursor and product ions and matched them with reference Δm’s from 11280 library MS2 spectra and molecular structures. We found 1) indication for the presence of degraded phenolic plant metabolites, unknown N- and S-containing molecules, and missing elements in formula annotation, 2) weak support for postulated Van Krevelen structural domains, 3) multiple significant links between precursor properties, Δm matches, and chemodiversity. Our paper highlights Δm matching by MS2 as a promising tool to reveal novel structural information and molecular ecosystem imprints in complex mixtures like DOM.
Quantitative Structure Activity Relationship (QSAR) study predicts small molecule binding to RNA structure
Authors: Cai Zhengguo , Zafferani Martina , Akande Olanrewaju , Hargrove Amanda
Published: February 2022

The diversity of RNA structural elements and their documented role in human diseases make RNA an attractive therapeutic target. However, progress in drug discovery and development has been hindered by challenges in the determination of high-resolution RNA structures and a limited understanding of the parameters that drive RNA recognition by small molecules, including a lack of validated quantitative structure-activity relationships (QSAR). Herein, we developed QSAR models that quantitatively predict both thermodynamic and kinetic-based binding parameters of small molecules and the HIV-1 TAR model RNA system. A set of small molecules bearing diverse scaffolds was screened against the HIV-1-TAR construct using surface plasmon resonance, which provided the binding kinetics and affinities. The data was then analyzed using multiple linear regression (MLR) combined with feature selection to afford robust models for binding of diverse RNA-targeted scaffolds. The predictivity of the model was validated on untested small molecules. The QSAR models presented herein represent the first application of validated and predictive 2D-QSAR using multiple scaffolds against an RNA target. We expect the workflow to be generally applicable to other RNA structures, ultimately providing essential insight into the small molecule descriptors that drive selective binding interactions and, consequently, providing a platform that can exponentially increase the efficiency of ligand design and optimization without the need for high-resolution RNA structures.
ZIF-C as non-viral delivery system for CRISPR/Cas9 mediated hTERT knockdown in cancer cells
Authors: Pyreddy Suneela , Poddar Arpita , Carraro Francesco , Polash Shakil Ahmed , Dekiwadia Chaitali , Nasa Zeyad , Telukutla Srinivasa Reddy , Falcaro Paolo , Shukla Ravi
Published: February 2022

Telomerase, a ribonucleoprotein coded by the hTERT gene, plays an important role in cellular immortalization and carcinogenesis. hTERT is a suitable target for cancer therapeutics as its activity is highly upregulated in 85-90% of cancer cells but absent in normal somatic cells. Here, we target the hTERT gene at the DNA level by applying the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology encapsulated in a recently discovered Metal-Organic Framework (MOF). We show that the MOF subtype ‘ZIF-C’ can efficiently load the hTERT targeting CRISPR system (CrhTERT@ZIF-C) and protect it from enzymatic degradation. The CrhTERT@ZIF-C is endocytosed by cancer cells and successfully disrupts the hTERT gene. The resultant inhibition of hTERT decreases cellular proliferation and causes apoptotic cancer cell death. Furthermore, hTERT knockdown shows a significant reduction in tumor metastasis and alters protein expression. Thus, our results conclusively establish ZIF-C based targeting of hTERT as a highly promising and novel approach for gene therapy in cancer.
Migration of Zeolite-Encapsulated Pt and Au Under Reducing Atmospheres
Authors: Hou Dianwei , Heard Christopher
Published: February 2022

Unbiased density functional global optimisation calculations, followed by kinetic Monte Carlo simulations are used to enumerate the potential energy surfaces for migration of noble metals Pt and Au inside the pore system of siliceous zeolite LTA. The effects of reducing adsorbates CO and H2 are determined. It is found that the two metals differ significantly in the strength and type of interaction with the framework, with strong, framework breaking interactions between Pt and and the zeolite, but only weak dispersive interactions between Au and the zeolite. Adsorbates are found to dramatically interfere with Pt-framework binding, leading to poorer atom-trapping, enhanced metal migration and faster equilibration.
Non-injective gas sensor arrays: identifying undetectable composition changes
Authors: Gantzler Nickolas , Henle Adrian , Thallapally Praveen , Fern Xiaoli , Simon Cory
Published: February 2022

A gravimetric, MOF-based (MOF = metal-organic framework) sensor array functions by measuring the mass of gas adsorbed in an array of MOFs. Changes in the gas composition are expected to produce detectable changes in the mass of gas adsorbed in the MOFs. In practical settings, multiple components of the gas adsorb into the MOFs. As a result, the map from gas compositions to sensor response vectors will be non-injective (many-to-one). Here, we outline a mathematical method to determine undetectable changes in gas composition to which non-injective gas sensor arrays are unresponsive. This is important for understanding their limitations and vulnerabilities. Our method relies on a mixed-gas adsorption model in the MOFs comprising the sensor array. We illustrate the identification of unresponsive subspaces and ranked responsive directions for gas sensor arrays based on Co-MOF-74 and HKUST-1 aimed at quantitative sensing of CH4/N2/CO2/C2H6 mixtures (relevant to the natural gas industry).
1,3-Asymmetric Induction in Diastereoselective Allylations of Chiral N-Tosyl Imines
Authors: Shaw Jared , Lo Anna , Gutierrez David , Toth-Williams Garrett , Fettinger James
Published: February 2022

Lewis-acid mediated allylations of β-alkoxy N-tosyl imines lead to 3-alkoxy homoallylic N-tosyl amines with anti diastereoselectivity. Diastereoselectivity and yields of reactions are comparable between two methods of Hosomi-Sakurai allylations. Observed selectivity trends and computational evidence suggest that 1,3 asymmetric induction occurs through the formation of a six- membered ring chelate which adopts a half-chair-like conformation. The product ratios of allylations to β-alkoxy N-tosyl imines are dependent on conformation preferences of the chelate and stereoelectronic interactions in the transition-state structures. Debenzylation and detosylation of these allylation products result in anti 1,3-amino alcohols, a privileged motif in synthetic and natural bioactive compounds.
Emissive Organogel Mediated Construction of Hydrazide Linked Flexible Covalent Organic Polymer for the Separation of Aniline for Water Purification
Authors: Das Apurba K. , Maiti Sayan , Ghosh Tapas , Samal Arati
Published: February 2022

A flexible covalent organic polymer (COP) has been successfully synthesized via dynamic covalent gel (DCG) formation through imine condensation reaction between 6-hydrazinonicotinic hydrazide hydrate and benzene-1,3,5-tricarboxaldehyde within 7 min. Herein, an emissive organogel mediated protocol has been developed for the construction of amorphous polymer (COP), selectively in N,N-dimethyl acetamide (DMA). Interestingly, two non-emissive building block units have been engaged for the construction of green emissive COP-gel. The green emission of COP-gel is generated by the intermolecular H-bonding assisted aggregation induced emission phenomenon. The dried COP can efficiently adsorb aniline molecules into its cavities and separate them from binary mixtures of aniline/nitrobenzene and aniline/water, respectively. The UV-vis and emission spectroscopy of COP solution in DMA with the addition of nitrobenzene and aniline have been further investigated. The dispersion solution of COP in DMA shows bluish-white light emission. Photophysical investigation of COP in DMA suggests that the origin of the distinct emission quenching of COP for aniline and nitrobenzene is different. Our findings mark a significant step forward in the development of functionalized COP as a material for the separation of aniline from miscible binary solvent mixtures.
Discovery of a novel class of D-amino acid oxidase (DAO) inhibitors with the Schrödinger computational platform
Authors: Tang Haifeng , Jensen Kristian , Houang Evelyne , McRobb Fiona , Bhat Sathesh , Svensson Mats , Bochevarov Art , Dahlgren Markus , Bell Jeff , Day Tyler , Frye Leah , Skene Robert , Lewis James , Osborne James , Tierney Jason , Gordon James , Palomero-Vazquez Maria , Gallati Caroline , Chapman Robert , Jones Daniel , Hirst Kim , Sephton Mark , Chauhan Alka , Sharpe Andrew , Tardia Piero , Dechaux Elsa , Taylor Andrea , Waddell Ross , Valentine Andrea , Janssens Holden , Aziz Omar , Bloomfield Dawn , Ladha Sandeep , Fraser Ian , Ellard John
Published: February 2022

D-Serine is a co-agonist of the N-methyl D-aspartate (NMDA) receptor, a key excitatory neurotransmitter receptor. In the brain, D-Serine is synthesized from its L-isomer by serine racemase and is metabolized by the D-amino acid oxidase (DAO, DAAO), a flavoenzyme that catalyzes the oxidative degradation of D-amino acids including D-serine to the corresponding α-keto acids. Many studies have linked decreased D-serine concentration and/or increased DAO expression and enzyme activity to NMDA dysfunction and schizophrenia. Thus, many companies have explored the possibility of employing DAO inhibitors for the treatment of schizophrenia and other indications. Powered by the Schrödinger computational modeling platform, we initiated a research program to identify novel DAO inhibitors with best-in-class properties. The program execution leveraged an hDAO FEP+ model to prospectively predict compound hDAO inhibitory potency and prioritize design ideas from both human design and computer enumeration by our AutoDesigner algorithm. A novel class of DAO inhibitors with desirable pharmacokinetic and brain penetration properties was discovered from this effort. In an in vivo mouse PK/PD model, tool compound 37 demonstrated modulation of D-serine concentrations in the plasma and brain through inhibition of DAO function. Continued SAR work has led to significant potency improvement in both DAO biochemical and cell assays. Our modeling technology on this program has not only enhanced the efficiency of medicinal chemistry execution, it has also helped to identify a previously unexplored subpocket for further SAR development.
High-pressure reaction profiles and activation volumes of 1,3-cyclohexadiene dimerizations computed by the extreme pressure-polarizable continuum model (XP-PCM)
Authors: Chen Bo , Houk K. N. , Cammi Roberto
Published: February 2022

Quantum chemical calculations are reported for the thermal dimerizations of 1,3-cyclohexadiene at 1 atm and high pressures up to 6 GPa. Previous experiments [Klärner et al. Angew. Chem. Int. Ed. 1986, 25, 108], based on measured activation energies and activation volumes, suggested concerted mechanisms for the formation of the endo [4+2] cycloadduct and a [6+4]-ene adduct, and stepwise mechanisms for the formation of the exo [4+2] cycloadduct and two [2+2] cycloadducts. Computed activation enthalpies (ωB97XD, CCSD(T) and SC-NEVPT2) of plausible dimerization pathways at 1 atm agree well with the experiment activation energies and the values from previous calculations [Ess et al. J. Org. Chem. 2008, 73, 7586]. High-pressure reaction profiles, computed by the recently-developed extreme pressure-polarizable continuum model (XP-PCM), show that the reduction of reaction barrier is more profound in concerted reactions than in stepwise reactions, which is rationalized on the basis of the volume profiles of different mechanisms. A clear shift of the transition state towards the reactant by high pressure is revealed for the [6+4]-ene reaction by the calculations. The computed activation volumes by XP-PCM agree excellently with the experimental values, confirming the existence of competing mechanisms in the thermal dimerizations of 1,3-cyclohexadiene.
COVID-19: Attacks the 1-beta Chain of Hemoglobin to Disrupt Respiratory Function and Escape Immunity
Authors: liu wenzhong , li hualan
Published: February 2022

Investigating poor respiratory function and high immunological escape in COVID-19 patients may aid in the prevention of additional deaths. The conserved domain search method was used to evaluate the biological roles of specific SARS-COV-2 proteins in this present study. The research findings indicate that the SARS-COV-2 virus contains domains capable of binding porphyrin and synthesizing heme. S and ORF3a can bind to hemoglobin. The S protein possesses hemocyanin-like function since it contains copper-oxygen binding, immunological agglutination, and phenoloxidase domains. ORF3a's Arg134 and E's Cys44 have heme-iron binding sites, respectively. The ORF3a protein has a region that degrades trapped heme into iron and porphyrin. Hemoglobin that has been attacked by ORF3a may preserve the majority of its native structure but with decreased oxygen delivery function. By targeting hemoglobin and destroying heme, the ORF3a protein caused varying degrees of respiratory distress and coagulation symptoms in COVID-19 individuals. ORF3a of Delta and Omicron variants also retained its capacity to target hemoglobin and heme. But the S protein's hemocyanin-like domain transported oxygen to enhance the patient's respiratory condition. Through a large load of hemocyanin-like proteins, the mutant virus achieved effective oxygen transport and alleviated the symptoms of respiratory distress in patients. Simultaneously, the variant S protein's immunological agglutination and phenol oxidase functions were decreased or eliminated, resulting in a decrease in the strength of the immune response and an increase in immune evasion ability, culminating in increased virus transmission.
Asymmetric Addition of Allylsilanes to Aldehydes – A Cr/Photoredox Dual Catalytic Approach Complementing the Hosomi–Sakurai Reaction
Authors: Schäfers Felix , Dutta Subhabrata , Kleinmans Roman , Mück-Lichtenfeld Christian , Glorius Frank
Published: February 2022

The allylation of aldehydes is a fundamental transformation in synthetic organic chemistry. Among the multitude of available reagents, especially allylsilanes have been established as preferred allyl source. As initially reported by Hosomi & Sakurai, these non-toxic and highly stable reagents add to carbonyls via an open transition state upon Lewis acid activation. Herein, we report a general strategy to access a variety of valuable homoallylic alcohols in opposite chemo- and diastereoselectivity to the established Hosomi–Sakurai conditions by switching to photocatalytic activation in combination with a closed transition state (Chromium catalysis). Moreover, this dual catalytic approach displays a straightforward way to introduce excellent levels of enantioselectivity and its mild conditions allow for a broad substrate scope including chiral boron-substituted products as a highlight. To emphasize the synthetic utility, our method was applied as the key step in the synthesis of a bioactive compound and in the late-stage functionalization of steroid derivatives. Detailed mechanistic studies and DFT calculations hint towards an unprecedented photo-initiated chain being operative.
Ion Exchange Conversion of Na-birnessite to Mg-buserite for Enhanced Cu2+ Removal via Membrane Capacitive Deionization (MCDI)
Authors: Li Feihu , Bao Yang , Jin Jie , Li Man
Published: February 2022

Layered manganese oxides (LMOs) have recently been demonstrated to be one of the most promising redox-active material platforms for electrochemical removal of heavy metal ions from solution via capacitive deionization (CDI). However, the impacts of phase transformation behaviors of the LMOs minerals, especially during the desalination operations, on the deionization performance of the LMOs/C electrodes have yet to be extensively evaluated. In this study, Mg-buserite derived from ion exchange of fresh Na-birnessite, Na- and K-birnessite were systematically evaluated as active electrode materials for removal of copper (Cu2+) ions from synthetic saline in a symmetric membrane capacitive deionization (MCDI) cell. In the cases of Na+, K+, Mg2+, and Ca2+ ions, the Mg-buserite/C electrode demonstrated the best deionization performance in terms of the salt and/or ion adsorption capacity, electrosorption rate, charge efficiency, and cycling stability, followed by K-birnessite/C, and then Na- birnessite/C. More importantly, the Mg-buserite/C electrode also exhibited the highest Cu2+ ion adsorption capacity (IAC) of 89.3 mg Cu2+/g active materials at a cell potential of 1.2 V in 500 mg L−1 CuCl2 solution, with an IAC retention as high as 96.3% after 60 electrosorption/desorption cycles. The underlying mechanisms for Cu2+ sequestration were investigated via ex-situ X-ray diffraction, indicating that the improving deionization performance toward Cu2+ from solution is mainly attributed to the expanded interlayer spacing through ion exchange of the original stabilizing Na+ ions of Na-birnessite with foreign Mg2+ ions, leading to a phase transformation from Na-birnessite into Mg-buserite that has larger ion diffusion channels and a higher ion storage capacity. Our work has demonstrated that expansion of interlayer spacing of LMOs minerals via ion exchange is a reliable and solid strategy for improving the desalination performance in CDI platforms, and provided insight for the rational design of smart electrodes for CDI applications towards heavy metal ion sequestration.
A Localized Enantioselective Catalytic Site on Short DNA Sequences and their Amphiphiles
Authors: Guo Jun , Wang Danyu , Pantatosaki Evangelia , Kuang Huihui , Papadopoulos George , Tsapatsis Michael , Kokkoli Efrosini
Published: February 2022

A DNA-based artificial metalloenzyme (ArM) consisting of copper (II) complex of 4,4’-dimethyl-2,2’-bipyridine (dmbipy-Cu) bound to double-stranded DNA (dsDNA) as short as 8 base pairs with only two contiguous central G•C pairs (G for guanine and C for cytosine), catalyzes highly enantioselective Diels-Alder reaction in water. Molecular simulations indicate that these minimal sequences provide a single site where dmbipy-Cu is groove-bound and able to function as an enantioselective catalyst. Enantioselective preference inverses when D-DNA is replaced with L-DNA. When the DNA is conjugated to a hydrophobic tail, the obtained ArMs exhibit enantioselective performance in a methanol-water mixture superior to that of non-amphiphilic dsDNA, and dsDNA-amphiphiles with more complex G•C-rich sequences.
Activation of Cellulose with Alkaline Earth Metals
Authors: Facas Gregory , Maliekkal Vineet , Neurock Matthew , Dauenhauer Paul
Published: February 2022

Alkaline earth metal ions accelerate the breaking of cellulose bonds and control the distribution of products in the pyrolysis of lignocellulose to biofuels and chemicals. Here, the activation of cellulose via magnesium ions was measured over a range of temperatures from 370 to 430 ⁰C for 20 to 2000 milliseconds and compared with activation of cellulose via calcium, another naturally-occurring alkaline earth metal in lignocellulose materials. The experimental approach of pulse heated analysis of solid/surface reactions (PHASR) showed that magnesium significantly catalyzes cellulose activation with a second order rate dependence on the catalyst concentration. An experimental barrier of 45.6 ± 2.1 kcal mol-1 and a pre-factor of 1.18 x 1016 (mmol Mg2+ / g CD)-2 * s-1 was obtained for the activation of α-cyclodextrin (CD), a cellulose surrogate, for catalyst concentrations of 0.1 to 0.5 mmol Mg+2 per gram of CD. First principles density functional theory calculations showed that magnesium ions play a dual role in catalyzing the reaction by breaking the hydrogen bonds with hydroxymethyl groups and destabilizing the reacting cellulose chain, thus making it more active. The calculated barrier of 47 kcal mol-1 is in agreement with the experimentally measured barriers and similar to that for calcium ion catalysts (~50 kcal mol-1).
Controlling Non-Native B12 Reactivity and Catalysis in the Transcription Factor CarH
Authors: Yang Xinhang , Gerroll Benjamin H. R. , Jiang Yuhua , Kumar Amardeep , Zubi Yasmine S. , Baker Lane A. , Lewis Jared , Lewis Jared C.
Published: February 2022

Vitamin B12 derivatives catalyze a wide range of organic transformations, but B12-dependent enzymes are underutilized in biocatalysis relative to other metalloenzymes. In this study, we engineered a variant of the transcription factor CarH, called CarH*, that catalyzes styrene C-H alkylation with improved yield and selectivity relative to B12 itself. While the native function of CarH involves transcription regulation via AdoCbl Co(III)-carbon bond cleavage and β-hydride elimination to generate 4’,5’-didehydroadenosine, CarH*-catalyzed styrene alkylation proceeds via non-native oxidative addition and olefin addition coupled with a native-like β-hydride elimination. Mechanistic studies on this reaction echo findings from earlier studies on AdoCbl homolysis under strong cage conditions to suggest that CarH* can enable non-native radical chemistry with improved selectivity relative to B12 itself. These findings lay the groundwork for the development of B12-dependent enzymes as catalysts for a wide range of non-native transformations.
Predicting Solvation Thermodynamics in Water and Ionic Liquids using the Multi-Scale Solvation Layer Interface Condition (SLIC)
Authors: Rahimi Ali Mehdizadeh , Jamali Safa , Bardhan Jaydeep , Lustig Steve
Published: February 2022

We highlight the most recent developments of the solvation-layer interface condition (SLIC) continuum dielectric model in predicting solvation thermodynamics of neutral small molecules in water and multiple ionic liquids. We demonstrate that a simple temperature-dependent solvent-accessible-surface-area (SASA) correlation and a cavity-dispersion-combinatorial (CDC) theory, combined with the SLIC electrostatics model, provide highly accurate predictions of Gibbs solvation energies, solvation entropies, and solvation heat capacities. The SLIC/SASA model parameters are temperature dependent, whereas the SLIC/CDC parameters are constant. To address the lack of experimental data pertaining to the accuracy of the models, we conducted an extensive literature search and data compilation to obtain credible experimental solvation data. This yielded 159 and 123 data points for hydration entropies and heat capacities of neutral small molecules, respectively. Compared to experimental data, the SLIC/SASA and SLIC/CDC models, respectively, achieve an RMS error 1.39 (1.24) and 1.15 (1.76) kcal/mol for hydration free energy (hydration entropy) predictions. Solvation heat capacities are predicted with RMS errors 24.42 and 46.17 cal/mol/K. Most remarkably, the SLIC/CDC predictions of solvation entropies and heat capacities are made without apriori knowledge of experimental solvation entropies. In addition, the SLIC/SASA predictions of Gibbs solvation energies (solvation entropies) of 12 amino acid side-chain analogs in seven (three) ionic liquids are compared to the available explicit-solvent simulation data from Paluch et al.~\cite{Paluch12} and Latif~\cite{Latif14} et al.
CASPT2 molecular geometries of Fe(II) spin-crossover complexes
Authors: Finney Brian A. , Roy Chowdhury Sabyasachi , Kirkvold Clara , Vlaisavljevich Bess
Published: February 2022

Using fully internally contracted (FIC)-CASPT2 analytical gradients, geometry optimizations of spin-crossover complexes are reported. This approach is tested on a series of Fe(II) complexes with different sizes, ranging from 13 to 61 atoms. A combination of active space and basis set choices are employed to investigate their role in determining reliable molecular geometries. The reported strategy demonstrates that a wave function-based level of theory can be used to optimize the geometries of metal complexes in reasonable times and enables one to treat the molecular geometry and electronic structure of the complexes using the same level of theory. For a series of smaller Fe(II) SCO complexes, strong field ligands in the LS state result in geometries with the largest differences between DFT and CASPT2; however, good agreement overall is observed between DFT and CASPT2. For the larger complexes, moderate sized basis sets yield geometries that compare well with DFT and available experimental data. We recommend using the (10e,12o) active space since convergence to a minimum structure was more efficient than with truncated active spaces (e.g., (6e,5o)) despite having similar Fe–ligand bond distances.
QM/MM study of proton transport process in [FeFe] hydrogenase enzyme
Authors: Puthenkalathil Rakesh , Ensing Bernd
Published: February 2022

Di-iron hydrogenases are a class of enzymes that are capable of reducing protons to form molecular hydrogen with high efficiency. In addition to the catalytic site, these enzymes have evolved dedicated pathways to transport protons and electrons to the reaction center. Here, we present a detailed study of the most likely proton trans- fer pathway in such an enzyme using QM/MM molecular dynamics simulations. The protons are transported through a channel lined out from the protein exterior to the di-iron active site, by a series of hydrogen-bonded, weakly acidic or basic, amino-acids and two incorporated water molecules. Proton transport takes place via a ”hole” mech- anism, rather than an excess proton mechanism, the free energy landscape of which is remarkably flat, with a highest transition state barrier of only 5 kcal/mol. These results confirm our previous assumptions that proton transport is not rate limiting in the H2 formation activity and that cystene C299 may be considered protonated at physiological pH conditions. Detailed understanding of this proton transport may aid in the ongoing attempts to design artificial bio-mimetic hydrogenases for hydrogen fuel production.
Design and Application of a Screening Set for Monophosphine Lig-ands in Metal Catalysis
Authors: Gensch Tobias , Smith Sleight , Colacot Thomas , Timsina Yam , Xu Guolin , Glasspoole Ben , Sigman Matthew
Published: February 2022

In reaction discovery, the search space of discrete reaction parameters such as catalyst structure is often not explored systematical-ly. We have developed a tool set to aid the search of optimal catalysts in the context of phosphine ligands. A virtual library, kra-ken, that is representative of the monodentate P(III)-ligand chemical space was utilized as the basis to represent the discrete lig-ands as continuous variables. Using dimensionality reduction and clustering techniques, we suggested a Phosphine Optimization Screening Set (PHOSS) of 32 commercially available ligands that samples this chemical space completely and evenly. We present the application of this screening set in the identification of active catalyst for various cross-coupling reactions and how well-distributed sampling of the chemical space facilitates identification of active catalysts. Furthermore, we demonstrate how proximi-ty in ligand space can be a useful guide to further explore ligands when very few active catalysts are known.
Insights into the Mechanism of an Allylic Arylation Reaction via Photoredox Coupled Hydrogen Atom Transfer
Authors: Spielvogel Ethan , Stevenson Bernard , Stringer Michael , Swierk John
Published: February 2022

Despite widespread use as a synthetic method, as well as rapid expansion of substrate scope, the precise mechanism and kinetics of photoredox coupled hydrogen atom transfer (HAT) reactions remain poorly understood. This results from a lack of detailed kinetic information, as well as the identification of side reactions and products. In this report, a mechanistic study of a prototypical tandem photoredox/HAT reaction coupling cyclohexene and 1,4-Dicyanobenzene (DCB) using an Ir(ppy)3 photocatalyst and thiol HAT catalyst is reported. Through a combination of electrochemical, photochemical, and spectroscopic measurements, key unproductive pathways and side products are identified and rate constants for main chemical steps are extracted. The reaction quantum yield was found to decline rapidly over the course of the 20-hour reaction. A previously unreported cyanohydrin side product was identified and thought to play a key role as proton acceptor in the reaction. Transient absorption spectroscopy (TAS) suggested a reaction mechanism that involves trapping of the DCB radical anion by cyclohexene with HAT occurring as the final step via a cooperative HAT step. Kinetic modeling of the reaction, using rate constants derived from TAS, demonstrates that the efficiency of the reaction is limited by parasitic absorption and unproductive quenching between excited Ir(ppy)3 and the cyanohydrin photoproduct.
Micellar photocatalysis enables divergent C-H arylation and N dealkylation of benzamides via N-acyliminium cations
Authors: Cybularczyk-Cecotka Martyna , Predygier Jędrzej , Crespi Stefano , Szczepanik Joanna , Giedyk Maciej
Published: February 2022

Micellar photocatalysis has recently opened new avenues to activate strong carbon halide bonds. So far, however, it has mainly explored strongly reducing conditions restricting the available chemical space to radical or anionic reactivity. Here, we demonstrate a radical-polar crossover process involving cationic intermediates, which enables chemodivergent modification of chlorinated benzamide derivatives via either C H arylation or N dealkylation. The catalytic system operates under mild conditions employing methylene blue as a photocatalyst and blue LEDs as the light source. Factors determining the reactivity of substrates and preliminary mechanistic studies are presented.
Rapid, modular secondary sphere assembly for enhanced Fe-catalyzed C(sp3)–H oxidation
Authors: Ghosh Sabari , Tran Phuong Nguyen , McElheney Dan , Perez Juan , Nguyen Andy
Published: February 2022

The inert nature of C(sp3)–H bonds makes their oxidative cleavage a difficult task. While metalloenzymes employ an array of non-covalent interactions to facilitate C(sp3)–H oxidation, this strategy is underexplored in abiotic catalysts due to time-consuming and low-yielding ligand syntheses, which impedes iterative design. To surmount these obstacles, we, herein, have developed a highly modular and rapid synthetic strategy that capitalizes on the efficiency of solid-phase peptide synthesis, which enables the generation of a ligand platform displaying at least four unique residues of varying electronics and sterics in the secondary coordination sphere of a C–H oxidizing Fe catalyst. Modulating the non-covalent interactions in seven variants significantly influences cyclohexane oxidation catalysis, with one variant that boosts the catalytic activity by more than two-fold. To better understand the catalytic trends, we have determined the catalysts’ solution-state structures by 2D NMR spectroscopy, which suggests that peptide conformation can control substrate access and binding. This work demonstrates that (1) tunable, diverse, and complex active sites can be made readily, and (2) these active sites can be optimized to significantly increase catalytic activity.
Developing simple boranes as phase transfer catalysts for nucleophilic fluorination using CsF
Authors: Kirschner Sven , Peters Matthew , Yuan Kang , Uzelac Marina , Ingleson Michael
Published: February 2022

Despite the general high fluorophilicity of boron, simple organoboranes such as BEt3 and 3,5-(CF3)2C6H3–BPin are shown herein for the first time, to our knowledge, to be effective phase-transfer catalysts for the fluorination of organohalides with CsF. Significant chiral induction during nucleophilic fluorination to form -fluoroamines using oxazaborolidine (CBS) (pre)catalysts and CsF also can be achieved. Screening different boranes revealed a correlation between calculated fluoride affinity of the borane and nucleophilic fluorination reactivity, with sufficent fluoride affinity required for boranes to react with CsF and form Cs[fluoroborate] salts, but too high a fluoride affinity leading to fluoroborates that are poor at transferring fluoride to an electrophile. Fluoride affinity is only one component controlling reactivity in this context; effective fluorination also is dependent on the ligation of Cs+ which effects the [Cs⋯F⋯BR3] interaction and thus the B–F bond strength. Effective ligation of Cs+ (such as by [2.2.2]-cryptand) weakens the Cs⋯FB interaction which strengthens the B–F bond - thus disfavours fluoride transfer to an electrophile. Combined these findings enables optimal fluorination outcomes to be expected using robust (to the fluorination conditions) boranes with fluoride affinity of ca. 110 kJ mol-1 (relative to Me3Si+) under conditions where a signficant Cs⋯F–B interaction persists.