bluuebunny/crossref_metadata_2025 huggingface dataset:
Routescore: Punching the Ticket to More Efficient Materials Development
Authors: Seifrid Martin , Hickman Riley J. , Aguilar-Granda Andrés , Lavigne Cyrille , Vestfrid Jenya , Wu Tony C. , Gaudin Théophile , Hopkins Emily J. , Aspuru-Guzik Alán
Published: February 2022

Self-driving labs, in the form of automated experimentation platforms guided by machine learning algorithms have emerged as a potential solution to the need for accelerated science. While new tools for automated analysis and characterization are being developed at a steady rate, automated synthesis remains the bottleneck in the chemical space accessible to self-driving labs. Combining automated and manual synthesis efforts immediately significantly expands the explorable chemical space. To effectively direct the different capabilities of automated (higher throughput and less labor) and manual synthesis (greater chemical versatility), we describe a protocol, the RouteScore, that quantifies the cost of combined synthetic routes. In this work, the RouteScore is used to determine the most efficient synthetic route to a well-known pharmaceutical (structure-oriented optimization), and to simulate a self-driving lab that finds the most easily synthesizable organic laser molecule with specific photophysical properties from a space of ~3500 possible molecules (property-oriented optimization). These two examples demonstrate the power and generality of our approach in mixed synthetic planning and optimization.
Surface NMR Using Quantum Sensors in Diamond
Authors: Liu Kristina , Henning Alex , Heindl Markus W. , Allert Robin , Bartl Johannes D. , Sharp Ian D. , Rizzato Roberto , Bucher Dominik Benjamin
Published: February 2022

Characterization of the molecular properties of surfaces under ambient or chemically reactive conditions is a fundamental scientific challenge. Nuclear magnetic resonance (NMR) spectroscopy would be the ideal technique, however it lacks the sen-sitivity to probe the small number of spins at interfaces. Here we use nitrogen vacancy (NV) centers in diamond as quantum sensors to optically detect NMR signals from chemically modified thin films. Aluminum oxide (Al2O3) layers, common supports in catalysis and materials science, are prepared by atomic layer deposition and are subsequently functionalized by phosphonate chemistry to form self-assembled monolayers (SAMs). The surface NV-NMR technique detects NMR signals from the monolayer, indicates chemical binding, and quantifies molecular coverage. In addition, it can monitor in real-time the formation kinetics at the solid-liquid interface. This work demonstrates the capability of NV quantum sensors as a sur-face-sensitive (femtomole) NMR tool for in-situ analysis in catalysis, materials and biological research.
Molecular Field Analysis Using Computational-Screening Data in Asymmetric N-Heterocyclic Carbene-Copper Catalysis toward Data-driven in silico Catalyst Optimization
Authors: Mukai Masakiyo , Nagao Kazunori , Yamaguchi Shigeru , Ohmiya Hirohisa
Published: February 2022

A molecular-field-based regression analysis using computational screening data for N-heterocyclic carbene (NHC)-Cu-catalyzed asymmetric carbonyl additions of a silylboronate to aldehydes is reported. A computational screening was performed to collect enantioselectivity data (ΔΔG‡: energy differences between the transitions states leading to each enantiomer) via transition-state (TS) calculations using density functional theory (DFT) methods. A molecular field analysis (MFA) was carried out using the obtained calculated ΔΔG‡ values and TS structures (30 samples in total). Important structural infor-mation for enantioselectivity extracted by the MFA was visualized on the TS structures, which provided insight into an asymmetric induction mechanism. Based on the obtained information, chiral NHC ligands were designed, which showed improved enantioselectivity in these carbonyl additions.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 4. Halogen ring-substituted octyl phenylcyanoacrylates
Authors: Deren Aleksandra D. , Bench Luke R. , Chaudhary Daniyal , Defrenza Antoinette M. , Devaney Ava E. , Folkes Kristen , Gohel Jigisha J. , G. de S. Sena Mylena , Hussain Omair S. , Rocus Sara M. , Emmett Shayla M. , Jones Massie , Schjerven William S. , Kharas Gregory B.
Published: February 2022

Novel trisubstituted ethylenes, halogen ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 4-bromo, 2-chloro, 3-chloro, 4-chloro, 2-fluoro, 3-fluoro, 4-fluoro, 2-iodo, 3-iodo, 4-iodo) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
High-throughput Screening of Vanadium (IV) Oxide via Continuous Hydrothermal Flow Synthesis Reactor
Authors: Tran Mai , Rasmussen Elizabeth , Shevchenko Elena , Li Jie
Published: February 2022

The synthesis of inorganic nanoparticles using continuous hydrothermal flow synthesis (CHFS) reactor systems is an up-and-coming process to manufacture high-quality nanomaterials with singular control of the experimental parameters on the scale of seconds as opposed to hours. VO2-based systems manufactured using an autoclave reactor lack scalability, and current commercial products feature particle sizes too large for feasible application. In this paper, the detailed implementation of a CHFS system that can operate at and above supercritical water conditions (22.06 MPa at 374˚C) is described. Control over the CHFS system’s temperature, flow rate, and precursor concentration parameters allowed the tunability of size, crystallinity, and shape of VO2 nanoparticles to be investigated across seven studies. The resulting VO2 nanoparticles were characterized for size, shape, morphology, and crystallinity using dynamic light scattering (DLS), scanning electron microscopy (SEM), and x-ray diffraction (XRD). This investigation resulted in new operating procedures that enable the synthesis of high-quality, uniform, spherical, and pure M-phase VO2 nanoparticles under 50 nm in diameter in the residence time of a few seconds. Additionally, the procedure described in this paper is performed in a single step, thus eliminating the tedious post-annealing process.
Lewis acid-mediated Suzuki–Miyaura Cross-Coupling Reaction
Authors: Niwa Takashi
Published: February 2022

The palladium-catalysed Suzuki–Miyaura cross-coupling (SMC) reaction of organohalides and organoborons is a reliable method for carbon–carbon bond formation. This reaction involves a base-mediated transmetalation process, but the presence of a base also promotes competitive protodeborylation, which reduces the efficiency. Herein, we established an SMC reaction via Lewis acid-mediated transmetalation of an organopalladium(II) intermediate with organoborons. Experimental and theoretical investigations indicate that the controlled release of the transmetalation-active intermediate enabled base-independent transmetalation under heating conditions and enhanced the applicable scope of this process. This system enabled us to avoid the addition of a base, and thus, rendered substrates with base-sensitive moieties available. Results from this research further expand the overall utility of cross-coupling chemistry.
3D Printed Reactors and Kessil Lamp Holders for Flow Photochemistry: Design and System Standardization
Authors: Penny Matthew , Hilton Stephen
Published: February 2022

A low-cost 3D printed standardized flow-photochemistry setup has been designed and developed for use with a pressure-driven flow system using photochemistry lamps available in most laboratories. In this research, photochemical reactors were 3D printed from polypropylene which facilitated rapid optimization of both reactor geometry and experimental setup of the lamp housing system. To exemplify the rapidity of this approach to optimization, a Kessil LED lamp was used in the bromination of a range of toluenes in the 3D printed reactors in good yields with residence times as low as 27 seconds. The reaction compared favorably with the batch photochemical procedure and was able to be scaled up to a productivity of 75 mmol h-1.
Direct and indirect role of Fe doping in NiOOH monolayer for water oxidation catalysis
Authors: Kumar Manish , Piccinin Simone , Srinivasan Varadharajan
Published: February 2022

The oxygen evolution reaction (OER) activity of pristine NiOOH is enhanced by doping with Fe. However, the precise role of Fe is still being debated. Here, we use first-principles DFT+U approach to study three different types of active sites: one on pristine and the other two on Fe-doped NiOOH monolayers to account for the direct and indirect roles of Fe. To compare the activity of the active sites, we consider two mechanisms of OER based on the source of O-O bond formation. Our results show that the mechanism involving the coupling of lattice oxygen is generally more favorable than water nucleophilic attack on lattice oxygen. On doping with Fe, the overpotential of NiOOH is reduced by 0.29 V in excellent agreement with experimental findings. Doping Fe in NiOOH results in different potential determining steps (PDS) in the two mechanisms, whereas pristine NiOOH has the same PDS regardless of the mechanism.
Internal and external catalysis in boronic ester networks
Authors: Kang Boyeong , Kalow Julia
Published: February 2022

In dynamic materials, the reversible condensation between boronic acids and diols provides adaptability, self-healing ability, and responsiveness to small molecules and pH. Recent work has shown that the thermodynamics and kinetics of bond exchange determine the mechanical properties of dynamic polymer networks. However, prior studies have focused on how structural and environmental factors influence boronic acid–diol binding affinity, and design rules for tuning the kinetics of this dynamic bond are lacking. In this work, we investigate the effects of diol (or polyol) structure and salt additives on the rate of bond exchange, binding affinity, and the mechanical properties of the corresponding polymer networks. To better mimic the environment of polymer networks in our small-molecule model systems, we incorporated proximal amide groups, which are used to conjugate diols to polymers, and included salts commonly found in buffers. Using one-dimensional selective exchange spectroscopy (1D EXSY), we find that both proximal amides and buffering anions induce significant rate acceleration consistent with internal and external catalysis, respectively. This rate acceleration is reflected in the stress relaxation of gels formed using PEG modified with different alcohols, and in the presence of salts containing acetate or phosphate. These findings contribute to the fundamental understanding of the boronic ester dynamic bond and offer new molecular strategies to tune the macromolecular properties of dynamic materials.
DFT insights into the bonding mechanism of five-membered aromatic heterocycles containing N, O, or S on Fe(110) surface
Authors: Pham Le Minh Thong , Phung Thanh Khoa , Ho Viet Thang
Published: February 2022

Understanding the interaction of five-membered aromatic heterocycles with Fe(110) surface is crucial for the development of novel inhibitors against the corrosion of iron and steel. Herein, we report a detailed study of the adsorption properties and the bonding mechanism of pyrrole, furan, and thiophene on Fe(110) surface employing density functional theory (DFT) calculations. In the most stable adsorption geometries, we found that the adsorbates lie flat at the hollow site and form chemical bondings with four Fe atoms on Fe(110) surface. The chemisorptions are indicated by large adsorption energies and charge transfers from the surface to the adsorbates. We also found that taking into account vdW corrections in the DFT calculations has a minimal effect on the adsorption geometries whereas it significantly increases the adsorption energies. The energetic and structural analysis reveals large molecular distortions induced by the adsorbate-surface interactions, and among the adsorbates, thiophene experiences the least molecular distortion, thereby having the largest adsorption energy. The electronic structure analysis also reveals that the nature of electronic interaction of pyrrole, furan, and thiophene with Fe(110) surface is due to the strong overlaps of the frontier  and * orbitals of the adsorbates with Fe-3dz2 and Fe-(3dxz+3dyz) states of the surface. The charge donation and back-donation between the adsorbates and Fe(110) surface were also elucidated by the Bader charge analysis and the charge density difference.
Chelator-based parameterization of the 12-6-4LJ molecular mechanics potential for more realistic metal ion-protein interactions
Authors: Kantakevičius Paulius , Mathiah Calvin , Johannissen Linus , Hay Sam
Published: February 2022

Metal ions are associated with a variety of proteins and play critical roles in a wide range of biochemical processes. There are multiple ways to study and quantify protein-metal ion interactions, including by molecular dynamics simulations. Recently, the Amber molecular mechanics forcefield was modified to include a 12-6-4LJ potential, which allows better description of non-bonded terms through the additional pairwise Cij coefficients. Here, we demonstrate a method of generating Cij parameters that allows parametrization of specific metal ion-ligating groups in order to tune binding energies computed by thermodynamic integration. The new Cij coefficients were tested on a series of chelators: EDTA, NTA, EGTA and the EF1 loop peptides from the proteins lanmodulin and calmodulin. The new parameters show significant improvements in computed binding energies relative to existing force fields and produce coordination numbers and ion-oxygen distances that are in good agreement with experimental values. This parametrization method should be extensible to a range of other systems and could be readily adapted to tune properties other than binding energies.
How much entropy is contained in NMR relaxation parameters?
Authors: Hoffmann Falk , Mulder Frans A. A. , Schäfer Lars V.
Published: February 2022

Solution-state NMR relaxation experiments are the cornerstone to study internalprotein dynamics at atomic resolution on time scales that are faster than the overallrotational tumbling time,τR. Since the motions described by NMR relaxation pa-rameters are connected to thermodynamic quantities like conformational entropies, thequestion arises how much of the total entropy is contained within this tumbling time.Using all-atom molecular dynamics (MD) simulations of T4 lysozyme, we found thatentropy build-up is rather fast for the backbone, such that the majority of the entropyis indeed contained in the short-time dynamics. In contrast, the contribution of slowdynamics of side chains on time scales beyondτRon the side chain conformationalentropy is significant and should be taken into account for the extraction of accuratethermodynamic properties.
Cationic-Palladium Catalyzed Regio- and Stereoselective Dicarbo-functionalization of Unsymmetrical Internal Alkynes
Authors: Dutta Shubham , Shandilya Shashank , Yang Shengwen , Gogoi Manash Protim , Gandon Vincent , Sahoo Akhila K.
Published: February 2022

Reported is the discovery of an approach to regio- and stereoselective syn-1,2-dicarbofuctionalization of unsymmetrical alkynes. A cationic Pd-catalyzed three-component coupling of two distinct carbon-bearing functionalities aryl diazonium salts and aryl boronic acids/olefins with unsymmetrical alkynes enables accessing to all-carbon substituted unsymmetrical olefins. The transformation features broad scope with labile functional group tolerance building a novel chemical space of structural diversity (82 molecules) and is scalable. The cationic Pd species plays crucial; notably, density functional theory (DFT) studies establish this observation. Synthetic versatility of the modifiable carboxylate bearing highly-substituted olefins is also presented.
Utilizing selective chlorination to synthesize new triangulenium dyes
Authors: Jensen Jesper Dahl , Bisballe Niels , Kacenauskaite Laura , Thomsen Maria Storm , Chen Junsheng , Hammerich Ole , Laursen Bo W.
Published: February 2022

Access to functionalization of new sites on the triangulenium core structure has been achieved at an early stage by chlorination with N-chlorosuccinimide (NCS), giving rise to two new triangulenium dyes (1 and 2). By introducing the chlorine functionalities in the acridinium precursor, positions complementary to those previously accessed by electrophilic aromatic substitution of the final dyes can be accesed. The chlorination is selective, giving only one regioisomer for both mono- and dichlorination products. For the monochlorinated acridinium compound a highly selective ring-closing reaction was discovered to generate only a single regioisomer of the cationic [4]helicene product. This discovery aspired further investigations into the mechanism of [4]helicene formation and to the first isolation of the previously proposed intermediate of the two-step SNAr reaction, key to all aza-bridged triangulenium and helicenium systems. A late stage functionalization of DAOTA+ with NCS gave rise to a different dichlorinated compound (2). The fully ring closed chlorinated triangulenium dyes 1, 2 and 3 show a redshift in absorption and emission relative to the non-chlorinated analogues, while still maintaining relatively high fluorescence quantum yields of 36%, 26%, and 41%, and long fluorescence lifetimes of 15 ns, 12.5 ns and 16 ns, respectively. Cyclic voltammetry shows that chlorination of the triangulenium dyes significantly lowers reduction potentials and thus allows for efficient tuning of redox and photo-redox properties.
High-Performance, Single-Crystal Gold Bowtie Nano-Antennas via Epitaxial Electroless Deposition
Authors: V. Grayli Sasan , Kamal Saeid , Leach Gary
Published: February 2022

Material quality can play a critical role in the performance of nanometer-scale plasmonic structures. Here, we highlight a novel deposition strategy for single-crystal noble metal deposition and provide a direct and quantitative comparison between the fabrication yield, durability, and efficiency of bowtie nano-antennas fabricated from monocrystalline and polycrystalline gold films using subtractive nanofabrication. Focused ion beam milling of monocrystalline Au(100) films deposited through epitaxial electroless deposition to form bowtie nano-antennas produces devices that demonstrate key performance enhancements over devices patterned identically from polycrystalline Au films deposited via physical vapor deposition. Single-crystal bowties reveal significant improvements in pattern transfer fidelity and device yield, the ability to tailor and model local plasmonic field enhancements and marked improvement in their thermal and mechanical stability over those fabricated from polycrystalline Au films. This work underscores the performance advantages of single-crystal nanoscale plasmonic materials and describes a straightforward, solution-phase deposition pathway to achieve them. We anticipate that this approach will be broadly useful in applications where local near-fields can enhance light−matter interactions, including for the fabrication of optical sensors, photocatalytic structures, hot carrier-based devices, and nanostructured noble metal architectures targeting nano-attophysics.
Phosphine/Photoredox Catalyzed anti-Markovnikov Hydroamination of Olefins with Primary Sulfonamides via a-Scission from Phosphoranyl Radicals
Authors: Chinn Alex , Sedillo Kassandra , Doyle Abigail
Published: February 2022

New strategies to access radicals from common feedstock chemicals hold the potential to broadly impact synthetic chemistry. We report a dual phosphine and photoredox catalytic system that enables direct formation of sulfonamidyl radicals from primary sulfonamides. The method is proposed to proceed via -scission of the sulfonamidyl radical from a phosphoranyl radical intermediate, generated upon sulfonamide nucleophilic addition to a phosphine radical cation. As compared to the recently well-explored β-scission chemistry of phosphoranyl radicals, this strategy is applicable to activation of N-based nucleophiles and is catalytic in phosphine. We highlight application of this activation strategy to an intermolecular anti-Markovnikov hydroamination of unactivated olefins with primary sulfonamides. A range of structurally diverse secondary sulfonamides can be prepared in good to excellent yields under mild conditions.
Probing the Impact of Solvent on Lewis Acid Catalysis via Fluorescent Lewis Adducts
Authors: Laturski Amy , Bentley Jordan , Gaffen Joshua , Caputo Christopher , Baumgartner Thomas
Published: February 2022

Over the years, various multiparameter methods have been developed to measure the strength of a Lewis acid. However, a major challenge for these measurements lies in the complexity that arises from variables such as solvent and other fundamental interactions, as well as perturbations of Lewis acids as their reaction environment changes. Herein, we evaluate the impact of solvent effects on the Fluorescent Lewis Adduct (FLA) method using a series of representative Lewis acids. The solution-state nature of the FLA method in particular offers the ability to correlate Lewis Acid Units (LAUs) obtained from the FLA measurement with reactivity. The binding of a Lewis acid in various solvents reveals a measurable dichotomy between both polarity and donor ability of the solvent. While not strictly separable, as solvent polarity increases observed LAUs increase; however, as solvent donor ability increases the observed LAUs decrease. This dichotomy was confirmed by titration data and catalytic Diels-Alder cycloaddition and hydrosilylation reactions with neutral boranes, illustrating that solvation effects can be appropriately gauged by LAU value determined from the FLA method.
Interlayer Interactions as Design Tool for Large-Pore COFs
Authors: Emmerling Sebastian , Schuldt Robin , Bette Sebastian , Yao Liang , Kästner Johannes , Lotsch Bettina
Published: February 2022

Covalent organic frameworks (COFs) with a pore size beyond 5 nm are still rarely seen in this emerging field. Besides obvious complications like the elaborated synthesis of large linkers with sufficient solubility, more subtle challenges regarding large-pore COF synthesis, including pore occlusion and collapse, prevail. Here we present two isoreticular series of large-pore imine COFs with pore sizes up to 5.8 nm and correlate the interlayer-interactions with the structure and thermal behavior of the COFs. By adjusting interlayer-interactionsthroughthe incorporation of methoxy groups acting as pore-directing “anchors”, different stacking modes can be accessed, resulting in modified stacking polytypes and, hence, effective pore sizes. A strong correlation between stacking energy towards highly ordered, nearly-eclipsed structures, higher structural integrity during thermal stress, and a novel, thermally induced phase transition of stacking modes in COFs was found, which sheds light on viable design strategies for increased structural control and stability in large-pore COFs.
Affordable Ab Initio Path Integral for Thermodynamic Properties via Molecular Dynamics Simulations Using Semiempirical Reference Potential
Authors: Xue Yuanfei , Wang Jia-Ning , Hu Wenxin , Zheng Jun , Li Yongle , Pan Xiaoliang , Mo Yan , Shao Yihan , Wang Lu , Mei Ye
Published: February 2022

Path integral molecular dynamics (PIMD) is becoming a routinely applied method for the incorporation of the nuclear quantum effect in computer simulations. However, direct PIMD simulations at an ab initio level of theory are formidably expensive. Using the protonated 1,8-bis(dimethylamino)naphthalene molecule as an example, we show in this work that the computational expense for the intra-molecular proton transfer between the two nitrogen atoms can be remarkably reduced by implementing the idea of reference-potential methods. The simulation time can be easily extended to a scale of nanosecond while maintaining the accuracy on an ab initio level of theory for thermodynamic properties. In addition, the post-processing can be carried out in parallel on massive computer nodes. A 545-fold reduction in the total CPU time can be achieved in this way as compared to a direct PIMD simulation at the same ab initio level of theory.
Structural insight on the mechanism of an electron-bifurcating [FeFe] hydrogenase
Authors: Furlan Chris , Chongdar Nipa , Gupta Pooja , Lubitz Wolfgang , Ogata Hideaki , Blaza James , Birrell James
Published: February 2022

Electron-bifurcation is a fundamental energy conservation mechanism in nature. The electron-bifurcating [FeFe] hydrogenase from Thermotoga maritima (HydABC) requires both NADH and ferredoxin to reduce protons generating hydrogen. The mechanism of electron-bifurcation in HydABC remains enigmatic primarily due to the lack of structural information. Here, we present a 2.3 Å electron cryo-microscopy structure of HydABC. The structure is a heterododecamer composed of two independent ‘halves’ each made of two strongly interacting HydABC trimers electrically connected via a [4Fe-4S] cluster, forming a bus-bar system. Symmetry expansion identified two conformations: a “closed bridge” and an “open bridge” conformation, where a Zn2+ site may act as a “hinge” allowing domain movement. Based on these structural revelations, we propose two new mechanisms of electron-bifurcation in HydABC.
Investigating Antimicrobial Peptide-Membrane Interactions Using Fast Photochemical Oxidation of Peptides in Nanodiscs
Authors: Reid Deseree , Rohrbough James , Kostelic Marius , Marty Michael
Published: February 2022

Antimicrobial peptides (AMPs) are an important part of the innate immune system and demonstrate promising applications in the fight against antibiotic resistant infections due to their unique mechanism of targeting bacterial membranes. However, it is challenging to study the interactions of these peptides within lipid bilayers, making it difficult to understand their mechanisms of toxicity and selectivity. Here, we used fast photochemical oxidation of peptides, an irreversible footprinting technique that labels solvent accessible residues, and native charge detection-mass spectrometry to study AMP-lipid interactions with different lipid bilayer nanodiscs. We observed differences in the oxidation of two peptides, indolicidin and LL-37, in three distinct lipid environments, which reveals their affinity for lipid bilayers. Our findings suggest that indolicidin interacts with lipid head groups via a simple charge-driven mechanism, but LL-37 is more specific for E. coli nanodiscs. These results provide complementary information on the potential modes of action and lipid selectivity of AMPs.
COVID-19: Attacks Immune Cells and Interferences with Antigen Presentation through MHC-Like Decoy System
Authors: wenzhong liu , hualan li
Published: February 2022

The high mortality of COVID-19 is related to poor antigen presentation and lymphopenia. In this present study, domain search results showed that many proteins of the SARS-COV-2 virus had MHC-like domains, which were similar to decoys for the human immune system. MHC-like structures could bind to MHC receptors of immune cells, interfering with antigen presentation. Then the oxygen-free radicals generated by E protein destroyed immune cells after MHC-like of S protein could bind to them. Mutations in the MHC-like region of the viral proteins such as S promoted weaker immune resistance and more robust transmission. S 127-194 were the primary reason for the robust transmission of delta variants. The S 144-162 regulated the formation of S trimer. The mutations of RdRP: G671S and N: D63G of delta variant caused high viral load. S 62-80 of alpha, beta, lambda variants were the important factor for fast-spreading. S 616-676 and 1014-1114 were causes of high mortality for gamma variants infections. These sites were in the MHC-like structure regions.
Understanding the effect of doping on the charging performance of the Li-O2 battery: the role of hole polarons and lithium vacancies
Authors: Cortés Páez Henry Andres , Zapata Cardona John Faber , Barral María Andrea , Vildosola Laura Veronica
Published: February 2022

In this work, we perform DFT calculations using the hybrid functional HSE to properly describe the insulating nature of lithium peroxide and study its more energetically favourable surfaces [0001], [1-100] and [11-20]. We then analyse how the insulating character and the correct description of the hole polarons at the Li2O2 surfaces affect the electrochemical steps of Li2O2 decomposition in the charging process of the Li-O2 battery. We then study the effect of doping and propose possible scenarios in which the ions as Na+ or K+ dissolved in the electrolyte can dope and promote Li vacancies generation in the Li2O2 that, in turn, reduce the energy barrier of the limiting steps of the Li2O2 decomposition. The origin of this reduction are the lattice distortions associated with doping that weaken the surface binding.
Selective degradation of styrene-contained plastics catalyzed by iron under visible light
Authors: Wang Miao , Wen Jinglan , Huang Yahao , Hu Peng
Published: February 2022

Efficient degradation of plastics, the vital challenge for a sustainable future, stands in need of better chemical recycling procedures that help produce commercially valuable small molecules and redefine plastic waste as a rich source of chemical feedstock. However, the corresponding chemical recycling methods, while being generally restricted to polar polymers, need improvement. Particularly, degradation of chemical inert nonpolar polymers, the major constitutes of plastics, are reported to have suffered from low selectivity and very harsh transformation conditions. Herein, we report an efficient method for the selective degradation of styrene-contained plastics under gentle conditions through oxidative multiple sp3 C-C bond cleavage. The unpresented procedure is catalyzed with inexpensive iron salts under visible light, using oxygen as the green oxidant. Furthermore, simple iron salts can be used to degrade plastics in the absence of solvent under natural conditions, highlighting the potential application of iron salts as additives for degradable plastics.
Omniligase-1-mediated ligation for insulin analog synthesis in solu-tion and on phage surface
Authors: Chou Danny Hung-Chieh , Lin Nai-Pin , Zhang Yi , Szabo-Fresnais Nicolas
Published: February 2022

The B-chain C-terminal region of insulin has been mutated or modified to achieve improved therapeutic efficacies. For ex-ample, all FDA-approved insulin analogs have altered C-terminal segments, which leads to improved pharmacokinetic prop-erties and provide significant clinical benefits on blood sugar regulation. Nonetheless, there is still no efficient method to synthesize insulin analogs with the altered C-terminal region. Herein, we report a facile synthesis using omniligase-1 to li-gate an insulin core with a peptide segment in high conversion. We further apply this ligation to M13 phage surface modifi-cations and demonstrate that the phage displayed insulin molecules can bind to insulin receptor ectodomain in an insulin-dependent manner. These results pave the way for building phage display insulin library for therapeutic selections and demonstrate the feasibility of using omniligase-1 to display other disulfide-rich peptides and proteins on phage.
Development of an Acrylamide-Based Inhibitor of Protein S-Acylation
Authors: Azizi Saara-Anne , Lan Tong , Delalande Clémence , Kathayat Rahul , Mejia Fernando Benales , Qin Alice , Brookes Noah , Sandoval Perla , Dickinson Bryan
Published: February 2022

Protein S-acylation is a dynamic lipid post-translational modification that can modulate the localization and activity of target proteins. In humans, the installation of the lipid onto target proteins is catalyzed by a family of 23 Asp-His-His-Cys domain-containing protein acyltransferases (DHHC-PATs). DHHCs are increasingly recognized as critical players in cellular signaling events and in human disease. However, progress elucidating the functions and mechanisms of DHHC “writers” has been hampered by a lack of chemical tools to perturb their activity in live cells. Herein, we report the synthesis and characterization of cyano-myracrylamide (CMA), a broad-spectrum DHHC family inhibitor with similar potency to 2-bromopalmitate (2BP), the most commonly used DHHC inhibitor in the field. Possessing an acrylamide warhead instead of 2BP’s α-halo fatty acid, CMA inhibits DHHC family proteins in cellulo while demonstrating decreased toxicity and avoiding inhibition of the S-acylation eraser enzymes – two of the major weaknesses of 2BP. Our studies show that CMA engages with DHHC family proteins in cells, inhibits protein S-acylation, and disrupts DHHC-regulated cellular events. CMA represents an improved chemical scaffold for untangling the complexities of DHHC-mediated cell signaling by protein S-acylation.
Study of strain-induced structural, electronic, mechanical, and transport properties of one-dimensional monoatomic ultrathin gold nanowire: A DFT-NEGF approach
Authors: Bhandari Sharma Shambhu , Bhatta Ramchandra , Sigdel Keshav Raj , Adhikari Rajendra P
Published: February 2022

We conduct the first principle calculation based on Density Functional Theory (DFT) and Non-equilibrium Green Function (NEGF) approach using Generalized Gradient Approximation (GGA). We have investigated the structural, electronic, mechanical, and electronic transport properties of a one-dimensional monoatomic gold nanowire (AuNW). Plus, the influence of strain in geometrical and electronic properties also investigated. The nanowire is stable with sustainable cohesive energy of -1.52 eV. The chemical stability is due to the partly ionic and covalent bonding between the gold atoms. The electronic band shows the metallic behavior of nanowire with a conductivity of 1G0 . Furthermore, the structural and electronic properties of AuNW change significantly due to the external strain. The compressive strain decreases the bond length conversely, tensile strain increases the bond length from the equilibrium length. Similarly, the higher electronic energy states shift towards the Fermi level due to tensile strain. Furthermore, the mechanical strength of the NW is calculated by finding the tensile stiffness of the nanowire which found to be 30.31 eV/Å that is threefold less than carbyne. The transport property is studied by designing the electrode-device-electrode regime by eliminating the current quantization effect due to the contacts. We obtain the current-voltage (IV ) characteristics by varying the chemical potential in the electrode region. The current-voltage profile shows AuNW follows Ohomic current-voltage relation until current gets saturated. All these findings show that monoatomic AuNW is a potential candidate for electronic, nanomechanical, and transport applications.
Stability Indicating Ion-Pair Reversed-Phase Liquid Chromatography Method for Modified mRNA
Authors: Currie Jonathan , Dahlberg Jacob. R , Eriksson Jonas , Schweikart Fritz , Nilsson Gunilla. A , Örnskov Eivor
Published: February 2022

Modified messenger RNA (mRNA) represents a promising new class of therapeutic drug product. Development of robust stability indicating methods, for control of product quality, are therefore critical to support successful pharmaceutical development. This paper presents the first ion pair reversed phase liquid chromatography (IP-RPLC) method to characterise modified mRNA exposed to a wide set of stress-inducing conditions, relevant for pharmaceutical development of an mRNA drug product. The optimised method could be used for separation and analysis of large RNA, sized up to 1000 nucleotides. The impacts of column temperature, mobile phase flow rate and ion-pair selection were studied and optimised. Baseline separations of the model RNA ladder sample were achieved using all examined ion-pairing agents. We established that the optimised method, using 100mM Triethylamine, enabled the highest resolution separations for the largest fragments in the RNA ladder (750/1000 nucleotides), in addition to the highest overall resolution for the selected modified mRNA compound (eGFP mRNA, 996 nucleotides). The stability indicating power of the method was demonstrated by analysing the modified eGFP mRNA, upon direct exposure to heat, hydrolytic conditions and treatment with ribonucleases. Our results showed that the resulting degradation products, which appeared as shorter RNA fragments in front of the main peak, could be well visualized, using the optimised method, and the relative stability of the mRNA under the various stressed conditions could be assessed.
Manganese Catalyzed Reformation of Ethylene Glycol to Glycolic acid and Lactic Acid
Authors: Waiba Satyadeep , Maji BIplab
Published: February 2022

Conversion of readily available feedstocks to valuable platform chemicals via a sustainable catalytic pathway has always been one of the key focuses of synthetic chemists. Cheaper, less toxic, and more abundant base metals as a catalyst for performing such transformations provide an additional boost. In this context, herein, we report a reformation of readily available feedstock, ethylene glycol, to value-added platform molecules, glycolic acid, and lactic acid. A bench stable base metal complex {[HN(C2H4PPh2)2]Mn(CO)2Br}, Mn-I, known as Mn-PhMACHO, catalyzed the reformation of ethylene glycol to glycolic acid at 140 oC in high selectivity with a turnover number TON = 2400, surpassing previously used homogeneous catalysts for such a reaction. Pure hydrogen gas is evolved without the need for an acceptor. On the other hand, a bench stable Mn(I)-complex, {(iPrPN5P)Mn(CO)2Br}, Mn-III, with a triazine backbone, efficiently catalyzed the acceptorless dehydrogenative coupling of ethylene glycol and methanol for the synthesis of lactic acid, even at a ppm level of catalyst loading, reaching the TON of 11,500. Detailed mechanistic studies were performed to elucidate the involvements of different manganese(I)-species during the catalysis.
Photophysical property and optical nonlinearity of cyclo[18]carbon (C18) precursors, C18-(CO)n (n = 2, 4, and 6): Focusing on the effect of carbonyl (-CO) groups
Authors: Wang Xia , Liu Zeyu , Yan Xiufen , Lu Tian , Wang Haowei , Xiong Weiwei
Published: February 2022

Considering their remarkable chemical stability, the precursors of cyclo[18]carbon (C18), C18-(CO)n (n = 2, 4, and 6), have more practical significance than the elusive C18 ring. In the present paper, the electronic spectrum and (hyper)polarizability of the C18-(CO)n (n = 2, 4, and 6) are studied by theoretical calculations and analyses for revealing the utility of introduction of carbonyl (-CO) groups on molecular optical properties. The analysis results show that the successive introduction of -CO groups leads to red-shift of the absorption spectrum, but maximum absorption of all molecules is mainly due to the charge redistribution caused by electron transition within C18 ring. Except for the vanishing first hyperpolarizability of C18-(CO)6 results from its octupolar character, the (hyper)polarizabilities of the precursors present an ascending trend with the increase of -CO groups in the molecule, and the higher-order response properties are more sensitive to the number of -CO groups. By means of (hyper)polarizability density analysis and (hyper)polarizability contribution decomposition, the fundamental reasons for the difference of (hyper)polarizability of different molecules were systematically discussed from the perspectives of physical and structural origins, respectively. As to the frequency dispersions under the incident light, the significant optical resonances were found on the hyperpolarizability of molecules C18-(CO)n (n = 2, 4, and 6), which contrast with the fact that it has inconspicuous influences on molecular polarizability.
Short and Long-Range Electron Transfer Compete to Determine Free-Charge Yield in Organic Semiconductors
Authors: Carr Joshua , Allen Taylor , Larson Bryon , Davydenko Iryna , Dasari Raghunath , Barlow Stephen , Marder Seth , REID OBADIAH , Rumbles Garry
Published: February 2022

Understanding how Frenkel excitons efficiently split to form free-charges in low-dielectric constant organic semiconductors has proven challenging, with many different models proposed in recent years to explain this phenomenon. Here, we present evidence that a simple model invoking a modest amount of charge delocalization, a sum over the available microstates, and the Marcus rate constant for electron transfer can explain many seemingly contradictory phenomena reported in the literature. We use an electron-accepting fullerene host matrix dilutely sensitized with a series of electron donor molecules to test this hypothesis. The donor series enables us to tune the driving force for photoinduced electron transfer over a range of 0.7 eV, mapping out normal, optimal, and inverted regimes for free-charge generation efficiency, as measured by time-resolved microwave conductivity. However, the photoluminescence of the donor is rapidly quenched as the driving force increases, with no evidence for inverted behavior, nor the linear relationship between photoluminescence quenching and charge-generation efficiency one would expect in the absence of additional competing loss pathways. This behavior is self-consistently explained by competitive formation of bound charge-transfer states and long-range or delocalized free-charge states, where both rate constants are described by the Marcus rate equation. Moreover, the model predicts a suppression of the inverted regime for high-concentration blends and efficient ultrafast free-charge generation, providing a mechanistic explanation for why Marcus-inverted-behavior is rarely observed in device studies.
Unified Total Synthesis of the Brevianamide Alkaloids Enabled by Chemical Investigations into their Biosynthesis.
Authors: Godfrey Robert C. , Jones Helen E. , Green Nicholas J. , Lawrence Andrew L.
Published: February 2022

The bicyclo[2.2.2]diazaoctane alkaloids are a vast group of natural products which have been the focus of attention from the scientific community for several decades. This interest stems from their broad range of biological activities, their diverse biosynthetic origins, and their topologically complex structures, which combined make them enticing targets for chemical synthesis. In this article, full details of our synthetic studies into the chemical feasibility of a proposed network of biosynthetic pathways towards the brevianamide family of bicyclo[2.2.2]diazaoctane alkaloids are disclosed. Insights into issues of reactivity and selectivity in the biosynthesis of these structures have aided the development of a unified biomimetic synthetic strategy, which has resulted in the total synthesis of all known bicyclo[2.2.2]diazaoctane brevianamides and the anticipation of an as-yet-undiscovered congener.
Multiple Resonance TADF Sensitizers Enable Green-to-Ultraviolet Photon Upconversion: Application in Photochemical Transformations
Authors: wei yaxiong , pan ke , li yuanming , cao xiaosong , zhou xiaoguo , yang chuoluo
Published: February 2022

Efficient visible-to-ultraviolet (UV) triplet-triplet annihilation upconversion (TTA-UC) with large anti-Stokes shift is highly promising in solar-powered and indoor applications. Nonetheless, the excitation wavelength is confined to the blue region (< 450 nm) mainly due to large energy loss during triplet sensitization. Herein, a series of multiple resonance thermal activated delayed fluorescence (MR-TADF) compounds are constructed as pure organic sensitizers for the purpose of energy-loss reduction, which also feature intense absorbance at visible region, high intersystem crossing efficiencies, and long triplet lifetimes. By pairing the MR-TADF sensitizers with appropriate UV-emissive acceptors, green-to-UV TTA-UC systems were realized with anti-Stokes shift up to 1.05 eV, upconversion quantum yield up to 7.6% and threshold excitation intensity as low as 9.2 mW cm-2 in solution. Proof-of-concept demonstrations suggest the TTA-UC pairs could be applied as internal or external source of UV photons to trigger energy-demanding photopolymerization and photoligation reactions even under excitation of low-power-density green LED light, suggesting the broad utility of these molecular upconverters.
Transient equilibrium mapping: A new tool for measuring the thermodynamics of slowly assembling supramolecular systems
Authors: Hennecker Christopher , Lachance-Brais Christophe , Sleiman Hanadi , Mittermaier Anthony
Published: February 2022

Supramolecular chemistry involves the non-covalent assembly of monomers into materials with unique properties and wide-ranging applications. Thermal analysis is a key analytical tool in this field, as it provides quantitative thermodynamic information on both the structural stability and nature of the underlying molecular interactions. However there exist many supramolecular systems whose kinetics are so slow under conditions approaching equilibrium that thermodynamic data are inaccessible. We have developed a simple and rapid spectroscopic method for extracting thermodynamic parameters from these systems. It is based on repeatedly raising and lowering the temperature during assembly and identifying the points of transient equilibrium as they are passed on the up- and down-scans. In a proof-of-principle application to the co-assembly of polydeoxyadenosine containing 15 adenosines (polyA15) and cyanuric acid (CA), we found that roughly 30% of the CA binding sites on the polyA chains were unoccupied, with implications for the assembly of high-valence systems.
Machine Learning Predictions of Drug Release from Polymeric Long Acting Injectables
Authors: Bannigan Pauric , Häse Florian , Aldeghi Matteo , Bao Zeqing , Aspuru-Guzik Alán , Allen Christine
Published: February 2022

Machine learning is enabling leap-step advances in a number of fields including drug discovery and materials science. The current study explores the application of machine learning to address a critical challenge in pharmaceutical formulation development: the prediction of drug release profiles from polymer-based long-acting injectables. Long acting injectables are considered one of the most promising therapeutic strategies for the treatment of chronic diseases as they can afford improved therapeutic efficacy, safety, and patient compliance. The use of polymer materials in such a drug formulation strategy can offer unparalleled diversity owing to the ability to synthesize materials with a wide range of properties. However, the interplay between multiple parameters, including the physicochemical properties of the drug and polymer, make it near to impossible to predict the performance of these systems a priori. This results in a need to develop and characterize a wide array of formulation candidates through extensive and time-consuming in vitro experimentation. In this study, various neural network architectures are constructed and trained, resulting in accurate predictions of drug release profiles that agree with experimental data. The simplicity with which these broadly applicable machine learning models are identified, using a limited amount of training data, is evidence of the promising potential of data-driven approaches in advanced pharmaceutical formulation development.