bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital-Dependent Photodynamics of Strongly Correlated Clusters
Authors: Garcia Jacob , Sayres Scott
Published: February 2022

Understanding the role of defect sites on the mechanism and lifetime of photoexcited state relaxation is critical for the ration-al design of advanced materials. Here, the ultrafast electronic relaxation dynamics of neutral nickel oxide clusters were inves-tigated with femtosecond pump-probe spectroscopy and supported with theoretical calculations to reveal that their excited state lifetimes are strongly dependent on the nature of the electronic transition. Absorption of a UV photon produces short lived (lifetime ~110 fs) dynamics in stoichiometric (NiO)n clusters (n < 6) that are attributed to a ligand to metal charge transfer (LMCT) and produces metallic-like electron-electron scattering. Oxygen vacancies introduce excitations with Ni-3d→Ni-4s and 3d→4p character, which increases the lifetimes of the sub-picosecond response by up to 80% and enables the formation of long-lived (lifetimes > 2.5 ps) states. The atomic precision and tunability of gas phase clusters are employed to highlight a unique reliance on the Ni orbital contributions to the photoexcited lifetimes, providing new insights to the anal-ogous band edge excitation dynamics of strongly correlated bulk-scale NiO materials.
The Aryne Phosphate Reaction
Authors: Haas Thomas , Wiesler Stefan , Dürr-Mayer Tobias , Ripp Alexander , Fouka Paraskevi , Qiu Danye , Jessen Henning
Published: February 2022

Condensed phosphates are a critically important class of molecules in biochemistry, with a myriad of derived structures being known. Moreover, non-natural analogues are important for various applications, such as single molecule real time DNA sequencing. Often, such analogues contain more than three phosphate units in their oligophosphate chain. Consequently, investigations into phosphate reactivity enabling new ways of phosphate functionalization and oligophosphorylation are an essential endeavour in the field. Here, we scrutinize the potential of phosphates to act as arynophiles, paving the way for follow-up oligophosphorylation reactions. The aryne phosphate reaction is a powerful tool to – depending on the perspective – (oligo)phosphorylate arenes or arylate (oligo-cyclo)phosphates. Based on Kobayashi-type o-silylaryltriflates, the aryne phosphate reaction enables rapid entry into a broad spectrum of arylated products, like monophosphates, diphosphates, phosphodiesters and polyphosphates. The synthetic potential of these new transformations is demonstrated by efficient syntheses of nucleotide analogues and an unprecedented one-flask octaphosphorylation.
Making molecules vibrate: Interactive web environment for the teaching of infrared spectroscopy
Authors: Jablonka Kevin Maik , Patiny Luc , Smit Berend
Published: February 2022

Infrared spectroscopy (IR) is a staple structural elucidation and characterization technique due to its ability to identify functional groups and its ease of use. Interestingly, it allows capturing electronic effects via their influence on the bond strength of "probes" such as the carbonyl group and also offers a wealth of examples for discussion on the theory of electronic transitions. For this reason, IR spectroscopy is typically taught both in theoretical classes and in applied structural analysis courses. In practice, there is rarely a link between those courses, and both suffer from the lack of exploratory learning, i.e., tools with which students can explore the interplay between symmetry and selection rules, as well as electronic effects and vibrational frequencies — with almost immediate feedback. In practice, this might lead to students that are well skilled in looking up vibrational frequencies in lookup tables but do not understand the links to electronic effects and reactivity. Here, we introduce a web app that leverages semi-empirical quantum mechanical (or force-field based) calculations, performed on a web service, in an interactive interface to provide an environment in which students can explore how slight changes to the structure manifest in changes of the spectrum. This approach avoids the time-consuming handling of potentially hazardous materials that might not be readily available and invites students to play with spectroscopy — to "see" and "test" electronic effects that are so commonplace in organic chemistry education. As a "side effect" our web app also provides a powerful aid for research scientists to investigate how different structural modifications, such as substitution, isomerism, or steric strain, would manifest in the infrared spectrum.
Covalent Functionalization of Nickel Phosphide Nanocrystals with Aryl-Diazonium Salts
Authors: Murphy Ian , Rice Peter , Monahan Madison , Zasada Leo , Miller Elisa , Raugei Simone , Cossairt Brandi
Published: February 2022

Covalent functionalization of Ni2P nanocrystals was demonstrated using aryl-diazonium salts. Spontaneous adsorption of aryl functional groups was observed, with surface coverages ranging from 20-96% depending on the native reactivity of the salt as determined by the aryl substitution pattern. Increased coverage was possible for low reactivity species using a sacrificial reductant. Functionalization was confirmed using thermogravimetric analysis, FTIR and X-ray photoelectron spectroscopy. The structure and energetics of this nanocrystal electrocatalyst system, as a function of ligand coverage, was explored with density functional theory calculations. The Hammett parameter of the surface functional group was found to linearly correlate with the change in Ni and P core-electron binding energies and the nanocrystal’s work-function. The electrocatalytic activity and stability of the functionalized nanocrystals for hydrogen evolution were also improved when compared to the unfunctionalized material, but a simple trend based on electrostatics was not evident.
Chain-Growth SuFEx Polycondensation: Molecular Weight Control and Synthesis of Degradable Polysulfates
Authors: Kim Hyunseok , Zhao Jiayu , Bae Jinhye , Klivansky Liana M. , Dailing Eric , Liu Yi , Cappiello John R. , Sharpless K. Barry , Wu Peng
Published: February 2022

Sulfur (Ⅵ) fluoride exchange (SuFEx) click chemistry has offered a facile and reliable approach to produce polysul-fates and polysulfonates. However, the current SuFEx polymerization methods lack precise control of target molecular weight and dispersity. Herein, we report the first chain-growth SuFEx polycondensation process by exploiting unique reactivity and selectivity of S-F bonds under SuFEx catalysis. Given the higher reactivity of iminosulfur oxydifluoride versus fluorosulfate, the chain-growth SuFEx polycondensation is realized by using an iminosulfur oxydifluoride-containing compound as the reactive chain initiator and deactivated AB-type aryl silyl ether-fluorosulfates bearing an electron-withdrawing group as monomers. When DBU was utilized as the polymerization catalyst, precise control over polymer molecular weight and polydispersity are achieved. The resulting polymers possess great thermal stability but are easily degradable under mild acidic and basic conditions.
Microfluidic Chain Reaction
Authors: Yafia Mohamed , Ymbern Oriol , Olanrewaju Ayokunle , Parandakh Azim , Kashani Ahmad Sohrabi , Renault Johan , Jin Zijie , Kim Geunyong , Ng Andy , Juncker David
Published: February 2022

Chain reactions are characterized by initiation, propagation and termination, are stochastic at microscopic scales and underlie vital chemical (e.g. combustion engines), nuclear and biotechnological (e.g. polymerase chain reaction) applications.1–5 At macroscopic scales, chain reactions are deterministic and limited to applications for entertainment and art such as falling domino and Rube Goldberg machines. Appositely, microfluidic lab-on-a-chip (also called a micro total analysis system),6,7 which were envisioned pursuant to microelectronic integrated circuits, are generally not integrated on a chip owing to an enduring dependency on cumbersome connections, peripherals, and on computers for automation.8–11 Capillary microfluidics integrate energy supply and flow control onto a single chip by using capillary phenomena, but programmability remains rudimentary with at most a handful (eight) operations possible.12–19 Here we introduce mesoscopic microfluidic chain reactions (MCRs) based on capillary phenomena for reliable programming and automation of complex liquid handling algorithms integrated in a chip. MCRs are encoded into the chip microarchitecture, 3D printed as a monolithic circuit, and deterministically propagated by the free-energy of a paper pump. With MCR, we sequentially triggered the release of 300 aliquots across chained, interconnected chips, and automated a protocol for SARS-CoV-2 antibodies detection in saliva with visual and quantitative results by cell phone imaging. We automated and miniaturized for the first time the labor-intensive thrombogram with serial and parallel operations including timers and iterative cycles of synchronous flow and stop-flow sequences. Thrombograms with normal, hemophilia-like, and anticoagulant-spiked plasma were generated. MCRs are generalizable, and both the density and number of chain reaction units are scalable. MCRs are untethered from and unencumbered by peripherals, encode programs structurally in situ, and form a frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics.
Microfluidic Chain Reaction: Conditional, Structurally Programmed Propagation of Capillary Flow Events
Authors: Yafia Mohamed , Ymbern Oriol , Olanrewaju Ayokunle , Parandakh Azim , Kashani Ahmad Sohrabi , Renault Johan , Jin Zijie , Kim Geunyong , Ng Andy , Juncker David
Published: February 2022

Chain reactions are characterized by initiation, propagation and termination, are stochastic at microscopic scales and underlie vital chemical (e.g. combustion engines), nuclear and biotechnological (e.g. polymerase chain reaction) applications.1-5 At macroscopic scales, chain reactions are deterministic and limited to applications for entertainment and art such as falling domino and Rube Goldberg machines. Appositely, the microfluidic lab-on-a-chips (also called a micro total analysis system),6,7 was envisioned as an integrated chip, akin to microelectronic integrated circuits, yet in practice remain dependent on cumbersome peripherals, connections, and a computer for automation.8-11 Capillary microfluidics integrate energy supply and flow control onto a single chip by using capillary phenomena, but programmability remains rudimentary with at most a handful (eight) operations possible.12-19 Here we introduce the microfluidic chain reaction (MCR) as the conditional, structurally programmed propagation of capillary flow events. Monolithic chips integrating a MCR are 3D printed, and powered by the free-energy of a paper pump, autonomously execute liquid handling algorithms step-by-step. With MCR, we automated (i) the sequential release of 300 aliquots across chained, interconnected chips, (ii) a protocol for SARS-CoV-2 antibodies detection in saliva, and (iii) a thrombin generation assay by continuous subsampling and analysis of coagulation-activated plasma with parallel operations including timers, iterative cycles of synchronous flow and stop-flow operations. MCRs are untethered from and unencumbered by peripherals, encode programs structurally in situ, and can form frugal, versatile, bona fide lab-on-a-chip with wide-ranging applications in liquid handling and point-of-care diagnostics.
A manipulative activity for exploring effective nuclear charge (Zeff)
Authors: Kasman Jillian , Slouka Taylor , Kiste Alan , Oza Javin
Published: February 2022

High-school and undergraduate college students may often rely on memorization when learning periodic trends, leading to an ineffective understanding of introductory chemistry concepts like atomic radius, ionization energy, and electron affinity. Comprehension of effective nuclear charge (Zeff) is foundational to a complete understanding of periodic trends. Zeff remains an abstract concept for many students, indicating that a manipulative activity for teaching the phenomenon could be a useful way to explain the concept for greater student comprehension. Here we report a hands-on learning activity to target this knowledge gap using magnetic attraction as an analogy for electrostatic attraction within the atom. This approach enables students to explore the phenomenon of effective nuclear charge at a macroscopic level and apply their learning to periodic trends and related concepts. We anticipate that this activity will fill a long-standing hole in the active learning of chemical principles. Importantly, this activity is low-cost and can be assembled using readily accessible materials to allow implementation in most classrooms and virtual learning environments.
A Neural Network Model Informs Total Synthesis of Clovane Sesquiterpenoids
Authors: Newhouse Timothy , Zhang Pengpeng , Eun Jungmin , Elkin Masha , Zhao Yizhou , Cantrell Rachel
Published: February 2022

Efficient syntheses of complex small molecules often involve speculative experimental approaches. The central challenge of such plans is that experimental evaluation of high-risk strategies is resource intensive, as it entails iterative attempts at unsuccessful strategies. Herein, we report a complementary strategy that combines creative human-generated synthetic plans with robust computational prediction of the feasibility of key steps in the proposed synthesis. A neural network model was developed to predict the outcome of a generally disfavored transformation, the 6-endo-trig radical cyclization, and applied to synthetic planning of clovan-2,9-dione, resulting in a 5-step total synthesis that improves on a prior 15-step approach. This work establishes how machine learning can guide multistep syntheses that employ innovative and high-risk human-generated plans.
New inhibitors of p38 mitogen-activated protein kinase: Repurposing of existing drugs with deep learning
Authors: Vermani Aakarsh , Kouznetsova Valentina , Tsigelny Igor
Published: February 2022

P38-alpha (MAPK14) is a protein kinase that is implicated in the pathological mechanisms of BAG3 P209L myofibrillar myopathy, cancers, Alzheimer’s disease and other diseases like rheumatoid arthritis. Inhibition of p38 has shown promise as treatment for these diseases. Traditional drug discovery methods were unable to create both effective and safe small molecule inhibitors, so we used machine learning to elucidate potential p38 blockers from existing FDA-approved drugs. Using available bioactivity data, we determined the best existing p38 inhibitors and applied fingerprint clustering to isolate the compounds with similar structures. Descriptors were calculated for these clustered compounds and the most important of these descriptors were determined through a machine-learning based feature selection algorithm. This data served as the training set for a deep neural network that was fine-tuned to a 92% validation accuracy. The neural network model was applied to a database of FDA-approved drugs, revealing 149 potential p38 inhibitors, whose efficacy were confirmed by docking simulations to be statistically significantly higher than random FDA drugs and slightly higher than known inhibitors. Our study not only reveals potential treatments for p38-mediated diseases but also demonstrates the capability of integrating various machine-learning techniques and computational algorithms to predict novel functions of existing pharmaceuticals.
Quantification of the Helicality of Helical Molecular Orbitals
Authors: Bro-Jørgensen William , Garner Marc H. , Solomon Gemma C.
Published: February 2022

The frontier molecular orbital (MO) topology of linear carbon molecules, such as polyynes, can be visually identified as helices. However, there is no clear way to quantify the helical curvature of these π-MOs and it is thus challenging to quantify correlations between the helical curvature and molecular properties. In this paper, we develop a method that enables us to compute the helical curvature of MOs based on their nodal planes. Using this method, we define a robust way of quantifying the helical nature of MOs (helicality) by their deviation from a perfect helix. We explore several limiting cases, including polyynes, metallacumulenes, cyclic allenes, and spiroconjugated sys- tems where the change in helical curvature is subtle, yet clearly highlighted with this method. For example, we show that strain only has a minor effect on the helicality of the frontier orbitals of cycloallenes and that the MOs of spiroconjugated systems are close to perfect helices around the spiro-carbon. Our work provides a well-defined method for assessing orbital helicality beyond visual inspection of MO isosurfaces, thus paving the way for future studies of how the helicality of π-MOs affects molecular properties.
Bayesian optimization of nanoporous materials
Authors: Deshwal Aryan , Simon Cory , Doppa Janardhan Rao
Published: February 2022

Nanoporous materials (NPMs) could be used to store, capture, and sense many different gases. Given an adsorption task, we often wish to search a library of NPMs for the one with the optimal adsorption property. The high cost of NPM synthesis and gas adsorption measurements, whether these experiments are in the lab or in a simulation, often precludes exhaustive search. We explain, demonstrate, and advocate Bayesian optimization (BO) to actively search for the optimal NPM in a library of NPMs-- and find it using the fewest experiments. The two ingredients of BO are a surrogate model and an acquisition function. The surrogate model is a probabilistic model reflecting our beliefs about the NPM-structure--property relationship based on observations from past experiments. The acquisition function uses the surrogate model to score each NPM according to the utility of picking it for the next experiment. It balances two competing goals: (a) exploitation of our current approximation of the structure-property relationship to pick the highest-performing NPM, and (b) exploration of blind spots in the NPM space to pick an NPM we are uncertain about, to improve our approximation of the structure-property relationship. We demonstrate BO by searching an open database of ~70,000 hypothetical covalent organic frameworks (COFs) for the COF with the highest simulated methane deliverable capacity. BO finds the optimal COF and acquires 30% of the top 100 highest-ranked COFs after evaluating only ~120 COFs. More, BO searches more efficiently than evolutionary and one-shot supervised machine learning approaches.
High-Temperature Decomposition of Diisopropyl Methylphosphonate (DIMP) on Alumina: Mechanistic Predictions from Ab Initio Molecular Dynamics
Authors: Biswas Sohag , Wong Bryan
Published: February 2022

The enhanced degradation of organophosphorous-based chemical warfare agents (CWAs) on metal-oxide surfaces holds immense promise for neutralization efforts; however, the underlying mechanisms in this process remain poorly understood. We utilize large-scale quantum calculations for the first time to probe the high-temperature degradation of diisopropyl methylphosphonate (DIMP), a nerve agent simulant. Our Born-Oppenheimer molecular dynamics (BOMD) calculations show that the gamma-Al2O3 surface shows immense promise for quickly adsorbing and destroying CWAs. We find that the alumina surface quickly adsorbs DIMP at all temperatures, and subsequent decomposition of DIMP proceeds via a propene elimination. Our BOMD calculations are complemented with metadynamics simulations to produce free energy paths, which show that the activation barrier decreases with temperature and DIMP readily decomposes on gamma-Al2O3. Our first-principle BOMD and metadynamics simulations provide crucial diagnostics for sarin decomposition models and mechanistic information for examining CWA decomposition reactions on other candidate metal oxide surfaces.
Amide-to-ester substitution as a strategy for optimizing PROTAC permeability and cellular activity
Authors: Klein Victoria , Bond Adam , Craigon Conner , Lokey R. Scott , Ciulli Alessio
Published: February 2022

Bifunctional PROTAC degraders belong to "beyond Rule of 5" chemical space, and criteria for predicting their drug-like properties are underdeveloped. PROTAC components are often combined via late-stage amide couplings, due to the reliability and robustness of amide bond formation. Amides, however, can give rise to low cellular permeability and poor ADME properties. We hypothesized that a bioisosteric replacement of an amide with a less polar ester could lead to improvements in both physicochemical properties and bioactivity. Using a library of model compounds, bearing either amides or esters at various linker-warhead junctions, we identify parameters for optimal compound lipophilicity and permeability. We next applied these learnings to design a set of novel amide-to-ester substituted, VHL-based BET degraders with increased permeability. Our ester-PROTACs remarkably retained intracellular stability, were overall more potent degraders than their amide counterparts and showed an earlier onset of the hook effect. These enhanced cellular features were found to be driven by greater cell permeability rather than improvements in ternary complex formation. This largely unexplored amide-to-ester substitution therefore provides a simple and practical strategy to enhance PROTAC permeability and degradation performance. Such approach could prove equally beneficial to other classes of beyond Ro5 molecules.
Using wide biological pores to cap and contain the COVID-19 spike protein
Authors: Sampath G
Published: February 2022

Geometric analysis shows that the spike (S) protein in the COVID-19 virus (SARS-Cov-2) can fully or partially enter into the channel of a wide biological pore like perforin (PFN) or streptolysin (SLO) when the latter is anchored in a bilayer lipid membrane. The PFN channel is a β barrel formed from multiple monomers, for example a ~14 nm diameter channel is formed from 22 monomers. Coincidentally the wide canopy of S (which has three identical chains) has an enclosing diameter of ~14 nm. While inside the channel peripheral residues in the canopy may bind with residues on the pore side of the barrel. If there are no adverse cross-reactions this would effectively prevent S from interacting with a target cell. Calculations with data obtained from PDB and other sources show that there are ~12 peripheral residue triples in S within a circle of diameter ~14 nm that can potentially bind with 22 exposed residues in each barrel monomer. The revised Miyazawa-Jernighan matrix is used to calculate the binding energy of canopy-PFN barrel residue pairs. The results show a large number of binding pairs over distances of up to 38 Å into the pore. This geometric view of capture and containment points to the possibility of using biological pores to neutralize SARS-Cov-2 in its many variant forms. Some necessary conditions that must be satisfied for such neutralization to occur are noted. A wide pore (such as PFN or SLO) can also be used in an electrolytic cell to detect the presence of SARS-Cov-2, which would cause a large-sized blockade of the base current (the ionic current in a fully open pore). It can further be used to quantify the virus level in the sample. Solid-state pores, which have several advantages over biological ones, can be used instead; immune rejection is not an issue and there is no need for the spike or the virus to bind to the pore.
A comprehensive investigation of Li-ion conductivity in lithium hydroxy halide antiperovskite solid electrolytes
Authors: Lee Hyeon Jeong , Darminto Brigita , Narayanan Sudarshan , Diaz-Lopez Maria , Xiao Albert , Chart Yvonne , Lee Ji Hoon , Dawson James , Pasta Mauro
Published: February 2022

Lithium hydroxide halide antiperovskite Li-ion conductors are ideal model systems for the systematic investigation of the effect of grain, grain boundary and interfacial resistance on the total Li-ion conductivity in solid-state batteries. Their low melting point (<300°C) empowers the use of melting and solidification to prepare pellets with high relative density without additional sintering steps and with control over grain size. The tunability of the halogen anion site enables control over grain conductivity and interfacial chemistry, with minimal structural perturbation. In this study, we conduct a comprehensive investigation of Li-ion conduction in Li2OHCl(1-x)Brx antiperovskites. We identify Li2OHCl0.9Br0.1 as the composition with the highest Li-ion conductivity of 2.52 E-3 mS/cm at room temperature. We highlight how the thermal expansion coefficient can serve as an indicator for the presence of structural defects hard to probe directly with X-ray techniques and essential in improving bulk Li-ion conduction. The detrimental effect of grain boundaries on ionic conductivity is demonstrated by atomistic calculations and validated experimentally by electrochemical impedance spectroscopy on pellets with controlled grain size. In-situ X-ray photoelectron spectroscopy experiments of Li2OHCl0.9Br0.1 demonstrate its chemical stability in contact with metallic lithium at room temperature. These insights provide design principles to improve Li-ion conductivity of lithium hydroxide halide antiperovskites.
Development of Rofecoxib-Based Fluorescent Probes and Investigations on Their AIE Activity, Solvatochromism, Mechanochromism and COX-2 Targeted Bioimaging
Authors: Xie Lijun , Li Renfu , Zheng Biyun , Xie Zuoxu , Fang Xuefen , Wang Yanqi , Cuny Gregory , Li Zhenli , Lin Bin , Chen Xueyuan , Hu Ming
Published: February 2022

Cyclooxygenase-2 (COX-2) fluorescent probes are promising tools for early cancer diagnosis. Traditionally, COX-2 probes were designed by connecting two parts, a fluorophore and a COX-2 binding unit, via a flexible linker. Herein, a new class of COX-2-specific fluorescent probes have been developed by one-step modification from rofecoxib by an integrative approach to combining the fluorophore and binding units into one. Among them, several new rofecoxib analogues not only retained their COX-2 binding ability but also exhibited attractive fluorescent properties, such as tunable Blue-Red emission, solvatochromism, AIE behavior and mechanochromism. Notably, the emission of 2a16 can be switched between greenish-yellow in the crystalline state to red-orange in the amorphous state by grinding and fuming treatments. Furthermore, the highly fluorescent compound 2a16 (Фf = 0.94 in powder) displayed much stronger fluorescent imaging of COX-2 in HeLa cancer cells overexpressing COX-2 than RAW264.7 normal cells with minimal expressing of COX-2. Most importantly, 2a16 can light up human cancer tissues from adjacent normal tissues with much brighter fluorescence by targeting COX-2 enzyme. These results illustrate the potential of 2a16 as a new red fluorescent probe for human cancer imaging in clinical applications.
Modelling the structure and interactions of intrinsically disordered peptides with multiple-replica, metadynamics-based sampling methods and force-field combinations
Authors: Li Lunna , Casalini Tommaso , Arosio Paolo , Salvalaglio Matteo
Published: February 2022

Intrinsically disordered proteins (IDPs) play a key role in many biological processes, including the formation of biomolecular condensates within cells. A detailed characterization of their configurational ensemble and structure-function paradigm is crucial for understanding their biological activity and for exploiting them as building blocks in material sciences. In this work, we incorporate bias-exchange metadynamics and parallel-tempering well-tempered metadynamics with CHARMM36m and CHARMM22* to explore the structural and thermodynamic characteristics of a short archetypal disordered sequence derived from a DEAD-box protein. The conformational landscapes emerging from our simulations are largely congruent across methods and forcefields. Nevertheless, differences in fine details emerge from varying forcefield/sampling method combinations. For this protein, our analysis identifies features that help to explain the low propensity of this sequence to undergo self-association in vitro, which can be common to all force-field/sampling method combinations. Overall, our work demonstrates the importance of using multiple force-field/enhanced sampling method combinations for accurate structural and thermodynamic information in the study of general disordered proteins.
Effects of molecular design parameters on plasticizer performance in poly(vinyl chloride): a comprehensive molecular simulation study
Authors: Li Dongyang , Panchal Kushal , Vasudevan Naveen Kumar , Mafi Roozbeh , Xi Li
Published: February 2022

Using all-atom molecular simulation, a wide range of plasticizers for poly(vinyl chlorid) (PVC), including ortho- and tere-phthalates, trimellitates, citrates, and various aliphatic dicarboxylates, are systematically studied. We focus on the effects of plasticizer molecular structure on its performance, as measured by performance metrics including its thermodynamic compatibility with PVC, effectiveness of reducing the material's Young's modulus, and migration rate in the PVC matrix. The wide variety of plasticizer types covered in the study allows us to investigate the effects of seven molecular design parameters. Experimental findings about the effects of plasticizer molecular design are also compiled from various literature sources and reviewed. Comparison with experiments establishes the reliability of our simulation predictions. The study aims to provide a comprehensive set of guidelines for the selection and design of high-performance plasticizers at the molecular level. Molecular mechanisms for how each design parameter influences plasticizer performance metrics are also discussed. Moreover, we report a nontrivial dependence of plasticizer migration rate on temperature, which reconciles seemingly conflicting experimental reports on the migration tendency of different plasticizers.
Gelation and Yielding Behavior of Polymer-Nanoparticle Hydrogels
Authors: Grosskopf Abigail , Saouaf Olivia , Lopez Hernandez Hector , Appel Eric
Published: February 2022

Polymer-Nanoparticle hydrogels are a unique class of self-assembled, shear-thinning, yield-stress fluids which have demonstrated potential utility in many impactful applications. Here we present a thorough analysis of the gelation and yielding behavior of these materials with respect to the polymer and nanoparticle component stoichiometry. Through comprehensive rheological and diffusion studies, we reveal insights into the structural dynamics of the polymer nanoparticle network which identify that stoichiometry plays a key role in gelation and yielding, ultimately enabling the development of hydrogel formulations with unique shear-thinning and yield-stress behaviors. Access to these materials opens new doors for interest- ing applications in a variety of fields including tissue engineering, drug delivery, and controlled solution viscosity.
Efficient molecular emitter
Authors: Nishijima Yoshiaki , Morimoto Shinya , Balcytis Armandas , Hashizume Tomoki , Matsubara Ryuske , Kubono Atsushi , To Naoki , Meguya Ryu , Morikawa Junko , Juodkazis Saulius
Published: February 2022

We demonstrate extraordinarily spectrally selective narrowband mid-infrared radiation absorbance and thermal emittance with resonant peak FWHM ~ 124 nm at l = 5.73 mm, corresponding to a Q-factor of ~ 92:3. This was achieved by harnessing mode coupling between a plasmonic metal-insulator-metal (MIM) metasurface and molecular vibrational mode resonances, with coupling constants ranging from h ~ 3.9% to 6.6%. In addition, thermal radiation emissivity is in close accordance to the metamaterial absorbance spectrum, as described by Kirchhoff’s law of thermal radiation, and furthermore, emission was not angle dependent, unlike that exhibited by grating-based emitters. The experimentally investigated MIM structures remained stable up to a 250C heating temperature. MIM metamatrials with strong and spectrally tailored vibrational coupling behaviors represent a new paradigm in photo-thermal energy conversion. The experimentally observed pronounced resonant coupling behaviour was well described by finite-difference time-domain simulations of the plasmonic structure, where molecular vibration contributions were modeled using the Lorenz oscillator approximation.
A High Temperature Lithium Metal-Air Primary Battery Based on Solid Electrolytes and Molten Salt
Authors: McConohy Geoff , Kim Dokyum , Lee Joon-Hyung
Published: February 2022

Developing metal-oxygen batteries with a high specific energy (gravimetric energy density) is a significant challenge due to the highly reactive nature of active materials used as the negative electrode, such as Li, Al, or Mg. In addition, the metal-oxide discharge products are highly stable and passivating to many oxygen-reduction catalysts. Here we present an alterative way of utilizing the high specific energy lithium metal-oxygen reaction by combining both cation and anion transport in a single device, operated at 550°C. To do this, we combined a Li6.4La2.8Al0.2Zr1.4Ta0.6O12 (LLZO) cation solid electrolyte, yttria stabilized zirconia oxygen ion conductor, and KCl-LiCl eutectic salt as an interlayer between the two solid electrolytes. We find that the constructed battery shows an open circuit voltage consistent with the thermodynamic value predicted for the Li-O2 reaction at 550°C. Furthermore, we found that the cell could be discharged at 20 mA, showing no significant passivation of the reaction until all of the lithium metal was depleted. However, we were unable to re-deposit the lithium metal electrochemically, possibly due to parasitic reduction of the LLZO tube upon charging. This work presents a unique device which may inspire other high temperature electrochemical devices in the field.
Can prebiotic reaction systems survive in the wild? An interference chemistry approach
Authors: Walton Craig , Rimmer Paul B. , Shorttle Oliver
Published: February 2022

The origin of life occurred by a series of prebiotic reaction pathways (collectively a system) hosted in one or more geochemical environments (together forming an origin of life scenario). State-of-the-art prebiotic chemistry links together reactions to create systems, intended to be more representative of the diverse chemical pathways that may have proceeded on early Earth. By practical necessity, prebiotic systems chemistry must be investigated under simplified conditions in comparison to likely natural environments. The mismatch in complexity between lab and environment poses a challenge: how to build systems chemistry that is robust not only in the idealised conditions of a lab, but also under natural levels of environmental stress? Here, we propose and formalise a conceptual framework for such work: interference chemistry. We define interference chemistry as the interaction between prebiotic systems chemistry and the environmental scenarios proposed to host it. Natural environments in which prebiotic chemistry could have occurred are messy, containing many spectator ions, mineral phases, and spatially and temporally variable physical processes, e.g., wet/dry cycles. Each of these environmental variables may interfere either constructively or destructively with prebiotic pathways, respectively aiding or inhibiting their efficacy. Exploring interference chemistry for a reaction system will point towards favoured or disfavoured regions of environmental parameter space. To do so, innovation is needed in both the investigation of early planetary environmental conditions, and the continued incorporation of these constraints into experimental systems chemistry. We argue that interference chemistry provides a compelling way to assess combinations of system and environment, leading the way to increasingly prebiotically plausible scenarios for the origin of life on Earth.
Rheological characterization and physical-stability of gamma irradiated anthocyanin-loaded albumin nanoparticles
Authors: Candido Sofia Leila , Siri Macarena , Achilli Estefania , Moreno Juan Cruz , Lillo Cristian , Risso Patricia Hilda , Bodycomb Jeffrey , Martinez Luis , Montanari Jorge , Alvira Fernando , Alonso Silvia del Valle
Published: February 2022

The active blueberry compounds called anthocyanins have poor oxidation stability, but, if encapsulated by protein nanoparticles, they can be protected due to the slowing down of the oxidation process. This work describes the advantages of using a γ-irradiated bovine serum albumin nanoparticle bound to anthocyanins. The interaction was characterized biophysically, mainly by rheology. By computational calculation and simulation based on model nanoparticles, we estimated the number of molecules forming to the albumin nanoparticles, which allowed us to infer a ratio of anthocyanin/nanoparticles. Measurements by UV-VIS spectroscopy, FT-IR spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), ζ potential, electron transmission microscopy and rheology at room (25 °C), and physiological (37 °C) temperatures were performed. The spectroscopy measurements allowed identifying additional hydrophobic sites created during the irradiation process of the nanoparticle. Based on the rheological studies, it was observed that for all the temperatures selected, the BSA-NP trend is a Newtonian flow behavior type, and there is a direct correlation between dynamic viscosity and temperature values. Furthermore, when anthocyanins are added, the system increases its resistance to the flow reflected in the morphological changes observed by TEM, confirming the relationship between viscosity values and aggregate formation
High-Resolution Ion-Flux Imaging of Proton Transport Through Graphene|Nafion Membranes
Authors: Bentley Cameron , Kang Minkyung , Bukola Saheed , Creager Stephen , Unwin Patrick
Published: February 2022

In 2014, it was reported that protons can traverse between aqueous phases separated by nominally pristine monolayer graphene and hexagonal boron nitride (h-BN) films (membranes) under ambient conditions. This “intrinsic proton conductivity” of the one-atom-thick crystals, with proposed through-plane conduction, challenged the notion that graphene is impermeable to atoms, ions and molecules. More recent evidence points to a defect-facilitated transport mechanism, analogous to transport through conventional ion-selective membranes based on graphene and h-BN. To clarify the nature of proton transmission through graphene, local ion-flux imaging is performed herein on graphene|Nafion membranes using an “electrochemical ion (proton) pump cell” mode of scanning electrochemical cell microscopy (SECCM). Targeting regions that are free from visible macroscopic defects (e.g., cracks, holes etc.), and assessing hundreds to thousands of different sites across the graphene surfaces in a typical experiment, most of the graphene|Nafion membrane is impermeable to proton transport, with transmission typically occurring at only ≈20 – 60 localized sites across a ≈0.003 mm2 area of membrane (>5000 measurements, total). When localized proton transport occurs, it can be a highly dynamic process, with new transmission sites “opening” and a small number of sites “closing” under an applied electric field, on the seconds timescale. Applying a simple equivalent circuit model of ion-transport through a cylindrical nanopore, the local transmission sites are estimated to possess dimensions (radii) on the (sub)nanometer-scale, implying that rare atomic defects are responsible for proton conductance through monolayer graphene. Overall, this work reinforces SECCM as a premier tool for the structure−property mapping of microscopically complex (electro)materials, with the local ion-flux mapping configuration introduced herein being widely applicable for functional membrane characterization and beyond, e.g., for diagnosing failure mechanisms in protective surface coatings.
Polymorphism of Garnet Solid Electrolytes and Its Implications on Grain Level Chemo-Mechanics
Authors: Dixit Marm , Vishugopi Bairav , Zaman Wahid , Kenesei Peter , Park Jun-Sang , Almer Jon , Mukherjee Partha , Hatzell Kelsey
Published: February 2022

Understanding and mitigating �filament formation, short-circuit, and solid electrolyte fracture is a key necessity towards achieving practical SSBs. Herein, we employ a coupled far-fi�eld high energy diffraction microscopy -tomography approach for assessing chemo-mechanical behavior for dense, polycrystalline garnet (Li7La3Zr2O12, LLZO) solid electrolytes with grain-level resolution. Tracking the stress response for individual grains through in situ testing, failure onset and short-circuit mechanism is confirmed to be a stochastic, isolated process governed by the presence of local phase heterogenity. Coupling high energy X-ray diffraction and far �eld high energy diffraction microscopy measurements, these local regions are proposed to be regions with the presence of a cubic polymorph of LLZO arising potentially from local dopant concentration variation. Interplay of mechanics and transport is evaluated and coupled tomography and FF-HEDM dataset is employed to illustrate the degradation of polycrystalline garnet solid electrolyte. The results showcase pathways for processing high performing SSBs.
Binding Free Energy of Protein/Ligand Complexes Calculated using Dissociation Parallel Cascade Selection Molecular Dynamics and Markov State Model
Authors: Hata Hiroaki , Tran Duy , Marzouk Mohamed , Kitao Akio
Published: February 2022

We recently proposed a computational procedure to simulate the dissociation of protein/ligand complexes using the dissociation Parallel Cascade Selection Molecular Dynamics simulation (dPaCS-MD) method and to analyze the generated trajectories using the Markov state model (MSM). This procedure, called dPaCS-MD/MSM, enables calculation of the dissociation free energy profile and the standard binding free energy. To examine whether this method can reproduce experimentally determined binding free energies for a variety of systems, we used it to investigate the dissociation of three protein/ligand complexes: trypsin/benzamine, FKBP/FK506, and adenosine A2A receptor/T4E. First, dPaCS-MD generated multiple dissociation pathways within a reasonable computational time for all the complexes, although the complexes differed significantly in the size of the molecules and in intermolecular interactions. Subsequent MSM analyses produced free energy profiles for the dissociations, which provided insights into how each ligand dissociates from the protein. The standard binding free energies obtained by dPaCS-MD/MSM are in good agreement with experimental values for all the complexes. We conclude that dPaCS-MD/MSM can accurately calculate the binding free energies of these complexes.
Controlled Experiments and Optimized Theory of Absorption Spectra of Li Metal and Salts
Authors: Roychoudhury Subhayan , Zhuo Zengqing , Qiao Ruimin , Wan Liwen , Liang Yufeng , Pan Feng , Chuang Yi-de , Prendergast David , Yang Wanli
Published: February 2022

Investigations of Li metal and ionic compounds through experimental and theoretical spectroscopy has been of tremendous interest due to their prospective applications in Li-metal and Li-ion batteries. Li K-edge soft X-ray absorption spectroscopy (sXAS) provides the most direct spectroscopic characterization; unfortunately, Li-K sXAS of Li metal has been extremely challenging, as evidenced by many controversial reports. Here, through controlled and ultra-high energy resolution experiments of two kinds of in-situ prepared samples, we report the intrinsic Li-K sXAS of Li-metal, which displays a prominent leading peak that has never been revealed before, and a series of Li salts. Furthermore, theoretical simulations show that the Li-K sXAS is strongly affected by the response of the valence electrons to the core-hole. We consider a number of relevant parameters such as temperature, resolution, total and single-particle energies, and especially, contributions from transitions which are forbidden in the single-particle treatment.
Urazole as an unorthodox functional group for fabrication of anionic hydrogels and ion-exchange materials
Authors: Hanay Saltuk , Fallah Ali , Senturk Efsun , Afghah Ferdows , Yilmaz Hulya , Culha Mustafa , Koc Bahattin
Published: February 2022

In this study, highly ionazable protons (pKa 5-6) of urazole were exploited to obtain an anionic hydrogel in two simple and scalable steps. Commercially available multiisocyanate, poly(hexamethylene)diisocyanate, was used to prepare urazole containing gel. Urazole formation was confirmed by FT-IR and 1H-NMR spectroscopy. The hydrogel were characterized by microscopy imaging, spectroscopic and gravimetric analysis. Mechanical analysis and cell viability test were performed for its initial biocompatibility evaluation. The prepared hydrogel is a highly porous hydrogel with a Young’s modulus of 0.91MPa, has swelling ratio of 87% and capable of exchanging ions in a medium. In this report, we demonstrated a strategy to overcome synthetic challenge of incorporating urazole into a material via precursor path rather than attempting to embeding urazole groups directly.
Catalytic Enantioselective Nucleophilic Desymmetrisation of Phosphonate Esters
Authors: Formica Michele , Rogova Tatiana , Shi Heyao , Sahara Naoto , Farley Alistair J. M. , Christensen Kirsten E. , Duarte Fernanda , Dixon Darren J.
Published: February 2022

Compounds containing one or more stereogenic phosphorous atoms in the P(V) oxidation state are important to chemistry, biology and medicine. These include marketed antiviral drugs such as Tenofovir alafenamide and Remdesivir, an effective treatment for Ebola which has also recently been approved for use against SARS-CoV-2 in the US. Existing approaches for the stereoselective synthesis of P-stereogenic centers, while elegant, remain mostly diastereoselective, with catalytic enantioselective approaches remaining limited in application. Accordingly, conceptually novel, broad-scope, catalytic strategies for the efficient stereoselective synthesis of diverse stereogenic P(V) containing compounds remain essential. To this end, we describe a novel enantioselective two-stage strategy, exploiting the first catalytic and highly enantioselective desymmetrisation of phosphonate esters. Pivoting on the stereocontrolled, sequential nucleophilic substitution of enantiotopic leaving groups from readily accessible pro-chiral P(V) precursors, a bifunctional iminophosphorane (BIMP) superbase catalyst was found to be essential in delivering reactive desymmetrised intermediates capable of downstream enantiospecific substitution. This uniquely modular, catalytic platform allows broad-scope, stereoselective access to a diverse library of chiral P(V) compounds including those with O, N and S-linkages.
Expedient Single Step Access to Strained Tricyclic Ketals
Authors: Jonnalagadda Sravan , Huwaimel Bader , Jonnalagadda Shirisha , Garrison Jered , Trippier Paul C.
Published: February 2022

The synthesis of cyclopropyl methyl ketones and highly strained fused substituted dihydrobenzopyran cyclopropyl lactones derived from coumarin carboxylates and chloroacetone in the presence of potassium carbonate is reported. One step synthetic access to the previously unknown dihydrobenzopyran cyclopropyl tricyclic ketals is achieved with wide substrate scope. Substituted coumarin carboxylates, phenylamides or a quinolin-2(1H)-one possessing alkyl electron donating (methyl, t-butyl) and electron withdrawing groups (F, Cl, Br, NO2) in the 4 or 6 positions formed the highly strained dihydrobenzopyran cyclopropyl tricyclic ketals in moderate yield alongside the expected coumarin carboxylate. Saturation or substitution at the 5-position or 6-OMe afforded no tricyclic ketal compound but solely coumarin carboxylates. The formation of both structures in selected derivatives was confirmed by X-ray crystallography. A plausible mechanism is proposed for the formation of the fused lactone; via intramolecular rearrangement of cis cyclopropyl methyl ketones with phenolic acetate via the formation of a hemiacetal.