bluuebunny/crossref_metadata_2025 huggingface dataset:
Powerful Statistical Tests for Ordered Data
Authors: Köfinger Jürgen , Hummer Gerhard
Published: February 2022

The inference of models from one-dimensional ordered data subject to noise is a fundamental and ubiquitous task in the physical and life sciences. A prototypical example is the analysis of small- and wide-angle solution scattering experiments using x-rays (SAXS/WAXS) or neutrons (SANS). In such cases, it is common practice to check the quality of a fit by using Pearson's chi-square test, which ignores the order of the data. We usually plot the residuals and check visually for systematic deviations without quantifying them. To quantify these deviations, we developed test statistics based on the distributions of the lengths of the runs of the signs of the residuals. Specifically, we use the probability of run-length distributions, for which we provide analytical expressions, to rank them and to calculate their P-values. We introduce the Shannon information distribution as an elegant and versatile tool for calculating P-values. We find that these distributions follow shifted gamma distributions, such that they are summarized by three parameters only. We show for a set of six models that our test statistics are more powerful than Pearson's chi-square test and common sign-based tests. We provide an open source Python 3 implementation of our tests free of charge at https://github.com/bio-phys/hplusminus.
Fast Equilibration of Water between Buried Sites and Bulk by MD with Parallel Monte Carlo Water Moves on GPUs
Authors: Ben-Shalom Ido , Lin Charles , Radak Brian , Sherman Woody , Gilson Michael
Published: February 2022

Molecular dynamics (MD) simulations of proteins are commonly used to sample from the Boltzmann distribution of conformational states, with wide-ranging applications spanning chemistry, biophysics, and drug discovery. However, MD can be inefficient at equilibrating water occupancy for buried cavities in proteins that are inaccessible to the surrounding solvent. Indeed, the time needed for water molecules to equilibrate between bulk solvent and the binding site can be well beyond what is practical with standard MD, which typically ranges to hundreds of nanoseconds to low microseconds. We recently introduced a hybrid Monte Carlo/MD (MC/MD) method, which speeds up the equilibration of water between buried cavities and the surrounding solvent, while sampling from the thermodynamically correct distribution of states. While the initial implementation of the MC functionality led to considerable slowing of the overall simulations, here we address this problem with a parallel MC algorithm implemented on graphical processing units (GPUs). This results in speedups of 10-fold to 1000-fold over the original MC/MD algorithm, depending on the system and simulation parameters. The present method is available for use in the AMBER simulation software.
Towards automation of operando experiments: A case study in contactless conductivity measurements
Authors: Kraus Peter , Wolf Elisabeth , Prinz Charlotte , Bellini Giulia , Trunschke Annette , Schlögl Robert
Published: February 2022

Automation of experiments is a key component on the path of digitalisation in catalysis and related sciences. Here we present the lessons learned and caveats avoided during the automation of our contactless conductivity measurement set-up, capable of operando measurement of catalytic samples. We briefly discuss the motivation behind the work, the technical groundwork required, and the philosophy guiding our design. The main body of this work is dedicated to the detailing of the implementation of the automation, data structures, as well as the modular data processing pipeline. The open-source toolset developed as part of this work allows us to carry out unattended and reproducible experiments, as well as post-process data according to current best practice. This process is illustrated by implementing two routine sample protocols, one of which was included in the Handbook of Catalysis, providing several case studies showing the benefits of such automation, including increased throughput and higher data quality. The datasets included as part of this work contain catalytic and operando conductivity data, and are self-consistent, annotated with metadata, and are available on a public repository in a machine-readable form. We hope the datasets as well as the tools and workflows developed as part of this work will be an useful guide on the path towards automation and digital catalysis.
Targeted Fluorogenic Cyanine Carbamates Enable In Vivo Analysis of Antibody-Drug Conjugate Linker Chemistry
Authors: Usama Syed , Marker Sierra , Caldwell Donald , Patel Nimit , Feng Yang , Kalen Joseph , Schnermann Martin , St Croix Brad
Published: February 2022

Antibody-drug conjugates (ADCs) are a rapidly emerging therapeutic platform. The chemical linker between the antibody and the drug payload plays an essential role in the efficacy and tolerability of these agents. New methods that quantitively assess cleavage efficiency in complex tissue settings could provide valuable insights into the ADC design process. Here we report the development of a near-infrared (NIR) optical imaging approach that measures the site and extent of linker cleavage in mouse models. This approach is enabled by a superior variant of our recently devised cyanine carbamate (CyBam) platform. We identify a novel tertiary amine-containing norcyanine, the product of CyBam cleavage, that exhibits dramatically in-creased cellular signal due to improved cellular permeability and lysosomal accumulation. The resulting cyanine lysosome-targeting carbamates (CyLBams) are ~50X brighter in cells, and we find this strategy is essential for high-contrast in vivo targeted imaging. Finally, we compare a panel of several common ADC linkers across two antibodies and tumor models. These studies indicate that cathepsin-cleavable linkers provide dramatically higher tumor activation relative to hindered or non-hindered disulfides – an observation that is only apparent with in vivo imaging. This strategy enables quantitative com-parisons of cleavable linker chemistries in complex tissue settings with implications across the drug delivery landscape.
Short and Long-Range Electron Transfer Compete to Determine Free-Charge Yield in Organic Semiconductors
Authors: Carr Joshua M. , Allen Taylor G. , Larson Bryon W. , Davydenko Iryna G. , Dasari Raghunath R. , Barlow Stephen , Marder Seth R. , Reid Obadiah G. , 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.
Identification of photocrosslinking peptide ligands by mRNA display
Authors: Wu Yuteng , Bertran M. Teresa , Joshi Dhira , Maslen Sarah , Hurd Catherine , Walport Louise
Published: February 2022

Photoaffinity labelling is a promising method for studying protein-ligand interactions. However, obtaining a specific crosslinker can require significant optimisation. We report a novel mRNA display strategy, photocrosslinking-RaPID (XL-RaPID), and exploit its ability to accelerate the discovery of cyclic peptides that photocrosslink to a target of interest. As a proof of concept, we generated a benzophenone-containing library and applied XL-RaPID screening against a model target, the second bromodomain of BRD3. This crosslinking screening gave two optimal candidates that selectively labelled the target protein in cell lysate. Overall, this work introduces direct photocrosslinking screening as a versatile technique for identifying covalent peptide ligands from mRNA display libraries incorporating reactive warheads.
Identifying sources of D-serine in Caenorhabditis elegans and their impact on behavior
Authors: Qiu Tian A. , Andersen Harvey M. , Larson Nissa J. , Schroeder Nathan E. , Sweedler Jonathan V.
Published: February 2022

Free D-serine (D-Ser) is a potent co-agonist of the N-methyl-D-aspartate receptor (NMDAR) in glutamate neurotransmission and regulates NMDAR functions in the nervous system. Serine racemases convert L-serine to D-Ser and are believed to be the major source of D-Ser in animals. In Caenorhabditis elegans, a knockout of the serine racemase serr-1 results in behavioral changes, but the level of D-Ser is unaffected. By growing C. elegans on peptone-free nematode growth medium (PF-NGM), we delineated the sources of D-Ser, both exogenous from peptone in culturing media and endogenous from the serine racemase serr-1, and a potential serine/aspartate racemase candidate, Y51H7C.9, identified by sequence similarity network analysis. We also discovered a new serine dehydratase (aka serine ammonia-lyase), K01C8.1, in C. elegans. We identified the serr-1 knockout and PF-NGM culturing conditions as two independent factors that impact C. elegans locomotion behavior after off-food, both short-term and long-term, and no interactions were found between the two factors.
Factors Controlling Oxophilicity and Carbophilicity of Transition Metals and Main Group Metals
Authors: Kayode Gbolade O. , Montemore Matthew M.
Published: February 2022

The strength of interaction between a metal and oxygen and/or carbon is a crucial factor for catalytic performance, materials stability, and other important applications. While these are fundamental properties in materials science, there is no general understanding of what makes a metal oxophilic or carbophilic, especially for main group metals. In this work, we elucidate the factors that control how oxophilic or carbophilic a metal is by creating a predictive model and applying it to a variety of data sets for transition metals and main group metals, including DFT-calculated adsorption energies and experimental formation energies. Our model is easily interpretable and accurately describes oxophilic and carbophilic trends across different regions of the periodic table. This model captures the ionic contribution to bonding, the adsorbate-sp contribution to bonding, and the adsorbate-d contribution to bonding by using the reduction potential, matrix coupling elements, band centers, and band filling. For transition metals, the adsorbate-surface d coupling is the major factor that determines oxophilicity relative to carbophilicity. For metals that do not contain d electrons either in their core or valence shell (Li, Be, Na, Mg, Al, K, and Ca), the reduction potential and the adsorbate-surface s coupling are the major factors. As a simple application, we demonstrate the utility of oxophilicity and carbophilicity in rapidly screening metal dopants for improved selectivity for ethylene epoxidation on silver-based catalysts. Using our model, we established a direct relationship between the electronic properties of the metal dopants and their selectivity for ethylene epoxidation. The results suggest that transition metals with high adsorbate-surface d coupling and main group metals with low adsorbate-surface s coupling are good silver-dopant candidates for this reaction. Overall, the improved linkage between a metal’s electronic structure and its interaction with carbon or oxygen will be broadly useful in design of functional materials for a variety of applications.
Unveiling the role of chemical and electronic structure in plasmon-assisted homolysis of alkoxyamines
Authors: Votkina Darya , Petunin Pavel , Miliutina Elena , Trelin Andrii , Lyutakov Oleksiy , Svorcik Vaclav , Audran Gérard , Havot Jeffrey , Valiev Rashid , Valiulina Lenara , Joly Jean-Patrick , Guselnikova Olga , Marque Sylvain , Postnikov Pavel
Published: February 2022

The excitation of localized plasmon resonance on nanoparticles followed by the interaction with organic molecules leads to new pathways of chemical reactions. Although a number of physical factors (temperature, illumination regime, type of nanoparticles, etc.) are affecting this process, the role of the chemical factors is underestimated. Challenging this assumption, here we studied the kinetic of plasmon-induced homolysis of five alkoxyamines (AAs) with different chemical and electronic structures using electron paramagnetic resonance (EPR). The kinetic data revealed the dependence of plasmonic homolysis rate constant (kd) with the HOMO energy of AAs, which cannot be described by the kinetic parameters derived from thermal homolysis experiments. The observed trend in kd allowed to suggest the key role of intramolecular excitation mechanism supported by the TDFDT calculations, additional spectroscopic characterization, and control experiments. Our work sheds light on the role of the electronic structure of organic molecules in plasmonic chemistry.
Special feature of COVID-19 in FMODB: Fragment molecular orbital calculations and interaction energy analysis of SARS-CoV-2 related proteins
Authors: Fukuzawa Kaori , Kato Koichiro , Watanabe Chiduru , Kawashima Yusuke , Handa Yuma , Yamamoto Ami , Watanabe Kazuki , Ohyama Tatsuya , Kamisaka Kikuko , Takaya Daisuke , Honma Teruki
Published: February 2022

SARS-CoV-2 is the causative agent of coronavirus, globally known as COVID-19. There are ongoing researches to develop effective therapeutics and vaccines against COVID-19 using various methods. We currently conduct research based on the fragment molecular orbital (FMO) method for calculating the electronic structure of protein complexes and analyzing their quantitative molecular interactions. This enables us to extensively analyze the molecular interactions in residues or functional group units acting inside protein complexes. Such precise interaction data are available in the FMO database (FMODB). We have performed several FMO calculations on the structures of SARS-CoV-2 related proteins registered in the protein data bank and published the results of 681 structures, including three structural proteins and eleven nonstructural proteins, on the COVID-19 special page.These data not only aid the interpretation of experimentally determined structures but also the understanding of protein functions, which is useful for rational drug design for COVID-19.
Donor/π-Bridge Manipulation for Constructing a Stable NIR-II Aggregation-Induced Emission Luminogen with Balanced Phototheranostic Performance
Authors: Yan Dingyuan , Xie Wei , Zhang Jianyu , Wang Lei , Wang Dong , Tang Ben Zhong
Published: February 2022

Taking advantages of the versatile functionality and tunable energy dissipation, aggregation-induced emission lumino-gens (AIEgens) emerge as a rising star to afford multimodal theranostics platform. Nevertheless, the construction of AIE-active phototheranostic agent in the second near-infrared window (NIR-II, 1000−1700 nm) which allows superior resolu-tion and minimized photodamage is still a formidably challenging suffering from the limited candidate of building blocks. Herein, benzo[c]thiophene is innovatively utilized as electron-rich and bulky donor (D)/π-bridge neighboring to the elec-tron acceptor (A), which can enlarge the conjugation length and distort the backbone. By precise D/π-bridge engineering, highly stable NIR-II AIEgen DPBTA-DPTQ NPs with acceptable NIR-II fluorescence quantum yield and excellent photo-thermal conversion efficiency of 40.6% under 808 nm laser irradiation are successfully obtained. Compared with the re-ported NIR-II AIEgens, the exactly spatial conformation of DPBTA-DPTQ is determined for the first time by associating X-ray single crystal diffraction and theoretical simulations, elaborately revealing the relationship between structure and AIE effect/photothermal performance. Extensive in vitro tests demonstrate that DPBTA-DPTQ NPs with good biocom-patibility show efficient photothermal therapeutic effects. Furthermore, their prominent performance on fluorescence-photoacoustic-photothermal trimodal imaging-guided photothermal eradication of tumor is verified in HepG2 and B16-F10 tumor-xenografted mice, demonstrating distinguished cancer theranostic capability.
Total Liquid-phase Sythesis, Head-to-tail Cyclization and Synergistic Self-cleavage of Peptide on Small-molecular Supports
Authors: Qin Chuanguang , Li Haidi , Li Junyou , Chao Jie , Zhang Zixin
Published: February 2022

To achieve the synthesis of head-to-tail cyclic peptides via the liquid-phase on-support cyclization and synergistic self-cleavage strategy, 4,4’-bis(diphenylphosphinyloxyl) diphenyl ketoxime (BDKO) and 4-diphenyl phospholoxy benzyl alcohol (DPBA) were designed and prepared as small-molecular supports for greener peptide synthesis. During liquid-phase peptide synthesis on BDKO (or DPBA) support for peptide chain extension by Boc protocol, the last amino acid at the N-terminus of the peptide chain ends with a Fmoc protected amino acid. With the removal of the Fmoc group, head-to-tail cyclization and self-cleavage of the peptide chain synchronously occurred on BDKO (or DPBA) support to release the target cyclic peptide and the original support itself. They can be easily separated and purified, and the support can be recycled for reusing directly. The total synthesis of naturally occurring cyclic peptides such as Mortiamide A-E, Gramicidin S and cyclo(Phe-Pro) on BDKO (or DPBA) support in a resin-free manner was successfully demonstrated.
Local and Regional-Scale Racial and Ethnic Disparities in Air Pollution Determined by Long-Term Mobile Monitoring
Authors: Chambliss Sarah , Pinon Carlos , Messier Kyle , LaFranchi Brian , Upperman Crystal , Lunden Melissa , Robinson Allen , Marshall Julian D. , Apte Joshua
Published: February 2022

Disparity in air pollution exposure arises from variation at multiple spatial scales: along urban-to-rural gradients, between individual cities within a metropolitan region, within individual neighborhoods, and between city blocks. Here, we improve on existing capabilities to systematically compare urban variation at several scales, from hyperlocal (<100m) to regional (>10km), and to assess consequences for outdoor air pollution experienced by residents of different races and ethnicities, by creating a set of uniquely extensive and high-resolution observations of spatially-variable pollutants: NO, NO2, black carbon (BC), and ultrafine particles (UFP). We conducted full-coverage monitoring of a wide sample of urban and suburban neighborhoods (93 km2, 450,000 residents) in four counties of the San Francisco Bay Area using Google Street View cars equipped with the Aclima mobile platform. Comparing scales of variation across the sampled population, greater differences arise from localized pollution gradients for BC and NO (pollutants dominated by primary sources) and from regional gradients for UFP and NO2(pollutants dominated by secondary contributions). Median concentrations of UFP, NO, and NO2 are, for Hispanic and Black populations, 8%-30% higher than the population average; for white populations, average exposures to these pollutants are 9%-14% lower than the population average. Systematic racial/ethnic disparities are influenced by regional concentration gradients due to sharp contrasts in demographic composition among cities and urban districts, while within-group extremes arise from local peaks. Our results illustrate how detailed and extensive fine-scale pollution observations can add new insights about differences and disparities in air pollution exposures at the population scale.
Mechanism for acetate formation in CO(2) reduction on Cu: Selectivity trends with pH and nanostructuring derive from mass transport
Authors: Heenen Hendrik H. , Kastlunger Georg , Shin Haeun , Overa Sean , Gauthier Joseph A. , Jiao Feng , Chan Karen
Published: February 2022

Nanostructured Cu catalysts have increased the selectivities and geometric activities for high value C-C coupled (C2) products in the electrochemical CO(2) reduction reaction (CO(2)RR). The selectivity among the high-value C2 products is also altered, where for instance the yield of acetate increases with alkalinity and is dependent on the catalyst morphology. The reaction mechanisms behind the selectivity towards acetate vs. other C2 products remain controversial. In this work, we elucidate the reaction mechanism behind selectivity towards acetate by using ab-initio simulations, a coupled kinetic-transport model, and loading experiments. We find that trends in acetate selectivity can be rationalized from variations in electrolyte pH and the local mass transport properties of the catalyst and not from changes of Cu’s intrinsic activity. The selectivity mechanism originates in the transport of ketene, a stable (closed shell) intermediate, away from the catalyst surface into solution where it reacts to acetate. While such a mechanism has not yet been discussed in CO(2)RR, variants of it may explain similar selectivity fluctuations observed for other stable intermediates like CO and acetaldehyde. Our proposed mechanism suggests acetate selectivity to increase with increasing pH, decreasing catalyst roughness and to significantly vary with applied potential.
Application of Virtual Reality in Chemical Education Using Intermolecular Force Display System HaptiChem
Authors: Satoh Hiroko , Narita Akira , Aoki Atsushi , Akahane Katsuhito , Sato Makoto
Published: February 2022

Virtual reality technology has been recently more intensively applied in chemistry. HaptiChem, which was developed in 2006, is one of the systems appeared in the early stage of this field. It is an intermolecular force display system, which makes it possible to touch and move molecules as feeling intermolecular force in a three-dimensional virtual space by using a haptic device. We introduced HaptiChem in chemical education. We held a high school chemistry class with 43 students entitled “Several Forces between Molecules” as being open to the media. The students learned about intermolecular force from a lecture together with experiences of the force using HaptiChem. They asked more questions about intermolecular force during the class than usual. Their answers to the questionnaires after the class indicated that the haptic system promoted curiosity and enhanced learning. The students could learn more effectively by combining with the active feeling with HaptiChem. The high-school teachers evaluated that such a system can more efficiently encourage students to learn and remember things by stimulating their sense of touch. The observations also suggested that a haptic device made it easier to establish three-dimensional perception, which is difficult only with 2D-display. This pilot experiment was performed on 15th March 2007. It was the first attempt at using it in the field of chemical education. The observation was done fourteen years ago. However, since the effectiveness of haptic device in chemical education has not been changed and the interests of the applications have been increased, we decided to report the data we observed, which should be still worth disclosing. We wish to dedicate the results to new developments now and in the future.
Application of Virtual Reality in Chemical Education Using Intermolecular Force Display System HaptiChem
Authors: Satoh Hiroko , Narita Akira , Aoki Atsushi , Akahane Katsuhito , Sato Makoto
Published: February 2022

Virtual reality technology has been recently more intensively applied in chemistry. HaptiChem, which was developed in 2006, is one of the systems appeared in the early stage of this field. It is an intermolecular force display system, which makes it possible to touch and move molecules as feeling intermolecular force in a three-dimensional virtual space by using a haptic device. The functions and graphic display were designed as simple as possible for educational use, so that learner can easily grasp the meaning of the concept of molecular forces. We introduced HaptiChem in chemical education. We held a high school chemistry class with 43 students entitled “Several Forces between Molecules” as being open to the media. The students learned about intermolecular force from a lecture together with experiences of the force using HaptiChem. They asked more questions about intermolecular force during the class than usual. Their answers to the questionnaires after the class indicated that the haptic system promoted curiosity and enhanced learning. The students could learn more effectively by combining with the active feeling with HaptiChem. The high-school teachers evaluated that such a system can more efficiently encourage students to learn and remember things by stimulating their sense of touch. The observations also suggested that a haptic device made it easier to establish three-dimensional perception, which is difficult only with 2D-display. This pilot experiment was performed on 15th March 2007. It was the first attempt at using it in the field of chemical education. The observation was done fourteen years ago. However, since the effectiveness of haptic device in chemical education has not been changed and the interests of the applications have been increased, we decided to report the data we observed, which should be still worth disclosing. We wish to dedicate the results to new developments now and in the future.
Radiative Contributions Dominate Plasmon Broadening for Post-Transition Metals in the Ultraviolet
Authors: Fonseca Guzman Maria , Ross Michael
Published: February 2022

We use classical electrodynamics calculations to investigate the plasmonic properties of the post-transition metals Al, Bi, Ga, In, and Sn, which are active in the ultraviolet, focusing in particular on the material- and resonance-dependent origins of plasmon broadening. Analytic Mie theory, the modified-long wavelength approximation, and the quasistatic dipole approximation together show that radiative processes dominate plasmon dephasing and damping in small (5–25 nm radius) Al, Bi, Ga, In, and Sn spheres. For Al, Ga, In, and Sn, the radiative contribution (~1–2 eV) to the plasmon linewidth is more than 100-fold greater than the non-radiative contribution (0.001–0.02 eV) derived from the bulk dielectric function. This is significantly different than what is observed for Ag spheres, where non-radiative contributions (~0.1 eV) are the primary source of broadening up to a radius of 25 nm. Overall, these data suggest that the plasmonic properties, dephasing, and lifetimes for Al, Ga, In, and Sn —and to a lesser extent Bi— spheres are qualitatively similar. To develop a more general understanding of the relationship between plasmon energy and linewidth, we use a model for ideal free-electron Drude metals. It is seen that the linewidth increases at higher energies even for lossless Drude metals, suggesting that the increased broadening observed in UV-active metals is a generalizable observation. These data have important implications for the use of these metals for ultraviolet plasmonics. The increased importance of radiative damping for post-transition metals could influence the ability to harvest photons, generate hot carriers, and enhance spectroscopy in the ultraviolet while providing new opportunities for manipulating high-energy photons.
Effective Carbon Number and Inter-Class Retention Time Conversion Enhances Lipid Identifications in Untargeted Clinical Lipidomics
Authors: White Jake , Trim Paul , Salagaras Thalia , Long Aaron , Psaltis Peter , Verjans Johan , Snel Marten
Published: February 2022

Chromatography is often used as a method for reducing sample complexity prior to analysis by mass spectrometry, the use of retention time (RT) is becoming increasingly popular to add valuable supporting information in lipid identification. The RT of lipids with the same headgroup in reverse-phase separation can be predicted using the effective carbon number (ECN) model. This model describes the effect of acyl chain length and degree of saturation on lipid RT, which increases predictably with acyl chain length and degree of saturation. Furthermore, we have found a robust correlation in the chromatographic separation of lipids with different headgroups that share the same fatty acid motive. By measuring a small number of lipids from each subclass it is possible to build a model that allows for the prediction of the RT of one lipid subclass based on another. Here, we utilise ECN modelling and inter-class retention time conversion (IC-RTC) to build a glycerophospholipid RT library with 481 entries based on 136 MS/MS characterised lipid RTs from NIST SRM-1950 plasma and lipid standards. The library was tested on a patient cohort undergoing coronary artery bypass grafting surgery (n=37). A total of 129 unique circulating glycerophospholipids were identified, of which, 57 (4 PC, 24 PE, 4 PG, 15 PI, 10 PS) were detected with IC-RTC, thereby demonstrating the utility of this technique for the identification of lipid species not found in commercial standards.
Ultrafast Proton Transfer Reaction in Phenol–(Ammonia)n Clusters: An Ab-Initio Molecular Dynamics Investigation.
Authors: Pant Rakesh , Singh Reman Kumar , Patwari G Naresh
Published: February 2022

The ability of phenol to transfer the proton to surrounding ammonia molecules in a phenol-(ammonia)n cluster will depend on the relative orientation of the ammonia molecules and a critical field of about 285 MV cm-1 is essential along the O–H bond for the transfer process. Ab-initio MD simulations reveal that for a spontaneous proton transfer process, the phenol molecule must be embedded in a cluster consisting of at least eight ammonia molecules, even though several local minima with proton transferred can be observed for clusters consisting of 5-7 ammonia molecules. Further, phenol solvated in large clusters of ammonia, the proton transfer is spontaneous with the proton transfer event being instantaneous (about 20-120 fs). These simulations indicate that the rate-determining step for the proton transfer process is the organization of the solvent around the OH group and the proton transfer process in phenol-(ammonia)n clusters follows a curvilinear path which includes the O–H bond elongation and out-of-plane movement of the proton and can be referred to as a “Bend-to-Break” process.
Measurement of Raman Optical Activity with High-Frequency Polarization Modulation
Authors: Lightner Carin R. , Gisler Daniel , Meyer Stefan A. , Niese Hannah , Keitel Robert C. , Norris David J.
Published: February 2022

Many chiroptical spectroscopic techniques have been developed to detect chirality in molecular species and probe its role in biological processes. Raman optical activity (ROA) should be one of the most powerful methods, as ROA yields vibrational and chirality information simultaneously and can measure analytes in aqueous and biologically relevant solvents. However, despite its promise, the use of ROA has been limited, largely due to challenges in instrumentation. Here, we report a new approach to ROA that exploits high-frequency polarization modulation. High-frequency polarization modulation, usually implemented with a photoelastic modulator (PEM), has long been the standard technique in other chiroptical spectroscopies. Unfortunately, the need for simultaneous spectral and polarization resolution has precluded the use of PEMs in ROA instruments. We combine a specialized camera system (the Zurich Imaging Polarimeter, or ZIMPOL) with PEM modulation to perform ROA measurements. We demonstrate performance similar to the current standard in ROA instrumentation while reducing complexity and polarization artifacts. This development should aid researchers in exploiting the full potential of ROA for chemical and biological analysis.
A Practical Guide to Analyzing and Reporting the Movement of Nanoscale Swimmers
Authors: Wang Wei , Mallouk Thomas
Published: February 2022

The recent invention of nanoswimmers– synthetic, powered objects with characteristic lengths in the range of 10-500 nm - has sparked widespread interest among scientists and the general public. As more researchers from different backgrounds enter the field, the study of nanoswimmers offers new opportunities but also significant experimental and theoretical challenges. In particular, the accurate characterization of nanoswimmers is often hindered by strong Brownian motion, convective effects, and the lack of a clear way to visualize them. When coupled with improper experimental designs and imprecise practices in data analysis, these issues can translate to results and conclusions that are inconsistent and poorly reproducible. This Perspective follows the course of a typical nanoswimmer investigation from synthesis through to applications and offers suggestions for best practices in reporting experimental details, recording videos, plotting trajectories, calculating and analyzing mobility, eliminating drift, and performing control experiments, in order to improve the reliability of the reported results.
Low-temperature and ammonia-free epitaxy of GaN/AlGaN/GaN heterostructure
Authors: Tobaldi David Maria , Triminì Valentina , Cretì Arianna , Lomascolo Mauro , Dicorato Stefano , Losurdo Maria , Passaseo Adriana , Tasco Vittorianna
Published: February 2022

Wide band gap semiconductors are very attractive because of their broad applications as electronics and optoelectronics materials − GaN-based materials being by far the most promising. For the production of such nitride-based optical and power devices, metal-organic chemical vapour deposition (MOCVD) is routinely used. However, this has disadvantages, such as the large consumption of ammonia gas, and the need for high growth temperature. To go beyond such a limit, in this study we successfully developed a remote plasma assisted MOCVD (RPA-MOCVD) approach for the epitaxial growth of high-quality GaN/AlGaN heterostructures on 4H-SiC substrates. Our RPA-MOCVD has the advantages of lower growth temperature (750 °C) compared to conventional MOCVD route, and the use of a remote N2/H2 plasma instead of ammonia for nitrides growth, generating in situ the NHx (x = 0−3) species needed for the growth. As assessed by structural, morphological, optical and electrical characterisation, the proposed strategy provides an overall cost-effective and green approach for high-quality GaN/AlGaN heteroepitaxy, suitable for high electron mobility transistors (HEMT) technology.
Development of an untargeted DNA adductomics method by ultra-high performance liquid chromatography coupled to high-resolution mass spectrometry
Authors: La Barbera Giorgia , Dragsted Lars Ove
Published: February 2022

Cancer may be initiated by covalent modification of DNA by genotoxic molecules coming from diet, environment, inflammation, and other sources. For most of these genotoxicants there is little evidence of their identity. DNA adductomics is a new research field, aiming to screen for unknown DNA adducts by high resolution mass spectrometry (HRMS). However, due to the low abundance of DNA adducts, DNA adductomics presents several analytical challenges. In this work, a sensitive untargeted DNA adductomics method was developed by using ultra-high performance liquid chromatography (UHPLC) coupled via an electrospray ionization source (ESI) to a quadrupole-time of flight MS instrumentation. Mobile phases with ammonium bicarbonate gave the best signal enhancement. The MS capillary voltage, cone voltage and detector voltage had most effect on the response of the DNA adducts. A low adsorption vial was selected for reducing analyte loss. A hybrid surface coated HSST3 premier column was tested for reducing adsorption of the DNA adducts. The optimized method was applied to analyse DNA adducts in calf thymus and cat colon DNA by performing a MSE acquisition and screening for loss of deoxyribose, both in-source and in the fragmentation spectra, and for the nucleobase fragment ions. The putative DNA adducts were matched with an in-house DNA adduct database. Thirteen DNA adducts were observed in DNA from calf thymus and cat colon, four of them never reported before, showing promise for the application of this untargeted method in future human studies.
Systematic study of triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases.
Authors: Porta Exequiel , Wilkinson Shane , Ballari María Sol , Tekwani Babu , Labadie Guillermo
Published: February 2022

A series of thirty 1,2,3-triazolylsterols were prepared by a stereocontrolled synthesis and inspired by azasterols with proven antiparasitic activity. Ten of these compounds constitute chimeras/hybrids of AZA and 1,2,3-triazolyl azasterols. The entire library was assayed against the etiological agents of the parasites responsible of kinetoplastid diseases (L. donovani, T. cruzi and T. brucei). Several of the compounds were active at submicromolar/nanomolar concentration with excellent selectivity index, when compared to their activity in mammalian cells. Studies of the physicochemical properties in silico were conducted to rationalize the activities.
Graphitic Cathodes for Aluminum Batteries with Aqueous Electrolytes
Authors: Smajic Jasmin , Alazmi Amira , Wehbe Nimer , Costa Pedro M. F. J.
Published: February 2022

Concerns over lithium-ion battery safety and environmental impact have led to increased exploration of alternative energy storage systems. Of these, aluminum is of particular interest, being environmentally friendly, safe and easy to handle. In this work, we explore graphitic cathodes with an aqueous electrolyte (aluminum trifluoromethanesulfonate) and study their electrochemical performance. Finally, a reduced graphene cathode with tailored porosity results in an eco-friendly and inherently safe rechargeable battery with promising electrochemical performance
Tert-Butoxide-Mediated Protodeformylation of Tertiary Homobenzaldehydes
Authors: Cai Xiao , Stokes Benjamin J.
Published: February 2022

Tert-butoxide mediates the protodeformylation of tertiary homobenzaldehydes and related compounds at ambient temperature. Both geminal dialkyl and geminal diaryl substituents are tolerated. Monocyclic aromatic homobenzaldehydes require cyclic gem-dialkyls or gem-diaryls for efficient protodeformylation, whereas gem-dimethyls are sufficient for protodeformylation of polycyclic arenyl substrates. Our data suggest a stabilized radical is generated upon attack of the aldehyde by tert-butoxide.
Ligand assisted hydrogenation of levulinic acid on Pt(111) from first principles calculations
Authors: Gell Lars , Honkala Karoliina
Published: February 2022

In this study, we investigate the hydrogenation reaction of levulinic acid to 4-hydroxypentanovic acidon a ligand-modified Pt(111) using DFT. Modifying nanoparticle surfaces with ligands can havebeneficial effects on the desired reaction such as improved selectivity or lower activation energies.The N3,N3-dimethyl-N2-(quinolin-2-yl)propane-1,2-diamine (AQ) ligand was selected to modify thesurface, since it combines good surface adsorption properties with functional groups that can influencethe reaction. The adsorption geometry of the AQ ligand was studied as well as the co-adsorptionof a second AQ for the possibility of self-assembly. We find that dissociated hydrogen from thePt(111) surface can protonate the AQ ligand and discuss the role this plays on the mechanism ofthe hydrogenation reaction of levulinic acid (LA). By comparing the ligand-modified Pt(111) surfaceto the bare Pt(111) surface we show that the reaction changes from a step-wise to a concertedmechanism due to the influence of the ligand molecule. This demonstrates the effect ligand-modifiedsurfaces can have in catalyzing reactions and shows that desired reactions can be achieved by tuningthe reaction environment.
Computing vibrational energy levels by solving linear equations using a tensor method with an imposed rank
Authors: Carrington Tucker , Kallullathil Sangeeth
Published: February 2022

Present day computers do not have enough memory to store the high-dimensional tensors required when using a direct product basis to compute vibrational energy levels of a polyatomic molecule with more than about 5 atoms. One way to deal with this problem is to represent tensors using a tensor format. In this paper, we use CP format. Energy levels are computed by building a basis from vectors obtained by solving linear equations. The method can be thought of as a CP realization of a block inverse iteration method with multiple shifts. The CP rank of the tensors is fixed and the linear equations are solved with an Alternating Least Squares method. There is no need for rank reduction, no need for orthogonalization, and tensors with rank larger than the fixed rank used to solve the linear equations are never generated. The ideas are tested by computing vibrational energy levels of a 64-D bilinearly coupled model Hamiltonian and of acetonitrile(12-D).
A general reactivity map for predicting outcomes in palladium-catalyzed cross-coupling
Authors: Lu Jingru , Donnecke Sofia , Paci Irina , Leitch David
Published: February 2022

Making accurate, quantitative predictions of chemical reactivity based on molecular structure is an unsolved problem in chemical synthesis, particularly for complex molecules. We report a generally applicable and mechanistically based structure-reactivity model for the oxidative addition of (hetero)aryl halides to palladium(0), which is a key step in myriad catalytic processes. This model links simple molecular descriptors – electrostatic potential, steric parameters, and bond strengths – to relative rates of oxidative addition for 71 electrophile substrates. Because oxidative addition often controls the rate and/or selectivity of palladium-catalyzed cross-coupling reactions, this model can be used to make predictions about catalytic reaction outcomes. Demonstrated applications include a quantitative model for the rate of 410 different Sonogashira coupling reactions, and successful site-selectivity predictions for a series of multihalogenated substrates relevant to the synthesis of pharmaceuticals and natural products.
A reactivity map for oxidative addition enables quantitative predictions for multiple catalytic reaction classes
Authors: Lu Jingru , Donnecke Sofia , Paci Irina , Leitch David
Published: February 2022

Making accurate, quantitative predictions of chemical reactivity based on molecular structure is an unsolved problem in chemical synthesis, particularly for complex molecules. We report a generally applicable, mechanistically based structure-reactivity approach to create a quantitative model for the oxidative addition of (hetero)aryl electrophiles to palladium(0), which is a key step in myriad catalytic processes. This model links simple molecular descriptors to relative rates of oxidative addition for 79 substrates, including chloride, bromide and triflate leaving groups. Because oxidative addition often controls the rate and/or selectivity of palladium-catalyzed reactions, this model can be used to make quantitative predictions about catalytic reaction outcomes. Demonstrated applications include a multivariate linear model for the initial rate of Sonogashira coupling reactions, and successful site-selectivity predictions for a series of multihalogenated substrates relevant to the synthesis of pharmaceuticals and natural products.
Discovering a hidden binding site of spermidine synthase inhibitors for Chagas disease by combining molecular simulations and X-ray crystallography
Authors: Yoshino Ryunosuke , Yasuo Nobuaki , Hagiwara Yohsuke , Ishida Takashi , Inaoka Daniel Ken , Amano Yasushi , Tateishi Yukihiro , Ohno Kazuki , Namatame Ichiji , Niimi Tatsuya , Orita Masaya , Kita Kiyoshi , Akiyama Yutaka , Sekijima Masakazu
Published: February 2022

Background Chagas disease is caused by the parasite Trypanosoma cruzi and is one of the neglected tropical diseases. Although two types of drugs are currently available, new drugs are still required because they have serious side effects. To develop a therapeutic agent for trypanosomiasis, we focused on spermidine synthase (SpdSyn) as the target protein and determined the hidden binding site which was not identified in the X-ray structure for obtaining seed compounds using a computational simulation. Methodology/Principal Findings Molecular dynamics (MD) simulation was performed for TcSpdSyn to predict new binding sites. These results indicated that the highly druggable binding site was discovered around Glu22. We also conducted docking simulation for the new binding site and in vitro assay to determine half-maximal inhibitory concentration (IC50) value. Furthermore, to confirm ligand of binding site and pose, we conducted X-ray crystallographic studies. As a result, two compounds were discovered as inhibitors of TcSpdSyn with IC50 values of 82.27 and 43.41 μM, respectively. X-ray crystallographic analysis shows that two inhibitors are bound to the hidden binding site which is detected by computational simulation. Conclusions/Significance MD simulation revealed that there are new sites in the TcSpdSyn that are not an active site. This site exists near Glu22 and Asp77, and crystal structures revealed that compounds 1 and 2 are bound to the hidden binding site, as predicted by MD simulations, and interacts with Glu22 and Asp77 through hydrogen bonds. 4MCHA which has been reported as known inhibitor binds to the TcSpdSyn active site while interacting with Asp171. Therefore, these inhibitors we discovered differs in binding mode from a known inhibitor and this new binding site is useful for antitrypanosomiasis target.
The Two Faces of the Liquid Ordered Phase
Authors: Schachter Itay , Paananen Riku , Fabian Balazs , Jurkiewicz Piotr , Javanainen Matti
Published: February 2022

The coexistence of liquid ordered Lo and liquid disordered Ld phases in synthetic and plasma membrane-derived vesicles serves as a model for biomembrane heterogeneity. However, the connection between the structures of microscopic phases present in vesicles at low temperatures and the tiny ordered "raft" domains of biomembranes at body temperature is unclear. To study the Lo phase structure across temperatures, we performed atomistic molecular dynamics simulations, differential scanning calorimetry, and fluorescence spectroscopy on the Lo phase in binary and ternary lipid mixtures. Our results reveal an Lo phase with highly ordered and hexagonally packed clusters of saturated lipid chains at low temperatures. These clusters melt upon heating, and numerous membrane properties reflect this transition as two regimes with different temperature dependence. Still, the transition between the regimes is continuous, and they both match the description of the Lo phase with high order and relatively high mobility. Our findings question the use of vesicles displaying Lo–Ld coexistence as models for heterogeneity in cellular membranes, as they likely correspond to different molecular organizations.