bluuebunny/crossref_metadata_2025 huggingface dataset:
Wittig olefination “baking powder”: a hexameric halogen-bonded phosphonium salt cage for encapsulation and mechanochemical transformation of small-molecule carbonyl compounds
Authors: Marrett Joseph , Titi Hatem , Friscic Tomislav
Published: February 2022

We report a hexameric supramolecular cage assembled from the components of a Wittig-type phosphonium salt, held together by charge-assisted R-Br· · ·Br-· · ·Br-R halogen bonds. The cage reliably encapsulates small polar molecules, including aldehydes and ketones, to provide host-guest systems in which components are pre-formulated in a near-ideal stoichiometry for a base-activated Wittig olefination in the solid-state. These pre-formulated solids enable a molecular-level “baking powder” approach for solvent-free Wittig reactions, based on a design of solid-state reactivity in which the host for molecular inclusion also acts as a complementary reagent for the chemical transformation of an array of guests. These host-guest solid-state complexes can also act as supramolecular surrogates to their Wittig olefination vinylbromide products, in a Sonogashira-type coupling that enables one-pot mechanochemical conversion of an aldehyde to an enediyne.
Production of a new 3D electrode skeleton of Ni with very high electrochemical surface area for oxygen evolution
Authors: Fakourihassanabadi Mohsen , Guay Daniel
Published: February 2022

Long and stable fibers (Tapes) of nickel with a thickness that can reach less than one hundred nanometers were produced through directional solidification of Ni-Al hypereutectic alloy on the surface of Ni and then, leaching the alloy in potassium hydroxide solution. Experimental results illustrated that the structure of the tapes is Raney nickel. In other words, a 3D structure consisting of a large number of Nano-dimensional tapes with a Nano-porous and Nano-crystalline structure was created. The activity of this structure was evaluated for oxygen evolution in alkaline media. The results showed that by increasing the number of Tapes per 〖cm〗^2 (density of Tapes), electrochemical surface area and double layer capacitance increase. As the density of Tapes increases, the OER overpotential decreases, but with further increase in density of Tapes, the OER overpotential increases again. Re-increase in overpotential was associated to trapping of oxygen bubbles. The best sample showed an overpotential 240 mV at 10 mA/〖cm〗^2 and 350 mV at 500 mA/〖cm〗^2. Also, this sample worked without any sign of degradation at 500 mA/〖cm〗^2 for 6 days (144 hours).
Diastereoselective Addition of Prochiral Nucleophilic Alkenes to a-Chiral N-Sulfonyl Imines
Authors: Shaw Jared , Gutierrez David , Fettinger James , Ando Kaori , Houk Kendall
Published: February 2022

The Lewis acid catalyzed addition of prochiral E and Z allyl nucleophiles to chiral -alkoxy N-tosyl imines is described. Alkene geometry is selectively transferred to the newly formed carbon-carbon bond, resulting in stereochemical control of C2, C3, and C4 of the resulting 2-alkoxy-3-N-tosyl-4-alkyl-5-hexenes. The C3 and C4 diastereoselectivity (dr) is influenced by the geometry of the alkene, size of N-sulfonyl substituent, and steric bulk of the substituted -alkoxy ether group. This work demonstrates that three of the four possible diastereomers can be synthesized in high diastereoselectivity and high yields using the current methods. A mechanistic computational analysis to elucidate the high selectivity is also presented.
Ni-Catalyzed Arylbenzylation of Alkenylarenes. Kinetic Studies Reveal Autocatalysis by ZnX2 and 3-Fold Catalytic Rate Increase
Authors: Dhungana Roshan K. , Sapkota Rishi R. , Wickham Laura M. , Niroula Doleshwar , Shrestha Bijay , Giri Ramesh
Published: February 2022

We report a Ni-catalyzed regioselective arylbenzylation of alkenylarenes with benzyl halides and arylzinc reagents. The reaction furnishes differently substituted 1,1,3-triarylpropyl structures that are reminiscent of the cores of oligoresveratrol natural products. The reaction is also compatible for the coupling of internal alkenes, secondary benzyl halides and variously substituted arylzinc reagents. Kinetic studies reveal that the reaction proceeds with a rate-limiting single electron transfer process and is autocatalyzed by in situ-generated ZnX2. The reaction rate is amplified by three-fold through autocatalysis upon addition of ZnX2.
3D Computer Vision Models Predict DFT-Level HOMO-LUMO Gap Energies from Force-Field-Optimized Geometries
Authors: Maser Michael R. , Reisman Sarah E.
Published: February 2022

We investigate 3D deep learning methods for predicting quantum mechanical energies at high-theory-level accuracy from inexpensive, rapidly computed molecular geometries. Using space-filled volumetric representations (voxels), we explore the effects of radial decay from atom centers and rotational data augmentation on learnability. We test several published computer vision models for 3D shape learning, and construct our own architecture based on 3D inception networks with physically meaningful kernels. We provide a framework for further studies and propose a modeling challenge for the computer vision and molecular machine learning communities.
A molecular (NCS2)Ni(II) electrocatalyst resembles [NiFe]hydrogenase pathway for H2 evolution
Authors: Sinha Soumalya , Tran Giang N. , Na Hanah , Mirica Liviu M.
Published: February 2022

The electrochemical hydrogen evolution reaction (HER) is considered a sustainable energy approach to advance fuel-cell technologies, and HER electrocatalysts that resembles the [NiFe] hydrogenases are highly desired. Herein, we report a bioinspired Ni(II) complex (NCHS2)Ni(OTf)2, where NCHS2 is 3,7-dithia-1(2,6)-pyridina-5(1,3)-benzenacyclooctaphane, that is an efficient electrocatalyst for HER with turnover frequencies up to 400,000 s–1 in the presence of low acid concentration, and compares favorably with the other reported Ni HER electrocatalysts. Importantly, in this complex the rationally designed NCHS2 ligand undergoes C-H bond activation and the resulting organometallic Ni-aryl complex restricts the formation of a Ni(0) species, which resembles the role of the cysteine ligands in [NiFe] hydrogenases. In addition, this electrocatalyst follows a unique HER mechanism via detectable Ni(I)/Ni(III) intermediates that are also proposed for [NiFe] hydrogenases, yet such a mechanism has not been observed to date in model systems.
Synthesis of the Macrolactone Cores of Maltepolides via a Diene–Ene Ring-Closing Metathesis Strategy
Authors: Sit Man Ki , Cao Hui Hui , Wu Yan-Dong , Yip Tsz Chun , Bendel Lars Eric , Zhang Wen , Dai Wei-Min
Published: February 2022

Synthesis of the C19-truncated maltepolide E has been accomplished via a diene–ene RCM strategy without damage to the C11–C14 alkenyl epoxy unit. Upon release of the C17-OH group, it attacked at the C14 position with double bond migration and epoxide ring-opening to furnish the C19-truncated maltepolide A and B as proposed for the biosynthesis of maltepolides. Preliminary cytotoxicity data of the synthesized C19-truncated maltepolides against L929 mouse fibroblast cell line suggest irrelevance of the vinyl epoxide and importance of the conjugated dienyl keto unit for the observed anticancer activity.
Contra-Thermodynamic Positional Isomerization of Olefins
Authors: Zhao Kuo , Knowles Robert
Published: February 2022

A light-driven method for the contra-thermodynamic positional isomerization of olefins is described. In this work, stepwise PCET activation of a more substituted and more thermodynami-cally stable olefin substrate is mediated by an excited-state oxi-dant and a Brønsted base to afford an allylic radical that is cap-tured by a Cr(II) co-catalyst to furnish an allylchromium(III) intermediate. In situ protodemetalation of this allylchromium complex by methanol is highly regioselective and affords an isomerized and less thermodynamically stable alkene product. The higher oxidation potential of the less substituted olefin isomer renders it inert to further oxidation by the excited-state oxidant, enabling it to accumulate in solution over the course of the reaction. A broad range of isopropylidene substrates is ac-commodated, including enol ethers, enamides, styrenes, 1,3-dienes, and tetrasubstituted alkyl olefins. Mechanistic investiga-tions of the protodemetalation step are also presented.
Low Density Interior in Supercooled Aqueous Nanodroplets Expels Ions to the Subsurface
Authors: Malek Shahrazad Moh'd , Kwan Victor , Saika-Voivod Ivan , Consta Styliani
Published: February 2022

The interaction between water and ions within droplets plays a key role in the chemical reactivity of atmospheric and man-made aerosols. Here we report direct computational evidence that in supercooled aqueous nanodroplets a lower density core of tetrahedrally coordinated water expels the cosmotropic ions to the denser and more disordered subsurface. In contrast, at room temperature, depending on the nature of the ion the radial distribution in the droplet core is nearly uniform or elevated towards the center. We analyze the spatial distribution of a single ion in terms of a reference electrostatic model. The energy of the system in the analytical model is expressed as the sum of the electrostatic and surface energy of a deformable droplet. The model predicts that the ion is subject to a harmonic potential centered at the droplet's center of mass. We name this effect ``electrostatic confinement''. The model's predictions are consistent with the simulation findings for a single ion at room temperature but not at supercooling. We anticipate this study to be the starting point for investigating the structure of supercooled (electro)sprayed droplets that are used to preserve the conformations of macromolecules originating from the bulk solution.
Activating [FeFe] hydrogenase mimic for hydrogen evolution under visible light
Authors: Buday Philipp , Kasahara Chizuru , Hofmeister Elisabeth , Kowalczyk Daniel , Farh Michael K. , Riediger Saskia , Schulz Martin , Wächtler Maria , Furukawa Shunsuke , Saito Masaichi , Ziegenbalg Dirk , Gräfe Stefanie , Bäuerle Peter , Kupfer Stephan , Dietzek-Ivanšić Benjamin , Weigand Wolfgang
Published: February 2022

Inspired by the active center of the natural [FeFe] hydrogenases, we designed a compact and precious metal-free photosensitizer-catalyst dyad (PS-CAT) for photocatalytic hydrogen evolution under visible light irradiation. PS-CAT represents a prototype dyad comprising pi-conjugated oligothiophenes as light absorbers. PS-CAT and its interaction with the sacrificial donor 1,3-dimethyl-2-phenylbenzimidazoline were studied by steady-state and time-resolved spectroscopy coupled with electrochemical techniques and visible light-driven photocatalytic investigations. Operando EPR spectroscopy revealed the formation of an active [Fe(I)Fe(0)] species – in accordance with theoretical calculations – presumably driving photocatalysis effectively (TON ≈ 210).
Extensive High-Accuracy Thermochemistry and Group Additivity Values for Halocarbon Combustion Modeling
Authors: Farina David , Sirumalla Sai Krishna , Mazeau Emily , West Richard
Published: February 2022

Standard enthalpies, entropies, and heat capacities are calculated for 16,813 halocarbons using an automated high-fidelity thermochemistry workflow. This workflow generates conformers at density functional tight binding (DFTB) level, optimizes geometries, calculates harmonic frequencies, and performs 1D hindered rotor scans at DFT level, and computes electronic energies at G4 level. The computed enthalpies of formation for 400 molecules show good agreement with literature references, but the majority of the calculated species have no reference in the literature. Thus, this work presents the most accurate thermochemistry for many halocarbons to date. This new data set is used to train an extensive ensemble of group additivity values and hydrogen bond increment groups within the Reaction Mechanism Generator (RMG) framework. On average, the new group values estimate standard enthalpies for halogenated hydrocarbons within 3 kcal/mol of their G4 values. A significant contribution towards automated mechanism generation of halocarbon combustion, this research provides thermochemical data for thousands of novel halogenated species and presents a self-consistent set of halogen group additivity values.
Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals the DNA Repair Protein XRCC5 as a Functional Target of Myrocin G
Authors: Abegg Daniel , Tomanik Martin , Qiu Nan , Pechalrieu Dany , Shuster Anton , Commare Bruno , Togni Antonio , Herzon Seth , Adibekian Alexander
Published: February 2022

Chemoproteomic profiling of cysteines has emerged as a powerful method for screening the proteome-wide targets of cysteine-reactive fragments, drugs and natural products. Herein, we report the development and an in-depth evaluation of a tetrafluoroalkyl benziodoxole as a cysteine-selective chemoproteomic probe. We show that this probe features numerous key improvements compared to the traditionally used cysteine-reactive probes, including a superior target occupancy, faster labeling kinetics, and broader proteomic coverage thus enabling profiling of cysteines directly in live cells. Further, the fluorine ‘signature’ of probe 7 constitutes an additional advantage resulting in a more confident adduct-amino acid site assignment in mass spectrometry-based identification workflows. We demonstrate the utility of our new probe for proteome-wide target profiling by identifying the cellular targets of (-)-myrocin G, an antiproliferative fungal natural product with a to-date unknown mechanism of action. We show that this natural product and its simplified analog target the X-ray repair cross-complementing protein 5 (XRCC5), an ATP-dependent DNA helicase that primes DNA repair machinery for non-homologous end joining (NHEJ) upon DNA double strand breaks, making them the first reported inhibitors of this biomedically highly important protein. We further demonstrate that myrocins disrupt the interaction of XRCC5 with DNA leading to sensitization of cancer cells to the chemotherapeutic agent etoposide as well as UV-light induced DNA damage. Altogether, our next generation cysteine-reactive probe enables broader and deeper profiling of the cysteinome rendering it a highly effective tool for elucidation of targets of electrophilic small molecules.
Tuning dynamic DNA- and peptide-driven self-assembly in DNA-peptide conjugates
Authors: Taylor Emerald , Sato Akiko , Gudeangadi Prashant , Beal David , Hopper James , Reithofer Michael , Serpell Christopher
Published: February 2022

DNA-peptide conjugates offer an opportunity to marry the benefits of both biomolecules, such as the high level of control and programmability found with DNA and the chemical diversity and biological stability of peptides. These hybrid systems offer great potential in fields such as therapeutics, nanotechnology, and robotics to name a few. Using the first DNA-β-turn peptide conjugate, we present three studies designed to investigate the self-assembly of DNA-peptide conjugates over a period of 28 days. Time-course studies, such as these have not been previously conducted for DNA-peptide conjugates, although they are common in pure peptide assembly, for example in amyloid research. By using aging studies to assess the structures produced, we gain insights into the dynamic nature of these systems. The first study explores the influence varying amounts of DNA-peptide conjugates have on the self-assembly of our parent peptide. Study 2 explores how DNA and peptide can work together to change the structures observed during aging. Study 3 investigates the presence of orthogonality within our system by switching the DNA and peptide control on and off independently. These results show that two orthogonal self-assemblies can be combined and operated either independently or in tandem within a single macromolecule, with both spatial and temporal effects upon the resultant nanostructures.
Characterisation of the Boson Peak from the Glass into the Liquid
Authors: Farrell Andrew , Jiménez Mario González , Tukachev Nikita , Turton David A. , Russell Ben A. , Guinane Sarah , Senn Hans Martin , Wynne Klaas
Published: February 2022

Phenomena ranging from vitrification to crystal nucleation are governed by locally ordered structures, in otherwise disordered phases, that can either inhibit or favour the growth of macroscopic order. However, such structures are ephemeral, do not typically have distinct spectral features, and are therefore critically important but largely unobservable by current methods. Illuminating these structures therefore presents the single greatest challenge in physical chemistry. The boson peak is characteristic of glasses and represents the locally ordered structures inhibiting crystallisation but is typically obscured by other spectral contributions. Here we show that depolarised Raman scattering—obtained using femtosecond optical Kerr-effect spectroscopy—in liquids consisting of highly symmetric molecules can be used to isolate the boson peak thereby allowing detailed characterisation of the intermolecular potential-energy landscape for the first time.
The min-max test: an objective method for discriminating mass spectra
Authors: Moorthy Arun , Sisco Edward
Published: February 2022

Deciding whether the mass spectra of seized drug evidence and a reference standard are measurements of two different compounds is a central challenge in forensic chemistry. Normally, an analyst will compute a mass spectral similarity score between spectra from the sample and reference and make a judgment using both the score and their visual interpretation of the spectra. This approach is inherently subjective and not ideal when rapid assessment of several samples is necessary. Making decisions using only the score and a threshold value greatly improves analysis throughput and removes analyst-to-analyst subjectivity, but selecting an appropriate threshold is itself a non-trivial task. In this manuscript, we describe and evaluate the min max test – a simple and objective method for classifying mass spectra that leverages replicate measurements from each sample to remove analyst subjectivity. We demonstrate that the min max test has an intuitive interpretation for decision-making, and its performance exceeds thresholding with similarity scores even when the best performing threshold for a fixed dataset is prescribed. Determining whether the underlying framework of the min-max test can incorporate retention indices for objectively deciding whether spectra are measurements of the same compound is on-going work.
Kinetic Resolution of Sulfur-Stereogenic Sulfoximines by Pd(II)-MPAA Catalyzed C-H Arylation and Olefination
Authors: Mukherjee Kallol , Grimblat Nicolas , Sau Somratan , Ghosh Koushik , Shankar Majji , Gandon Vincent , Sahoo Akhila
Published: February 2022

A direct Pd(II)-catalyzed kinetic resolution of heteroaryl-enabled sulfoximines through an ortho-C-H alkenylation/arylation of arenes has been developed for the first time. The coordination of sulfoximine pyridyl-motif and the chiral amino acid MPAA ligand to the Pd(II)-catalyst controls the enantio-discriminating C(aryl)-H activation. This method provides access to a wide range of enantiomerically enriched unreacted aryl-pyridyl-sulfoximine precursors and C(aryl)-H alkenylation/arylation products in good yields with high enantioselectivity (up to >99% ee), and selectivity factor up to >200; which are inaccessible by conventional methods. The coordination preference of the directing group, ligand effect, geometry constraints, and the transient six-membered concerted-metalation-deprotonation species dictate the stereoselectivity; DFT studies validate this hypothesis.
Computational data analysis shows that key developments towards the periodic system occurred in the 1840s
Authors: Leal Wilmer , Llanos Eugenio J. , Bernal Andres , Stadler Peter F. , Jost Jürgen , Restrepo Guillermo
Published: February 2022

The periodic system arose from knowledge about substances, which constitute the chemical space. Despite the importance of this interplay, little is known about how the expanding space affected the system. Here we show, by analysing the space between 1800 and 1869, how the periodic system evolved until its formulation. We found that after an unstable period culminating around 1826, the system began to converge to a backbone structure, unveiled in the 1860s, which was clearly evident in the 1840s. Hence, contrary to the belief that the ``ripe moment'' to formulate the system was in the 1860s, it was in the 1840s. The evolution of the system is marked by the rise of organic chemistry in the first quarter of the nineteenth-century, which prompted the recognition of relationships among main group elements and obscured some of transition metals, which explains why the formulators of the periodic system struggled accommodating them. We also introduced an algorithm to adjust the chemical space according to different sets of atomic weights, which allowed for estimating the resulting periodic systems of chemists using one or the other nineteenth-century atomic weights. These weights produce orderings of the elements very similar to that of 1869, while providing different similarity relationships among the elements, therefore producing different periodic systems. By analysing these systems, from Dalton up to Mendeleev, we found that Gmelin's atomic weights of 1843 produce systems remarkably similar to that of 1869, a similarity that was reinforced by the atomic weights on the years to come.
Gaussian accelerated molecular dynamics with the weighted ensemble method: a hybrid method improves thermodynamics and kinetics sampling
Authors: Ahn Surl-Hee , Ojha Anupam , Amaro Rommie , McCammon James
Published: February 2022

Gaussian accelerated molecular dynamics (GaMD) is a well-established enhanced sampling method for molecular dynamics (MD) simulations that effectively samples the potential energy landscape of the system by adding a boost potential, which smoothens the surface and lowers energy barriers between states. Although equilibrium properties can be recovered exactly in principle, GaMD is unable to give time-dependent properties such as kinetics directly. On the other hand, the weighted ensemble (WE) method can efficiently sample transitions between states with its many weighted trajectories, which directly yield rates and pathways. However, the performance of the WE method (i.e., convergence and efficiency) depends heavily on its initial conditions or initial sampling of the potential energy landscape. Hence, we have developed a hybrid method that combines the two methods, wherein GaMD is first used to sample the potential energy landscape of the system, and the WE method is subsequently used to further sample the potential energy landscape and kinetic properties of interest. We show that the hybrid method can sample both thermodynamic and kinetic properties more accurately and quickly compared to using either method alone.
Gaussian accelerated molecular dynamics with the weighted ensemble method: a hybrid method improves thermodynamic and kinetic sampling
Authors: Ahn Surl-Hee , Ojha Anupam , Amaro Rommie , McCammon James
Published: February 2022

Gaussian accelerated molecular dynamics (GaMD) is a well-established enhanced sampling method for molecular dynamics (MD) simulations that effectively samples the potential energy landscape of the system by adding a boost potential, which smoothens the surface and lowers energy barriers between states. GaMD is unable to give time-dependent properties such as kinetics directly. On the other hand, the weighted ensemble (WE) method can efficiently sample transitions between states with its many weighted trajectories, which directly yield rates and pathways. However, the performance of WE (i.e., convergence and efficiency) depends heavily on its initial conditions or initial sampling of the potential energy landscape. Hence, we have developed a hybrid method that combines the two methods, wherein GaMD is first used to sample the potential energy landscape of the system, and WE is subsequently used to further sample the potential energy landscape and kinetic properties of interest. We show that the hybrid method can sample both thermodynamic and kinetic properties more accurately and quickly compared to using either method alone.
Towards Understanding the Angiomotin Membrane Fusion Activity
Authors: Sears Seth , Evans Brenner , Kimble-Hill Ann
Published: February 2022

Angiomotins (Amot) are a family of adaptor proteins that regulate cellular differentiation and proliferation signaling. These cellular events are linked to the initiation of invasive ductal carcinoma, the most common form of breast cancer. Their characteristic coiled-coil homology (ACCH) domain selectively binds phosphatidylinositol lipids (PI), leading to membrane deformation and fusion events necessary for the trafficking polarity proteins to and from the apical membrane. We have previously shown that the ACCH domain has the ability to reorganize and homogenize the PI-enriched microdomains in membranes. However, the connection between the membrane fusion activity and the homogenization of PI has not been well described. In this study, we use small angle x-ray scattering (SAXS) to demonstrate the lipid reorganization function and fluorescence resonance energy transfer (FRET) to characterize the vesicle fusion activity. As a result, we found 6 mutations in the ACCH domain that caused a loss of fusion activity. Furthermore, these mutations also have lost lipid reorganization activity. The results presented provide insight into the role of the Amot ACCH domain residues in driving membrane fusion events involved in targeting and recycling cellular polarity proteins to maintain normal cellular phenotypes.
Real-time Voltammetric Anion Sensing Under Flow
Authors: Patrick Sophie C. , Hein Robert , Sharafeldin Mohamed , Li Xiaoxiong , Beer Paul D. , Davis Jason J.
Published: February 2022

The development of real-life applicable ion sensors, in particular those capable of repeat use and long-term monitoring, remains a formidable challenge. Herein, we demonstrate, in a proof-of-concept, the real-time voltammetric sensing of anions under continuous flow at electroactive anion receptive halogen bonding (XB) and hydrogen bonding (HB) ferrocene-isophthalamide-(iodo)triazole interfaces. Upon exposure to anions, the cathodic perturbations of the ferrocene redox-transducer are monitored by repeat square-wave voltammetry (SWV) cycling and peak fitting of the voltammograms by a custom-written MATLAB script. This enables the facile and automated data processing of thousands of SW scans and is associated with an over one order-of-magnitude improvement in LODs. In addition, this improved analysis enables tuning of the measurement parameters such that high temporal resolution can be achieved. More generally, this novel flow methodology is extendable to a variety of other analytes, including cations, and presents an important step towards translation of voltammetric ion sensors from laboratory to real-world applications.
A Unified Strategy to Access Trans-Syn-Fused Drimane Meroterpe-noids: Chemoenzymatic Total Syntheses of Polysin, N-Acetyl-Polyveoline and the Chrodrimanins
Authors: Li Fuzhuo , Renata Hans
Published: February 2022

Trans-syn-fused drimane meroterpenoids are unique natural products that arise from contra-thermodynamic polycyclizations of their polyene precursors. Herein we report the first total syntheses of four trans-syn-fused drimane meroterpenoids, namely polysin, N-acetyl-polyveoline, chrodrimanin C and verruculide A in 7–18 steps from sclareolide. The trans-syn-fused drimane unit is accessed through an efficient acid-mediated C9 epimerization of sclareolide. Subsequent applications of enzy-matic C–H oxidation and contemporary annulation methodologies install the requisite C3 hydroxyl group and enable rapid gen-eration of structural complexity to provide concise access to these natural products.
Hidden Hemibonding in the Aqueous Hydroxl Radical
Authors: Rana Bhaskar , Herbert John
Published: February 2022

The existence of a two-center, three-electron hemibond in the first solvation shell of OH(aq) has long been a matter of debate. The hemibond manifests in ab initio molecular dynamics simulations as a small-r feature in the oxygen radial distribution function (RDF) for H2O...OH, but that feature disappears when semilocal density functionals are replaced with hybrids, suggesting a self-interaction artifact. Using periodic simulations at the PBE0+D3 level, we demonstrate that the hemibond is actually still present (as evidenced by delocalization of the spin density onto nearby water molecules) but is obscured by the hydrogen-bonded feature in the RDF, due to a slight elongation of the hemibond. Computed electronic spectra for OH(aq) are in excellent agreement with experiment and confirm that hemibond-like configurations play an outsized role in the spectroscopy due to an intense charge-transfer transition that is strongly attenuated in hydrogen-bonded configurations. Apparently, 25% exact exchange does not eliminate delocalization of unpaired spins.
Comprehensive chemical description of pyrolysis chars from low-density polyethylene (LDPE) by thermal analysis hyphenated to different mass spectrometric approaches
Authors: Friederici Lukas , Schneider Eric , Burnens Gaëtan , Streibel Thorsten , Giusti Pierre , Rüger Christopher Paul , Zimmermann Ralf
Published: February 2022

The production and demand of plastics has drastically increased, with severe environmental impact. Waste incineration is not favored, and efficient recycling strategies are needed. Pyrolysis is a promising approaches but the nature of the residual char is not fully understood. To explore the value of this feedstock, thermal analysis with mass spectrometric detection is deployed. With soft photoionization, we were able to identify alkenes, dienes, and polycyclic aromatic hydrocarbons, which were emitted at four distinct mass loss events. Resonance-enhanced multiphoton ionization allows selectively addressing the aromatic constituents. Interestingly, we found an enrichment of UV-stabilizers, such as benzophenone, within the macromolecular nature. High-resolution mass spectrometry addressing the isobaric complexity and pyrolysis gas chromatography was used for structural elucidation. We hypothesize island- and archipelago-type structural motives comparable to asphaltenes but with almost no heteroatoms. The in-depth chemical description of plastic pyrolysis coke will be valuable knowledge in reactor design and material science.
Computational study of electron transport in [FeFe] hydrogenase enzymes
Authors: Puthenkalathil Rakesh , Ensing Bernd
Published: February 2022

[FeFe] hydrogenase enzymes can reversibly catalyze the conversion of protons into molecular hydrogen. The active site of the [FeFe] hydrogenase enzyme is buried inside the protein. The transport of electrons and protons to the active site of the protein is crucial for an efficient catalytic cycle. A chain of iron-sulfur cubane cofactors forms a pathway for the electron transfer in these [FeFe] hydrogenases. We have studied the electron transfer process via the iron-sulfur clusters in the enzyme using classical molecular dynamics simulations. Our simulations show that the protein matrix acts as a porous medium for the transport of water molecules in and out during the electron transfer process. When an electron is transferred through the pathway, solvent water molecules penetrate the protein, forming hydrogen bonded networks and hydrating the electron accepting cubane clusters. The reorganization of the protein and the penetrating water molecules have a large effect on the free energy landscape of the electron transfer, via the formation of favorable hydrogen bonds with the reduced iron- sulfur cluster, thereby stabilizing the electron at the cofactors.
Excited States of Xanthophylls Revisited: Towards the Simulation of Biologically Relevant Systems
Authors: Bondanza Mattia , Jacquemin Denis , Mennucci Benedetta
Published: February 2022

Xanthophylls are an important class of oxygen containing carotenoids, which play a fundamental role both in light harvesting pigment-protein complexes and in many other photo-responsive proteins. The complexity of the manifold of the electronic states and the large sensitivity to the environment still prevent a clear and coherent interpretation of their pho-tophysics and photochemistry. In this Letter, we first apply cutting-edge ab-initio methods (CC3, DMRG/NEVPT2) on model C2h keto-carotenoids to critically asses the performances +of single and multi-reference methods. We then lift symmetry restrictions and extend the tested methods to time dependent DFT and Semiempirical CI (SECI). From this analysis, we demonstrate that SECI can indeed represent an optimal method for describing light-induced processes of xanthophylls in biologically relevant systems. As an example, we investigate canthaxanthin in the Orange Carotenoid Protein showing that the conical intersections between excited states ...
On the Use of Real-World Datasets for Reaction Yield Prediction
Authors: Saebi Mandana , Nan Bozhao , Herr John , Wahlers Jessica , Guo Zhichun , Zurański Andrzej , Kogej Thierry , Norrby Per-Ola , Doyle Abigail , Wiest Olaf , Chawla Nitesh
Published: February 2022

The lack of publicly available, large, and unbiased datasets is a key bottleneck for the application of machine learning (ML) methods in synthetic chemistry. Data from electronic laboratory notebooks (ELNs) could provide less biased, large datasets, but no such datasets have been made publicly available. The first real-world dataset from the ELNs of a large pharmaceutical company is disclosed and its relationship to high-throughput experimentation (HTE) datasets is described. For chemical yield predictions, a key task in chemical synthesis, an attributed graph neural network (AGNN) performs as good or better than the best previous models on two HTE datasets for the Suzuki and Buchwald-Hartwig reactions. However, training of the AGNN on the ELN dataset does not lead to a predictive model. The implications of using ELN data for training ML-based models are discussed in the context of yield predictions.
Red-Light-Induced nPr-DMQA+-Catalyzed [3+2] Cycloaddition of Cyclopropylamines with Alkenes or Alkynes
Authors: stull savannah , Mei Liangyong , Gianetti Thomas
Published: February 2022

A red-light-mediated [3+2] annulation of cyclopropylamines with akenes or alkynes in the presence of nPr-DMQA+ has been reported. An array of cyclopentane or cyclopentene derivatives with diverse functional groups have been obtained in moderate to excellent yields under mild conditions
Understanding the Role of Geometric and Electronic Structure in Bioinspired Catalyst Design: the Case of Formate Dehydrogenase
Authors: Liu Mingjie , Nazemi Azadeh , Taylor Michael , Nandy Aditya , Duan Chenru , Steeves Adam , Kulik Heather
Published: February 2022

The design of bioinspired synthetic inorganic molecular complexes is challenging, due to a lack of understanding of enzyme action and the degree to which that action can be translated into mimics. Exemplary of this challenge is the reversible conversion of formate into CO2 by formate dehydrogenase (FDH) enzymes with Mo/W centers in large molybdopterin cofactors. Despite numerous efforts to synthesize Mo/W-containing molecular complexes, none have been demonstrated to reproduce the full reactivity of FDH. Here, we carry out a large-scale, high-throughput screening study on all mononuclear Mo/W complexes currently deposited in Cambridge Structural Database (CSD). Using density functional theory, we systematically investigate the individual effects of metal identity, ligand identity, oxidation state, and coordination number on structural, electronic and catalytic properties. We compare our results on molecular complexes with quantum mechanics/molecular mechanics simulations on a representative FDH enzyme to further elucidate the influence of the enzyme environment. These comparisons reveal that the enzyme environment primarily influences the metal-local geometry, and these metal-local structural variations can improve catalysis. Through a series of computational mutations on molecular complexes, we extend beyond the CSD structures to further identify the limits of varied chalcogen and metal identity. This broad set and comparison reveal relatively little variation of electronic properties of the metal center due to the presence of the enzyme environment or changes in metal-distant ligand chemistry. Instead, these properties are found to be much more sensitive to the identity of the metal and the nature of the bound terminal chalcogen.
Enhanced Stability of MAPbI3 Perovskite Films with Zirconium Phosphate-Phosphonomethylglycine Nanosheets as Additive
Authors: Vanni Nadir , Morelli Venturi Diletta , Radicchi Eros , Quaglia Giulia , Cambiotti Elena , Latterini Loredana , De Angelis Filippo , COSTANTINO FERDINANDO
Published: February 2022

Methylammonium Lead Iodide perovskite (MAPbI3) is today considered the most promising component for highly efficient third generation solar cells. However, the lifetime of the solar devices is strongly affected by the stability of the MAPbI3 films towards humidity, UV irradiation and temperature. The search for efficient protective additives to be used for building up composite perovskite films with enhanced stability is a topic of great interest in the scientific community. In the present paper we have applied a layered zirconium phosphate-phosphonate based on N,N-phosphonomethyl glycine, exfoliated in thin nanosheets (NS), as additive for the stabilization of MAPbI3 crystalline films towards humidity, UV-irradiation and temperature changes. Notably, the additive resulted extremely efficient to prevent degradation of the perovskite film, preserving the optical and structural properties and avoiding the phase transitions normally observed due to temperature increase.
Cross-⍺/β Polymorphism of PSMα3 Fibrils
Authors: Cracchiolo Olivia , Edun Dean , Betti Vincent , Goldberg Jacob , Serrano Arnaldo
Published: February 2022

The formation of ordered cross-β amyloid protein aggregates is associated with a variety of human disorders. While conventional infrared methods serve as sensitive reporters of the presence of these amyloids, the recently discovered amyloid secondary structure of cross- fibrils presents new questions and challenges. Herein, we report results using Fourier Transform infrared (FTIR) spectroscopy and two-dimensional infrared (2DIR) spectroscopy, to monitor the aggregation of one such cross-alpha forming peptide, phenol soluble modulin alpha 3 (PSM⍺3). Phenol soluble modulins (PSMs) are involved in the formation and stabilization of Staphylococcus aureus biofilms, making sensitive methods of detecting and characterizing these fibrils a pressing need. Our experimental data, coupled with spectroscopic simulations, reveals the simultaneous presence of cross-⍺ and cross-β polymorphs within samples of PSM⍺3 fibrils. We also report a new spectroscopic feature indicative of cross-alpha fibrils.
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 polysulfates 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.
Accelerating AutoDock VINA with GPUs
Authors: Shidi Tang , Ruiqi Chen , Mengru Lin , Qingde Lin , Yanxiang Zhu , Jiansheng Wu , Haifeng Hu , Ming Ling
Published: February 2022

AutoDock VINA is one of the most-used docking tools in the early stage of modern drug discovery. It uses a Monte-Carlo based iterated search method and multithreading parallelism scheme on multicore machines to improve docking accuracy and speed. However, virtual screening from huge compound databases is common for modern drug discovery, which puts forward a great demand for higher docking speed of AutoDock VINA. Therefore, we propose a fast method VINA-GPU, which expands the Monte-Carlo based docking lanes into thousands of ones coupling with a largely reduced number of search steps in each lane. Furthermore, we develop a heterogeneous OpenCL implementation of VINA-GPU that leverages thousands of computational cores of a GPU, and obtains a maximum of 403-fold acceleration on docking runtime when compared with a quad-threaded AutoDock VINA implementation. In addition, a heuristic function was fitted to determine the proper size of search steps in each lane for a convenient usage. The VINA-GPU code can be freely available at https://github.com/DeltaGroupNJUPT/Vina-GPU for academic usage.
Operando Studies of Iodine Species in an Advanced Oxidative Water Treatment Reactor
Authors: Moustafa Ahmed , Evans Alex , Hofstetter Simmon , Boutros Jenny , Pourrezaei Parastoo , Zhang Cheng , Patterson-Fortin Laura , Laing Charles , Goertzen Carter , Smith Richard , Code Kenneth R , Cheng Ning , Blanchard Peter E R , Bettman Nathan , Alam Raquibul , McPhedran Kerry , Fallah Zohreh , Roberts Edward P L , Gaultois Michael
Published: February 2022

We present an electrochemical advanced oxidation process (eAOP) reactor employing expanded graphite, potassium iodide (KI), and electrical current, which demonstrates an exceptionally high rate of inactivation of E. coli (6log reduction in viable cells) at low current density 0.12 mA/cm^2), with low contact time (5 minutes) and low concentration of KI (10 ppm). Operando X-ray fluorescence mapping is used to show the distribution of iodine species in the reactor, and operando X-ray absorption spectroscopy in the anodic chamber reveals iodine species with higher effective oxidation state than periodate. Operando electrochemical measurements confirm the conditions in the anodic chambers are favourable for the creation of highly oxidized iodine products. The killing efficiency of this new eAOP reactor far exceeds that expected from either traditional iodine-based electrochemical water treatment or advanced oxidation systems alone, a phenomenon that may be associated with the production of highly oxidized iodine species reported here.
ChemPlot, a Python library for chemical space visualization
Authors: Sorkun Murat Cihan , Mullaj Dajt , Koelman J. M. Vianney A. , Er Süleyman
Published: February 2022

Visualizing chemical spaces streamlines the analysis of molecular datasets by reducing the information to human perception level, hence it forms an integral piece of molecular engineering, including chemical library design, high-throughput screening, diversity analysis, and outlier detection. We present here ChemPlot, which enables users to visualize the chemical space of molecular datasets in both static and interactive ways. ChemPlot features structural and tailored similarity methods, together with three different dimensionality reduction methods: PCA, t-SNE, and UMAP. ChemPlot is the first visualization software that tackles the activity/property cliff problem by incorporating tailored similarity. With tailored similarity, the chemical space is constructed in a supervised manner considering target properties. Additionally, we propose a metric, the Distance Property Relationship score, to quantify the property difference of similar (i.e. close) molecules in the visualized chemical space. ChemPlot can be installed via Conda or PyPi (pip). Its web application is freely accessible at https://www.amdlab.nl/chemplot/.
: Strong bidentate coordination for surface passivation and ligand-shell engineering of lead halide perovskite nanocrystals in the strongly quantum confined regime
Authors: Malinoski Aaron , Hu Guoxiang , Wang Chen
Published: February 2022

The surface of lead halide perovskite nanocrystals (PNCs) is unique compared to conventional metal chalcogenide or pnictogenide semiconductor nanoparticles for its ionic character and the dynamic ligand layer, which makes them unstable in stock solutions and hinders the development of surface engineering strategies. This work employs a chelating strategy to form stable coordination on the PNC surface. Through screening a series of heterocyclic aromatic carboxylates, we found the best ligand, picolinate (PIC), with exceptional passivation effect to the surface traps of CsPbBr3 PNCs in the strongly quantum confined regime, resulting in > 0.8 photoluminescence quantum yields. The exciton lifetime in the passivated PNC approaches the radiative decay limit in various solvents. From an NMR titration experiment, the binding affinity of PIC is estimated to be at least 15 to 30 folds stronger than the original ligand from synthesis. The NMR and FTIR spectroscopic data and first-principles calculations elucidate the bidentate nature of the PIC coordination at the surface Pb site and the coadsorption of the ammonium-PIC ion pair. In apolar solvents, such as cyclohexane, the binding of PIC is stoichiometric to the available surface sites, suggesting the structure as a potent candidate for anchoring functional molecular structures to the PNC surface. In polar solvents, the strong affinity of PIC on the PNC surface provides protection for carrying out the precipitation-redissolution purification procedure that removes synthetic residual from the as-synthetic PNC samples. By modifying the purification procedure, we also develop a cation exchange procedure to replace the original oleylammonium cation with desired structures that consist of an ammonium anchoring group. Our results provide a direction for constructing strong interactions to protect the vulnerable surface of PNCs and pave the road for developing surface engineering strategies to functionalize these nanoparticles.
Screening for inhibitors of main protease in SARS-CoV-2: in silico and in vitro approach avoiding secondary amides
Authors: Yamamoto Kazuki , Yasuo Nobuaki , Sekijima Masakazu
Published: February 2022

In addition to vaccines, antiviral drugs are essential for suppressing COVID-19. Although several inhibitor candidates were reported for SARS-CoV-2 main protease, most are highly polar peptidomimetics with poor oral bioavailability and cell membrane permeability. Here, we conducted structure-based virtual screening and in vitro assays to obtain hit compounds belonging to a new chemical space excluding secondary amides. In total, 180 compounds were subjected to the primary assay at 20 μM, and nine compounds with inhibition rates higher than 5% were obtained. The IC50 of six compounds was determined in dose-response experiments, with the values on the order of 100 μM. Although nitro groups were enriched in the substructure of the hit compounds, they did not significantly contribute to the binding interaction in the predicted docking poses. Physicochemical properties prediction showed good oral absorption. These new scaffolds are promising candidates for future optimization.