bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Exploration of Bio-inspired Cascade Reactions: A One-Pot Total Synthesis of Nesteretal A
Authors: Leblond Axel , Houari Inès , Leblanc Karine , Poupon Erwan , Beniddir Mehdi
Published: February 2022

Nesteretal A was recently isolated from a marine actinomycete. An appealing and challenging cage-structure along with an unusual biosynthetic pathway prompted us to explore an expeditious bio-inspired total synthesis of nesteretal A. An unconventional strategy was chosen and a cascade reaction starting from diacetyl was studied. Under organocatalytic conditions mimicking an aldolase-type sequence with a cyclic secondary amine, nesteretal A was detected and targeted through LC-MS/MS and NMR analyses. Starting from a double aldolization of three units, an intramolecular succession of aldolizations and acetalizations probably drives the highly reproducible formation of nesteretal A. An easy isolation protocol has been devised to overcome a non-surprising low yield but largely counterbalanced by the straightforwardness and cost-effectiveness of this first total synthesis of nesteretal A.
Multiscale Modeling of Electronic Spectra Including Nuclear Quantum Effects
Authors: Fehér Péter , Madarász Ádám , Stirling András
Published: February 2022

Theoretical prediction of electronic absorption spectra without input from experiment is no easy feat as it requires addressing all the factors that affect line shapes. In practice, however, the methodologies are limited to treat these ingredients only to a certain extent. Here we present a multiscale protocol that addresses the temperature, solvent and nuclear quantum effects, anharmonicity and reconstruction of the final spectra from the individual transitions. First, QM/MM molecular dynamics is conducted to obtain trajectories of solute-solvent configurations, from which the corresponding quantum corrected ensembles are generated through the Generalized Smoothed Trajectory Analysis (GSTA). The optical spectra of the ensembles are then produced by calculating vertical transitions using TDDFT with implicit solvation. To obtain the final spectral shapes, the stick spectra from TDDFT are convoluted with Gaussian kernels where the half-widths are determined by a statistically motivated strategy. We have tested our method by calculating the UV-vis spectra of a recently discovered acridine photocatalyst in two redox states. Vibronic progressions and broadenings due to the finite lifetime of the excited states are not included into the methodology yet. Nuclear quantization affects the relative peak intensities and widths, which is necessary to reproduce the experimental spectrum. We have also found that using only the optimized geometry of each molecule works surprisingly well if a proper empirical broadening factor is applied. This is explained by the rigidity of the conjugated chromophore moieties of the selected molecules which are mainly responsible for the excitations in the spectra. In contrast, we have also shown that other parts of the molecules are flexible enough to feature anharmonicities that impair the use of other techniques such as Wigner sampling.
Controlling the Optical and Catalytic Properties of Artificial Metalloenzyme Photocatalysts Using Chemogenetic Engineering
Authors: Zubi Yasmine S. , Liu Bingqing , Gu Yifan , Sahoo Dipankar , Lewis Jared
Published: February 2022

Visible light photocatalysis enables a broad range of organic transformations that proceed via single electron or energy transfer. Metal polypyridyl complexes are among the most commonly employed visible light photocatalysts. The photophysical properties of these complexes have been extensively studied and can be tuned by modifying the substituents on the pyridine ligands. On the other hand, ligand modifications that enable substrate binding to control reaction selectivity remain rare. Given the exquisite control that enzymes exert over electron and energy transfer processes in nature, we envisioned that artificial metalloenzymes (ArMs) created by incorporating Ru(II) polypyridyl complexes into a suitable protein scaffold could provide a means to control photocatalyst properties. This study describes approaches to create covalent and non-covalent ArMs from a variety of Ru(II) polypyridyl cofactors and a prolyl oligopeptidase scaffold. A panel of ArMs with enhanced photophysical properties were engineered, and the nature of the scaffold/cofactor interactions in these systems was investigated. These ArMs provided higher yields and rates than Ru(Bpy)32+ for the reductive cyclization of dienones and the [2+2] photocycloaddition between C-cinnamoyl imidazole and 4-methoxystyrene, suggesting that protein scaffolds could provide a means to improve the efficiency of visible light photocatalysts.
Continuous Flow Bioconjugations of NIR-AZA Fluorophores via Strained Alkyne Cycloadditions with Intra-chip Fluorogenic Monitoring
Authors: O'Shea Donal , Fitzgerald Sheila
Published: February 2022

The importance of bioconjugation reactions continues to grow as the need for cell specific targeting and dual therapeutic plus diagnostic medical applications increase. This necessitates new bioconjugation chemistries, synthetic and analytical methods. With this goal, continuous flow bioconjugations were readily achieved with short residence times for strained alkyne substituted carbohydrate and peptide biomolecules in reaction with azide and tetrazine substituted fluorophores. The catalyst and reagent-free inverse electron demand tetrazine cycloadditions proved more favourable than the azide 1,3-dipolar cycloadditions. The use of a fluorogenic tetrazine fluorophore in a glass channelled reactor chip allowed for intra-chip reaction monitoring by recording fluorescence intensities at various positions throughout the chip. As the Diels-Alder reactions proceeded through the chip, the fluorescence intensity increased accordingly in real-time. This novel approach to continuous flow bioconjugation reaction with monitoring may offer advantages over post-chip analysis.
MoloVol: an easy-to-use program to calculate various volumes and surface areas of chemical structures and identify cavities
Authors: Maglic Jasmin B. , Lavendomme Roy
Published: February 2022

Cavities are a ubiquitous feature of chemical structures encountered in various fields ranging from supramolecular chemistry to molecular biology. They are involved in the encapsulation, transport, and transformation of guest molecules, thus necessitating a precise and accessible tool for estimating and visualizing their size and shape. MoloVol, a free, user-parametrizable, open-source software, developed for calculating a range of geometric features for both unit cell and isolated structures is presented here. MoloVol utilizes up to two spherical probes to define cavities, surfaces, and volumes. The program was optimized by combining an octree data structure with voxel-partitioned space allowing for even high-resolution protein structure calculations at reasonable timescales. MoloVol comes with a user-friendly graphic interface along with a command line interface for high throughput calculations. It was written in C++ and is available on Windows, macOS, and Linux distributions.
COVID-19:Attacks the 1-Beta Chain of Hemoglobin and Captures the Porphyrin to Inhibit Human Heme Metabolism
Authors: wenzhong liu , hualan li
Published: February 2022

The novel coronavirus pneumonia is a contagious acute respiratory disease caused by the SARS-COV-2 coronavirus. The pathogenic mechanism of the novel coronavirus is unknown, which presents a significant impediment to the patient rescue. A conserved domain search strategy was utilized in this work to determine that a large number of viral proteins could bind to hemoglobin. S could bind to extracellular hemoglobin. SARS-COV-2 virus proteins interacted with porphyrins. SARS-COV-2 viruses could synthesize heme from porphobilinogen and encode all the similar enzymes required for the process. Both E and ORF3a contained heme-binding sites. ORF3a's Arg134 and E's Cys44 were the heme-iron binding sites, respectively. ORF3a also contained homologous domains to human cytochrome C reductase and bacterial EFeB protein. The molecular docking analysis revealed that ORF3a and ORF8 proteins were shown to be capable of attacking hemoglobin's 1-beta chain, whereas ORF3a was found to be effective in capturing heme for dissociation to iron and porphyrin. Deoxyhemoglobin was more susceptible to viral attack than oxidized hemoglobin. In summary, the combination of viral proteins to porphyrins and their metal compounds would improve the ability to permeate cell membranes and generate oxygen free radicals (ROS). It may be associated with viral infections and epidemic transmission. Viral proteins regulated the production and function of NO, CO and CO2 by inhibiting the activity of hemoglobin, thereby affecting immune cell function. Viral proteins' attack on hemoglobin could result in symptoms such as respiratory distress and blood clotting, damage to numerous organs and tissues, and disruption of normal human heme metabolism.
Synthesis of Aryl Sulfides by Metal-Free Arylation of Thiols with Diaryliodonium Salts
Authors: Sarkar Sudeep , Wojciechowska Natalia , Rajkiewicz Adam A. , Kalek Marcin
Published: February 2022

Metal-free arylation of thiols with diaryliodonium salts has been developed. The application of a strong organic base ena-bles the C–S bond formation under mild and experimentally simple conditions. The method allows for the synthesis of aryl sulfides containing a broad range of aryl groups from an array of thiols, including aryl, heteroaryl, and alkyl ones. The mechanism of the reaction was studied by DFT calculations, demonstrating that is follows the inner sphere pathway involv-ing the incipient formation of Ar2I(SR) intermediate, followed by the reductive elimination.
The impact of binary water-CO2 isotherm models on the optimal performance of sorbent-based direct air capture processes.
Authors: Young John , García-Díez Enrique , Garcia Susana , van der Spek Mijndert
Published: February 2022

Direct air capture (DAC) is an auspicious technology in pursuing negative CO2 emissions. A promising process is temperature vacuum swing adsorption (TVSA) employing amine functionalised adsorbents such as Lewatit® VP OC 1065, which is selected as a benchmark sorbent in this study. To further improve process design, and critically lower costs, detailed modelling of DAC cycles is imperative. However, the multi-component adsorption on these materials, particularly the cooperative adsorption of CO2 and H2O, is crudely understood, and yet to be described in mathematical terms, prohibiting sound modelling efforts. Here, we commit in-depth understanding of the effect of humidity on CO2 adsorption and demonstrate how this impacts modelling of DAC cycles. We present two novel mechanistic co-adsorption isotherm models to describe water's effect on CO2 adsorption and find a good fit to original experimental co-adsorption data. We also show the considerable improvement in predictions of these models when compared to an empirical co-adsorption isotherm model from literature. A detailed TVSA DAC cycle process model is then used elucidating how different co-adsorption models affect the predicted process performance. It is found that the two novel isotherm models generate similar results and Pareto fronts, whilst the minimum work equivalent calculated using the more conservative of the two models is found to be 2.49 MJ kg-1 for the case study considered. These mathematical descriptions laid out will lead to more accurate modelling and optimisation of cyclic DAC adsorption processes, prompting a greater understanding of the material-process combinations ideal for DAC and how costs can be driven down in the years to come. Importantly, they allowed us to independently benchmark a Climeworks type DAC process, providing key DAC performance data to the public domain.
Molecular Electrochemical Reductive Splitting of Dinitrogen with a Molybdenum Complex
Authors: Merakeb Lydia , Bennaamane Soukaina , Clot Eric , Mézailles Nicolas , Robert Marc
Published: February 2022

Nitrogen reduction in mild conditions (i.e. room temperature and atmospheric pressure) and using a non-fossil source of hydrogen remains a high chemistry challenge. Molecular metal complexes, notably Mo based, have recently shown to be active for such nitrogen fixation. In this work, we report about the electrochemical N2 splitting with MoIII triphosphino com-plex ((PPP)MoI3), at room temperature and a moderately negative potential. A MoIV nitride species was generated, which was confirmed by electrochemistry and NMR studies. The reaction goes through the bi-electronic reduction of the starting Mo species, coordination of an N2 molecule, and further splitting to a MoIV nitride complex. Preliminary DFT investigation supports the intermediacy of a bridging MoIN2MoI dinitrogen dimer evolving to the Mo nitride via a low energy transition state. This example joins a short list of molecular electrochemical complexes for N2 reductive cleavage. It opens a door to molecular electrochemical PCET conversion studies of N2 to NH3.
How much can novel solid sorbents reduce the cost of post-combustion CO2 capture? A techno-economic investigation on the cost limits of pressure-vacuum swing adsorption
Authors: Subraveti Sai Gokul , Roussanaly Simon , Anantharaman Rahul , Riboldi Luca , Rajendran Arvind
Published: February 2022

This paper focuses on identifying the cost limits of two single-stage pressure-vacuum swing adsorption (PVSA) cycles for post-combustion CO2 capture if the ``ideal'' zero-cost adsorbent can be discovered. Through an integrated techno-economic optimisation, we simultaneously optimise the adsorbent properties (adsorption isotherms and particle morphology) and process design variables to determine the lowest possible cost of CO2 avoided (excluding the CO2 conditioning, transport and storage) for different industrial flue gas CO2 compositions and flow rates. The CO2 avoided cost for PVSA ranges from 87.1 to 10.4 € per tonne of CO2 avoided, corresponding to CO2 feed compositions of 3.5 mol% to 30 mol%, respectively. The corresponding costs for a monoethanolamine based absorption process, using heat from a natural gas plant, are 76.8 to 54.8 EUR per tonne of CO2 avoided, respectively showing that PVSA can be attractive for flue gas streams with high CO2 compositions. The ``ideal" adsorbents needed to attain the lowest possible CO2 avoided costs have a range of CO2 affinities with close to zero N2 adsorption, demonstrating promise for adsorbent discovery and development. The need for simultaneously optimizing the particle morphology and the process conditions are emphasized.
Controllable phycobilin modification: an alternative photoacclimation response in cryptophyte algae
Authors: Spangler Leah , Yu Mina , Jeffrey Philip , Scholes Gregory
Published: February 2022

Cryptophyte algae are well known for their ability to survive under low light conditions through the use of their auxiliary light harvesting antennas, phycobiliproteins. Mainly acting to absorb light where chlorophyll cannot (500-650 nm), phycobiliproteins also play an instrumental role in helping cryptophyte algae respond to changes in light intensity through the process of photoacclimation. Until recently, photoacclimation in cryptophyte algae was only observed as a change in the cellular concentration of phycobiliproteins; however, an additional photoacclimation response was recently discovered that causes shifts in the phycobiliprotein absorbance peaks following growth under red, blue, or green light. Here, we reproduce this newly identified photoacclimation response in two other species of cryptophyte algae, P. sulcata and H. pacifica, and elucidate the origin of the response on the protein level. We compare isolated native and photoacclimated phycobiliproteins for these two species using spectroscopy and mass spectrometry, and we report the x-ray structures of the PC577 light harvesting complex and corresponding photoacclimated complex. We find that neither the protein sequences, nor the protein structures are modified by photoacclimation. We conclude that cryptophyte algae change a chromophore in one site of their phycobiliprotein beta-subunits as part of the photoacclimation response to changes in the spectral quality of light. Ultrafast pump-probe spectroscopy shows that the energy transfer is weakly affected by the photoacclimation.
Water-mediated adhesion of oil sands on solid surfaces at low temperature
Authors: Yang Qimeng , You Jae Bem , Tian Boran , Sun Shaofeng , Daniel Dan , Liu Qi , Zhang Xuehua
Published: February 2022

Adhesion of frozen granular materials on solid surfaces creates various problems for surface cleaning, reduces the carrying capacity of vehicles, and increases energy consumption for in-land transportation. Here we report that water content determines the adhesion strength of oil sands on solid surfaces at temperature of -2.5 ◦C to -20 ◦C. Our measurements by X-ray micro-computed tomography revealed that water forms capillary bridges between the sand particles and the solid substrate and more air gaps at the interface between oil sands and the substrate are filled with interstitial water at a higher content. We experimentally measured the minimal force required to push the frozen oil sands off the substrate and identified that the adhesion strength increased linearly with water content from 4% to 14% on both rubber and steel substrate. For short freezing time at a fixed water content, lowering the temperature increased the adhesion strength on the steel substrate. Fouling from a layer of bitumen or asphaltenes aggravated the adhesion of oil sands on steel. A theoretical model was proposed to rationalize the linear relationship between water content and the adhesion strength, based on the contact area between ice and the substrate. We also found an effective method to reduce the adhesion of oil sands by spraying a little amount of anti-freezing liquid on the substrate. Our approach may reduce the energy consumption in transport and processing of wet granular materials, and potentially save manpower and the cost from cleaning in industrial operations. The insight from our work may have wide applicability to many natural/industrial processes, such as soil formation, food processing, and porous structures in ice crystal-templating nanomaterials synthesis by freezing-drying.
Chemical Potential Driven Reorganization of Anions between Stern and Diffuse Layers at the Air/Water Interface
Authors: Kumal Raju , Nayak Srikanth , Bu Wei , Uysal Ahmet
Published: February 2022

Ion adsorption and transfer at charged interfaces play key roles in various industrial and environmental processes. Molecular scale details of ion-ion, ion-water, and ion-surface interactions and their dependence on the character of the ion (ion-specific effects) are still debated. Complex ions, such as SCN- and SeCN-, are particularly interesting due to their unexpected adsorption trends which are ascribed to their permanent dipole moment and non-spherical shape. Here, we combine vibrational sum frequency generation (VSFG) spectroscopy and surface sensitive synchrotron X-ray studies to provide a detailed description of SeCN- adsorption at a charged surfactant monolayer at the air/aqueous interface. The results show that the increasing chemical potential may lead to further reorganization of the adsorbed ions, even though the total interfacial ion population does not change.
Total Synthesis via Biomimetic Late-stage Heterocyclization, Assignment of the Relative Configuration and Biological Evalu-ation of the Nitraria Alkaloid (±)-Nitrabirine
Authors: Kagho Mervic Dongock , Hintersatz Helen , Ihle Andreas , Zeng Haoxuan , Schrey Hedda , Colisi Wera , Klahn Philipp , Stadler Marc , Bruhns Clemens , Rüffer Tobias , Lang Heinrich , Banert Klaus
Published: February 2022

The racemic total synthesis of nitrabirine (5) together with its previously undescribed epimer 2-epi nitrabirine (5’) is accomplished via a six-step route based on a biomimetic late-stage heterocyclization. This allowed the assignment of the relative configuration of nitrabirine by the lanthanide-induced shifts (LIS) experiment, later on confirmed by X-ray diffrac-tion of obtained single crystals. Furthermore, oxidation studies demonstrated that the direct N-oxidation of nitrabirine does not yield nitrabirine N-oxide as reported earlier. In contrast, the reaction of hydrogen peroxide with nitrabirine (5) yields the salt 24’ whereas, under the same conditions, 2-epi nitrabirine (5’) surprisingly leads to a beforetime uncharac-terized product 22. Finally, a Fischer-Indole reaction gave access to novel tetracyclic nitrabirine derivatives 26a-d. A comprehensive biological evaluation of nitrabirine (5), 2-epi nitrabirine (5’), and all derivatives synthesized in this study revealed general biofilm dispersal effects against Candida albicans. Moreover, specific compounds showed moderate antibacterial as well as potent cytotoxic activities.
Why Is Tetrahydrofuran a Good Solvent for Calcium Batteries? Insights From Ab Initio Molecular Dynamics Simulations
Authors: Pathreeker Shreyas , Hosein Ian
Published: February 2022

Calcium batteries are rapidly emerging as a potential, future energy storage technology; however, their advancement relies heavily on understanding of the liquid electrolyte component in terms of stability and interactions with a calcium metal anode. Tetrahydrofuran, a cyclic ether, is an experimentally common and promising solvent for the preparation of stable and efficient calcium electrolytes. However, insights into the reasons why are lacking, which could unveil key principles to electrolyte design. In this report, we provide a theoretical study employing ab initio molecular dynamics (AIMD) simulations of the interactions of Ca metal with the cyclic ether tetrahydrofuran (THF). The results show that the electrochemical breakdown and decomposition of THF at the Ca surface is highly orientation- and surface-site dependent, thereby significantly reducing the likelihood of its instability in a randomly organized bulk solvent. Likewise, in bulk electrolytes, its likelihood for breakdown is further diminished, in preference for coordination Ca2+ to form solvated structure. Hence, the finding that molecules require such strict conditions for their decomposition is an important selection and design principle for any solvent to prepare suitable calcium electrolytes. These findings are critical to the advancement of the calcium batteries.
Why Is Tetrahydrofuran a Good Solvent for Calcium Batteries? Insights From Ab Initio Molecular Dynamics Simulations
Authors: Pathreeker Shreyas , Hosein Ian D.
Published: February 2022

Calcium batteries are rapidly emerging as a potential, future energy storage technology; however, their advancement relies heavily on understanding of the liquid electrolyte component in terms of stability and interactions with a calcium metal anode. Tetrahydrofuran, a cyclic ether, is an experimentally common and promising solvent for the preparation of stable and efficient calcium electrolytes. However, insights into the reasons why are lacking, which could unveil key principles to electrolyte design. In this report, we provide a theoretical study employing ab initio molecular dynamics (AIMD) simulations of the interactions of Ca metal with the cyclic ether tetrahydrofuran (THF). The results show that the electrochemical breakdown and decomposition of THF at the Ca surface is highly orientation- and surface-site dependent, thereby significantly reducing the likelihood of its instability in a randomly organized bulk solvent. Likewise, in bulk electrolytes, its likelihood for breakdown is further diminished, in preference for coordination Ca2+ to form solvated structure. Hence, the finding that molecules require such strict conditions for their decomposition is an important selection and design principle for any solvent to prepare suitable calcium electrolytes. These findings are critical to the advancement of the calcium batteries.
Direct Aerobic Generation of a Ferric Hydroperoxo Intermediate via a Preorganized Secondary Coordination Sphere
Authors: Jesse Kate , Anferov Sophie , Collins Kelsey , Valdez-Moreira Juan , Filatov Alexander , Anderson John
Published: February 2022

Enzymes exert control over the reactivity of metal centers with precise tuning of the secondary coordination sphere of active sites. One particularly elegant illustration of this principle is in the controlled delivery of proton and electron equivalents in order to activate abundant but kinetically inert oxidants such as O2 for oxidative chemistry. Chemists have drawn inspiration from biology in designing molecular systems where the secondary coordination sphere can shuttle protons or electrons to substrates. However, a biomimetic activation of O2 requires the transfer of both protons and elec-trons, and molecular systems where ancillary ligands are designed to provide both of these equivalents are comparative-ly rare. Here we report the use of a dihydrazonopyrrole (DHP) ligand complexed to Fe to perform exactly such a biomi-metic activation of O2. In the presence of O2, this complex directly generates a high spin Fe(III)-hydroperoxo intermediate which features a DHP• ligand radical via ligand-based transfer of an H-atom. This system displays oxidative reactivity and ultimately releases hydrogen peroxide, providing insight on how secondary coordination sphere interactions influence the evolution of oxidizing intermediates in Fe-mediated aerobic oxidations.
Photoredox Catalyzed Site-Selective Generation of Carbanions from C(sp3)-H bonds in Amines
Authors: Murugesan Kathiravan , Donabauer Karsten , Narobe Rok , Bauer Armin , Derdau Volker , Koenig Burkhard
Published: February 2022

The selective activation of sp3 carbon-hydrogen bonds in presence of multiple C¬-H bonds is challenging and remains of supreme importance in chemical research. Herein, we describe the activation of a C(sp3) H bond in α position to an amine via a carbanion intermediate. In the presence of several α amine sites, only one specific position is selectively activated. Applying this protocol, the proposed carbanion intermediate was effectively trapped with different electrophiles such as deuterium (D+), tritium (T+), or carbonyl compounds compiling over 50 examples. Further, this methodology was used to install deuterium or tritium in different drug derivatives (> 10 drugs) at a selected position in a late-stage functionalization. In addition, the protocol is suitable for a gram-scale synthesis and a detailed mechanistic investigation has been carried out to support our hypothesis.
Diketopyrrolopyrrole (DPP)-based polytriazoles: Synthesis and Immobilization by click reaction†
Authors: samanta debasis , Ramar P , Raghavendra V
Published: February 2022

Diketopyrrolopyrrole-based polymers are generally immobilized to various surfaces for device fabrications and sensor applications. preparative methods as well as Immobilization processes play a significant role for device efficacy. In this paper, we demonstrated that while "click" polymerization can be conveniently used for the preparation of diketopyrrolopyrrole DPP-based polymer, self-assembled monolayer (SAM) formation technique is convenient for efficient Immobilization to surfaces. Computational models have been used to theoretically calculate various energy parameters. Finally, some of those surfaces have been used as reusable photocatalytic chips, in line with mechanistically similar photovoltaic chips
Comparing dimerization free energies and binding modes of small aromatic molecules with dierent force �elds
Authors: Patmanidis Ilias , Alessandri Riccardo , de Vries Alex H. de Vries , Marrink Siewert J.
Published: February 2022

Dimerization free energies are fundamental quantities that describe the strength of interaction of dierent molecules. Obtaining accurate experimental values for small molecules and disentangling the conformations that contribute most to the binding can be extremely dicult, due to the size of the systems and the small energy dierences. In many cases, one has to resort to computational methods to calculate such properties. In this work, we used molecular dynamics simulations in conjunction with metadynamics to calculate the free energy of dimerization of small aromatic rings comparing three models from popular online servers for atomistic force �elds, namely G54a7, CHARMM36 and OPLS. We show that, regardless of the force �eld, the pro�les for the dimerization free energy of these compounds are very similar. However, signi�cant care needs to be taken when studying larger molecules, since the deviations from the trends increase with the size of the molecule, resulting in force �eld dependent preferred stacking modes, e.g. pyrene and tetracene. Our results provide a useful background for using topology builders to model systems which rely on stacking of aromatic moieties, relevant in areas ranging from drug design to supramolecular assembly.
Role of adatom defects in the adsorption of polyaromatic hydrocarbons on metallic substrates
Authors: Dissanayake Dushanthi , Hassan Yarra , Tuca Emilian , Paci Irina
Published: February 2022

The adsorption of polyaromatic hydrocarbons (PAHs) on metallic substrates has been of interest in the field of optoelectronics due to the possibility of designing complex materials with tunable properties through surface functionalization with organic molecules. Much of the modelling research in this field has focused on perfectly symmetrical (idealized) substrates. Limited research has investigated the effect of substrate irregularities, such as adatoms, on the binding of PAHs onto substrates. Here, we examine how the presence of substrate-bound adatoms affects the binding of coronene and hexahelicene monomers and dimers onto Au(111) and Cu(111) substrates using a density functional theory approach. We found that helicene monomers were more effectively able to adapt to the presence of the adatoms than coronene by coiling around the adatoms. Whereas upon adsorption on an ideal (111) surface, coronene can establish significantly stronger dispersive interactions than helicenes, adatom defects reverse the trend. For helicenes, the degree of flattening near the surface and molecular coiling were strongly influenced by the extent of the adatom defect, as a result of the interplay between the molecule’s drive to maximize overlap with the underlying surface and the enhanced reactivity of lower-coordinated adatoms.
Biological activity In vitro, absorption, BBB penetration and toxicity of nanoformulation of BT44, a RET agonist with disease-modifying potential for the treatment of neurodegeneration
Authors: Haider Malik Salman , Mahato Arun Kumar , Kotliarova Anastasiia , Forster Stefan , Böttcher Bettina , Stahlhut Philipp , Sidorova Yulia , Luxenhofer Robert
Published: February 2022

BT44 is a novel, second generation glial cell line-derived neurotropic factor (GDNF) mimetic, with improved biological activity and a lead compound for the treatment of neurodegenerative disorders. Like many other small molecules, it suffers from intrinsic poor aqueous solubility, posing significant hurdles at various levels for its preclinical development and clinical translation. Herein, we report a novel poly(2-oxazoline)s (POx) based BT44 micellar nanoformulation with ultra-high drug loading capacity of 47 wt.%. The BT44 nanoformulations were comprehensively characterized by 1H-NMR spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), dynamic light scattering (DLS) and cryo-transmission/scanning electron microscopy (cryo-TEM/SEM). The DSC, XRD and redispersion studies collectively confirmed that the BT44 formulation can be stored as a lyophilized powder and can be redispersed when needed. The DLS further suggested that the redispersed formulation is suitable for parenteral administration (Dh ≈ 70nm). The cryo-TEM analysis revealed the presences of worm like structures. The BT44 formulation retains biological activity in immortalized cells and in cultured dopamine neurons. The micellar formulation of BT44 exhibited improved absorption and blood-brain barrier (BBB) penetration and produced no acute toxic effects in mice. In conclusion, herein, we have developed an ultra-high BT44 loaded aqueous injectable nanoformulation, which can be used to pave way for its preclinical and clinical development for the management of neurodegenerative disorders.
A Study in Red: The Overlooked Role of Azo-Moieties in Polymeric Carbon Nitride Photocatalysts with Strongly Extended Optical Absorption
Authors: Mitoraj Dariusz , Krivtsov Igor , Li Chunyu , Rajagopal Ashwene , Im Changbin , Adler Christiane , Köble Kerstin , Khainakova Olena , Hniopek Julian , Neumann Christof , Turchanin Andrey , da Silva Ivan , Schmitt Michael , Leiter Robert , Lehnert Tibor , Popp Jürgen , Kaiser Ute , Jacob Timo , Streb Carsten , Dietzek Benjamin , Beranek Radim
Published: February 2022

The unique optical and photoredox properties of heptazine-based polymeric carbon nitride (PCN) materials make them promising semiconductors for driving various productive photocatalytic conversions. However, their typical absorption onset at ca. 430-450 nm is still far from optimum for efficient sunlight harvesting. Despite many reports of successful attempts to extend the light absorption range of PCNs, the determination of the structural features responsible for the red shift of the light absorption edge beyond 450 nm has often been obstructed by the highly disordered structure of PCNs and/or low content of the moieties responsible for changes in optical and electronic properties. In this work, we implement a high-temperature (900 °C) treatment procedure for turning the conventional melamine-derived yellow PCN into a red carbon nitride. This approach preserves the typical PCN structure but incorporates a new functionality that promotes visible light absorption. A detailed characterization of the prepared material reveals that partial heptazine fragmentation accompanied by de-ammonification leads to the formation of azo-groups in the red PCN, a chromophore moiety whose role in shifting the optical absorption edge of PCNs has been overlooked so far. These azo moieties can be activated under visible-light (470 nm) for H2 evolution even without any additional co-catalyst, but are also responsible for enhanced charge-trapping and radiative recombination, as shown by spectroscopic studies. Our work thus highlights the importance of careful determination of structural features governing the complex interplay between the light absorption, charge separation and catalytic turnover in PCN-based polymers tailored for visible light-driven photocatalysis.
Evaluating scalable supervised learning for synthesize-on-demand chemical libraries
Authors: Alnammi Moayad , Liu Shengchao , Ericksen Spencer S , Ananiev Gene E , Voter Andrew F , Guo Song , Keck James L , Hoffmann F Michael , Wildman Scott A , Gitter Anthony
Published: February 2022

Traditional small molecule drug discovery is a time consuming and costly endeavor. High-throughput chemical screening can only assess a tiny fraction of drug-like chemical space. The strong predictive power of modern machine learning methods for virtual chemical screening enables training models on known active and inactive compounds and extrapolating to much larger chemical libraries. However, there has been limited experimental validation of these models' extensibility toward practical applications on large commercially-available or synthesize-on-demand chemical libraries. Through a prospective evaluation with the bacterial protein-protein interaction PriA-SSB, we demonstrate that ligand-based virtual screening can identify many chemically-diverse active compounds in a large commercial library. We use cross validation to compare many supervised learning models and select a random forest classifier as the best model for this target. When predicting the activity of more than 8 million compounds from Aldrich Market Select, the random forest substantially outperforms a naïve baseline based on chemical structure similarity. 48% of the random forest's 701 selected compounds are active. The random forest model easily scales to score one billion compounds from the synthesize-on-demand Enamine REAL database. We tested 68 chemically-diverse top predictions from Enamine REAL and observed 31 hits (46%), including one with an IC50 value of 1.3 µM.
Preparation of LDO@TiO2 core-shell nanosheets for enhanced photocatalytic degradation of organic pollutions
Authors: Wang Can , Zhang Ruikang , Miao Yucong , Xue Qihui , Yu Borong , Gao Yuanzhe , Han Zhan-gang , Shao Mingfei
Published: February 2022

TiO2-based nanosheets materials with core-shell structure are expected to be one of the promising photocatalysts to degradation of organic pollutions. However, it is a challenge to synthesis of TiO2 shell on functional core materials by desired nucleation and growth process. Layered double hydroxides (LDHs) are considered as ideal platforms to in-situ grow TiO2 and further serve as additional components to construct heterojunction to improve the separation of photo-generated charge carriers. In this work, we report the design and fabrication of anatase TiO2 coated ZnAl-layered double oxide (LDO@TiO2) nanosheets, which involves the in-situ growth of TiO2 on ZnAl-LDH followed by a subsequent calcination treatment. The resulting LDO@TiO2 photocatalyst gives typical core-shell nanosheets morphology with mesoporous structure, which exhibiting excellent photodegradation and mineralization efficiency for organic pollutions.
A Generalized Kinetic Model for Compartmentalization of Organometallic Catalysis
Authors: Jolly Brandon , Liu Chong
Published: February 2022

Compartmentalization is an attractive approach to enhance catalytic activity by retaining reactive intermediates and mitigating deactivating pathways. Such a concept has been well explored in biochemical and more recently, organometallic catalysis to ensure high reaction turnovers with minimal side reactions. However, a scarcity of theoretical framework towards confined organometallic chemistry impedes a broader utility for the implementation of compartmentalization. Herein, we report a general kinetic model and offer design guidance for a compartmentalized organometallic catalytic cycle. In comparison to a non-compartmentalized catalysis, compartmentalization is quantitatively shown to prevent the unwanted intermediate deactivation, boost the corresponding reaction efficiency (𝛾), and subsequently increase catalytic turnover frequency (𝑇𝑂𝐹). The key parameter in the model is the volumetric diffusive conductance (𝐹 ) that describes catalysts’ diffusion propensity across a compartment’s boundary. Optimal values of 𝐹 for a specific organometallic chemistry are needed to achieve maximal values of 𝛾 and 𝑇𝑂𝐹. Our model suggests a tailored compartment design, including the use of nanomaterials, is needed to suit a specific organometallic catalysis. This work provides justification and design principles for further exploration into compartmentalizing organometallics to enhance catalytic performance.
Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane-Sodium Iodide Promoted Vorbrüggen Glycosylation
Authors: Mear Sarah Jane , Nguyen Long V. , Rochford Ashley J. , Jamison Timothy F.
Published: February 2022

By simply adding water and sodium iodide (NaI) to chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis ox-athiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from an achiral tartrate ester.
A copper(I)-catalyzed sulfonylative Hiyama cross-coupling
Authors: Adenot Aurélien , Anthore-Dalion Lucile , Nicolas Emmanuel , Berthet Jean-Claude , Thuéry Pierre , Cantat Thibault
Published: February 2022

An air-tolerant Cu-catalyzed sulfonylative Hiyama cross-coupling reaction enabling the formation of diaryl sulfones is described. Starting from aryl silanes, DABSO and aryliodides, the reaction tolerates a large variety of polar functional groups (amines, ketones, esters, aldehydes). Control experiments coupled with DFT calculations shed light on the mechanism, where the reductive elimination showcases an usual high energy barrier for a Cu(III)/Cu(I) process.
Pumping Between Phases With a Pulsed-Fuel Molecular Ratchet
Authors: Thomas Dean , Tetlow Daniel , Ren Yansong , Kassem Salma , Karaca Ulvi , Leigh David
Published: February 2022

The sorption of species from solution into and onto solids, surfaces, crystals, gels and other matrices, underpins the sequestering of waste and pollutants, the recovery of precious metals, heterogeneous catalysis, many forms of chemical and biological analysis and separation science, and numerous other technologies. In such cases the transfer of the substrate between phases tends to proceed spontaneously, in the direction of equilibrium. Molecular ratchet mechanisms, where kinetic gating selectively inhibits or accelerates particular steps in a process, makes it possible to drive dynamic systems out of equilibrium. Here we report on a small-molecule pump immobilised on and near the surface of polymer beads, that uses an energy ratchet mechanism to actively transport substrates from solution onto the beads away from equilibrium. One complete cycle of the pump occurs with each pulse of a chemical fuel, synchronizing the ratchet dynamics so that the immobilised molecular machines all act in unison. Upon addition of the trichloroacetic acid fuel, micrometre-diameter polystyrene beads functionalised with an average of ~8×10exp10 molecular pumps per bead, sequester from solution crown ethers appended with a fluorescent tag. Following consumption of the fuel, the rings are mechanically trapped in a higher energy, out-of-equilibrium, state on the beads and cannot be removed by dilution nor by switching the binding interactions off. This differs from dissipative assembled materials that require a continuous supply of energy to persist. Addition of a second pulse of fuel causes the uptake of more macrocycles, which can be labelled with a different fluorescent tag. This drives the system progressively further away from equilibrium and also confers sequence information on the deposited structure. The polymer-bound substrates (and the stored energy) can subsequently be released back to the bulk on demand, either emptying one compartment at a time or all at once. Non-equilibrium sorption by using immobilised artificial molecular machines to pump substrates from solution onto and into materials, offers potential for the transduction of energy from chemical fuels for the storage and release of energy and information.
Chemodivergence made possible by micellar photocatalysis: C-H arylation vs. N-dealkylation of chlorinated benzamides in aqueous media
Authors: Cybularczyk-Cecotka Martyna , Predygier Jędrzej , Crespi Stefano , Szczepanik Joanna , Giedyk Maciej
Published: February 2022

Micellar photocatalysis has recently provided new opportunities for the activation of strong carbon chlorine bonds and enabled the valorization of cheap and readily available chlorinated starting materials. Thus far, however, it has mainly explored strongly reducing conditions, which restrict the available chemical space to radical or anionic reactivity. Here, we demonstrate a radical-polar crossover process involving cationic intermediates, which enable chemodivergent functionalization of chlorinated benzamide derivatives in aqueous solutions. The reaction can be guided towards either C H arylation or N dealkylation by simple adjustment of reaction parameters such as the amount of water, the type of surfactant or the amine. The system operates under mild conditions where methylene blue is used as a photocatalyst and blue light emitting diodes are the light source. Tuning the reaction environment not only affects the selectivity of the ionic process, but also alters the mechanism of substrate activation - different forms of the photocatalyst are involved in each of the two reactions.
Measuring Attitude Towards Chemistry, Biology, and Math at a Hispanic-Serving Institution
Authors: Chang Jordan , Menke Erik
Published: February 2022

This work describes the evaluation of the Attitude toward the Subject of Chemistry Inventory (ASCI), as well as two modifications (one for measuring attitude toward math and one for measuring attitude toward biology), for college students at a Hispanic Serving Institution. Instrument reliability was tested via multiple administrations of the instruments,and confirmatory factor analysis supported a two-factor structure similar to an existing model of a revised version of the ASCI for all three instruments. The similar factor structure of the three instruments, coupled with interviews with students, provide validity evidence for the instruments and support an interpretation that one of the subscales aligns with a cognitive aspect of attitude while the other subscale aligns with an affective aspect. The results of these instruments indicate that students have a more positive attitude towards biology than either chemistry or math, and more positive affective attitude than cognitive attitude for all three subjects, although student attitudes show little change with respect to biology, chemistry, or math during a typical semester. However, major perturbations, such as switching to remote instruction mid-semester, can lead to small but significant increases and decreases in attitude.
Electrochemical nano-roughening of gold microstructured electrodes for the enhanced detection of copper and glucose
Authors: Gonzalez Martinez Eduardo , Saem Sokunthearath (Kevin) , Beganovic Nadine , Moran-Mirabal Jose
Published: February 2022

One of the main challenges for electrochemical sensor miniaturization is the fabrication of electrodes with a smaller footprint, while maintaining, or even increasing, their sensitivity for the targeted application. Our research group has previously demonstrated the enhancement of the electroactive surface area of gold electrodes up to 6-fold, relative to planar gold electrodes with the same footprint, through the generation of a wrinkled thin film surface via thermal shrinking. In this work, the electroactive surface area of wrinkled gold electrodes was further enhanced up to 5-fold (30-fold over flat electrodes) using a chronoamperometric pulsing technique. Scanning electron microscopy images showed progressive increase of surface roughness in response to an increasing number of applied pulses. The resulting nanoroughened electrodes present several advantages in addition to the enhanced electroactive surface area. These electrodes offer superior fouling resistance compared to that of wrinkled and flat electrodes when submerged in a solution containing bovine serum albumin at high concentrations. Cyclic voltammetry data also revealed greater sensitivity of nanoroughened electrodes toward anodic copper stripping, where the limit of quantification of copper by the nano-roughened electrodes was 0.3 ppm. Nano-roughened electrodes also allowed the highly sensitive enzyme-free detection of glucose through chronoamperometry, with a limit of detection of 0.5 mM, whereas planar electrodes did not demonstrate any ability to oxidize glucose. We foresee that this methodology to fabricate nanostructured electrodes will accelerate the development of simple, cost-effective and high sensitivity electrochemical platforms.