bluuebunny/crossref_metadata_2025 huggingface dataset:
Au(I)-Catalyzed 6-endo-dig Cyclizations of Aromatic 1,5-Enynes to 2-(Naphthalen-2-yl)anilines Leading to Divergent Syntheses of Benzo[α]carbazole, Benzo[c,h]cinnoline and Dibenzo[i]phenanthridine Derivatives
Authors: Fu Jiayue , Li Bingbing , Wang Xiugui , Liang Qida , Peng Xiaoshi , Yang Lu , Wan Tao , Wang Xinxiu , Lin Bin , Cheng Maosheng , Liu Yongxiang
Published: February 2022

A gold(I)-catalyzed 6-endo-dig cyclization of aromatic 1,5-enyne was developed to synthesize 2-(naphthalen-2-yl)aniline. The functional group tolerance of this cyclization was examined systematically and a possible mechanism was proposed. The derivatization of 2-(naphthalen-2-yl)aniline was carried out to facile access to benzo[α]carbazole, benzo[c,h]cinnoline and dibenzo[i]phenanthridine derivatives in a divergent way.
Molecular Rotor based on an Oxidized Resorcinarene
Authors: Payne Daniel T. , Labuta Jan , Futera Zdenĕk , Březina Václav , Hanyková Lenka , Chahal Mandeep K. , Hill Jonathan P.
Published: February 2022

Molecular single stator-double rotor activity of an oxidized resorcinarene (fuchsonarene) macrocycle containing unsaturated hemiquinonoid groups at its meso positions was investigated. Fuchsonarenes containing two hemiquinonoid substituents at diagonally-opposed meso-positions with two electron rich phenol groups at the remaining meso-positions between the hemiquinonoid groups. All meso-substituents are in proximity at one side of the resorcinarene macrocycle (so-called rccc-type isomer) with rotational activity of the phenol meso-substituents. Rotation rates of the phenol moieties can be controlled by varying temperature, solvent polarity and acidity of the medium of study with rotation being thermally activated in neutral and acidic media and tunable in the range from 2 s-1 to 20,000 s-1. Experimental and computational data indicate that rotation of the mobile phenol meso-substituents is remotely affected by interactions with acidic solvents at the carbonyl C=O groups of macrocyclic acetyloxy groups, which occurs with the emergence of a lower energy electronic absorption band whose intensity is correlated with both the acidity of the medium and the rotation rate of the phenol substituents. Time-dependent DFT calculations suggest that the low energy band is due to a molecular conformational adjustment affecting electronic conjugation caused by strong interaction of macrocyclic acetyloxy carbonyl groups with the acid medium. The work presents a molecular mechanical model for estimating solution acidity and also gives insight into a possible method for modulating rotor activity in molecular machines.
Using Automated Synthesis to Understand the Role of Side Chains on Molecular Charge Transport
Authors: Li Songsong , Jira Edward , Angello Nicholas , Li Jialing , Yu Hao , Moore Jeffrey , Diao Ying , Burke Martin , Schroeder Charles
Published: February 2022

The development of next-generation organic electronic materials critically relies on understanding structure-function relationships in conjugated polymers. However, unlocking the full potential of organic materials requires access to their vast chemical space while efficiently managing the large synthetic workload to survey new materials. In this work, we use automated synthesis to prepare a library of conjugated oligomers with systematically varied side chain composition followed by single-molecule characterization of charge transport. Our results show that molecular junctions with long alkyl side chains exhibit a concentration-dependent bimodal conductance with an unexpectedly high conductance state that arises due to surface adsorption and backbone planarization, which is supported by a series of control experiments using asymmetric, planarized, and sterically hindered molecules. Density functional theory simulations and experiments using different anchors and alkoxy side chains highlight the role of side chain chemistry on charge transport. Overall, this work opens new avenues for using automated synthesis for the development and understanding of organic electronic materials.
Silylium ion Migration Dominated Hydroamidation of Siloxy-alkynes
Authors: Wang Hengding , Jiang Ling , Fan Hongjun
Published: February 2022

ABSTRACT: Intermolecular hydroamidation of internal alkynes has been a long-standing challenge, one of the most successful examples so far is silver-catalyzed hydroamidation of siloxy-alkynes for which meet the standards of atom economic and mild reaction conditions of ideal hydroamidation. However, the mechanism of this reaction remains controversy. Using density function theory (DFT), we revealed that the reaction takes place through a silylium ion migration mediated hydroamidation (SMH) pathway. The SMH pathway goes through two steps, the first step is Ag+ promoted proton and silylium ion exchange between siloxy-alkynes and amide, leading to ketene and silyl-imines, the second step is Ag+ catalyzed nucleophilic addition between ketene and silyl-imines, following with a silylium ion migration afford the final product. In this reaction, Ag+ activate the siloxy-alkyne into silylium ion and silver-ketene through p-π conjugate effect, the silylium ion then act as catalyst. According to our calculation, the scopes of alkynes in this reaction may be extend to silyl-substituted ynamines or silyl-substituted ynamides, and the scopes of amide maybe expanded into p-π conjugate system such as diazoles, diazepines and so on. Our calculations also reveal a concise way to construct substituted enamides through Ag+ catalyzed nucleophilic addition between ketenes (or ketene imines) and silyl-substituted p-π conjugate system such as silyl-imines, silyl-diazoles.
Small but effective: potent light-weight additives modulate prenucleation clusters by specific interactions on the molecular level
Authors: Duchstein Patrick , Schodder Philipp I. , Leupold Simon , Dao Thi Quynh Nhi , Kababya Shifi , Cicconi Maria R. , de Ligny Dominique , Pipich Vitaliy , Eike David , Schmidt Asher , Zahn Dirk , Wolf Stephan E.
Published: February 2022

Small-molecular-weight (MW) additives can strongly impact amorphous calcium carbonate (ACC), playing an elusive role in biogenic, geologic, and industrial calcification. Here, we present molecular mechanisms by which additives regulate stability and composition of both CaCO3 solutions and solid ACC. Potent antiscalants inhibit ACC precipitation by interacting with prenucleation clusters (PNC); they specifically trigger and integrate into PNCs or feed PNC growth. Only PNC-interacting additives are traceable in ACC, considerably stabilizing it against crystallization. The selective incorporation of potent additives in PNCs is a reliable chemical label that provides conclusive chemical evidence that ACC is a molecular precipitate derived PNCs. Our results reveal additive-cluster interactions beyond established mechanistic conceptions. They reassess the role of small-MW molecules in crystallization and biomineralization, while breaking grounds for new sustainable antiscalants.
Open-source Δ-quantum machine learning for medicinal chemistry
Authors: Atz Kenneth , Isert Clemens , Böcker Markus N. A. , Jiménez-Luna José , Schneider Gisbert
Published: February 2022

Certain molecular design tasks benefit from fast and accurate calculations of quantum-mechanical (QM) properties. However, the computational cost of QM methods applied to drug-like compounds currently makes large-scale applications of quantum chemistry challenging. In order to mitigate this problem, we developed DelFTa, an open-source toolbox for predicting small-molecule electronic properties at the density functional (DFT) level of theory, using the Δ-machine learning principle. DelFTa employs state-of-the-art E(3)-equivariant graph neural networks that were trained on the QMugs dataset of QM properties. It provides access to a wide array of quantum observables by predicting approximations to ωB97X-D/def2-SVP values from a GFN2-xTB semiempirical baseline. Δ-learning with DelFTa was shown to outperform direct DFT learning for most of the considered QM endpoints. The software is provided as open-source code with fully-documented command-line and Python APIs.
Δ-Quantum machine learning for medicinal chemistry
Authors: Atz Kenneth , Isert Clemens , Böcker Markus N. A. , Jiménez-Luna José , Schneider Gisbert
Published: February 2022

Many molecular design tasks benefit from fast and accurate calculations of quantum-mechanical (QM) properties. However, the computational cost of QM methods applied to drug-like molecules currently renders large-scale applications of quantum chemistry challenging. Aiming to mitigate this problem, we developed DelFTa, an open-source toolbox for the prediction of electronic properties of drug-like molecules at the density functional (DFT) level of theory, using Δ-machine-learning. Δ-Learning corrects the prediction error (Δ) of a fast but inaccurate property calculation. DelFTa employs state-of-the-art three-dimensional message-passing neural networks trained on a large dataset of QM properties. It provides access to a wide array of quantum observables on the molecular, atomic and bond levels by predicting approximations to DFT values from a low-cost semiempirical baseline. Δ-Learning outperformed its direct-learning counterpart for most of the considered QM endpoints. The results suggest that predictions for non-covalent intra- and intermolecular interactions can be extrapolated to larger biomolecular systems. The software is fully open-sourced and features documented command-line and Python APIs.
Mapping Ambiphile Reactivity Trends in the Anti-(Hetero)annulation of Non-Conjugated Alkenes via Pd(II)/Pd(IV) Catalysis
Authors: Ni Hui-Qi , Cooper Phillippa , Yang Shouliang , Wang Fen , Sach Neal , Bedekar Pranali , Donaldson Joyann , Tran-Dubé Michelle , McAlpine Indrawan , Engle Keary
Published: February 2022

In this study, we systematically evaluate different ambiphilic organohalides for their ability to participate in anti-selective carbo- or heteroannulation with non-conjugated alkenyl amides under Pd catalysis. Detailed optimization of reaction conditions has led to protocols for synthesizing tetrahydropyridines, tetralins, pyrrolidines, and other carbo/heterocyclic cores via [n+2] (n = 3–5) (hetero)annulation. Expansion of scope to otherwise unreactive ambiphilic haloketones through Pd(II)/amine co-catalysis is also demonstrated. Compared to other annulation processes, this method proceeds via a distinct Pd(II)/Pd(IV) mechanism involving Wacker-type directed nucleopalladation. This distinction results in unique reactivity and selectivity patterns, as revealed through assessment of reaction scope and competition experiments.
Fragment-based Sequential Translation for Molecular Optimization
Authors: Chen Benson , Fu Xiang , Barzilay Regina , Jaakkola Tommi
Published: February 2022

Searching for novel molecular compounds with desired properties is an important problem in drug discovery. Many existing frameworks generate molecules one atom at a time. We instead propose a flexible editing paradigm that generates molecules using learned molecular fragments---meaningful substructures of molecules. To do so, we train a variational autoencoder (VAE) to encode molecular fragments in a coherent latent space, which we then utilize as a vocabulary for editing molecules to explore the complex chemical property space. Equipped with the learned fragment vocabulary, we propose Fragment-based Sequential Translation (FaST), which learns a reinforcement learning (RL) policy to iteratively translate model-discovered molecules into increasingly novel molecules while satisfying desired properties. Empirical evaluation shows that FaST significantly improves over state-of-the-art methods on benchmark single/multi-objective molecular optimization tasks.
Systematic Study of the Thermal Properties of Zeolitic Frameworks
Authors: Ducamp Maxime , Coudert François-Xavier
Published: February 2022

We report a systematic study of the thermal and mechanical properties of 134 pure SiO2 zeolites through DFT-based calculations by making use of the quasi-harmonic approximation (out of a total of 242 known fully ordered zeolitic frameworks). The comparison of our results with reported experimental data for several zeolites revealed a very good accuracy and validated our simulation methodology. We observe a wide range of thermal expansion coefficients (from −5 to −35 MK−1), highlighting the great influence of the framework topology over this physical property, while demonstrating that all pure-silica zeolites exhibit negative thermal expansion (NTE). Our simulations also provide a path for the computation of the bulk modulus for each structure, as well as its pressure and temperature dependence. Results revealed a large gamut of bulk modulus values (from 8 to 134 GPa), showing that most frameworks display pressure-induced softening — but not all!
Development of a Modified System to Provide Improved Diastereocontrol in the Linear-Selective Cu-Catalyzed Reductive Coupling of Ketones and Allenamides
Authors: Ho Dang , Gargaro Samantha , Klake Raphael , Sieber Joshua
Published: February 2022

Chiral g-lactones are prevalent organic architectures found in a large array of natural products. In this work, we disclose the development of a modified catalytic system utilizing a commercially available Cu-phosphite catalyst for the diastereoselective reductive coupling of chiral allenamides and ketones to afford chiral -lactone precursors in 80:20 to 99:1 dr.
Electronic coherences steer the strong isotope effect in the ultrafast Jahn-Teller structural rearrangement of methane cation upon tunnel ionization
Authors: Blavier Martin , Komarova Ksenia , Goncalves Cayo , Levine Raphael , Remacle Francoise
Published: February 2022

We report on fully quantum electronic-nuclear dynamics following sudden ionization from the neutral in the three lowest electronic states of the CH4+ and CD4+ cations. There is a strong Jahn-Teller effect in the Franck-Condon region and we employ two nuclear degrees of freedom that span the internal coordinates involved in the Jahn-Teller coupling. The initial state results from tunneling ionization by a strong IR field which coherently pumps the three lowest states of the cation, D0, D1 and D2. The quantum dynamical simulations show that a strong isotope effect occurs when the ionization accesses significantly the D2 state of the cation in the Franck-Condon region. The computed isotope effect is larger than expected on the basis of the effective mass ratio. The strong effect is due to fast oscillations of the electronic coherences between the D2 and the D1 and D0 electronic states and their modulation by the non adiabatic couplings before a significant onset of nuclear motion. The magnitude of the effect is similar to the one that we previously reported for a sudden photoionization process. A strong isotope effect has been observed in high harmonic spectroscopy studies of the very short time dynamics Jahn-Teller structural rearrangement of the methane cation upon sudden ionization.
An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems
Authors: Célerse Fréderic , Jaffrelot-Inizan Theo , Lagardère Louis , Adjoua Olivier , Monmarché Pierre , Miao Yinglong , Derat Etienne , Piquemal Jean-Philip
Published: February 2022

We detail a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We then introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field. By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual-water approach is tested on the 1D Potential of Mean Force (PMF) of the CD2-CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS--GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 compared to GaMD--US and US.
An Efficient GaMD Multi-Level Enhanced Sampling Strategy: Application to Polarizable Force Fields Simulations of Large Biological Systems
Authors: Célerse Fréderic , Jaffrelot-Inizan Theo , Lagardère Louis , Adjoua Olivier , Monmarché Pierre , Miao Yinglong , Derat Etienne , Piquemal Jean-Philip
Published: February 2022

We introduce a novel multi-level enhanced sampling strategy grounded on Gaussian accelerated Molecular Dynamics (GaMD). First, we propose a GaMD multi-GPUs-accelerated implementation within the Tinker-HP molecular dynamics package. We introduce the new "dual-water" mode and its use with the flexible AMOEBA polarizable force field.By adding harmonic boosts to the water stretching and bonding terms, it accelerates the solvent-solute interactions while enabling speedups thanks to the use of fast multiple--timestep integrators. To further reduce time-to-solution, we couple GaMD to Umbrella Sampling (US). The GaMD—US/dual--water approach is tested on the 1D Potential of Mean Force (PMF) of the solvated CD2--CD58 system (168000 atoms) allowing the AMOEBA PMF to converge within 1 kcal/mol of the experimental value. Finally, Adaptive Sampling (AS) is added enabling AS-GaMD capabilities but also the introduction of the new Adaptive Sampling--US--GaMD (ASUS-GaMD) scheme. The highly parallel ASUS--GaMD setup decreases time to convergence by respectively 10 and 20 times compared to GaMD-US and US. Overall, beside the acceleration of PMF computations, Tinker-HP now allows for the simultaneous use of Adaptive Sampling and GaMD-"dual water" enhanced sampling approaches increasing the applicability of polarizable force fields to large scale simulations of biological systems.
Ring-Opening Fluorination of Bicyclic Azaarenes
Authors: Komatsuda Masayuki , Suto Ayane , Kondo Jr. Hiroki , Takada Hiroyuki , Kato Kenta , Saito Bunnai , Yamaguchi Junichiro
Published: February 2022

We have discovered a ring-opening fluorination of bicyclic azaarenes. Upon treatment of bicyclic azaarenes such as pyrazolopyridines with electrophilic fluorinating agents, fluorination of the aromatic ring is followed by a ring-opening reaction. Although this overall trans-formation can be classified as an electrophilic fluorination of an aromatic ring, it is a novel type of fluorination that results in construction of tertiary carbon–fluorine bonds. The present protocol can be applied to a range of bicyclic azaarenes, tolerating azines and a variety of functional groups. Additionally, mechanistic studies and enantioselective fluorination have been examined.
Wildfire-derived pyrogenic carbon modulates riverine organic matter and biofilm enzyme activities in an in-situ flume experiment
Authors: Thuile Bistarelli Lukas , Poyntner Caroline , Santín Cristina , Doerr Stefan H. , Talluto Matthew V. , Singer Gabriel , Sigmund Gabriel
Published: February 2022

Wildfires produce large amounts of pyrogenic carbon (PyC), including charcoal, known for its chemical recalcitrance and sorption affinity for organic molecules. Wildfire-derived PyC can be transported to fluvial networks. Here it may alter dissolved organic matter (DOM) concentration and composition as well as microbial biofilm functioning. Employing in-stream flumes with a control vs treatment design (PyC pulse addition), we present evidence that field-aged PyC inputs to rivers can increase dissolved organic carbon (DOC) concentration, and alter DOM composition. Decreased DOM aromaticity indicated by lower SUVA245 (-0.31 units), and higher pH (0.25 units) were associated with changes in enzymatic activities in benthic biofilms, including a lower recalcitrance index (β-glucosidase/phenol oxidase), suggesting preferential usage of recalcitrant over easily available DOM by biofilms. Particulate PyC deposition onto biofilms may further modulate the impacts of PyC due to direct contact with the biofilm matrix.
Metal-catalyzed organic reactions by Resonant Acoustic Mixing
Authors: Gonnet Lori , Lennox Cameron , Do Jean-Louis , Malvestiti Ivani , Koenig Stefan , Nagapudi Karthik , Friscic Tomislav
Published: February 2022

We introduce catalytic organic synthesis by Resonant Acoustic Mixing (RAM): a mechanochemical methodology that does not require bulk solvent or milling media. Using as model reactions ruthenium-catalyzed ring-closing metathesis, ene-yne metathesis and copper-catalyzed sulfonamide-isocyanate coupling, we demonstrate RAM-based mechanochemical synthesis that is faster and operationally simpler than conventional ball milling. Moreover, the method can be readily scaled-up, as demonstrated by straightforward catalytic synthesis of the antidiabetic drug Tolbutamide from hundreds of milligrams to at least 10 grams, without any significant changes in reaction conditions.
Lipophilic Salirasib analogs with enhanced antiproliferative activity against human solid tumor cell lines
Authors: Porta Exequiel O. J. , Ballari María Sol , Padrón José M. , Labadie Guillermo R.
Published: February 2022

Aim: We proposed to determine the antiproliferative activity of a series of synthetic salirasib analogs, presenting or not a 1,2,3-triazole linker, against five different cancer cell lines. Results: Bioassay, cheminformatic, and in silico ADME-Tox allowed the identification of new potent analogs. SAR analysis allowed the identification of structural and physicochemical features that benefit the antiproliferative activity. Conclusion: Isoprenyl R chains with three or more isoprene units, or long aliphatic R chains are the preferred ones within the active compounds. Likewise, we have identified three compounds with better activity profiles than salirasib against all the cell lines tested.
A chemoproteomics approach to profile phospholipase D-derived phosphatidyl alcohol interactions
Authors: Yu Weizhi , Baskin Jeremy
Published: February 2022

Alcohol consumption leads to formation of phosphatidylethanol (PEth) via the transphosphatidylation activity of phospholipase D (PLD) enzymes. Though this non-natural phospholipid routinely serves as a biomarker of chronic alcoholism, its pathophysiological roles remain unknown. We use a minimalist diazirene alkyne alcohol as an ethanol surrogate to generate clickable, photoaffinity lipid reporters of PEth localization and lipid–protein interactions via PLD-mediated transphosphatidylation. We use these tools to visualize phosphatidyl alcohols in a manner compatible with standard permeabilization and immunofluorescence methods. We also use click chemistry tagging, enrichment, and proteomics analysis to define the phosphatidyl alcohol interactome. Our analysis reveals an enrichment of putative interactors at various membrane locations, and we validate one such interaction with the single-pass transmembrane protein basigin/CD147. This study provides a comprehensive view of the molecular interactions of phosphatidyl alcohols with the cellular proteome and points to future work to connect such interactions to potential pathophysiological roles of PEth.
Palladium-Catalyzed C-C Bond Activation and Regioselective Alkenyla-tion between Cyclopropanol and 1,3-Diyne: One-Step Synthesis of Di-verse Conjugated Enynes
Authors: Pati Bedadyuti Vedvyas , Ghosh Asit , Yadav Komal , Banjare Shyam Kumar , Lourderaj Upakarasamy , Ravikumar Ponneri C.
Published: February 2022

We report here the first example of the use of 1,3-dialkynes in C-C bond activation with any metal. The regio- and stereo-selective synthesis of 1,3-enynes from 1,3-diynes is demonstrated by the palladium-catalyzed C-C bond activation of cyclo-propanol. Exclusive formation of mono-alkenylated adduct was achieved by eliminating the possibility of di-functionalization with high regio- and stereo-selectivity. Indeed, this protocol worked very well with electronically and sterically diverse substrates. Several studies, including deuterium labeling experiments and intermolecular competitive experiments, were carried out to understand the mechanistic details. The atomic-level mechanism followed in the catalytic process was also validated using DFT calculations, and the rate-controlling states in the catalytic cycle were identified. Further, preliminary mechanistic investigations with radical scavengers revealed non-involvement of the radical pathway for this transformation.
Racemization-free synthesis of dipeptide, amide and ester by oxalyl chloride and catalytic triphenylphosphine oxide
Authors: Ni Feng , Ren Ji-Wei , Tong Meng-Nan , Zhao Yu-Fen
Published: February 2022

An efficient triphenylphosphine oxide (Ph3PO) catalyzed amidation and esterification reaction for rapid synthesis of a series of dipeptides, amides and esters under mild condition is described. This reaction is applicable to challenging couplings of hindered carboxylic acid with low nucleophilic amine or alcohol, giving products in good yields (67-90%) without any racemization. This system employs highly reactive intermediate Ph3PCl2 as activator of carboxylate, in a catalytic manner, and drive the reac-tion to complete in short reaction time (less than 10 min). It has the advantages of good functional group tolerance, broad sub-strate scope and good atom-economy. A 100 mmol scale reaction with good yield shed light on its potential for industrial ap-plication. A plausible mechanism is proposed based on 31P NMR monitor of reaction process.
Navigate flying molecular elephants safely to the ground: mass-selective soft landing up to the Mega-Dalton range by Electrospray Controlled Ion-Beam Deposition
Authors: Walz Andreas , Stoiber Karolina , Huettig Annette , Schlichting Hartmut , Barth Johannes V
Published: February 2022

The prototype of a highly versatile and efficient preparative mass spectrometry system used for the deposition of molecules in ultra-high vacuum (UHV) is presented along with encouraging performance data obtained on model species which are thermolabile or not sublimable. The test panel comprises two organic compounds, a protein, and DNA covering a 4-log mass range up to 1.7 MDa as part of a broad spectrum of analyte species. Three designs of innovative ion guides, a novel digital mass-selective quadrupole (dQMS) and a standard electrospray ionization (ESI) source are combined to an integrated device, abbreviated Electrospray Controlled Ion Beam Deposition (ES-CIBD). Full control is achieved by i) the square-wave-driven radiofrequency (RF) ion guides with steadily tunable frequencies, including a dQMS allowing for investigation, purification and deposition of a virtually unlimited m/z range, ii) the adjustable landing energy of ions down to ~2 eV/z enabling integrity-preserving soft-landing, iii) the deposition in UHV with high ion beam intensity (up to 3 nA) limiting contaminations and deposition time, and iv) direct coverage control via the deposited charge. The maximum resolution of R=650 and overall efficiency up to T-total=4.4% calculated from solution to UHV deposition are remarkable as well, while the latter is mainly limited by the not yet optimized ionization performance. In the setup presented, a scanning tunneling microscope (STM) is attached for in situ UHV investigation of the deponents demonstrating a selective, structure-preserving process and atomically clean layers.
Tuning Valley Degeneracy with Band Inversion
Authors: Toriyama Michael Y. , Brod Madison K. , Gomes Lidia C. , Bipasha Ferdaushi A. , Assaf Badih A. , Ertekin Elif , Snyder G. Jeffrey
Published: February 2022

Valley degeneracy is a key feature of the electronic structure that benefits the thermoelectric performance of a material. Despite recent studies which claim that high valley degeneracy can be achieved with inverted bands, our survey of rock-salt IV-VI compounds demonstrates that mere band inversion is an insufficient condition for high valley degeneracy; rather, there is a critical degree to which the bands must be inverted to induce multiple carrier pockets. The so-called “band inversion parameter” is a chemically-tunable parameter, offering a design route to achieving high valley degeneracy in compounds with inverted bands. We predict that the valley degeneracy of rock-salt IV-VI compounds can be increased from NV = 4 to NV = 24, which could result in a corresponding increase in the thermoelectric figure of merit zT.
Monolithic dynamic covalent polymer aerogels via ambient pressure drying with super-flexibility, weldability, closed-loop recyclability, and multifunctionality
Authors: Zhang Xinhai , Zhao Jun , Liu Kai , Li Guangfeng , Zhao Dong , Zhao Zhaoming , Wan Junjun , Yang Xue , Bai Ruixue , Wang Yongming , Zhang Wei , Yan Xuzhou
Published: February 2022

Owing to their low density, high porosity and unique micro-nanostructures, aerogels are attractive for applications in various aspects, but at the same time, suffer from shrinkage and/or cracking during preparation, mechanical brittleness, low production efficiency, and non-degradation. Herein, we introduce the concept of dynamic covalent polymer chemistry to produce a new class of aerogelsreferred to as DCPAs. The resulting light DCPAs display large-scale preparation prospect and feature high porosity (90.7-91.3%), large degrees of compression (80% strain) and bending (diametral deflection of 30 mm) without any cracks, as well as considerable tensile property (elongation at break of 32.7%). In addition, our DCPAs showcase emergent characteristics of weldability, repairability, and closed-loop recyclability that are highly desirable for affording versatile materials platforms but hardly achieved by traditional aerogels. Benefiting from the robust porous structures, we demonstrate the potential of the DCPAs for applications in thermal insulation and emulsion separation.
Nonadiabatic dynamics with spin-flip versus linear-response time-dependent density functional theory: A case study for the protonated Schiff base C5H6NH2+
Authors: Zhang Xing , Herbert John
Published: February 2022

Nonadiabatic trajectory surface hopping simulations are reported for trans-C5H6NH2+, a model of the rhodopsin chromophore, using the augmented fewest-switches algorithm. Electronic structure calculations were performed using time-dependent density functional theory (TDDFT) in both its conventional linear-response (LR) and its spin-flip (SF) formulations. In the SF-TDDFT case, spin contamination in the low-lying singlet states is removed by projecting out the lowest triplet component during iterative solution of the TDDFT eigenvalue problem. The results show that SF-TDDFT is able to correctly describe the photoisomerization of trans-C5H6NH2+, with favorable comparison to previous studies using multireference electronic structure methods. In contrast, conventional LR-TDDFT affords qualitatively different photodynamics due to an incorrect excited-state potential surface near the Franck-Condon region. In addition, the photochemistry (involving pre-twisting of the central double bond) appears to be different for SF- and LR-TDDFT, which may be a consequence of different conical intersection topographies afforded by these two methods. The present results contrast with previous surface-hopping studies suggesting that the LR-TDDFT method's incorrect topology around S1/S0 conical intersections is immaterial to the photodynamics.
Divergent Stereochemical Outcomes in the Insertion of Donor/Donor Carbenes into the C–H Bonds of Stereogenic Centers
Authors: Dishman Sarah , Laconsay Croix , Fettinger James , Tantillo Dean , Shaw Jared
Published: February 2022

Intramolecular C–H insertions with donor/donor dirhodium carbenes provide a concise and highly stereoselective method to set two contiguous stereocenters in a single step. Herein, we report the insertion of donor/donor carbenes into stereogenic carbon centers allowing access to trisubstituted benzodihydrofurans in a single step. This study illuminates, for the first time, the stereochemical impact on the carbene center and delineates the structural factors that enable control over both stereogenic centers. Sterically bulky, highly activated C–H insertion centers exhibit high substrate control yielding a single diastereomer and a single enantiomer of product regardless of the catalyst used. Less bulky, less activated C–H insertion centers exhibit catalyst control over the diastereomeric ratio (dr) wherein a single enantiomer of each diastereomer is observed. A combination of experimental studies and DFT calculations elucidates the origin of these results. First, hydride transfer from the stereogenic insertion site proceeds with high stereoselectivity to the carbene center, thus determining the absolute configuration of the product. Second, the short lived zwitterionic intermediate can undergo diastereoselective ring-closure by an SE2 mechanism that is either controlled by the substrate or the catalyst. These results demonstrate that donor/donor carbenes exhibit uniquely stereoselective reactions that originate from a stepwise reaction mechanism, in contrast to the analogous concerted reactions of carbenes with one or more electron-withdrawing groups attached.
Site correlations, capacitance, and polarizability from protein protonisation fluctuations
Authors: Božič Anže , Podgornik Rudolf
Published: February 2022

We generalize the Kirkwood-Shumaker theory of protonisation fluctuation for an anisotropic distribution of dissociable charges on a globular protein. The fluctuations of the total charge and the total dipole moment, in contrast to their average values, depend on the same proton occupancy correlator, thus exhibiting a similar dependence also on the solution pH. This has important consequences for the Kirkwood-Shumaker interaction and its dependence on the bathing solution conditions.
Nonlinear Correlation between Reduced Mass and Computed Activation Energy
Authors: Kawashima Masatoshi
Published: February 2022

Correlation between activation energies of the aldol and ene reactions and the reduced masses of the raw materials was revealed by semi-empirical molecular orbital calculations. It was found that there is a singular point where the activation energy changes from decreasing to increasing or to nearly unchanging as the reduced mass increases, and the nonlinear change can be approximated by a quadratic curve. When the coefficient of determination of the correlation was greater than 0.8, the the reduced mass at the singular point was 40-120.
Deciphering the role of anions and secondary coordination sphere in tuning anisotropy in Dy(III) air-stable D5h SIMs
Authors: Gupta Sandeep , Dey Sourav , Rajeshkumar Thayalan , Rajaraman Gopalan , Murugavel Ramaswamy
Published: February 2022

Precise control of the crystal field and symmetry around the paramagnetic spin centre has recently facilitated the engineering of high-temperature single-ion magnets (SIMs), the smallest possible units for future spin-based devices. In the present work, we report a series of air-stable seven coordinate Dy(III) SIMs {[L2Dy(H2O)5][X]3·L2·n(H2O), n = 0, X = Cl (1), n = 1, X = Br (2), I (3)} possessing pseudo-D5h symmetry or pentagonal bipyramidal coordination geometry with high anisotropy energy barrier (Ueff) and blocking temperature (TB). While the strong axial coordination from the sterically encumbered phosphonamide, tBuPO(NHiPr)2 (L), increases the overall anisotropy of the system, the presence of high symmetry significantly quenches quantum tunnelling of magnetization, which is the prominent deactivating factor encountered in SIMs. Although the local coordination geometry and the symmetry around the Dy(III) in all the three complexes are similar and display only slight deviations, the variation of halide anions in the secondary coordination sphere which is hydrogen-bonded to the coordinated equatorial water molecules, show subtle alteration in the magnetic properties. The energy barrier (Ueff) and the blocking temperature (TB) decrease in the order 3 > 2 > 1 with the change of anions from larger iodide to smaller strongly hydrogen-bonded chloride in the secondary coordination sphere. Ab initio CASSCF/RASSI-SO/SINGLE_ANISO calculations further provide deeper insights into the dynamics of magnetic relaxation in addition to the role of the secondary coordination sphere in modulating the anisotropy of the D5h systems, using diverse models. Thus, in addition to the importance of the crystal field and the symmetry to obtain high-temperature SIMs, this study also probes the significance of the secondary coordination sphere that can be tailored to accomplish novel SIMs.
Putting MicroED to the Test: An Account of the Evaluation of 30 Diverse Pharmaceutical Compounds
Authors: Burch Jessica E. , Smith Austin G. , Caille Seb , Walker Shawn D. , Wurz Ryan , Cee Victor J. , Rodriguez Jose , Gostovic D. , Quasdorf Kyle , Nelson Hosea M.
Published: February 2022

The application of microcrystal electron diffraction (microED) to a variety of pharmaceutical compounds is reported. The examples and work detailed showcase the utility of microED as a routine technique for the rapid collection, analysis, and generation of structural data on a number of pharmaceutically relevant compounds, requiring minimal sample preparation and often without the need for time-consuming vitrification and cryo transfer processes. The development of a scripted data processing workflow allowed for simultaneous collection and processing of electron diffraction data, further expediting structural analysis of fifteen compounds.
Raman Tweezers for Tire and Road Wear Micro- and Nanoparticles analysis
Authors: gucciardi pietro giuseppe , Raymond Gillibert , Magazzù Alessandro , Callegari Agnese , Brente Ciriza David , Antonino Foti , Donato Maria Grazia , Maragò Onofrio M. , Volpe Giovanni , Lamy de La Chapelle Marc , Lagarde Fabienne
Published: February 2022

Tire and Road Wear Particles (TRWP) are non-exhaust particulate matter generated by road transport means during the mechanical abrasion of tires, brakes and roads. TRWP accumulate on the roadsides and are transported into the aquatic ecosystem during stormwater runoffs. Due to their size (sub-millimetric) and rubber content (elastomers), TRWP are considered microplastics (MPs). While the amount of the MPs polluting the water ecosystem with sizes from ~ 5 μm to more than 100 μm is known, the fraction of smaller particles is unknown due to the technological gap in the detection and analysis of < 5 μm MPs. Here we show that Raman Tweezers, a combination of optical tweezers and Raman spectroscopy, can be used to trap and chemically analyze individual TWRPs in a liquid environment, down to the sub-micrometric scale. Using tire particles mechanically grinded from aged car tires in water solutions, we show that it is possible to optically trap individual sub-micron particles, in a so-called 2D trapping configuration, and acquire their Raman spectrum in few tens of seconds. The analysis is then extended to samples collected from a brake test platform, where we highlight the presence of sub-micrometric agglomerates of rubber and brake debris, thanks to the presence of additional spectral features other than carbon. Our results show the potential of Raman Tweezers in environmental pollution analysis and highlight the formation of nanosized TRWP during wear.
Comprehensive Basis-Set Testing of Extended Symmetry Adapted Perturbation Theory
Authors: Gray Montgomery , Herbert John
Published: February 2022

Hybrid or "extended" symmetry-adapted perturbation theory (XSAPT) replaces traditional SAPT's treatment of dispersion with better-performing alternatives, while at the same time extending two-body (dimer) SAPT to a many-body treatment of polarization, via a self-consistent charge-embedding procedure. The present work presents a systematic study of how total interaction energies and also energy components converge with respect to the choice of Gaussian basis set in XSAPT. Pople-style basis sets, while very efficient, consistently afford errors > 1 kcal/mol with respect to benchmark interaction energies for standard data sets of noncovalent complexes, whereas Dunning's correlation-consistent basis sets and Karlsruhe basis sets perform much better. Hybrid treatments of dispersion afford must faster basis-set convergence as compared to traditional SAPT, and benchmark-quality results can be obtained using basis sets of triple-zeta quality, although the use of diffuse functions proves to be essential. The use of dimer Hartree-Fock calculations as a correction for higher-order induction can be performed in even smaller basis sets with negligible error, leading to a composite approach that offers speedups of 100x even for small systems.
A microfluidic approach for synthesis and kinetic profiling of branched gold nanostructure
Authors: Cai Qi , Castagnola Valentina , Boselli Luca , Moura Alirio , Lopez Hender , Zhang Wei , de Araujo João M. , Dawson Kenneth A.
Published: February 2022

Automatized approaches for nanoparticle synthesis and characterization represent a great asset to their applicability in the biomedical field by improving reproducibility and standardization, which help to meet the selection criteria of regulatory authorities. The scaled-up production of nanoparticles with carefully defined characteristics, including intrinsic morphological features, minimal intra-batch, batch-to-batch, and operator variability, is an urgent requirement to elevate nanotechnology towards more trustable biological and technological applications. In this work, microfluidic approaches were employed to achieve fast mixing and good reproducibility in synthesizing a variety of gold nanostructures. The microfluidic setup allowed exploiting spatial resolution to investigate the growth evolution of the complex nanoarchitectures. By physically isolating intermediate reaction fractions, we performed an advanced characterization of the shape properties during their growth, not possible with routine characterization methods. Employing an in-house developed method to assign a specific identity to shapes, we followed the particle growth/deformation process and identified key reaction parameters for more precise control of the generated morphologies. Besides, this investigation led to the optimization of a one-pot multi-size and multi-shape synthesis of a variety of gold nanoparticles. In summary, we describe an optimized platform for highly controlled synthesis and a novel approach for the mechanistic study of shape-evolving nanomaterials.
Ferrocene Metallopolymers of Intrinsic Microporosity (MPIMs)
Authors: Zhai Tianran , Ambrose Kenson , Nyayachavadi Adit , Walter Kelly G. , Rondeau-Gagné Simon , Feldblyum Jeremy I.
Published: February 2022

We show here that non-network metallopolymers can possess intrinsic microporosity stemming from contortion introduced by metallocene building blocks. Metallopolymers constructed from ferrocenyl building blocks linked by phenyldiacetylene bridges are synthesized and possess BET surface areas up to 400 m2/g. As solubility imparted by pendant groups reduces porosity, copolymerization is used to simultaneously improve both accessible surface area and solubility. Spectroscopic analysis provides evidence that mixed valency between neighboring ferrocenyl units is supported in these polymers.
Radical Ring-Opening of Oxetanes Enabled by Co-Catalysis
Authors: Potrząsaj Aleksandra , Ociepa Michał , Chaładaj Wojciech , Gryko Dorota
Published: February 2022

Oxetanes are valuable building blocks due to their well-explored propensity to undergo ring-opening reactions with diverse nucleophiles. However, their application as precursors of radical species remains unexplored. Herein, we present a cobalt catalysis-based strategy to access various modes of radical reactivity via oxetane ring opening. The developed method involves formation of an alkylated Co-complex intermediate from vitamin B12 and oxetane. Homolytic cleavage of the Co-C bond generates nucleophilic radicals that engage in reactions with SOMOphiles and low-valent transition metals. The scope of the developed reactions is broad with various functional groups being well tolerated. Importantly, the regioselectivity of these processes complements known methodologies.
Drug-target affinity prediction using applicability domain based on data density
Authors: Sugita Shunya , Ohue Masahito
Published: February 2022

In the pursuit of research and development of drug discovery, the computational prediction of the target affinity of a drug candidate is useful for screening compounds at an early stage and for verifying the binding potential to an unknown target. The chemogenomics-based method has attracted increased attention as it integrates information pertaining to the drug and target to predict drug-target affinity (DTA). However, the compound and target spaces are vast, and without sufficient training data, proper DTA prediction is not possible. If a DTA prediction is made in this situation, it will potentially lead to false predictions. In this study, we propose a DTA prediction method that can advise whether/when there are insufficient samples in the compound/target spaces based on the concept of the applicability domain (AD) and the data density of the training dataset. AD indicates a data region in which a machine learning model can make reliable predictions. By preclassifying the samples to be predicted by the constructed AD into those within (In-AD) and those outside the AD (Out-AD), we can determine whether a reasonable prediction can be made for these samples. The results of the evaluation experiments based on the use of three different public datasets showed that the AD constructed by the k-nearest neighbor (k-NN) method worked well, i.e., the prediction accuracy of the samples classified by the AD as Out-AD was low, while the prediction accuracy of the samples classified by the AD as In-AD was high.
Automated analysis of microplastics based on vibrational spectroscopy: Are we measuring the same metrics?
Authors: Dong Mingtan , She Zhenbing , Xiong Xiong , Luo Zejiao
Published: February 2022

The traditional manual analysis of microplastics has been criticized because it is labor intensive, inaccurate for identifying very small microplastics, and difficult to standardize or compare. There are already three automated analysis strategies for microplastics based on vibrational spectroscopy, laser direct infrared (LDIR)-based particle analysis, Raman-based particle analysis, and focal plane array-Fourier transform infrared (FPA-FTIR) imaging. We compared the performances of these strategies in terms of their quantification, detection limit, size measurement, and material identification accuracy and analysis speed by analyzing the same standard and environmental samples. Unfortunately, the automated analysis strategies are not consistent in terms of the quantification and material identification results. The number of particles smaller than 60 μm recognized by Raman-based particle analysis is far greater than that recognized by LDIR-based particle analysis. Raman-based particle analysis has a submicrometer detection limit but should not be used in the automated analysis of microplastics in environmental samples because of the strong fluorescence interference. LDIR-based particle analysis provides the fastest analysis speed, but we suggest using a reliable detection limit of approximately 60 μm and considering the material identification results and reference database used because the wavenumbers LDIR spectra are in the range of 975-1800 cm-1. FPA-FTIR imaging provides relatively reliable quantification and material identification for microplastics in environmental samples but might provide an imprecise description of the particle shapes. As a technological advancement, automated analysis of microplastics should be encouraged, but we need to foster the strengths and circumvent the weaknesses of different strategies. The automated analysis of microplastics should be further validated and standardized.