bluuebunny/crossref_metadata_2025 huggingface dataset:
Unraveling Electronic Structure, Magnetic States, and Topological Phenomena in Pristine, Defected, and Strained Ti2N MXene
Authors: Limbu Yogendra , Kaphle Gopi Chandra , Karn Alok Lal , Shah Niraj Kumar , Paudyal Durga
Published: February 2022

We unravel the evolution of structural, electronic, magnetic, and topological properties of graphene-like pristine, defected, and strained titanium nitride MXene with different functional groups (-F, -O, -H, and -OH) employing first-principles calculations. The formation and cohesive energies reveal their chemical stability. The MAX phase and defect free functionalized MXenes are metallic in nature except for oxygen terminated one, which is 100% spin polarized half-metallic. Additionally, the bare MXene is nearly half-metallic ferromagnet. The spin-orbit coupling significantly influences the bare MXene possessing band inversion. The strain effect sways the Fermi level thereby shifting it toward lower energy state under compression and toward higher energy state under tensile strain in Ti2NH2. These properties are reversed in Ti2N, Ti2NF2, and Ti2N(OH)2. The half-metallic nature changes to semi-metallic under 1% compression and is completely destroyed under 2% compression. In single vacancy defect, the band structure of Ti2NO2 remarkably transforms from half-metallic to semi-conducting (with large band gap of 1.73 eV) in 12.5% Ti, weakly semi-conducting in 5.5% Ti, and topological semi-metal in 12.5% oxygen. The 25% N defect changes the half-metallic to the metallic with certain topological features. Further, the 12.5% Co substitution in Ti2NO2 preserves the half-metallic character, whereas Mn substitution allows to convert half-metallic into weak semi-metallic preserving ferromagnetic character. However, Cr substitution converts half-metallic ferromagnetic to half-metallic anti-ferromagnetic state. The understanding made here on collective structural stability, and magnetic and topological phenomena in novel 2D MXenes open up their possibility in designing them for synthesis and thereby taking to applications.
Cavity Catalysis: Modifying Linear Free-energy Relationship under Cooperative Vibrational Strong Coupling
Authors: GEORGE Jino , Lather Jyoti , Ahammad N. K. Thabassum , Singh Jaibir
Published: February 2022

Recent understanding of light-matter strong coupling brought a new niche in molecular-level control of chemical reactions. Vibrational strong coupling is unique in this category that overcomes the issue associated with coherent chemistry. Here, a vibrational transition is coupled to a standing wave of electromagnetic field, result in strong interaction, generating vibro-polaritonic states. This process reshuffles the entire energy-reaction coordinate. The chemical reaction rate can be boosted, stirred, or decelerated with this unconventional tool. Here, we used the idea of cooperative vibrational strong coupling of solute and solvent molecules to enhance the chemical reaction rate. This process is called cavity catalysis. Different derivatives of p-nitrophenyl benzoate (solute) and isopropyl acetate (solvent) are cooperatively coupled to an infrared Fabry-Perot cavity. The apparent reaction rates are increased by more than six times at the ON resonance condition, and the rate enhancement follows the lineshape of the vibrational envelope. Very interestingly, strong coupled system doesn't follow a linear free-energy relationship. The nonlinear rate enhancement can be due to the reshuffling of energy distribution between the substituents and the reaction center. Thermodynamic parameters suggest an entropy-driven process for the coupled molecules. The free energy of activation decreased by 2-5 kJ/mol, suggesting a clear role of vibrational strong coupling in catalyzing the reaction. Here, the enthalpy of the system compensates for the entropy by preserving the isokinetic relationship. These findings will help further understanding of chemical reaction control in polariton chemistry.
Multitarget, Selective Compound Design Yields Picomolar Inhibitors of a Kinetoplastid Pteridine Reductase 1
Authors: Poehner Ina , Quotadamo Antonio , Panecka-Hofman Joanna , Luciani Rosaria , Santucci Matteo , Linciano Pasquale , Landi Giacomo , Pisa Flavio Di , Iacono Lucia Dello , Pozzi Cecilia , Mangani Stefano , Gul Sheraz , Witt Gesa , Ellinger Bernhard , Kuzikov Maria , Santarem Nuno , Cordeiro-da-Silva Anabela , Costi Maria Paola , Venturelli Alberto , Wade Rebecca
Published: February 2022

The optimization of compounds with multiple targets is a difficult multidimensional problem in the drug discovery cycle. Here, we present a systematic, multidisciplinary approach to the development of selective anti-parasitic compounds. Computational fragment-based design of novel pteridine derivatives along with iterations of crystallographic structure determination allowed for the derivation of a structure-activity relationship for multitarget inhibition. The approach yielded compounds showing picomolar inhibition of T. brucei pteridine reductase 1 (PTR1), nanomolar inhibition of L. major PTR1, and selective submicromolar inhibition of parasite dihydrofolate reductase (DHFR) versus human DHFR. Moreover, by combining design for polypharmacology with a property-based on-parasite optimization, we found three compounds that exhibited micromolar EC50 values against T. brucei brucei, whilst retaining their target inhibition. Our results provide a basis for the further development of pteridine-based compounds, and we expect our multitarget approach to be generally applicable to the design and optimization of anti-infective agents.
Synthesis and characterization of nanoscale composite particles formed by 2D layers of Cu-Fe sulfide and Mg-based hydroxide
Authors: Mikhlin Yuri , Borisov Roman , Vorobyev Sergey , Tomashevich Yevgeny , Romanchenko Alexander , Likhatski Maxim , Karacharov Anton , Bayukov Oleg , Knyazev Yurii , Velikanov Dmitriy , Zharkov Sergey , Krylov Alexander , Krylova Svetlana , Nemtsev Ivan
Published: February 2022

We introduce here a multifunctional material composed of alternating atomic sulfide sheets close to CuFeS2 and Mg-based hydroxide ones (valleriite), which are assembled due to their electric charges of opposite sign. Valleriite particles of 50-200 nm in the lateral size and 10-20 nm thick were synthesized via a simple hydrothermal pathway using various concentrations of precursors and dopants, and examined with XRD, TEM, EDS, X-ray photoelectron spectroscopy, reflection electron energy loss spectroscopy (REELS), Mössbauer, Raman and UV-vis-NIR spectroscopies, magnetic, dynamic light scattering, zeta potential measurements. The electronic, magnetic and optical characteristics are found to be critically dependent of the charge (electron density) at the narrow-gap sulfide layers containing Cu+ and Fe3+ cations, and can be tuned via the composition of hydroxide part. Particularly, substitution of Mg2+ with Al3+ increases the negative charge of the hydroxide layers and reduces the content of Fe3+-OH centers (10-45% of total iron); the effects of Cr and Co dopants entering both layers are more complicated. Mössbauer doublets of paramagnetic Fe3+ detected at room temperature transform to several Zeeman sextets at 4.2 K; the hyperfine fields up to 500 kOe and complex magnetic behavior, but not pure paramagnetism or antiferromagnetism, were observed for valleriites with the higher positive charge of the sulfide sheets, probably due to the depopulation of the minority-spin 3d states of S-bonded Fe3+ ions. Aqueous colloids of valleriite show optical absorption at 500 - 750 nm, which, along with the peaks at the same energies in REELS, may arise due to quasi-static dielectric resonance involving the vacant Fe 3d band and being dependent on the composition of both layers too. These and other findings call attention to the of valleriites as a new rich family of 2D materials for a variety of potential applications.
Sanitize It Yourself: Web-based molecular sanitization for machine-generated chemical structures
Authors: Yoshikawa Naruki , Rikimaru Kentaro , Yamamoto Kazuki
Published: February 2022

Many computer-aided drug design (CADD) methods using deep learning have recently been proposed to explore the chemical space toward novel scaffolds efficiently. However, there is a tradeoff between the ease of generating novel structures and the chemical feasibility of structural formulas. To overcome the limitations of computational filtering, we have implemented a web-based software in which users can share and evaluate computer-generated compounds. The web service is available at https://sanitizer.chemical.space/.
Multimodal Plasmonic Hybrids: Efficient and Selective Photocatalysts
Authors: Negrín-Montecelo Yoel , Kong Xiang-Tian , Besteiro Lucas , Carbo-Argibay Enrique , Wang Zhiming , Pérez-Lorenzo Moisés , Govorov Alexander , Comesana-Hermo Miguel , Correa-Duarte Miguel A.
Published: February 2022

Important efforts are currently under way in order to implement plasmonic phenomena in the growing field of photocatalysis, striving for improved efficiency and reaction selectivity. A significant fraction of such efforts has been focused on distinguishing, understanding and enhancing specific energy transfer mechanisms from plasmonic nanostructures to their environment. Herein we report a synthetic strategy that brings together two of the main physical mechanisms driving plasmonic photocatalysis into an engineered system by rationally combining the photochemical features of energetic charge carriers and the electromagnetic field enhancement inherent to the plasmonic excitation. We do so by creating hybrid photocatalysts that integrate multiple plasmonic resonators in a single entity, controlling their joint contribution through spectral separation and differential surface functionalization. This strategy allows us to study the combination of different photosensitization mechanisms when activated simultaneously. Our results show that hot electron injection can be combined with an energy transfer process mediated by near-field interaction, leading to a significant increase of the final photocatalytic response of the material. In this manner, we overcome the limitations that hinder photocatalysis driven only by a single energy transfer mechanism, and move the field of plasmonic photocatalysis closer to energy-efficient applications. Furthermore, our multimodal hybrids offer a test system to probe the properties of the two targeted mechanisms in energy-related applications such as the photocatalytic generation of hydrogen and open the door to wavelength-selective photocatalysis and novel tandem reactions.
Immunotargeting of Nanocrystals by SpyCatcher Conjugation of Engineered Antibodies
Authors: Pedroso Cassio , Mann Victor , Zuberbühler Kathrin , Bohn Markus-Frederik , Yu Jessica , Altoe Virginia , Craik Charles , Cohen Bruce
Published: February 2022

Inorganic nanocrystals such as quantum dots (QDs) and upconverting nanoparticles (UCNPs) are uniquely suited for quanti-tative live-cell imaging and are typically functionalized with ligands to study specific receptors or cellular targets. Antibod-ies (Ab) are among the most useful targeting reagents owing to their high affinities and specificities, but common nanocrys-tal labeling methods may orient Ab incorrectly, be reversible or denaturing, or lead to Ab-NP complexes too large for some applications. Here, we show that SpyCatcher proteins, which bind and spontaneously form covalent isopeptide bonds with cognate SpyTag peptides, can conjugate engineered Ab to nanoparticle surfaces with control over stability, orientation, and stoichiometry. Compact SpyCatcher-functionalized QDs and UCNPs may be labeled with short-chain variable fragment Ab (scFv) engineered to bind urokinase-type plasminogen activator receptors (uPAR) that are overexpressed in many human can-cers. Confocal imaging of anti-uPAR scFv-QD conjugates shows the Ab mediates specific binding and internalization by breast cancer cells expressing uPAR. Time-lapse imaging of photostable scFv-UCNP conjugates show that Ab binding caus-es uPAR internalization with a ∼20-minute half-life on the cell surface, and uPAR is internalized to endolysosomal com-partments distinct from general membrane stains and without significant recycling to the cell surface. The controlled and stable conjugation of engineered Ab to NPs enables targeting of diverse receptors for live-cell study of their distribution, trafficking, and physiology.
On the influence of template size, canonicalization and exclusivity for retrosynthesis and reaction prediction applications
Authors: Heid Esther , Liu Jiannan , Aude Andrea , Green William H.
Published: February 2022

Heuristic and machine learning models for rank-ordering reaction templates comprise an important basis for computer-aided organic synthesis regarding both product prediction and retrosynthetic pathway planning. Their viability relies heavily on the quality and characteristics of the underlying template database. With the advent of automated reaction and template extraction software and consequently the creation of template databases too large to be curated manually, a data-driven approach to assess and improve the quality of template sets is needed. We therefore systematically studied the influence of template generality, canonicalization and exclusivity on the performance of different template ranking models. We find that duplicate and non-exclusive templates, \textit{i.e.} templates which describe the same chemical transformation on identical or overlapping sets of molecules, decrease both the accuracy of the ranking algorithm and the applicability of the respective top-ranked templates significantly. To remedy the negative effects of non-exclusivity, we developed a general and computationally efficient framework to deduplicate and hierarchically correct templates. As a result, performance improved for both heuristic and machine learning template ranking algorithms across different template sizes. The canonicalization and correction code was made freely available.
Towards a 3D-resolved model of Si/Graphite composite electrodes from manufacturing simulations
Authors: Liu Chaoyue , Arcelus Oier , Lombardo Teo , Oularbi Hassan , Franco Alejandro A.
Published: February 2022

Composite graphite/silicon (Si) electrodes with low Si weight percentages are considered as a promising anode for next generation Li-ion batteries. In this context, understanding the microstructural changes due to Si volume expansion and the complex electrochemical interplay between graphite and Si becomes crucial to unlock real-life applications of such composite electrodes. This work presents a three-dimensional (3D) physics-based model coupling electrochemistry and mechanics, using as input electrode microstructures obtained from manufacturing-related Coarse-Grained Molecular Dynamics models. The slurry and dried electrode microstructure are first generated by considering graphite and additives only, while the Si is included in an additional step. The model herein presented is a step further into obtaining a fundamental understanding of the complex processes happening in graphite/Si composite electrodes, paving the way towards their optimization.
Layered Structures of Assembled Imine-Linked Macrocycles and Two-Dimensional Covalent Organic Frameworks Give Rise to Prolonged Exciton Lifetimes
Authors: Helweh Waleed , Flanders Nathan , Wang Shiwei , Phelan Brian , Kim Pyosang , Strauss Michael , Li Rebecca , Kelley Matthew , Kirschner Matthew , Edwards Dillon , Spencer Austin , Schatz George , Schaller Richard , Dichtel William , Chen Lin
Published: February 2022

Ordered organic materials and assemblies have great potential to be tailored to have desirable properties for optoelectronic applications, such as long exciton lifetime and high directional exciton mobility. Framework materials, such as twodimensional covalent organic frameworks (2D COFs), as well as their truncated macrocyclic analogues, are versatile platforms to organize functional aromatic systems into designed assemblies and robust materials. Here we investigate the exciton dynamics in a 2D COF, its corresponding hexagonal macrocycle, and extended nanotubes comprised of stacked macrocycles. The excitonic behavior of these three systems provide an understanding of excitonic processes that occur in the plane of the covalently bonded 2D macromolecules and between layers of the nanotubes and 2D COF. The nanotube and analogous 2D COF exhibit longer excited-state lifetimes (~100 ps) compared to the individual, solvated macrocycles (<0.5 ps). These differences are attributed to the internal conversion facilitated by the internal motions of the imine linkages which are significantly reduced in the assembled macrocycles in the nanotube and 2D COF sheets in the layered structures. The exciton diffusion processes in the assembled nanotubes and 2D COF systems were characterized by the autocorrelations of the transition dipole moment of the excitons, giving the depolarization time constants for both systems to be ~1 ps. This work also reveals the anisotropic exciton dynamics related to the in-plane and inter-plane structural factors in these systems. These studies provide guidance for the design of future COF materials, where the longer excited state lifetimes imparted by assembly are beneficial for optoelectronic applications.
Predicting the stability and electronic structure of alkali metal aurides
Authors: Gaona Carranza Axel Melchor , Siqueiros Jesús María , García Díaz Reyes , Guerrero Sánchez Jonathan
Published: February 2022

Density functional theory calculations of phonon modes predict that some compounds of the alkali metal aurides family, general formula A2MAu6 (A = K+, Rb+ or Cs+; M = Ti, Zr, Hf, Sn or Pb), have stable three-dimensional phase with a double perovskite-type structure and cubic Fm3m space group (K2PtCl6-type). Bader’s charge analysis shows that most electron density is located within the six atoms at the octahedra vertices like double perovskite halides. However, the short spacing between Au anions enables d-orbital interactions between them. Compounds of this family, with group 4 metals only, carry conduction states around the Gamma point (k = 0). On the other hand, compounds with group 14 metals possess more conduction states around all the Brillouin zone and have electron pockets in their bandstructure. These compounds provide further insights into the unusual anionic behavior of gold and present other alternatives for the construction of divergent nanodevices.
Comparative Studies of IR Spectra of Deprotonated Serine with Classical and Thermostated Ring Polymer Molecular Dynamics Simulations
Authors: Inakollu V. S. Sandeep , Yu Haibo
Published: February 2022

Here we report the vibrational spectra of deprotonated serine calculated from the classical molecular dynamics (MD) simulations and thermostated ring-polymer molecular dynamics (TRPMD) simulation with DFTB3. In our earlier study1 of deprotonated serine, we observed a significant difference in the vibrational spectra with the classical MD simulations compared to the infrared multiple photon dissociation (IRMPD) spectra. It was postulated that this is due to neglecting the nuclear quantum effects (NQEs). In this work, NQEs are considered in the spectral calculation using the TRPMD simulations. With the help of potential of mean force (PMF) calculations, the conformational space of deprotonated serine is analysed and used to understand the difference in the spectra of classical MD and TRPMD simulations at 298.15 K and 100 K. The high-frequency vibrational bands in the spectra are characterised using Fourier transform localised vibrational mode (FT-νNAC) and interatomic distance histograms. At room temperature, the quantum effects are less significant, and the free energy profiles in the classical MD and the TRPMD simulations are very similar. However, the hydrogen bond between the hydroxyl-carboxyl bond is slightly stronger in TRPMD simulations. At 100 K, the quantum effects are more prominent, especially in the 2600-3600 cm−1, and the free energy profile slightly differs between the classical MD and TRPMD simulations. Using the FT-νNAC and the interatomic distance histograms, the high-frequency vibrational bands are discussed in detail.
Designer Compartment for Artificial Metalloenzymes through Controlled Liquid-Liquid Phase Separation
Authors: Wu Tong , Chen Xianhui , Huang Guopu , Deng Yingjiao , Yang Anming , Feng Xinxin , Bai Yugang
Published: February 2022

Artificial metalloenzymes with different protein scaffolds, cofactors and functions have been prepared to expand the natural enzymatic repertoire with abiotic reactions. However, due to the sensitivity of metal centers toward various biomolecules, especially glutathione, low activity and turnover of artificial metalloenzymes in vivo are systematic problems not fully solved. Apart from straightforward routes such as the use of neutralizing agents, metal cofactors modification and directed evolution, one may notice that nature can create isolated microenvironments for diverse biological processes within cells. Following this way, here we report the in vivo assembly of artificial metalloenzymes based on HaloTag-SNAPTag fusion protein. These metalloenzymes have metal cofactors bound on protein interfaces, and can trigger liquid-liquid phase separation to form liquid condensates inside Escherichia coli. These condensates serve as membraneless, isolated compartments for artificial metalloenzymes to efficiently perform intracellular catalysis, mediating abiotic unmasking, coupling and polymerization reactions. The cellular compartmentalization also enables spatial control of reactions, either facilitating a cascade reaction within the confined spaces, or concurrent reactions with spatial separation. Such engineered Escherichia coli can work as whole-cell catalyst with confined metal species, colonizing at mice intestine to effect in vivo abiotic transformations with a lower chance of heavy metal poisoning. These results represent a systematic strategy to stabilize and potentiate artificial metalloenzyme in vivo, with potential applications in fields such as non-natural metabolism, fermentation and drug delivery.
A General Picture of Cucurbit[8]uril Host-Guest Binding
Authors: Sun Zhaoxi , Huai Zhe , He Qiaole , Liu Zhirong
Published: February 2022

Describing, understanding, and designing complex interaction networks within macromolecular systems remain challenging in modern chemical research. Host-guest systems, despite their relative simplicity in both the structural feature and interaction patterns, still pose problems in theoretical modelling. The barrel-shaped supra-molecular container Cucurbit[8]uril (CB8) shows promising functionalities in various areas, e.g., catalysis and molecular recognition. It can stably coordinate a series of structurally diverse guests with high affinities. In this work, we examine the binding of 7 commonly abused drugs to the CB8 host, aiming at providing a general picture of CB8-guest binding. A thorough comparison of widely used fixed-charge models for drug-like molecules is presented. Extensive sampling of the configurational space of these host-guest systems is performed, and the binding pathway and interaction patterns of CB8-guest complexes are investigated in detail. Iterative refitting of the atomic charges suggests significant conformation-dependence of charge generation. The initial model generated at the original conformation could be inaccurate for new conformations explored during conformational search. Our investigations of the configurational space of CB8-drug complexes suggest that the host-guest interactions are more complex than expected. Despite the structural simplicities of these molecules, the conformational fluctuations of the host and the guest molecules and orientations of functional groups lead to the existence of an ensemble of binding modes (e.g., bracelet-like guest conformations and crescent free energy landscapes). Thus, understandings obtained from static calculations based on a single or several structures are limited for these host-guest interactions. The investigation protocol provides useful guidelines for studying host-guest binding, and the insights of the binding thermodynamics, performance of fixed-charge models, and binding patterns of the CB8-guest systems are useful for elucidating the binding mechanism of other host-guest complexes.
Structural and Functional Annotation of Hypothetical Protein AVO28_00330 of Yersinia pestis: An In Silico Approach
Authors: Ahmed Sunzid
Published: February 2022

Yersinia pestis is an infamous gram-negative, coccobacillus enterobacterium responsible for three devastating plague pandemics worldwide. The recent outbreak of this zoonotic disease demands in silico study of the hypothetical proteins for efficient drug and vaccine discovery. As hypothetical proteins constitute a substantial portion of the proteome, it’s essential to annotate them structurally and functionally. The current study characterized physicochemical properties, predicted homology-based 3D structure and annotated functions of the hypothetical protein AVO28_00330 of Y. pestis using a range of bioinformatic tools and softwares. Swiss Model and Phyre2 server were utilized to predict the tertiary model which was minimized energetically using YASARA server. The quality assessment servers found the model as a good one. For future molecular docking analysis, active binding sites were predicted using CASTp. Protein-protein interaction analysis was performed in STRING server. For functional prediction InterPro, Pfam, Motif and other tools were used. The hypothetical protein revealed tricopeptide repeat domain and rubredoxin metal-binding domain which regulates lipopolysaccharide metabolic process in the outer cell membrane which contributes to virulence property of the protein. Therefore, this in silico analysis will improve the current understanding of the protein and aid in the future analysis regarding therapeutic drug and vaccine investigation.
Visualization and Quantification of Geometric Diversity in Metal–Organic Frameworks
Authors: Nicholas Thomas C. , Alexandrov Eugeny V. , Blatov Vladislav A. , Shevchenko Alexander P. , Proserpio Davide M. , Goodwin Andrew L. , Deringer Volker L.
Published: February 2022

With ever-growing numbers of metal–organic framework (MOF) materials being reported, new computational approaches are required for a quantitative understanding of structure–property correlations in MOFs. Here we show how structural coarse-graining and embedding (“unsupervised learning”) schemes can together give new insight into the geometric diversity of MOF structures. Based on a curated dataset of 1,262 reported experimental structures, we automatically generate coarse-grained and rescaled representations which we couple to a kernel-based similarity metric and to widely used embedding schemes. This approach allows us to visualize the breadth of geometric diversity within individual topologies, and to quantify the distributions of local and global similarities across the structural space of MOFs. The methodology is implemented in an openly available Python package, and is expected to be useful in future high-throughput studies.
Forecasting Nonadiabatic Dynamics using Hybrid Convolutional Neural Network/Long Short-Term Memory Network
Authors: Wu Daxin , Hu Zhubin , Li Jiebo , Sun Xiang
Published: February 2022

Modeling nonadiabatic dynamics in complex molecular or condensed-phase systems has been challenging especially for the long-time dynamics. In this work, we propose a time series machine learning scheme based on the hybrid convolutional neural network/long short-term memory (CNN-LSTM) framework for predicting the long-time quantum behavior given only the short-time dynamics. This scheme takes advantage of both the powerful local feature extraction ability of CNN and the long-term global sequential pattern recognition ability of LSTM. With feature fusion of individually trained CNN-LSTM models for the quantum population and coherence dynamics, the proposed scheme is shown to have high accuracy and robustness in predicting the linearized semiclassical and symmetrical quasiclassical mapping dynamics of various spin-boson models with learning time up to 0.3 ps. Furthermore, if the hybrid network has learned the dynamics of a system, this knowledge is transferable that could significantly enhance the accuracy in predicting the dynamics of a similar system. The hybrid CNN-LSTM network is thus believed to have high predictive power in forecasting the nonadiabatic dynamics in realistic charge and energy transfer processes in photoinduced energy conversion.
In silico all-atom approach to thermodiffusion in dilute aqueous solutions
Authors: Diaz-Marquez Alejandro , STIRNEMANN Guillaume
Published: February 2022

Thermodiffusion (or thermophoresis) is the phenomenon by which the spatial distributions of constituents of liquid or gas phases become inhomogeneous in response to a temperature gradient. It has been evidenced in a variety of systems and has many practical applications, as well as implications in the context of the origins of life. A complete molecular picture of thermophoresis is still missing and phenomenological approaches are often employed to account for the experimental observations. In particular, the amplitude of the resulting concentration-gradients (quantified by the Soret coefficient) depends on many factors that are not straightforwardly rationalized. All-atom molecular dynamics simulations appear as an exquisite tool to shed light on the molecular origins for this phenomenon in molecular systems, but the practical implementation of thermophoretic settings in silico poses significant challenges. Here, we propose a robust approach to tackle thermophoresis in dilute realistic solutions at the molecular level. We rely on a recent enhanced heat-exchange algorithm to generate temperature-gradients. We carefully assess the convergence of thermophoretic simulations in dilute aqueous solutions. We show that simulations typically need to be propagated on long timescales (hundreds of nanoseconds). We find that the magnitude of the temperature gradient and the box sizes have little effect on the measured Soret coefficients. Practical guidelines are derived from such observations. Provided with this reliable setup, we discuss the results of thermophoretic simulations on several examples of molecular, neutral solutes, which we find in very good agreement with experimental measurements regarding the concentration-, mass-, and temperature-dependence of the Soret coefficient.
Benchmarking computational methods to calculate the octanol/water partition coefficients of a diverse set of organic molecules
Authors: López-Colón Alondra , Santiago-Mercado Mariela E. , Aguirre-Santiago Jonathan I. , de Jesús-Hernández Ariana , Negrón-Hernández Jenlyan , Negrón Luis M. , Méndez-Hernández Dalvin D.
Published: February 2022

In the discovery process of new drugs and the development of novel therapies in medicine, computational modeling is a complementary tool for the design of new molecules by predicting for example their solubility in different solvents. Here, we benchmarked several computational methods to calculate the partition coefficients of a diverse set of 161 organic molecules with experimental logP values obtained from the literature. In general, density functional theory methods yielded the best correlations and lower average deviations. Although results are obtained faster with semiempirical and molecular mechanics methodologies, these methods yielded higher average deviations and lower correlation coefficients than hybrid density functional theory methods. We recommend the use of an empirical formula to correct the calculated values with each methodology tested.
Coarse-Grained Density Functional Theory Predictions via Deep Kernel Learning
Authors: Jackson Nicholas , Sivaraman Ganesh
Published: February 2022

Scalable electronic predictions are critical for soft materials design. Recently, the Electronic Coarse-Graining (ECG) method was introduced to renormalize all-atom quantum chemical (QC) predictions to coarse-grained (CG) molecular representations using deep neural networks (DNN). While DNN can learn complex representations that prove challenging for traditional kernel-based methods, they are susceptible to overfitting and the overconfidence of uncertainty estimations. Here, we develop ECG within the GPU-accelerated Deep Kernel Learning (DKL) framework to enable CG QC predictions of a conjugated oligomer using range-separated hybrid density functional theory. DKL-ECG provides accurate reproduction of QC electronic properties in conjunction with prediction uncertainties that facilitate efficient training over multiple temperature data sets via active learning. We show that while active learning algorithms enable efficient sampling of a more diverse configurational space relative to random sampling, the predictive accuracy of DKL-ECG models is effectively identical across all active learning methodologies employed. We attribute this result to the low conformational barriers of our test molecule and the redundant sampling of configurations induced by Boltzmann sampling, even for distinct temperature ensembles.
Electrochemistry Enabled Selective Vicinal Fluorosulfenylation and Fluorosulfoxidation of Alkenes
Authors: Yu Yi , Jiang Yi-Min , Wu Shao-Fen , Shi Zhaojiang , Wu Jin-Nan , Yuan Yaofeng , Ye Ke-Yin
Published: February 2022

Both sulfur and fluorine play important roles in organic synthesis, the life science, and materials science. The direct incorporation of these elements into organic scaffolds with precise control of the oxidation states of sulfur moieties is of great significance. Herein, we report the highly selective electrochemical vicinal fluorosulfenylation and fluorosulfoxidation reactions of alkenes, which were enabled by the unique ability of electrochemistry to dial in the potentials on demand. Preliminary mechanistic investigations revealed that the fluorosulfenylation reaction proceeded through a radical-polar crossover mechanism involving a key episulfonium ion intermediate. Subsequent electrochemical oxidation of fluorosulfides to fluorosulfoxides were readily achieved under a higher applied potential with the adventitious H2O in the reaction mixture.
Molecular Environment Specific Atomic Charges Improve Binding Affinity Predictions of SAMPL5 Host-Guest Systems
Authors: Gonzalez Duvan , Macaya Luis , Vöhringer-Martinez Esteban
Published: February 2022

Host-guest systems are widely used in benchmarks as model systems to improve computational methods for absolute binding free energy predictions. Recent advances in sampling algorithms for alchemical free energy calculations and the increase in computational power have made their binding affinity prediction primarily dependent on the quality of the force field. Here, we propose a new methodology to derive the atomic charges of host-guest systems based on QM/MM calculations and the MBIS partitioning of the polarized electron density. A newly developed interface between the OpenMM and ORCA software package provides D-MBIS charges that best represent the guest’s average electrostatic interactions in the hosts or the solvent. The simulation workflow also calculates the average energy required to polarize the guest in the bound and unbound state. Alchemical free energy calculations using the GAFF force field parameters with D-MBIS charges improve the binding affinity prediction of six guests bound to two octa-acid hosts compared to the AM1-BCC charge set after correction with the average energetic polarization cost. This correction results from the difference in the energetic polarization cost between the bound and unbound state and contributes significantly to the binding affinity of anionic guests.
A Simplified State Interaction for Matrix Product State Wave Functions
Authors: Freitag Leon , Baiardi Alberto , Knecht Stefan , González Leticia
Published: February 2022

We present an approximation to the state-interaction approach for matrix product state (MPS) wave functions (MPSSI) in a non-orthogonal molecular orbital basis, first presented by Knecht et al. [J. Chem. Theory Comput., 2016, 28, 5881], that allows for a significant reduction of the computational cost without significantly compromising its accuracy. The approximation is well-suited if the molecular orbital basis is close to orthogonality, and its reliability may be estimated a-priori with a single numerical parameter. For an example of a platinum azide complex, our approximation offers up to 63-fold reduction in computational time compared to the original method for wavefunction overlaps and spin-orbit couplings, while still maintaining numerical accuracy.
Facile diazonium modification of pomegranate peel biochar: A stupendous derived relationship between thermal and Raman analyses
Authors: Khalil Ahmed , Msaadi Radhia , Sassi Wafa , Ghanmi Imen , Michely Laurent , Snoussi Youssef , Chevillot Alexandre , Lau-Truong Stéphanie , CHEHIMI Mohamed
Published: February 2022

There is an ever growing interest worldwide in the development of biochar from a large variety of agrowastes. This work contributes to the domain by tackling an agrowaste represented in pomegranate peels powder. The latter was activated by acid treatment and then pyrolyzed to generate low cost biochar. To enrich the surface of the resulting biochar, it was arylated with various in-situ generated diazonium salts of 4-aminobenzoic acid (H2N-C6H4-COOH), sulfanilic acid (H2N-C6H4-SO3H) and Azure A dye. At a certain point, it was important to monitor the effect of diazonium nature and concentration on the arylation process. Surface modification of biochar was characterized with TGA and Raman analyses which showed gradual changes in the arylation of biochar at low concentrations of 10-5, 10-4 and 10-3 M of 4-aminobenzoic acid. Interestingly, Azure A diazonium salt induces lower extent of surface modification, likely due to steric hindrance. One key feature of this work is the correlation between D/G Raman peak intensity ratios and the mass loading of the aryl groups. To the very best of our knowledge this is the first report ever on diazonium modification of biochar and opens new avenues for this carbon allotrope, its surface arylation and applications.
Synthesis and Evaluation of a Novel Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins
Authors: Kopf Adrian H. , Lijding Odette , Elenbaas Barend O. W. , Koorengevel Martijn C. , van Walree Cornelis A. , Killian J. Antoinette
Published: February 2022

Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer properties that are important for MP solubilization and stability. MP extraction efficiency was determined using KcsA from E.coli membranes and general solubilization efficiency was investigated via turbidimetry experiments on membranes of E.coli, yeast mitochondria and synthetic lipids. Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all systems, while substituents on the copolymer backbone improved resistance to Ca2+. Relevant polymer properties were found to include hydrophobic balance, size and positioning of substituents, rigidity and electronic effects. The library thus contributes to the rational design of copolymers for the study of MPs.
Phosphorescence Enables Identification of Electronic State for Acridinium Salt in Solutions
Authors: Zhang Xiaolong , Du Jiajun , Liao Fan , Su Hao , Zhang Xuepeng , Zhang Guoqing
Published: February 2022

Understanding intermolecular interactions between Lewis acid and base pairs is of fundamental importance in predicting non-covalent bonding and chemical reactivity. Here we show that an acridinium derivative, a Lewis acid, exhibits various degrees of interactions with Lewis bases of increasing nucleophilicity, including water (HOH), methanol (CH3OH), tetrahydrofuran (ROR), amines (R3N) and t-butoxide (RO-). Each interaction appears to result in a different type of solution state: solvation (e.g., water), coordination (e.g., tetrahydrofuran), chemical bonding (e.g., triethylamine), and radicals (e.g., t-butoxide). The solvated and coordinated acridinium molecules exhibit almost identical 1H-NMR spectra, but possess drastically different UV absorption and luminescence emission, particularly phosphorescence; on the other hand, coordinated and chemically bonded acridinium species which are differentiated by heat calorimetry titration, share the same luminescence spectra but show two different sets of 1H-NMR peaks. These distinct solution states could only be revealed by a combination of NMR and molecular fluorescence/phosphorescence spectroscopic methods, which could provide important clues in the mechanistic understanding of many important processes such as photo-redox reactions. The current report serves as an example of using phosphorescence spectroscopy as a complementary tool for characterizing electronic structures for interaction between organic molecules.
Ritter-Type Iodo(III)amidation of Unactivated Alkynes for the Stereoselective Synthesis of Multisubstituted Enamides
Authors: Yoshikai Naohiko , Chai Jinkui , Ding Wei , Ito Shingo , Wu Junliang
Published: February 2022

The Ritter reaction, Brønsted- or Lewis acid-mediated amidation of alkene or alcohol with nitrile via a carbocation, represents a classical method for the synthesis of tertiary amides. Although analogous reaction through a vinyl cation or a species alike may offer a route to enamide, an important synthetic building block as well as a common functionality in bioactive compounds, such transformations remain largely elusive. Herein, we report on a Ritter-type trans- difunctionalization of alkynes with trivalent iodine electrophile and nitrile, which affords β-iodanyl enamides in moderate to good yields. Mediated by benziodoxole triflate (BXT), the reaction proves applicable to a variety of internal alkynes as well as to various alkyl- and arylnitriles. The benziodoxole group in the product serves as a versatile handle for further transformations, thus allowing for the preparation of various tri- and tetrasubstituted enamides that are not readily accessible by other means.
Hybrid ionic plastic crystals in the race for enhanced low-pressure barocaloric materials
Authors: Salgado-Beceiro Jorge , Bermúdez-García Juan Manuel , Stern-Taulats Enric , García-Ben Javier , Castro-García Socorro , Sánchez-Andújar Manuel , Moya Xavier , Señarís-Rodríguez María Antonia
Published: February 2022

In this work, we introduce a new family of barocaloric hybrid organic-inorganic compounds with colossal barocaloric effects. The here reported hybrid materials, [(CH3)3(CH2Cl)N]FeCl4 and [(CH3)3S]FeCl4, exhibit a molecular structure composed by discrete inorganic anions and organic cations with weak elestrostatic interactions. Our calorimetric studies reveal colossal barocaloric effects of similar magnitude than organic plastic crystals (ΔS > 100 J K-1 kg-1) near room temperature and under smaller pressures (p ≤ 1000 bar), which leads to higher barocaloric strengths. Furthermore, these materials exhibit densities similar to barocaloric hybrid perovskites enhancing the volumetric barocaloric effects (ΔS ~ 200 J K-1 l-1), which could provide more compact cooling devices. Therefore, the colossal values of the mass and volumetric barocaloric effects and large barocaloric strength, in addition to the low working pressure and near-room-temperature operation, offer a new family of compounds to further explore in the search for improved barocaloric materials.
Changing the Nature of the Chelating Ligand of Tetracoordinate Boron-Containing PAH Multi-resonant Thermally Activated Delayed Fluorescence Emitters Tunes the Emission from Green to Deep Red
Authors: Meng Guoyun , Liu Lijie , He Zhechang , Hall David , Wang Xiang , Peng Tai , Yin Xiaodong , Chen Pangkuan , Beljonne David , olivier Yoann , Zysman-Colman Eli , Wang Nan , Wang Suning
Published: February 2022

Multi-resonant thermally activated delayed fluorescence (MR-TADF) materials have attracted considerable attention recently. The molecular design frequently incorporates cycloboration. However, to the best of our knowledge MR-TADF compounds containing nitrogen chelation to boron is still unknown. Reported herein is a new class of tetracoordinate boron-containing MR-TADF emitters bearing a C^N^C- and N^N^N-chelating ligands. We demonstrate that the replacement of B−C covalent bond in C^N^C-chelating ligand by B−N covalent bond affords a regioisomer, which dramatically influences the optoelectronic properties of the molecule. The resulting N^N^N-chelating compounds show bathochromically shifted absorption and emission spectra relative to C^N^C-chelating compounds. The incorporation of tert-butylcarbazole group to the 4-position of the pyridine significantly enhances both the thermal stability and the reverse intersystem crossing rate, yet has a negligible effect on the emission properties. Consequently, high-performance hyperfluorescence organic light-emitting diodes (HF-OLEDs) that utilize these molecules as green and yellow-green emitters show maximum external quantum efficiency (ηext) of 11.5% and 25.1%, and a suppressed efficiency roll-off with ηext of 10.2% and 18.7% at a luminance of 1000 cd m−2, respectively.
Effects of Axial Solvent Coordination to Dirhodium Complexes on Reactivity and Selectivity in C–H Insertion Reactions: A Computational Study
Authors: Laconsay Croix , Pla-Quintana Anna , Tantillo Dean
Published: February 2022

Density functional theory calculations were used to systematically explore the effects of axial ligation by solvent molecules on the reactivity and selectivity of dirhodium tetracarboxylates with diazo compounds in the context of C–H insertion into propane. Insertions on three types of diazo compounds—acceptor/acceptor, donor/acceptor, and donor/donor—promoted by dirhodium tetraformate were tested with and without axial solvent ligation for no surrounding solvent, dichloromethane, isopropanol, and acetonitrile. Magnitudes, origins, and consequences of structural and electronic changes arising from axial ligation were characterized. The results suggest that axial ligation affects barriers for N2 extrusion and C–H insertion, the former to a larger extent.
Reversal of Regioselectivity in Reactions of Donor-Acceptor Cyclopropanes with Eelectrophilic Olefins
Authors: Turkowska Joanna , Durka Jakub , Ociepa Michał , Gryko Dorota
Published: February 2022

Cyclopropanes bearing donor and acceptor groups at the opposite ends of the C-C bond should react with both nucleophiles and electrophiles. Their reactivity towards nucleophiles is well explored while only few specific electrophilic reagents give desired products.These methods are limited by the specific philicity of the carbon atoms resulting from the strong polarization of the central C-C bond. Herein, we report that vitamin B12 catalysis enables the transformation of initially electrophilic center into a nucleophilic radical that as such reacts with SOMOphiles. This radical-based strategy reverses the standard regioselectivity and thus complements the classical approaches.