bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyethylene Glycol Wrapped Alginate/Graphene Hollow Microfibers as Flexible Supercapacitors
Authors: Nasirian Vahid , Niaraki-Asli Amir Ehsan , Aykar Saurabh , Taghavimehr Mehrnoosh , Montazami Reza , Hashemi Nicole
Published: February 2022

Carbon-modified fibrous structures with high biocompatibility have attracted much attention as supercapacitors due to their low cost, sustainability, abundance, and excellent electrochemical performance. However, some of these carbon-based materials suffer from low specific capacitance and electrochemical performance, which have been significant challenges in developing biocompatible electronic devices. In this regard, several studies have been reported on the development of 3D carbon-based micro architectures that provided high conductivity, energy storage potential, and 3D porosity frameworks. This study reports manufacturing of microfluidic Alginate hollow microﬁber modified by water-soluble modified Graphene (BSA-Graphene). These architectures successfully exhibited conductivity enhancement conductivity of about 20 times more compared to Alginate hollow microfibers, and without any signiﬁcant change in the inner-dimension values of hollow region (220.0 ± 10.0 µm) in comparison with pure alginate hollow microfibers. In the presence of Graphene, more obtained specific surface permeability and active ion adsorption sites could successfully provide as shorter pathways. These obtained continuous ion transport networks resulted in improved electrochemical performance. These desired electrochemical properties of the microfibers make Alginate/Graphene hollow fibers an excellent choice for further use in the development of lightweight flexible supercapacitors with scalable potential to be used in intelligent health electronic gadgets.
Boosting Palladium Catalyzed Aryl–Nitro Bond Activation Reaction by Understanding the Electronic, Electrostatic and Polarization Effect: A Computational Study from Basic Understanding to Ligand Design
Authors: Ma Yumiao , Wang Zhaohong
Published: February 2022

Although cross coupling reactions with nitroarene as the electrophilic partner has gained high interest recently, the palladium catalyzed aryl–nitro bond activation reaction still requires rather high temperature and hash condition. In this work, based on Nakao’s nitrogen heterocyclic carbene (NHC) ligand, we systematically explored the substituent effect on the oxidative addition step, the known rate determining step of the whole reaction, by density functional theory (DFT) calculation. The key aryl ring on the ligand skeleton, namely Ring A, acts as a π-donor and stabilizes the palladium center of the transition state, as shown by Extended Transition State Natural Orbital of Chemical Valance (ETS-NOCV) analysis, and thus an electron-rich Ring A is expected to lower the barrier. On the other hand, however, the polarization and electrostatic effects were shown to be as or even more important, although they were often ignored before. These effects originate from through-space interaction with the nitro group in the resting state, and the overall effect is that any polarizable or partly negative group nearby the ortho- or meta¬- site of Ring A is harmful for the reaction. Based on these discoveries, we proposed a list of guidelines for successful ligand development, and designed several new ligands. These ligands exhibit significantly lower barrier than the reported Nakao’s ligand by as large as ~5 kcal/mol in both gas phase and solvation, and might be good candidates for further experimental study.
Filter feature selection for unsupervised clustering of designer drugs using DFT simulated IR spectra data
Authors: He Kedan
Published: February 2022

The rapid emergence of novel psychoactive substances (NPS) poses new challenges and requirements for forensic testing/analysis techniques. This paper aims to explore the application of unsupervised clustering of NPS compounds' infrared spectra. Two statistical measures, Pearson and Spearman, were used to quantify the spectral similarity and to generate the affinity matrices for hierarchical clustering. The correspondence of spectral similarity clustering trees to the commonly used structural/pharmacological categorization was evaluated and compared to the clustering generated using 2D/3D molecular fingerprints. Hybrid model feature selections were applied using different filter-based feature ranking algorithms developed for unsupervised clustering tasks. Since Spearman tends to overestimate the spectral similarity based on the overall pattern of the full spectrum, the clustering result shows the highest degree of improvement from having the non-discriminative features removed. The loading plots of the first two principal components (PCs) of the optimal feature subsets confirmed that the most important vibrational bands contributing to the clustering of NPS compounds were selected using NDFS feature selection algorithms.
An Explosophore-Based Approach Towards the Prediction of Energetic Material Sensitivity Properties
Authors: Rein Jonas , Meinhardt Jonathan M. , Hofstra Wahlman Julie L. , Sigman Matthew S. , Lin Song
Published: February 2022

Accurate prediction of the sensitivity properties of high-energy materials (HEMs) and the study of their decomposition mechanisms are two major focuses within energetics research. Due to the hazards associated with the synthesis and handling of energetic materials, predictive models for HEM sensitivity are of great importance in enabling the safe and efficient development of future HEMs. Traditional predictive modeling of HEM decomposition via machine learning algorithms generally displays limited interpretability, while mechanistic studies of HEMs typically focus on small subsets of structurally analogous compounds lacking generalizability. This study aims to bridge the gap between predictive modeling and computational mechanistic analysis of HEMs, with the goal of providing chemically interpretable models for HEM sensitivity property prediction. Herein, we disclose the use of multivariate linear regression (MLR) modeling for the prediction of the decomposition temperature and impact sensitivity of HEMs. We report an explosophore-based approach to sensitivity property prediction featuring an ensemble of quantum mechanical parameters and computational workflows that enable rapid parameterization and modeling of energetic functional groups. We then employ these methods to accurately predict sensitivity properties of nitrogen-rich tetrazole and azide HEMs. These statistical MLR models are readily interpreted based on the principles of physical organic chemistry, producing structure-property relationships to guide the rational design of new HEMs. Furthermore, we extend our explosophore-based approach to predict the sensitivity properties of HEMs containing multiple, non-equivalent energetic functional groups through the identification of molecular triggers for the bulk decomposition of HEMs. Finally, we showcase the viability of our methods towards ab initio virtual screening of HEMs through predictive modeling of external test sets of tetrazole HEMs using structures and parameters generated exclusively in silico.
Time-Dependent Long-Range-Corrected Double-Hybrid Density Functionals with Spin-Component and Spin-Opposite Scaling: A Comprehensive Analysis of Singlet-Singlet and Singlet-Triplet Excitation Energies
Authors: Casanova Paez Marcos , Goerigk Lars
Published: February 2022

Following the work on spin-component and spin-opposite scaled (SCS/SOS) global double hybrids for singlet-singlet excitations by Schwabe and Goerigk [J. Chem. Theory Comput. 2017, 13, 4307-4323] and our own works on new long-range corrected (LC) double hybrids for singlet-singlet and singlet-triplet excitations [J. Chem. Theory Comput. 2019, 15, 4735- 4744; J. Chem. Phys. 2020, 153, 064106], we present new LC double hybrids with SCS/SOS that demonstrate further improvement over previously published results and methods. We introduce new unscaled and scaled versions of different global and LC double hybrids based on Becke88 or PBE exchange combined with LYP, PBE or P86 correlation. For singlet-singlet excitations, we cross-validate them on six benchmark sets that cover small to medium-sized chromophores with different excitation types (local valence, Rydberg, and charge transfer). For singlet-triplet excitations, we perform the cross-validation on three different benchmark sets following the same analysis as in our previous work in 2020. In total, 203 unique excitations are analyzed. Our results confirm and extend those of Schwabe and Goerigk regarding the superior performance of SCS and SOS variants compared to their unscaled parents by decreasing mean absolute deviations, root-mean-square deviations or error spans by more than half and bringing absolute mean deviations closer to zero. Our SCS/SOS variants show to be highly efficient and robust for the computation of vertical excitation energies, which even outperform specialized double hybrids that also contain an LC in their perturbative part. In particular, our new SCS/SOS-ωPBEPP86 and SCS/SOS-ωB88PP86 functionals are four of the most accurate and robust methods tested in this work and we fully recommend them for future applications. However, if the relevant SCS and SOS algorithms are not available to the user, we suggest ωPBEPP86 as the best unscaled method in this work.
Hydrazones in anion transporters: The detrimental effect of a second binding site
Authors: Martínez-Crespo Luis , Halgreen Lau , Soares Márcio , Marques Igor , Félix Vítor , Valkenier Hennie
Published: February 2022

Synthetic anion transporters can be developed using anion receptors that are able to bind the anion and stabilize it in the lipophilic interior of a bilayer membrane, and they usually contain functional groups with acidic NHs, such as ureas, thioureas and squaramides. To assess the suitability of acylhydrazones as a new functional group for the preparation of anion transporters, we have studied a family of thioureas functionalized with these and related functional groups. 1H NMR titrations and DFT calculations indicate that the thioureas bearing acylhydrazone groups behave as chloride receptors with two separate binding sites, of which the acylhydrazone binds weaker than the thiourea. Chloride transport studies show that the additional binding site has a detrimental effect on thiourea-based transporters, and this phenomenon is also observed for bis(thio)ureas with two separate binding sites. We propose that the presence of a second anion binding unit hinders the transport activity of the thiourea due to additional interactions with the phospholipids of the membrane. In agreement with this hypothesis, extensive molecular dynamics simulations suggest that the molecules will tend to be positioned in the water/lipid interface, driven by the interaction of the NHs of the thiourea and of the acylhydrazone groups with the POPC polar head groups and water molecules. Moreover, the interaction energies show that the poorest transporters have indeed the strongest interactions with the membrane phospholipids, inhibiting chloride transport. This detrimental effect of additional functional groups on transport activity should be considered when designing new ion transporters, unless these groups cooperatively promote anion recognition and transmembrane transport.
Photoredox-Mediated, Nickel-Catalyzed Trifluoromethylthiolation of Aryl and Heteroaryl Iodides
Authors: Gravatt Christopher S. , Johannes Jeffrey W. , Ghosh Avipsa
Published: February 2022

While the area of trifluoromethylthiolation of aryl halides has been extensively explored, the current methods require complex and/or air-sensitive catalysts. Reported here is a method employing a bench-stable nickel(II) salt and an iridium photocatalyst that can mediate the trifluoromethylthiolation of a wide range of electronically diverse aryl and heteroaryl iodides, likely via a Ni(I)/Ni(III) catalytic cycle. The reaction has broad functional group tolerance and potential for application in medicinal chemistry, as demonstrated by a late-stage functionalization approach to access (racemic)-Monepantel.
Stable open-shell aromatic nitric acid radicals: accessing highly efficient photothermal conversion with restricted radiative decay
Authors: wang zejun , Jiawen Zhou , Zhang Yiheng , Zhu Weiya , Li Yuan
Published: February 2022

Most of the open-shell radicals are usually thermodynamically or kinetically unstable in air due to their incompletely satisfied valency. As phenol radical without steric hindrance group protection, aromatic nitric acid radical exhibits high electrochemical and thermal stability due to its rich resonance structures including closed-shell nitro-like and open-shell nitroxide structure with unpaired electrons delocalized in conjugated backbones. Herein, a series of star-shaped aromatic nitric acid radical materials were prepared via facile demethylation and consequent oxidation of their phenolic hydroxyl precursors in air. Interestingly, they exhibit extremely high spin concentration and highly enhanced nonradiative decay, which make them exhibit great potential for photothermal conversion. Among them, TPA-TPA-O6 exhibits high photothermal conversion efficiency and negligible photobleaching effect in seawater desalination. Under irradiation of one sunlight, the water evaporation efficiency of TPA-TPA-O6 is recorded as high as 89.41% and the water evaporation rate is 1.293 kg/m2 h, which represent as the top performance in pure organic small molecule photothermal materials.
Dimeric cyclobutane formation under continuous flow conditions using organophotoredox catalysed [2+2]-cycloaddition
Authors: Grantham Helena , Kimber Marc
Published: February 2022

Radical cation-initiated dimerization of electron rich alkenes is an expedient method for the synthesis of cyclobutanes. By merging organophotoredox catalysis and continuous flow technology a batch versus continuous flow study has been performed providing a convenient synthetic route to an important carbazole cyclobutane material dimer t-DCzCB using less only 0.1 mol% of an organophotoredox catalyst. The scope of this methodology was explored giving a new class of functional materials, as well as an improved synthetic route to styrene based lignan dimeric natural products. The cyclobutane dimers could be isolated in higher chemical yields under continuous flow conditions and reaction times were reduced significantly compared to traditional batch reaction conditions.
Hard Carbon Derived from Avocado Peels as a High-Capacity, High-Performance Anode Material for Sodium-Ion Batteries
Authors: Genier Francielli , Pathreeker Shreyas , Schuarca Robson , Islam Mohammad , Hosein Ian
Published: February 2022

Deriving battery grade materials from natural sources is a key element to establishing sustainable energy storage technologies. In this work, we present the use of avocado peels as a sustainable source for conversion into hard carbon based anodes for sodium ion batteries. The avocado peels are simply washed and dried then proceeded to a high temperature conversion step. Materials characterization reveals conversion of the avocado peels in high purity, highly porous hard carbon powders. When prepared as anode materials they show to the capability to reversibly store and release sodium ions. The hard carbon-based electrodes exhibit excellent cycling performance, namely, a reversible capacity of 352.55 mAh/g at 0.05 A/g, rate capability up to 86 mAh/g at 3500 mA/g, capacity retention of >90%, and 99.9% coulombic efficiencies after 500 cycles. This study demonstrates avocado derived hard carbon as a sustainable source that can provide excellent electrochemical and battery performance as anodes in sodium ion batteries.
Jahn-Teller Effects in a Vanadate-Stabilized Manganese-Oxo Cubane Water Oxidation Catalyst
Authors: Mai Sebastian , Holzer Marcus , Andreeva Anastasia , González Leticia
Published: February 2022

We report Jahn–Teller effects in different oxidation states of the water oxidation catalyst [(Mn4O4)(V4O13)(OAc)3]n- and its activated form [(Mn4O4)(V4O13)(OAc)2(H2O)(OH)]n-. Based on all combinatorially possible Jahn–Teller axis arrangements of the Mn(III) atoms, the energetically stable minima are identified. We also derive five heuristic rules that associate a particular energetic cost with certain structural features, like crossings of multiple Jahn–Teller axes, the location of Jahn–Teller axes, or the ligand that is involved in a Jahn–Teller axis. It is found that the different oxidation states seem to localize on different Mn centers, giving rise to clear Jahn–Teller distortions, unlike in previous crystallographic findings where an apparent valence delocalization was found. We conclude that the combination of cubane-vanadate bonds that are chemically inert, cubane-acetate/water bonds that can be activated through a Jahn–Teller axis, and low activation barriers for intramolecular rearrangement of the Jahn–Teller axes plays an important role in the reactivity of this and related compounds.
A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E
Authors: Shiomi Shinya , Shennan Benjamin D. A. , Yamazaki Ken , Fuentes de Arriba Ángel L. , Vasu Dhananjayan , Hamlin Trevor A. , Dixon Darren J.
Published: February 2022

The enantioselective total synthesis of madangamine E has been completed in 30 steps, enabled by a new catalytic and highly enantioselective desymmetrizing intramolecular Michael addition reaction of a prochiral ketone to a tethered β,β’-disubstituted nitroolefin. This key carbon–carbon bond forming reaction efficiently constructed a chiral bicyclic core in near-perfect enantio- and diastereo-selectivity, concurrently established three stereogenic centers, including a quaternary carbon stereocenter, and proved highly scalable. Furthermore, the pathway and origins of enantioselectivity in this catalytic cyclisation were probed using density functional theory (DFT) calculations, which revealed the crucial substrate/catalyst interactions in the enantio-determining step. Following construction of the bicyclic core, the total synthesis of madangamine E could be completed, with key steps including a mild one-pot oxidation-lactamisation, a two-step Z-selective olefination of a sterically hindered ketone, and ring-closing metatheses to install the two macrocyclic rings.
Identifying high performance and durable methylammonium-free lead halide perovskites through high throughput synthesis and characterization
Authors: An Yu , Perini Carlo Andrea Riccardo , Hidalgo Juanita , Castro-Méndez Andrés-Felipe , Jacob N. Vagott , Li Ruipeng , Saidi Wissam A. , Wang Shirong , Li Xianggao , Correa-Baena Juan-Pablo
Published: February 2022

One of the organic component in the perovskite photo-absorber, the methylammonium cation, has been suggested to be a roadblock to long-term operation of organic-inorganic hybrid perovskite-based solar cells. Methylammonium-free perovskites thus represent a possible direction for more stable photo-absorbers that are also compatible with multijunction solar cells. However, most work on methylammonium-free perovskites involves cesium and formamidinium as the A-site cations, which are thermodynamically less stable than the methylammonium-based materials. In this work we systematically explore the crystallographic and optical properties of the compositional space of mixed cation and mixed halide lead perovskites, where formamidinium (FA+) is gradually replaced by cesium (Cs+), and iodide (I-) is substituted by bromide (Br-), i.e., CsyFA1–yPb(BrxI1–x)3. The crystal phases, which could be tuned by changing the tolerance factor for mixed perovskite alloys, are qualitatively determined and the composition–structure relationship is established in the CsyFA1–yPb(BrxI1–x)3 compositional space. We find that higher tolerance factors lead to more cubic structures, whereas lower tolerance factors lead to more orthorhombic. We also find that while some correlation exists between tolerance factor and structure, tolerance factor does not provide a holistic understanding of whether a perovskite structure will fully form. Given the wide range of bandgaps produced by this compositional space, an empirical expression is devised to predict the optical bandgap of CsyFA1–yPb(BrxI1–x)3 perovskites – which changes as a function of composition –, conducive to the design of absorbers with bandgaps tailor-made for specific tandem and single-junction applications. By screening 26 solar cells with different compositions, we find that Cs1/6FA5/6PbI3 delivers the highest efficiency and long-term stability among I-rich compositions. This work sheds light on the fundamental structure-property relationships in the CsyFA1–yPb(BrxI1–x)3 compositional space, providing vital insight to the design of durable perovskite materials. Our approach provides a library of structural and optoelectronic information of this compositional space.
Adsorbed Cobalt Porphyrins Act like Metal Surfaces in Electrocatalysis
Authors: Kaminsky Corey J. , Weng Sophia , Wright Joshua , Surendranath Yogesh
Published: February 2022

Carbon electrodes chemically modified with molecular active sites are potent catalysts for key energy conver-sion reactions. Generally, it is assumed that these molecularly modified electrodes operate by the same redox mediation mechanisms observed for soluble molecules, in which electron transfer and substrate activation occur in separate elementary steps. Here, we uncover that, depending on the solvent, carbon-bound cobalt porphyrin can carry out electrolysis by the non-mediated mechanisms of metal surfaces in which electron transfer and substrate activation are concerted. We chemically modify glassy carbon electrodes with cobalt tetraphenylpor-phyrin units that are anchored by flexible aliphatic linkages to form CH-CoTPP. In acetonitrile, CH-CoTPP dis-plays a clear outer-sphere Co(II/I) process which catalyzes the H2 evolution reaction by a step-wise, redox-mediated reaction sequence. In contrast, clear surface redox waves are not observed for CH-CoTPP in aqueous media and H2 evolution proceeds via a non-mediated, concerted proton-electron transfer reaction sequence over a wide pH range. The data suggest that, in aqueous electrolyte, the CoTPP fragments reside inside the electro-chemical double layer and are electrostatically coupled to the surface. This coupling allows CH-CoTPP to carry out catalysis without being pinned to the redox potential of the molecular fragment. These studies highlight that the simple adsorption of molecules can lead to reaction mechanisms typically reserved for metal surfaces, ex-posing new principles for the design of molecularly-modified electrodes.
MD Simulations and QM/MM Calculations Reveal the Key Mechanistic Ele-ments which are Responsible for the Efficient C-H Amination Reaction Per-formed by a Bioengineered P450 Enzyme
Authors: Kalita Surajit , Shaik Sason , Dubey Kshatresh
Published: February 2022

An enzyme which is capable of catalyzing C-H amination reactions, is considered to be a dream tool for chemists due to its pharmaceutical potential and greener approach. Recently, the Arnold group achieved this feat using an engineered CYP411 enzyme, which further undergoes a random directed evolution which increases its efficiency and selectivity. The present study provides the mechanistic insight and the root cause of the success of these mutations to enhance the reactivity and selectivity of the mutant enzyme. This is achieved by means of comprehensive MD simulations and hybrid QM/MM calculations. The study shows that the efficient C-H amination by the so-engineered CYP411 is a combined outcome of electronic and steric effects. The mutation of axial cysteine ligand to serine relays electron density to the Fe ion in the heme, and thereby enhances the bonding capability of the heme-iron to the nitrogen atom of the tosyl azide. By comparison, the native cysteine-ligated P450, cannot bind the tosyl azide. On top, the A78V and A82L mutations in P411 provide ‘bulk’ to the active site which thereby increases the enantioselectivity via steric effect. At the same time, the QM/MM calculations elucidate the C-H amination by the iron nitrenoid, revealing a mechanism analogous to Compound I in the native- C-H hydroxylation by P450.
An Optical Probe for Real-Time Monitoring of Self-Replicator Emergence and Distinguishing between Replicators
Authors: Hatai Joydev , Altay Yigit , Sood Ankush , Kiani Armin , Eleveld Marcel , Motiei Leila , Margulies David , Otto Sijbren
Published: February 2022

Self-replicating systems play an important role in research on the synthesis and origin of life. Monitoring of these systems has mostly relied on techniques such as NMR or chromatography, which are limited in throughput and demanding when monitoring replication in real time. To circumvent these problems, we now developed a pattern-generating fluorescent molecular probe (an ID-probe) capable of discriminating replicators of different chemical composition and monitoring the process of replicator formation in real time, giving distinct signatures for starting materials, intermediates and final products. Optical monitoring of replicators dramatically reduces the analysis time and sample quantities compared to most currently used methods and opens the door for future high-throughput experimentation in protocell environments.
Quantification and characterization of the sludge generated from synthetic acid mine drainage treatment using sodium ferrate (VI) as an advance oxidation process
Authors: Munyengabe Alexis , Zvinowanda Caliphs , Ramontja James , Zvimba John Ngoni
Published: February 2022

A major problem in the active treatment of acid mine drainage (AMD) is the generation of large volumes of sludge through pH neutralization, oxidation of iron (II) and subsequent metal precipitation. The sludge settling rate, sludge volume index (SVI) and sedimentation process are ones of parameters identifying a good treatment of AMD. Sodium ferrate (VI) (Na2FeO4) is one reagent currently used to treat water due to its quick reaction rate, easy implementation and relatively low chemical and operational costs. However, very limited information is available in the literature related to the detailed characterization and dewaterability of Na2FeO4-treated AMD sludge. This study aimed at characterizing and monitoring settling rate and densification process of synthetic AMD sludge after treatment with Na2FeO4. The results confirmed a complete removal of iron from the synthetic AMD due to high oxidation strength of ferrate (VI) in acidic medium (Eᵒ = 2.2V) and showed the presence of different minerals formed in the sludge after treatment. The concentrations of the sludge collected at different intervals were justified by the densification process and high density of the sludge was obtained after 25 minutes while high weight percent of iron was found at 10 min and Fe and O dominated other elements in the sludge. The study demonstrated very good settling properties of the sludge and the low SVI value ranging between 30 and 60 mL/g TSS.
A mechanism of abiogenesis based on complex reaction networks organized by seed-dependent autocatalytic systems
Authors: Peng Zhen , Linderoth Jeff , Baum David
Published: February 2022

The core of the origin-of-life problem is to explain how a complex dissipative system could emerge spontaneously from a simple environment, perpetuate itself, and complexify over time. This would only be possible, we argue, if prebiotic chemical reaction networks had autocatalytic features organized in a way that permitted the accretion of complexity even in the absence of genetic control. To evaluate this claim, we developed tools to analyze the autocatalytic organization of food-driven reaction networks and applied these tools to both abiotic and biotic networks. Both networks contained seed-dependent autocatalytic systems (SDASs), which are subnetworks that can use a flux of food chemicals to self-propagate if, and only if, they are first seeded by some non-food chemicals. Moreover, SDASs were organized such that the activation of a lower-tier SDAS could render new higher-tier SDASs accessible. The organization of SDASs is, thus, similar to trophic levels (producer, primary consumer, etc.) in a biological ecosystem. Furthermore, similar to ecological succession, we found that higher-tier SDASs may produce chemicals that enhance the ability of the entire chemical ecosystem to utilize food more efficiently. The SDAS concept explains how driven abiotic environments, namely ones receiving an ongoing flux of food chemicals, can incrementally complexify even without genetic polymers. This framework predicts that it ought to be possible to detect the spontaneous emergence of life-like features, such as self-propagation and adaptability, in driven chemical systems in the laboratory. Additionally, SDAS theory may be useful for exploring general properties of other complex systems.
Pd-pincer complexes containing six-membered rings that are more active allylation catalysts than five-membered ring analogues
Authors: Wise Dan , Pridmore Natalie , Pringle Paul
Published: February 2022

A series of symmetric and non-symmetric PCP-pincer complexes have been prepared and an evaluation of their activity in catalytic allylic alkylation carried out. The X-ray crystallography and NMR spectroscopy data suggest that metallacycles containing one (or two) 6-membered rings are inherently more rigid than initially anticipated. The observed catalyst activity is found to increase as the metallacycle size increases from 5 to 6.
Using molecular dynamics simulation to study the polarization response of the liquid water interface to surface charge heterogeneity
Authors: Shin Sucheol , Willard Adam
Published: February 2022

The hydration shells of proteins mediate interactions, such as small molecule binding, that are vital to their biological function or in some cases their dysfunction. However, even when the structure of a protein is known, the properties of its hydration environment cannot be easily predicted due to the complex interplay between protein surface heterogeneity and the collective fluctuations of water's hydrogen bonding network. This manuscript presents a theoretical study of the influence of surface charge heterogeneity on the polarization response of the liquid water interface. We introduce a new computational method for analyzing simulation data that is capable of quantifying water's nonlinear polarization response and determining the effective surface charge distribution of hydrated surfaces over atomistic length scales. When applied to a protein, this method is capable of revealing new insight into the influence of conformational dynamics on hydration structure, as we highlight by illustrating how salt-bridge formation enhances the polarization of the local hydration shell. To illustrate the utility of this method, we present the results of molecular dynamics simulations of liquid water in contact with a heterogeneous model surface and the CheY protein.
Papyrus - A large scale curated dataset aimed at bioactivity predictions
Authors: Béquignon Olivier J. M. , Bongers Brandon J. , Jespers Willem , IJzerman Ad P. , van de Water Bob , van Westen Gerard J. P.
Published: February 2022

With the recent rapid growth of publicly available ligand-protein bioactivity data, there is a trove of viable data that can be used to train machine learning algorithms. However, not all data is equal in terms of size and quality, and a significant portion of researcher’s time is needed to adapt the data to their needs. On top of that, finding the right data for a research question can often be a challenge on its own. As an answer to that, we have constructed the Papyrus dataset (DOI: 10.4121/16896406), comprised of around 60 million datapoints. This dataset contains multiple large publicly available datasets such as ChEMBL and ExCAPE-DB combined with several smaller datasets containing high quality data. The aggregated data has been standardised and normalised in a manner that is suitable for machine learning. We show how data can be filtered in a variety of ways, and also perform some baseline quantitative structure-activity relationship analyses and proteochemometrics modeling. Our ambition is this pruned data collection constitutes a benchmark set that can be used for constructing predictive models, while also providing a solid baseline for related research.
Electrochemical Reduction of CO2 on Au Electrocatalysts in a Zero-Gap, Half-Cell Gas Diffusion Electrode Setup: a Systematic Performance Evaluation and Comparison to a H-cell Setup
Authors: Alinejad Shima , Quinson Jonathan , Wiberg Gustav K.H. , Schlegel Nicolas , Zhang Damin , Li Yao , Reichenberger Sven , Barcikowski Stephan , Arenz Matthias
Published: February 2022

Much research effort has been devoted to the development of effective catalysts for the electrochemical reduction of CO2 (CO2RR). For CO2RR, the most common catalyst screening method is performed in a H-cell configuration where the reactant CO2 gas is usually dissolved in an aqueous bicarbonate-based electrolyte. However, the low solubility of CO2 in aqueous solutions (∼35 mM at 298 K and 1 atm pressure) causes mass transport limitations in such setups. Based on H-cell measurements gold (Au) is one of the most selective catalysts for the CO2RR to CO. The preparation of small Au nanoparticles (NPs) based on conventional synthesis methods often requires the use of surfactants and capping agents such as polyvinylpyrrolidone (PVP). Here, we present a systematic evaluation of the performance of Au NPs for the CO2RR in our recently developed gas diffusion electrode (GDE) setup and compare the results to investigations in a conventional H-cell configuration. The GDE setup can be characterized as a zero gap, half-cell setup and supplies a continuous CO2 stream at the electrode−membrane electrolyte interface to circumvent CO2 mass transport limitations encountered in conventional H-cells. We investigate the influence of the catalyst loading as well as the influence of PVP. The results comparing the two screening methods show that the performance of the same catalyst can be substantially different in the different setups, which highlights the importance of having commercially relevant conditions for catalyst screening. In both setups, it is found that the presence of PVP favours the hydrogen evolution reaction (HER), however, in the GDE setup PVP is more detrimental for the performance than in conventional H-cells.
Driving Aspirational Process Mass Intensity Using SMART-PMI and Innovative Chemistry
Authors: Sherer Edward , Bagchi Ansuman , Kosjek Birgit , Maloney Kevin , Peng Zhengwei , Robaire Sandra , Sheridan Robert , Metwally Essam , Campeau Louis-Charles
Published: February 2022

An important metric for gauging the impact a synthetic route has on chemical resources, cost, and sustainability is process mass intensity (PMI). Calculating the overall PMI or step PMI for a given synthesis from a process description is more and more common across the industry. Our company has established a strong track record of delivering on our Corporate Sustainability goals, being recognized with seven EPA Green Chemistry Challenge Awards in the last 15 years. While green chemistry principles help in optimizing PMI and developing more sustainable processes, a key challenge for the field is defining what ‘good’ looks like for any given molecule. Predicting aspirational PMI for a synthetic target is not yet possible from chemical structure alone. The only tool chemists have at their disposal to predict PMI requires the synthetic route to be available, which is inherently retrospective. We have developed SMART-PMI (in-Silico MSD Aspiration-al Research Tool) to fill this glaring gap. Using only a 2D chemical structure, which enables a measure of molecular complexity, we can generate a predicted SMART-PMI using historical PMI data from our company’s clinical and commercial portfolio of processes. From this SMART-PMI prediction, we have established target ranges for Successful, World Class, and Aspirational PMI. Using this model, chemists can develop powerful synthetic strategies that make the biggest impact on PMI and, in turn, drive improvements to the model. The potential of SMART-PMI to set industry-wide aspirational PMI targets is discussed.
Visible Light-Induced Sulphide Anion-Catalysed Decarboxylative Alkylations in Batch and Continuous Flow
Authors: Wang Guangzu , Liu Mengting , Liu Deguang , Qin Zhiwei
Published: February 2022

We demonstrated herein a versatile protocol for visible-light-induced sulphide anion-catalysed decarboxylative cross-couplings. An array of primary, secondary, tertiary and amino acid-derived redox-active esters (RAEs) were all amenable substrates to undergo radical decarboxylation to be coupled with a diverse range of nucleophiles, creating challenging C(sp3)-C(sp3) and C(sp3)-C(sp2) bonds with high efficiency. We note that Katritzky’s salt and Togni’s reagent were also suitable substrates, affording deaminative alkylation and trifluoromethylation products in high yields. Density functional theory calculations and mechanism experiments indicate that a charge-transfer complex was formed between sulphide anions and RAEs in the amide solvent. Additionally, a one-pot two-step telescoped procedure and continuous-flow process further increase the synthetic utility of this catalytic system.
Selective amide bond formation in redox-active coacervate protocells
Authors: Wang Jiahua , Abbas Manzar , Wang Junyou , Spruijt Evan
Published: February 2022

Membraneless compartments, like complex coacervates droplets, are promising protocell models because of their ability to sequester a wide range of guest molecules and their catalytic properties. However, it remains unclear how the building blocks of life, including peptides, could be synthesized from primitive precursor molecules inside such protocells. Here, we develop a new protocell model formed by phase separation of prebiotically relevant small redox-active ferricyanide (Fe(CN)_6^{3−})/ferrocyanide (Fe(CN)_6^{4−}) molecules and a cationic peptide. The assembly of these coacervate protocells can be regulated by redox chemistry and they act as oxidizing hubs for sequestered metabolites, such as NAD(P)H, and fiber precursors. Interestingly, we show that the oxidizing potential of ferricyanide inside coacervates can be harnessed to drive the selective formation of amide bonds between prebiotically relevant amino thioacids and amino acids or peptides. We demonstrate that aminoacylation is enhanced in Fe(CN)_6^{3−}/peptide coacervate dispersions compared to the surrounding dilute phase, and selective for amino acids that interact less strongly with the coacervates. We finally use this amide bond formation to create self-reinforcing coacervates by reacting hydrophobic amino thioacids to amines on the protocell scaffold and show that this significantly enhances their salt resistance. These results provide an important step towards the prebiotically relevant integration of redox chemistry in cell-like compartments.
An eight-state molecular sequential switch featuring a dual single-bond rotation photoreaction
Authors: Gerwien Aaron , Jehle Benjamin , Irmler Marvin , Mayer Peter , Dube Henry
Published: February 2022

Typical photowitches interconvert between two different states by simple isomerization reactions, which represents a fundamental limit for applications. To expand the switching capacity usually different photoswitches have to be linked together leading to strong increase in molecular weight, diminished switching function, and less precision and selectivity of switching events. Herein we present an approach for solving this essential problem with a different photoswitching concept. A basic molecular switch architecture provides precision photoswitching between eight different states via controlled rotations around three adjacent covalent bonds. All eight states can be populated one after another in an eight-step cycle by alternating between photochemical Hula-Twist isomerizations and thermal single bond rotations. By simply changing solvent and temperature the same switch can also undergo a different cycle instead interconverting just five isomers in a selective sequence. This behavior is enabled through the discovery of an unprecedented photoreaction, a one photon dual single bond rotation.
Unexpected Inverse Correlations and Cooperativity in Ion-pair Phase Transfer
Authors: Kumar Nitesh , Clark Aurora
Published: February 2022

Liquid/liquid extraction is one of the most widely used separation and purification methods, where a forefront of research is the study of transport mechanisms for solute partitioning and the relationships that these have to solution structure at the phase boundary. To date, organized surface features that include protrusions, water-fingers, and molecular hinges have been reported. Many of these equilibrium studies have focused upon small-molecule transport - yet the extent to which the complexity of the solute and the competition between different solutes, influence transport mechanisms have not been explored. Here we report molecular dynamics simulations that demonstrate that a metal salt LiNO3 can be transported via a protrusion mechanism that is remarkably similar to that reported for H2O by tri-butyl phosphate (TBP), a process that involves dimeric assemblies. Yet the LiNO3 out-competes H2O for a bridging position between the extracting TBP dimer, which in-turn changes the preferred transport pathway of H2O. Examining the electrolyte concentration dependence on ion-pair transport unexpectedly reveals an inverse correlation with the extracting surfactant concentration. As [LiNO3] increases, surface adsorbed TBP becomes a limiting reactant in correlation with an increased negative surface charge induced by excess interfacial NO3-, however, the rate of transport is enhanced. Within the highly dynamic interfacial environment, we hypothesize that this unique cooperative effect may be due to perturbed surface organization that either decreases the energy of formation of transporting protrusion motifs or makes it easier for these self-assembled species to disengage from the surface.
Difluoroalkylation of tertiary amides and lactams by an iridium-catalyzed reductive Reformatsky reaction
Authors: Biallas Phillip , Yamazaki Ken , Dixon Darren J.
Published: February 2022

The synthesis of medicinally relevant α-difluoroalkylated amines by an iridium-catalyzed reductive alkylation of tertiary amides and lactams with difluoro-Reformatsky reagents, is described. This report features the introduction of various geminal difluoro-acetates and -acetamides as well as late stage derivatization of APIs, gram scale synthesis and downstream functionalizations.
Evidence of sulfur centered hydrogen bond with sulfur atoms as a donor in aromatic thiols and aliphatic thiols on complexation with water using quantum mechanical methods
Authors: Paul Arnav , Thomas Renjith
Published: February 2022

It has been more than a century since the discovery of hydrogen bonds, but the knowledge about its impact on day to day life of people is getting enhanced even now. It has a pivotal role in the stabilization of various biomolecules and subsequent bioactivity. Sulfur cantered hydrogen bond (SCHB), which is a weak interaction, has attracted the attention of many scientists in the last few decades. In this work, we report the nature of the SCHB between aliphatic/aromatic thiols and water. B3LYP-D3(BJ) with cc-pVTZ level was used for modeling the hydrogen bonded thiol-water complexes. Domain-based local pair natural orbitals coupled-cluster theory with single, double, and perturbative triple excitation DLPNO-CCSD(T) method was used for local energy decomposition analysis. QTAIM analysis helped to examine hydrogen bonds, weak non-covalent interactions, and the various electron density delocalization. Natural Bond Orbital (NBO) analysis explains the reason for the sulfur atom being the H-bond donor. Second-order perturbation energy from NBO findings supports the data obtained by LED and AIM calculations. Aromatic thiols form stronger hydrogen bonds than aliphatic thiols. The effect of substituents was also explored by studying aromatic systems with electron-withdrawing groups and donating groups. EDG substituted have more vital interaction, and EWG substituted thiols form stronger S-H…O hydrogen bonds.
A scalable and continuous access to pure cyclic polymers enabled by quarantined heterogeneous catalysts
Authors: Yoon Ki-Young , Noh Jinkyung , Gan Quan , Edwards Julian , Tuba Robert , Choi Tae-Lim , Grubbs Robert
Published: February 2022

Cyclic polymers are topologically interesting and envisioned as a lubricant material. However, scalable synthesis of pure cyclic polymers remains elusive. The most straightforward way is to recycle a used catalyst for the synthesis of cyclic polymers. Unfortunately, it is demanding because of the catalyst’s vulnerability and inseparability from polymers, which depreciates the practicality of the process. Here, we develop a continuous process streamlined in a circular way that polymerization, polymer separation, and catalyst recovery happen in situ, to dispense a pure cyclic polymer after bulk ring-expansion metathesis polymerization of cyclopentene. It is enabled by introducing silica-supported ruthenium catalysts and a newly-designed glassware. Also, different depolymerization kinetics of the cyclic polymer from its linear analogue is discussed. This process minimizes manual labor, maximizes security of vulnerable catalysts, and guarantees purity of cyclic polymers, thereby showcasing a prototype of a scalable access to cyclic polymers with increased reusability of precious catalysts (≥415,000 turnovers).
La3+ and Y3+ interactions with the carboxylic acid moiety at the liquid/vapour interface: identification of binding complexes, charge reversal, and detection limits.
Authors: Sthoer Adrien , Sengupta Sanghamitra , Adams Ellen , Corkery Robert , Allen Heather , Tyrode Eric
Published: February 2022

Specific interactions of yttrium and lanthanum ions with a fatty acid Langmuir monolayer were investigated using vibrational sum frequency spectroscopy (VSFS). The trivalent ions were shown to interact with the charged form of the carboxylic acid group from nanomolar concentrations (<300 nM). Analysis of the spectral features from both the symmetric and the asymmetric carboxylate modes reveals the presence of at least three distinct coordination structures linked to specific binding configurations. Although the same species were identified for both La3+ and Y3+, they display a different concentration dependence, highlighting the ion-specificity of the interaction. From the response of interfacial water molecules, charge reversion, as well as the formation of yttrium hydroxide complexes, were detected upon increasing the amount of salt in the solution. The binding interaction and kinetics of absorption are sensitive to the solution pH, showing a distinct ion speciation in the interfacial region when compared to the bulk. Changing the subphase pH or adding a monovalent background electrolyte that promotes deprotonation of the carboxylic acid headgroup, could further improve the detection limit of La3+ and Y3+ to concentrations <100 nM. These findings demonstrate that nM concentrations of trace metals contaminants, typically found on monovalent salts, can significantly influence the binding structure and kinetics in Langmuir monolayers.