bluuebunny/crossref_metadata_2025 huggingface dataset:
Chebyshev Matrix Product States with Canonical Orthogonalization for Spectral Functions of Many-Body Systems
Authors: Jiang Tong , Ren Jiajun , Shuai Zhigang
Published: February 2022

We propose a method to calculate the spectral functions of many-body systems by Chebyshev expansion in the framework of matrix product states coupled with canonical orthogonalization (coCheMPS). The canonical orthogonalization can improve the accuracy and efficiency significantly because the orthogonalized Chebyshev vectors can provide an ideal basis for constructing the effective Hamiltonian in which the exact recurrence relation can be retained. In addition, not only the spectral function but also the excited states and eigen energies can be directly calculated, which is usually impossible for other MPS-based methods such as time-dependent formalism or correction vector. The remarkable accuracy and efficiency of coCheMPS over other methods are demonstrated by calculating the spectral functions of spin chain and ab initio hydrogen chain. For the first time we demonstrate that Chebyshev MPS can be used to deal with ab initio electronic Hamiltonian effectively. We emphasize the strength of coCheMPS to calculate the low excited states of systems with sparse discrete spectrum. We also caution the application for electron-phonon systems with dense density of states.
The Open Force Field Evaluator: An automated, efficient, and scalable framework for the estimation of physical properties from molecular simulation
Authors: Boothroyd Simon , Wang Lee-Ping , Mobley David , Chodera John , Shirts Michael
Published: February 2022

Developing accurate classical force field representations of molecules is key to realizing the full potential of molecular simulations, both as a powerful route to gaining fundamental insight into a broad spectrum of chemical and biological phenomena, and for predicting physicochemical and mechanical properties of substances. The Open Force Field Consortium is an industry-funded open science effort to this end, developing open source tools for rapidly generating new, high-quality small molecule force fields. An integral aspect of this is the parameterization and assessment of force fields against high-quality, condensed phase physical property data, curated from open data sources such the NIST ThermoML Archive, alongside quantum chemical data. The quantity of such experimental data in open data archives alone would require an onerous amount of human and compute resources to both curate and estimate manually, especially when estimations must be made for numerous sets of force field parameters. Here we present an entirely automated, highly scalable framework for evaluating physical properties and their gradients in terms of force field parameters. It is written as a modular and extensible Python framework, which employs an intelligent multiscale estimation approach that allows for the automated estimation of properties from simulation and cached simulation data, and a pluggable API for estimation of new properties. In this study we demonstrate the utility of the framework by benchmarking the OpenFF 1.0.0 small molecule force field, GAFF 1.8 and GAFF 2.1 force fields against a test set of binary density and enthalpy of mixing measurements curated using the frameworks utilities. Further, we demonstrate the framework's utility as part of force field optimization by using it alongside ForceBalance, a framework for systematic force field optimization, to retrain a set of non-bonded van der Waals parameters against a training set of density and enthalpy of vaporization measurements.
Targeting transthyretin in Alzheimer’s disease: drug discovery of small-molecule chaperones as disease-modifying drug candidates for Alzheimer’s disease
Authors: Cotrina Ellen Y , Santos Luis Miguel , Rivas Josep , Blasi Dani , Leite Jose Pedro , Liz Marcia A , Busquets Maria Antònia , Planas Antoni , Prohens Rafel , Gimeno Ana , Jiménez_Barbero Jesús , Gales Luis , Llop Jordi , Quintana Jordi , Cardoso Isabel , ARSEQUELL GEMMA
Published: February 2022

Transthyretin (TTR) has a well-established role in neuroprotection, evidenced in Alzheimer’s Disease (AD). By targeting TTR we have setup a drug discovery program of small-molecule compounds that act as chaperones, enhancing TTR/ amyloid-β peptide (Aβ) interactions. In a first stage, we carried out two computational drug repurposing approaches. In a second stage, the computationally selected compounds were assessed for their ability to bind and stabilize the TTR tetramer, using thyroxine displacement tests, and by assessing the level of monomers, respectively. In a third stage, the selected 53 best performing molecules were run through our in-house validated high-throughput screening ternary test. By targeting TTR in our AD drug discovery program, small-molecule chaperones (SMCs) have been discovered, providing the basis for a novel target for Alzheimer’s disease (AD) based on their enhancement of the TTR/Abeta interaction. Among the SMCs, we have found our lead small-molecule compound Iododiflunisal (IDIF), a molecule in the discovery phase, one investigational drug (luteolin), and 3 marketed drugs (sulindac, olsalazine and flufenamic), which could be directly repurposed or repositioned for clinical use. Importantly, we found that not all TTR tetramer stabilizers are good SMCs in vitro, emphasizing the importance of our discovery program. A small set of these SMCs will be prioritized to enter preclinical safety studies, to validate TTR as a target in vivo, and to select one repurposed drug as a candidate to enter clinical trials for AD. We envisage that this new target will feed the currently exhausted pipeline of drugs in phase I for AD with the goal of increasing AD disease-modifying therapies.
Finding the Order in Complexity: The Electronic Structure of 14-1-11 Zintl Compounds
Authors: Liu Yukun , Toriyama Michael , Cai Zizhen , Zhao Mengjia , Liu Fei , Snyder G. Jeffrey
Published: February 2022

Yb14MnSb11 and Yb14MgSb11 have rapidly risen to prominence as high-performing p-type thermoelectric materials for potential deep space power generation. However, the fairly complex crystal structure of 14-1-11 Zintl compounds renders the interpretation of the electronic band structure obscure, making it diﬃcult to chemically guide band engineering and optimization eﬀorts. In this work, we delineate the valence balanced Zintl chemistry of A14MX11 compounds (A = Yb, Ca; M = Mg, Mn, Al, Zn, Cd; X = Sb, Bi) using molecular orbital theory analysis. By analyzing the electronic band structures of Yb14MgSb11 and Yb14AlSb11 , we show that the conduction band minimum is composed of either an antibonding molecular orbital originating from the (Sb3)7− trimer, or a mix of atomic orbitals of A, M, and X. The singly degenerate valence band is comprised of non-bonding Sb p-z orbitals primarily from the Sb atoms in the (MSb4)m- tetrahedra and the of isolated Sb atoms distributed throughout the unit cell. Such a chemical understanding of the electronic structure enables strategies to engineer electronic properties (e.g., the band gap) of A14MX11 compounds.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 6. Methyl, halogen and oxy ring-disubstituted octyl phenylcyanoacrylates
Authors: Clajus Emma J. , Cote Natalie , Garcia Yesenia , Gijsbers Nathalie A. , Kaila Jay H. , Malik Amina S. , Mulk Anaa , Mohiuddin Madeeha I. , Rocus Sara M , Dalloul Rama , DiMarco Giulia M. , Kharas Gregory B. , Patel Neil T. , Kharas Gregory B , Eriksson Mollie J. , Schjerven William S.
Published: February 2022

Novel trisubstituted ethylenes, methyl, halogen, and oxy ring-disubstituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 4-methoxy-2-methyl, 4-methoxy-3-methyl, 3-ethoxy-4-methoxy, 4-ethoxy-3-methoxy, 3-benzyloxy-4-methoxy, 4-benzyloxy-3-methoxy, 2,3-(methylenedioxy), 3-bromo-4-methoxy, 5-bromo-2-methoxy, 2-chloro-3-methoxy, 2-chloro-6-methyl, 3-chloro-4-methyl) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 9. Halogen, methyl, methoxy and nitro ring-substituted octyl phenylcyanoacrylates
Authors: Etnyre Christian D. , Font Carlos S. , Frutos Azxiel , Fung Emily L. , Gil Cardenas Ashley G. , Gomez Cassandra E. , Martinez Leticia , Lopez Alexander P. , Schjerven William S. , Kharas Gregory B. , Razak Ruanum H. , Rocus Sara M. , Kharas Gregory
Published: February 2022

Novel trisubstituted ethylenes, halogen, methyl, methoxy and nitro ring-substituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-chloro-6-fluoro, 3-chloro-4-fluoro, 2-chloro-5-nitro, 4-chloro-3-nitro, 5-chloro-2-nitro, 5-iodo-2-methoxy, 2,4,5-trimethyl, 2,4,6-trimethyl, pentamethyl, 2,3-dimethyl-4-methoxy, 2,5-dimethyl-4-methoxy, 2,4-dimethoxy-3-methyl) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Synthesis and styrene copolymerization of novel trisubstituted ethylenes: 10. Ring-monosubstituted octyl phenylcyanoacrylates
Authors: Howard OWEN , Jurkowski Stephanie M. , Kriebel Charlie W. , Le Tuyet Anh H. , Leung Anne , Kharas Gregory B. , Rocus Sara M. , Claudio Ryan , Rios Oscar , Sevald Paige E. , Schjerven William S.
Published: February 2022

Novel trisubstituted ethylenes, ring-monosubstituted octyl phenylcyanoacrylates, RPhCH=C(CN)CO2CH2(CH2)6CH3 (where R is 2-(4-chlorophenoxy), 3-(4-methoxyphenoxy), 4-(4-methoxyphenoxy), 4-acetoxy, 4-acetamido, 4-cyano, 4-dimethylamino, 4-diethylamino, 2-bromo, 3-bromo, 2-trifluoromethyl, 3-trifluoromethyl, 4-trifluoromethyl, 3-trifluoromethoxy, 4-trifluoromethoxy) were prepared and copolymerized with styrene. The ethylenes were synthesized by the piperidine catalyzed Knoevenagel condensation of ring-substituted benzaldehydes and octyl cyanoacetate, and characterized by CHN analysis, IR, 1H and 13C NMR. All the ethylenes were copolymerized with styrene in solution with radical initiation (ABCN) at 70C. The compositions of the copolymers were calculated from nitrogen analysis.
Origin of the different reactivity of the high-valent coinage-metal complexes [RCuIIIMe3]− and [RAgIIIMe3]− (R = allyl)
Authors: Auth Thomas , Stein Christopher Johannes , O'Hair Richard A.J. , Koszinowski Konrad
Published: February 2022

High-valent tetraalkylcuprates(III) and -argentates(III) are key intermediates of copper and silver-mediated C−C coupling reactions. Here, we investigate the previously reported contrasting reactivity of [RM III Me 3 ] − complexes (M = Cu, Ag and R =allyl) with energy-dependent collision-induced dissociation experiments, advanced quantum-chemical calculations and kinetic computations. The gas-phase fragmentation experiments confirmed the preferred formation of the [RCuMe] − anion upon collisional activation of the cuprate(III) species, consistent with a homo-coupling reaction, whereas the silver analogue primarily yielded [AgMe 2 ] − , consistent with a cross-coupling reaction. For both complexes, density functional theory calculations identified one mechanism for homo coupling and four different ones for cross coupling. Of these pathways, an unprecedented concerted outer-sphere cross coupling is of particular interest, because it can explain the formation of [AgMe 2 ] − from the argentate(III) species. Remarkably, the different C−C coupling propensities of the two [RM III Me 3 ] − complexes become only apparent when properly accounting for the multi-configurational character of the wave function for the key transition state of [RAgMe 3 ] − . Backed by the obtained detailed mechanistic insight for the gasphase reactions, we propose that the previously observed cross-coupling reaction of the silver complex in solution proceeds via the outer-sphere mechanism.
Solution additives promoting the onset of MgCO3 nucleation
Authors: Toroz Dimitrios , Song Fu , Uddin Amira , Chass Gregory A. , Di Tommaso Devis
Published: February 2022

Formed via aqueous carbonation of Mg2+ ions, the crystallization of magnesite (MgCO3) is a promising carbon capture and reuse technology, albeit limited by the slow precipitation of MgCO3. Although magnesite is naturally abundant, forming at low temperature conditions, its production is an energy-intensive process due to the temperatures required to prevent the formation of hydrated phases. The principle difficulty arises from the very strong Mg2+···H2O interaction, raising barriers to dehydration. Using atomistic simulations, we have investigated the influence of thirty additive anions (Xn–, n = 1–3), ranging from simple halides to more complex molecules, on the first two steps of MgCO3 aggregation from solution: Mg2+ dehydration and Mg2+∙∙∙CO32– pairing. We have computed the thermodynamic stability of solvent shared ion pairs, Mg2+···H2O···Xn–, and contact ion pairs, Mg2+···Xn–, with Mg2+ to reveal the propensity of solution additives to inhibit Mg2+∙∙∙CO32– formation. We have determined the stabilization of undercoordinated hydrated Mg2+ states with a vacant coordination site to which CO32– can bind, subsequently initiating MgCO3 nucleation or Mg2+ incorporation into the crystal lattice. Extensive molecular dynamics simulations of electrolyte solutions containing Na2CO3 with different sources of Mg2+, MgCl2, MgSO4 and Mg(CH3COO)2, further shows that the degree of dehydration of Mg2+ and the structure of prenucleation MgCO3 clusters changes depending on the type counterion. Through a fundamental understanding of the role of solution additives in the mechanism of Mg2+ dehydration, our computational study can rationalize previously reported experimental observation of the effect of solvation environments on the growth of magnesite. This understanding may contribute to identifying solution composition conditions that could promote the low-temperature CO2 conversion into MgCO3.
Screening and quantification of the encapsulation of dyes in supramolecular particles
Authors: Prieto-Costas Luis A. , Quiñones-Jurgensen Carla M. , Milton Logan J. , Rivera Jose M.
Published: February 2022

The encapsulation of therapeutic agents, like drugs and vaccines, into colloidal particles, offers an attractive strategy to enhance their efficacy. Previously, we reported the development of guanosine-based supramolecular colloidal particles suitable for encapsulating a broad array of guests ranging from small molecule drugs, like doxorubicin, to proteins, like GFP. Many biomedical applications of such particles require a precise determination of the amount of encapsulated therapeutic agents. Despite the many publications describing the development of particle-based delivery systems, a general method for the precise and quick quantification of the encapsulated payload is still lacking. Here we report a method based on flow cytometry (FC) measurements complexes made from guanosine-based particles and a variety of commercially available fluorescent dyes. This method allows us to determine the apparent affinities of such dyes for two variants of these particles, which in turn unveils insightful structure affinity relationships. In contrast to current methods, such as those that rely on fluorescence microscopy based on measurements of absorption/fluorescence of dissolved particles or on the supernatant of the solution, the reported method is suitable for high throughput screening and more reproducible results. The protocol described here should be applicable to a wide variety of colloidal particles being developed around the world. Our group is currently expanding the scope to quantify the encapsulation of other molecules of biomedical interest, such as proteins and nucleic acids.
Thin-Layer Electroanalysis Microchip Reveals More about Electrochemical Reactions of Organic Compounds
Authors: Shin Samuel Jaeho , Kim Ji Yong , An Sohee , Kim Moonjoo , Seo Minjee , Go Su Yong , Chung Hyunho , Lee MinKeun , Kim Min-Gyeong , Lee Hong Geun , Chung Taek Dong
Published: February 2022

It is important but challenging to elucidate the electrochemical reaction mechanisms of organic compounds using electroanalytical methods. In this work, we exploited the advantages of classic thin-layer electrochemistry to develop a thin-layer electroanalysis microchip (TEAM). The TEAM provided better resolved voltammetric peaks than measurements under semi-infinite diffusion conditions. Importantly, because the analyte solution was mechanically isolated using a polyelectrolyte gel, rapid small-volume electrolysis allowed the accurate determination of the number of electrons transferred, n. The performance of the TEAM was validated using both voltammetry and coulometry of standard redox couples. Moreover, a spectroelectrochemical analysis of FM 1-43, an organic dye widely used in neuroscience, was successfully performed. Harnessing the analytical power of the TEAM, the electrochemical oxidation mechanisms of pivanilides and alkyltrifluoroborate salts were studied. Thus, the TEAM has the potential to provide invaluable mechanistic information and promote the rational design of electrosynthetic strategies.
Stereoselective Palladium-Catalyzed C(sp3)–H Mono-Arylation of Piperidines and Tetrahydropyrans with a C(4) Directing Group
Authors: Piticari Amalia-Sofia , Antermite Daniele , Higham Joe I. , Moore J. Harry , Webster Matthew P. , Bull James A
Published: February 2022

A selective Pd-catalyzed C(3)–H cis-functionalization of piperidine and tetrahydropyran carboxylic acids is achieved using a C(4) aminoquinoline amide auxiliary. High mono- and cis-selectivity is attained by using mesityl carboxylic acid as an additive. Conditions are developed with significantly lower reaction temperatures (≤50 °C) than other reported heterocycle C(sp3)–H functionalization reactions, which is facilitated by a DoE optimization. A one-pot C–H functionalization-epimerization procedure provides the trans-3,4-disubstituted isomers directly. Divergent aminoquinoline removal is accomplished with the installation of carboxylic acid, alcohol, amide and nitrile functional groups. Overall fragment compounds suitable for screening are generated in 3–4 steps from readily-available heterocyclic carboxylic acids.
Competitive Gold/Nickel Transmetalation
Authors: Demchuk Mitchell , Zurakowski Joseph , Austen Brady , Nelson David , Drover Marcus
Published: February 2022

Transmetalation is a key method for the construction of element-element bonds. Here, we disclose the reactivity of [NiII(Ar)(I)(diphosphine)] compounds with arylgold(I) transmetalating agents, which is directly relevant to cross-coupling catalysis. Both aryl-for-iodide and unexpected aryl-for-aryl transmetalation are witnessed. Despite the strong driving force expected for Au-I bond formation, aryl scrambling can occur during transmetalation and may complicate the outcomes of attempted catalytic cross-coupling reactions.
A Two-Step Baro-Mechanical Cycle for Repeated Activation and Deactivation of Mechanophores
Authors: Kumar Sourabh , Zeller Felix , Stauch Tim
Published: February 2022

Mechanophores that are embedded in a polymer backbone respond to the application of mechanical stretching forces by geometric changes such as bond rupture. Typically, these structural changes are irreversible, which limits the applicability of functional materials that incorporate mechanophores. Using computational methods, we here present a general method of restoring a force-activated mechanophore to its deactivated form by using hydrostatic pressure. We use the well-known spiropyran-merocyanine (SP-MC) interconversion to show that repeated activation and deactivation of the SP mechanophore can be achieved by alternating application of mechanical stretching forces and hydrostatic compression. In the baro-mechanical cycle, MC plays the role of a “barophore” that responds to hydrostatic pressure by bond formation. The activation and deactivation pathways of SP and MC are understood in terms of strain and electronic effects. Beneficially, this two-step baro-mechanical cycle can be observed in real time by using UV/Vis spectroscopy. Our calculations pave the way for massively improving the applicability and reusability of force-responsive materials.
Chemical Synthesis and Immunological Evaluation of Cancer Vaccines Based on Ganglioside Antigens and α-Galactosylceramide
Authors: Romanò Cecilia , Jiang Hao , Tahvili Sahar , Wei Peng , Keiding Ulrik Bering , Clergeaud Gael , Henriksen Jonas Rosager , Andresen Thomas Lars , Hansen Anders Elias , Christensen Dennis , Clausen Mads Hartvig
Published: February 2022

iNKT cells – often referred as the “Swiss Army knife” of the immune system ‒ have emerged as central players in cancer vaccine therapies. Glycolipids activating iNKT cells, such as α-galactosylceramide (αGalCer), can enhance the immune response against co-delivered cancer antigens and have been applied in the design of self-adjuvanting anti-tumor vaccines. In this context, this work focuses on the chemical synthesis of ganglioside tumor-associated carbohydrate antigens (TACAs), namely GM3 and (Neu5Gc)GM3 antigens, their conjugation to αGalCer, and their formulation into liposomes as an efficient platform for their in vivo delivery. Liposomes containing GM3‒αGalCer, (Neu5Gc)GM3‒αGalCer, and equimolar amounts of the two conjugates have been fully characterized and their ability to activate iNKT cell has been confirmed in vitro. Finally, the candidates were tested in in vivo immunization studies, demonstrating an ability to induce both Th1 and Th2 cytokines further leading to the production of all subclasses of IgG antibodies. Notably, the study also demonstrated that serum antibodies raised against the two TACAs alone and in combination were cross-reactive. This finding has consequences for future vaccine designs – even if a highly tumor-selective antigen is chosen, the resulting antibody response may be broader than anticipated.
Hypervalent Carbon Atoms in a Ferrocene Dication Derivative - [Fe(Si2C5H2)2]2+
Authors: Thimmakondu Venkatesan S.
Published: February 2022

Pentacoordinate carbon atoms are theoretically predicted here in a ferrocene dication derivative in both staggered- [Fe(Si2C5H2)2]2+(1; C2h) and eclipsed-[Fe(Si2C5H2)2]2+(2; C2v) forms for the first time. The barrier between these two ranges from -38.11 to 4.90 kJ/mol at different levels. The planar tetracoordinate carbon atom in the ligand Si2C5H2 becomes a hypervalent pentacoordinate carbon upon complexation.
Hypervalent Carbon Atoms in a Ferrocene Dication Derivative - [Fe(Si2C5H2)2]2+
Authors: Thimmakondu Venkatesan S.
Published: February 2022

Pentacoordinate carbon atoms are theoretically predicted here in a ferrocene dication derivative in both staggered- [Fe(Si2C5H2)2]2+ (1; C2h) and eclipsed-[Fe(Si2C5H2)2]2+ (2; C2v) forms for the first time. Relative energy difference between these two ranges from -40.34 to 2.47 kJ/mol at different levels. The planar tetracoordinate carbon atom in the ligand Si2C5H2 becomes a hypervalent pentacoordinate carbon upon complexation.
Hybrid Computational-Experimental Data-Driven Design of Self-Assembling Pi-Conjugated Peptides
Authors: Shmilovich Kirill , Panda Sayak , Stouffer Anna , Tovar John , Ferguson Andrew
Published: February 2022

Biocompatible molecules with electronic functionality provide a promising substrate for biocompatible electronic devices and electronic interfacing with biological systems. Synthetic oligopeptides composed of an aromatic pi-core flanked by oligopeptide wings are a class of molecules that can self-assemble in aqueous environments into supramolecular nanoaggregates with emergent optical and electronic activity. We present an integrated computational-experimental pipeline employing all-atom molecular dynamics simulations and experimental UV-visible spectroscopy within an active learning workflow using deep representational learning and Bayesian optimization to design pi-conjugated peptides programmed to self-assemble into elongated pseudo-1D nanoaggregtes with a high degree of H-type co-facial stacking of the pi-cores. We consider as our design space the 694,982 unique pi-conjugated peptides comprising a quaterthtiophene pi-core flanked by symmetric oligopeptide wings up to five amino acids in length. After sampling only 1181 molecules (~0.17% of the design space) by computation and 28 (~0.004%) by experiment, we identify and experimentally validate a diversity of previously unknown high-performing molecules and extract interpretable design rules linking peptide sequence to emergent supramolecular structure and properties.
Controlling Polymer Morphologies by Intramolecular and Intermolecular Dynamic Covalent Iron(III)/Catechol Complexation – From Polypeptide Single Chain Nanoparticles to Hydrogels
Authors: Hebel Marco , Gačanin Jasmina , Lückerath Thorsten , Ng David Y. W. , Weil Tanja
Published: February 2022

Responsive biomaterials, tunable from the molecular to the macroscopic scale, are attractive for various applications in nanotechnology. Herein, a long polypeptide chain derived from the abundant serum protein human serum albumin was cross-linked by dynamic-coordinative iron(III)/catechol bonds. By tuning the binding stoichiometry and the pH, reversible intramolecular folding into polypeptide nanoparticles with controllable sizes was achieved. Moreover, upon varying the stoichiometry, intermolecular cross-links became predominant yielding smart and tunable macroscopic protein hydrogels. By adjusting the intra-and intermolecular interactions, biocompatible and biodegradable materials were formed with varying morphologies and dimensions covering several lengths scales featuring rapid gelation without toxic reagents, fast and autonomous self-healing, tunable mechanical properties and high adaptability to local environmental conditions. Such material characteristics could be particularly attractive for tissue engineering approaches to recreate soft tissues matrices with highly customizable features in a fast and simple fashion.
Calculation of Metallocene Ionization Potentials via Auxiliary Field Quantum Monte Carlo: Towards Benchmark Quantum Chemistry for Transition Metals
Authors: Rudshteyn Benjamin , Weber John L. , Coskun Dilek , Devlaminck Pierre A. , Zhang Shiwei , Reichman David R. , Shee James , Friesner Richard A.
Published: February 2022

The accurate ab initio prediction of ionization energies is essential to understanding the electrochemistry of transition metal complexes in both materials science and biological applications. However, such predictions have been complicated by the scarcity of gas-phase experimental data, the relatively large size of the relevant molecules, and the presence of strong electron correlation effects. In this work, we apply all-electron phaseless auxiliary-field quantum Monte Carlo (ph-AFQMC) utilizing multi-determinant trial wavefunctions to six metallocene complexes to compare the computed adiabatic and vertical ionization energies to experimental results. We find that ph-AFQMC yields mean averaged errors (MAE) of 1.69±1.02 kcal/mol for the adiabatic energies and 2.85±1.13 kcal/mol for the vertical energies. We also carry out density functional theory (DFT) calculations using a variety of functionals, which yields MAE’s of 3.62 to 6.98 and 3.31 to 9.88 kcal/mol, as well as a localized coupled cluster approach (DLPNO-CCSD(T0)), which has MAEs of 4.96 and 6.08 kcal/mol, respectively. We also test the reliability of DLPNO-CCSD(T0) and DFT on acetylacetonate (acac) complexes for adiabatic energies measured in the same manner experimentally, and find much higher MAE’s, ranging from 4.56 kcal/mol to 10.99 kcal/mol (with a different ordering) for DFT and 6.97 kcal/mol for DLPNO-CCSD(T0). Finally, by utilizing experimental solvation energies, we show that accurate reduction potentials in solution for the metallocene series can be obtained from the AFQMC gas phase results.
Proline transport inhibitors trigger differential responses in Trypanosoma cruzi growth inhibition
Authors: Ballari María Sol , Fargnoli Lucía , Pagura Lucas , Cricco Julia , Silber Ariel , Labadie Guillermo
Published: February 2022

Background: Proline is a fundamental amino acid for Trypanosoma cruzi, the etiological agent of Chagas disease. Proline is mainly incorporated from the extracellular medium by amino acid transport systems. Different proline analogues proved to interact with the proline permease TcAAAP069 and inhibit the proline uptake by T. cruzi. Methods: Decyl- (1), oleyl- (2) and farnesyl- (3) substituted proline analogues were evaluated on six T. cruzi DTUs. Cell death type was determined by flow cytometry, and the effect on the parasite metabolism was analysed by directed NMR exometabolomics. Structural modifications of 1 (compounds 4 – 6) were implemented to have more information on the mode of action (MoA). Results: The compounds showed broad-spectrum activity against all DTUs. Compound 3 at high concentration (116 µM) induced necrosis. The removal of the triazole from 1 proved to be important for the activity. Compounds 1 and 2 induced deep changes in the exometabolome, diminishing the amounts of succinate, lactate, acetate, and ethanol excreted. The fluorescent labelling and subsequent microscopy showed that compound 1 can be taken up by epimastigotes. Conclusions: Two different MoA related to proline transport for decyl and farnesyl-substituted proline analogues are proposed. The former presented an in-cell action while the latter was not taken up by the parasites but interacted with the extracellular side of the proline permease. General Significance: Subtle structural variations in the compounds determine differences in the MoA. This finding opens new perspectives that should be examined on the development of new drugs targeting metabolite permeases.
Retrosynthesis Prediction using Grammar-based Neural Machine Translation: An Information-Theoretic Approach
Authors: Mann Vipul , Venkatasubramanian Venkat
Published: February 2022

Retrosynthetic prediction is one of the main challenges in chemical synthesis because it requires a search over the space of plausible chemical reactions that often results in complex, multi-step, branched synthesis trees for even moderately complex organic reactions. Here, we propose an approach that performs single-step retrosynthesis prediction using SMILES grammar-based representations in a neural machine translation framework. Information-theoretic analyses of such grammar-representations reveal that they are superior to SMILES representations and are better-suited for machine learning tasks due to their underlying redundancy and high information capacity. We report the top-1 prediction accuracy of 43.8% (syntactic validity 95.6%) and maximal fragment (MaxFrag) accuracy of 50.4%. Comparing our model’s performance with previous work that used character-based SMILES representations demonstrate significant reduction in grammatically invalid predictions and improved prediction accuracy. Fewer invalid predictions for both known and unknown reaction class scenarios demonstrate the model’s ability to learn the underlying SMILES grammar efficiently.
Kinetically corrected Monte Carlo-molecular dynamics simulations of solid electrolyte interphase growth
Authors: Abbott Joseph W , Hanke Felix
Published: February 2022

We present a kinetic approach to the Monte Carlo-molecular dynamics (MC-MD) method for simulating reactive liquids using non-reactive forcefields. A graphical reaction representation allows definition of reactions of arbitrary complexity, including their local solvation environment. Reaction probabilities and molecular dynamics (MD) simulation times are derived from ab initio calculations. Detailed validation is followed by studying the development of the solid electrolyte interphase (SEI) in lithium-ion batteries. We reproduce the experimentally observed two-layered structure on graphite, with an inorganic layer close to the anode and an outer organic layer. This structure develops via a near-shore aggregation mechanism.
A transient initiator for polypeptoids post-polymerization α-functionalization via activation of thioester group
Authors: Borova Solomiia , Schlutt Christine , Nickel Joachim , Luxenhofer Robert
Published: February 2022

Here we introduce a post-polymerization modification method of an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine. We utilized 4-(methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity and high end-group fidelity, as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectroscopy. The introduced method could be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.
Recommendation System to Predict Missing Adsorption Properties of Nanoporous Materials
Authors: Sturluson Arni , Raza Ali , McConachie Grant D. , Siderius Daniel , Fern Xiaoli , Simon Cory
Published: February 2022

Nanoporous materials (NPMs) selectively adsorb and concentrate gases into their pores, and thus could be used to store, capture, and sense many different gases. Modularly synthesized classes of NPMs, such as covalent organic frameworks (COFs), offer a large number of candidate structures for each adsorption task. A complete NPM-property table, containing measurements of the relevant adsorption properties in the candidate NPMs, would enable the matching of NPMs with adsorption tasks. However, in practice the NPM-property matrix is only partially observed (incomplete); (i) many properties of any given NPM have not been measured and (ii) any given property has not been measured for all NPMs.

The idea in this work is to leverage the observed (NPM, property) values to impute the missing ones. Similarly, commercial recommendation systems impute missing entries in an incomplete item-customer ratings matrix to recommend items to customers. We demonstrate a COF recommendation system to match COFs with adsorption tasks by training a low rank model of an incomplete COF--adsorption-property matrix. A low rank model, trained on the observed (COF, adsorption property) values, provides (i) predictions of the missing (COF, adsorption property) values and (ii) a "map" of COFs, represented as points, wherein COFs with similar (dissimilar) adsorption properties congregate (separate). We find the performance of the COF recommendation system varies for different adsorption tasks and diminishes precipitously when the fraction of missing entries exceeds 60%. The concepts in our COF recommendation system can be applied broadly to many different materials and properties.
High Stability and Properties of Adsorbed Polycyclic Aromatic Hydrocarbons (PAHs) onto Phosphorene: An atomistic DFT study
Authors: Cortés-Arriagada Diego
Published: February 2022

In this work, we report the structure, intermolecular forces, electronic/optical properties, and stability in solution of complexes formed between polycyclic aromatic hydrocarbons (PAH) and phosphorene nanoflakes by density functional theory modeling. PAH molecules reach a strong affinity with phosphorene by forming well-ordered domains, whose interaction strength decreases 13-21% compared to the interaction onto carbonaceous surfaces, e.g., graphene. The adsorption energies are in linear relation with the NH:NC ratio of PAHs, where NH and NC are the numbers of H and C atoms; consequently, the cohesive energy of phosphorene-graphene heterostructures is estimated in 44 meV/atom. Energy decomposition (ALMO-EDA) and electron-density-based analyses support the major role of electrostatics driving forces in the interaction mechanism, which is balanced with dispersion effects for larger PAHs. In addition, phosphorene-PAH complexes display outstanding stability in solution under polar/non-polar solvents, which is due to the high polarity of the complexes and strong overcompensation of destabilizing solvation energies with stabilizing electrostatic effects. Moreover, PAHs behave as n-dopants for phosphorene, inducing small bandgap opening and weak effects on the photophysical fingerprint of phosphorene. Nevertheless, strong electron acceptor/donor and larger PAHs (NH:NC<0.5) lead to major effects on the bandgap control, acting as active sites for orbital-controlled interactions. These findings serve as a framework for further investigation of phosphorene-based materials for remediation of PAH pollutants in water treatment technologies and uses of PAHs for phosphorene surface passivation or bandgap engineering for sensing.
Formation of HCO+ ion by protonation of carbon monoxide in zeolites: the origin of catalytic activity in methanol carbonylation
Authors: Kwak Ja-Hun , Jaegers Nicholas , Szanyi Janos , Khivantsev Konstantin
Published: February 2022

We show that CO can be protonated by Brønsted acid sites to form the super-electrophilic HCO+ cation in H-zeolites such as mordenite. This reactivity stems from the confining environment of small 8-ring side pockets of H-MOR. HCO+ is a catalytically active super-electrophile: it carbonylates dimethyl ether and hydrocarbons to methyl acetate and aldehydes.
Allenic Phosphonium Borate Zwitterions via a Transient Phosphonium Allenylidene
Authors: Torres Lucas , Dobrovetsky Roman , Caputo Christopher
Published: February 2022

We describe the synthesis of alkynyl phosphanes of the type R2P-C≡C-C(OCH3)Ph2, (R = Ph, Cy) and investigate their transformation to geminally substituted phosphonium borato-allene zwitterions upon their reaction with B(C6F5)3. The mechanism for this transformation was studied experimentally and by density functional theory computations (DFT), suggesting the intermediacy of an unsaturated 3-coordinate phosphonium electrophile akin to a methylene phosphonium cation.
Illuminating mechanochemical reactions by combining real-time fluorescence emission monitoring and periodic time-dependent density-functional calculations
Authors: Julien Patrick A. , Arhangelskis Mihails , Germann Luzia S. , Etter Martin , Dinnebier Robert E. , Morris Andrew J. , Friscic Tomislav
Published: February 2022

We provide a proof-of-principle demonstration of the first dual-spectroscopic method for direct and real-time observation of mechanochemical reactions by ball milling, supported by high-level molecular and periodic density-functional theory (DFT) calculations, including periodic time-dependent (TD-DFT) calculations to model solid-state fluorescence spectra. By combining standard Raman and fluorescence benchtop spectrometers in a single readily accessible tandem monitoring technique, we simultaneously observe changes to the supramolecular structure during mechanochemical polymorph transformation and cocrystallization of the model pharmaceutical system indometacin. The observed time-resolved in situ spectroscopic data is supported by ex situ X-ray diffraction and solid-state nuclear magnetic resonance spectroscopy measurements. First principles calculations facilitate the interpretation of both real-time spectroscopic and ex situ data by demonstrating how changes in crystalline environment affect vibrational and electronic excited states.
Machine-learning photodynamics simulations uncover the role of substituent effects on the photochemical formation of cubanes
Authors: Li Jingbai , Stein Rachel , Adrion Daniel , Lopez Steven
Published: February 2022

Photochemical [2+2]-photocycloadditions are used to efficiently access strained organic molecular architectures, storing solar energy in chemical bonds. Functionalized [3]-ladderenes have been shown to undergo [2+2]-photocycloadditions to afford cubanes, an energy-dense class of organic molecules. The substituents (e.g., methyl, trifluoromethyl, and cyclopropyl) affect the overall reactivities of these cubane precursors leading to a yield from 1% to 48%. We now integrate single and multireference calculations and our machine-learning-accelerated non-adiabatic molecular dynamics (ML-NAMD) to understand how substituents affect the mechanistic photodynamics of [2+2]-photocycloadditions. Our calculations show that steric clashes destabilize the 4π-electrocyclic ring-opening pathway and minimum energy conical intersections by 0.72–1.15 eV and reaction energies by 0.68–2.34 eV. In contrast, favorable dispersive interactions stabilize the [2+2]-photocycloaddition pathway, lower the conical intersection energies by 0.31–0.85 eV and cubane reaction energies by 0.03–0.82 eV. The 2 ps ML-NAMD trajectories reveal that closed-shell repulsions block a 6π-conrotatory electrocyclic ring-opening pathway with increasing steric bulk. 57% of the methyl-substituted [3]-ladderene trajectories proceed through the 6π-conrotatory electrocyclic ring-opening, whereas the trifluoromethyl- and cyclopropyl-substituted 3-ladderenes chemoselectively proceed through [2+2]-photocycloaddition pathways. The predicted cubane yields (H: 0.4% < CH3: 1% < CF3: 14% < cPr: 20%) match the experimental trend; these substituents pre-distort the reactants to resemble the conical intersection leading to cubane.
A Molecular Model of Secondary Battery Cycle-life Pointing Towards a Final Regularity Resembling Carnot-efficiency
Authors: Pawelke Roland Hermann
Published: February 2022

A transition state theory-influenced ideal model of battery cycle-life is outlined and validated by example of the Panasonic NCR18650B Li-battery cell, which shows after 500 cycles a residual capacity of 68.2 % at 100 % depth of discharge (DoD) as by its datasheet. The ideal model, which bases on a minimum failure causality of one reaction event failing per half-cycle, overstates on the logarithmic scale by just 1.9 % for the conditions given, corresponding to an ideal cycle-life of 563 cycles. Generalization of the model towards DoD-ranges yields for the exemplary (70; 30) % and (100; 60) % margins the cycle-life values of 43252 and 23480, respectively. Because the model relies solely on natural constants, temperature(s) and C-rate(s), the conclusion is drawn that a thermodynamic final regularity similar to Carnot-efficiency governs secondary battery cycle-life; this is in contrast to hitherto academic consensus opinion attesting the matter a basically empiric nature.
Halide-selective, proton-coupled anion transport by phenylthiosemicarbazones
Authors: Howe Ethan N.W. , Chang Vai-Vai Tiffany , Wu Xin , Lewis William , Macreadie Lauren K. , Gale Philip Alan
Published: February 2022

Phenylthiosemicarbazones (PTSCs) are proton-coupled anion transporters with pH-switchable behaviour known to be regulated by an imine protonation equilibrium. Previously, chloride/nitrate exchange by PTSCs was found to be inactive at pH 7.2 due to locking of the thiourea anion binding site by an intramolecular hydrogen bond, and switched ON upon imine protonation at pH 4.5. The rate-determining process of the pH switch, however, was not examined. We here develop a new series of PTSCs and demonstrate their conformational behaviour by X-ray crystallographic analysis and pH-switchable anion transport properties by liposomal assays. We report the surprising finding that these compounds are extremely selective for halides over oxyanions in membrane transport. Owing to the high chloride over nitrate selectivity, the pH-dependent chloride/nitrate exchange of PTSCs originates from the rate-limiting nitrate transport process being inhibited at neutral pH, whereas chloride transport remains efficient under both neutral and acidic conditions.
Correlating ZnSe Quantum Dot Absorption with Particle Size and Concentration
Authors: Toufanian Reyhaneh , Zhong Xingjian , Kays Joshua , Saeboe Alexander , Dennis Allison
Published: February 2022

The focus on heavy metal-free semiconductor nanocrystals has increased interest in ZnSe semiconductor quantum dots (QDs) over the past decade. Reliable and consistent incorporation of ZnSe cores into core/shell heterostructures or devices requires empirical fit equations correlating the lowest energy electron transition (1S peak) to their size and molar extinction coefficients (ε). While these equations are known and heavily used for CdSe, CdTe, CdS, PbS, etc., they are not well established for ZnSe and are non-existent for ZnSe QDs with diameters < 3.5 nm. In this study, a series of ZnSe QDs with diameters ranging from 2 to 6 nm were characterized with small angle X-ray scattering (SAXS), transmission electron microscopy (TEM), UV-Vis spectroscopy, and microwave plasma atomic emission spectroscopy (MP-AES). SAXS-based size analysis enabled practical inclusion of small particles in the evaluation, and elemental analysis with MP-AES elucidates a non-stoichiometric Zn:Se ratio consistent with zinc-terminated spherical ZnSe QDs. Using these combined results, empirical fit equations correlating QD size with its lowest energy electron transition (i.e., 1S peak position), Zn:Se ratio, and molar extinction coefficients for 1S peak, 1S integral, and high energy wavelengths are reported. Finally, the equations are used to track the evolution of a ZnSe core reaction. These results will enable the consistent and reliable use of ZnSe core particles in complex heterostructures and devices.
Total Synthesis of (±)-Setigerumine I: Biosynthetic Origins of the Elusive Racemic Papaveracaea Isoxazolidine Alkaloids
Authors: Serna Ana Victoria , Kürti László , Siitonen Juha Henrik
Published: February 2022

The biosynthetic origins of the structurally related racemic isoxazolidine Papaveracaea alkaloids Setigerumine I, Dactylicapnosinine and Dactylicapnosine have remained elusive since their original isolation over two decades ago. Herein we report the first biosynthetic hypothesis for their formation and, inspired by it, the first synthesis of (±)-Setigerumine I with accompanying computational rationale. Based on the results, these isoxazolidine alkaloids arise from racemizing oxidative rearrangements of prominent isoquinoline alkaloids Noscapine and Hydrastine. The key steps featured in this synthesis are a room temperature Cope elimination and a domino C–H oxidation/inverse-electron demand 1,3-dipolar cycloaddition of an axially chiral, yet configurationally unstable, intermediate.