bluuebunny/crossref_metadata_2025 huggingface dataset:
A simplistic computational procedure for the tunneling splittings caused by the proton transfer
Authors: Tikhonov Denis
Published: February 2022

In this manuscript we present an approach for computing tunneling splittings for large amplitude motions.

The core of the approach is a solution of an effective one-dimensional Schrödinger equation with an effective mass and an effective potential energy surface composed of electronic and harmonic zero-point vibrational energies of small amplitude motions in the molecule.

The method has been shown to work in cases of three model motions: nitrogen inversion in ammonia, single proton transfer in malonaldehyde, and double proton transfer in the formic acid dimer. In the current work we also investigate the performance of different DFT and post-Hartree-Fock methods for prediction of the proton transfer tunneling splittings, quality of the effective Schrödinger equation parameters upon the isotopic substitution, and possibility of a complete basis set (CBS) extrapolation for the resulting tunneling splittings.
Ferromagnetic 1H-LaBr2 monolayer: a promising 2D piezoelectric
Authors: Noor A-Alam Mohammad , Nolan Michael
Published: February 2022

Abstract The discovery of two dimensional (2D) materials that have excellent piezoelectric response along with intrinsic magnetism is promising for nanoscale multifunctional piezoelectric or spintronic devices. Piezoelectricity requires non-centrosymmetric structures with an electric band-gap, whereas magnetism demands broken time-reversal symmetry. Most of the well-known 2D piezoelectric materials – e.g., 1H-MoS2 monolayer – are not magnetic. Being intrinsically magnetic, semiconducting 1H-LaBr2and 1H-VS2 monolayers can combine magnetism and piezoelectricity. We compare piezoelectric properties of 1H-MoS2, 1H-VS2 and 1H-LaBr2 using density functional theory. Our results show that ferromagnetic 1H-LaBr2 2D monolayer displays a larger piezoelectric strain co-efficient (d_{11}= -4.527 pm/V, which is close to d_{11}= 4.104 pm/V of 1H-VS2 monolayer) compared to that of well-known 1H-MoS2 monolayer (d_{11}= 3.706 pm/V), while 1H-MoS2 monolayer has a larger piezoelectric stress co-efficient (e_{11}= 370.675 pC/m) than the 1H-LaBr2 monolayer (e_{11}= -94.175 pC/m, which is also lower than e_{11}= 298.100 pC/m of 1H-VS2 monolayer). These in-plane piezoelectric d_{11} coefficients are quite comparable with piezo-response of bulk wurtzite nitrides – e.g., d_{33} of GaN is about 3.1 pm/V. The large d_{11} for 1H-LaBr2 monolayer originates from the low elastic constants, C_{11}= 30.338 N/m and C_{12} = 9.534 N/m. Interestingly, the sign of the piezoelectric co-coefficients for 1H-LaBr2 monolayer is different to that of the 1H-MoS2 or 1H-VS2 monolayers. The negative sign arises from the negative ionic contribution of e_{11}, which dominates in the 1H-LaBr2 monolayer, whereas the electronic part of e_{11} dominates in 1H-MoS2 and 1H-VS2. Furthermore, we explain the origin of this large ionic contribution of e_{11} for 1H-LaBr2 in terms of the Born effective charges (Z_{11}) and the sensitivity of the atomic positions to the strain (\frac{du}{d\eta}). Surprisingly, we observe a sign reversal in the Z_{11} of Mo and S compared to the nominal oxidation states, which makes both the electronic and ionic parts of e_{11} positive, and results in the high value of e_{11}. Additionally, our interatomic bond analysis using crystal orbital Hamilton populations indicates that the weaker covalent bond in 1H-LaBr2 monolayer is responsible for large \frac{du}{d\eta} and elastic softening (lower elastic constants).
Probing Molecular Chirality of Ground and Electronically Excited States in the UV-vis and X-ray Regimes: An EOM-CCSD Study
Authors: Andersen Josefine , Nanda Kaushik D. , Krylov Anna I. , Coriani Sonia
Published: February 2022

We present several strategies for computing electronic circular dichroism (CD) spectra across different frequency ranges at the equation-of-motion coupled-cluster singles and doubles level of theory. CD spectra of both ground and electronically excited states are discussed. For selected cases, the approach is compared with coupled-cluster linear response results as well as time-dependent density functional theory. The extension of the theory to include the effect of spin-orbit coupling is presented and illustrated by calculations of X-ray CD spectra at the L edge.
Thermal transport in planar sp2-hybridized carbon allotropes: A comparative study of biphenylene network, pentaheptite and graphene
Authors: Ying Penghua , Liang Ting , Du Yao , Zhang Jin , Ma Qiangqiang , Zeng Xiaoliang , Zhong Zheng
Published: February 2022

The biphenylene network with periodically arranged four-, six-, and eight-membered rings has been successfully synthesized in very recent experiments. This novel two-dimensional (2D) carbon allotrope has potentials in applications of lithium storage and carbon-based circuitry. Understanding the thermal transport property of biphenylene network is of critical importance for the performance and reliability of its practice applications. To this end, the thermal transport in biphenylene network is comprehensively investigated in this paper with the aid of homogeneous non-equilibrium molecular dynamics (HNEMD), equilibrium molecular dynamics (EMD) and nonequilibrium molecular dynamics (NEMD) simulations. For the sake of comparison, the thermal conductivity of some other 2D sp2-hybridized carbon allotropes such as graphene and pentaheptite is also investigated using the same methods. The thermal conductivities of biphenylene network and pentaheptite predicted from the HNEMD method are, 208.3 W/(mK) and 342.7 W/(mK), respectively, which only equal to one-thirteenth and one-eighth of the value (2812.4 W/(mK)) of graphene. These results obtained from the HNEMD method are found to be in good agreements with the results extracted from EMD and NEMD methods, indicating the reliability of the present results. Based on the spectral heat current decomposition method, the thermal conductivity of all three 2D carbon allotropes is found to be mainly attributed to the flexural phonon mode. Through the analysis of phonon property, mechanical property and electron density distribution, the low thermal conductivity of biphenylene network and pentaheptite smaller than that of graphene is found to stem from the decline in their structural symmetry, which leads to the aggravation of phonon scattering, the decrease of phonon group velocity and the reduction of phonon mean free path.
Low-Frequency Vibrational Spectroscopy: A Powerful Tool for Revealing Crystalline Magnetic Structures
Authors: Song Zihui , Liu Xudong , Ochani Anish , Shen Suling , Li Qiqi , Sun Yiwen , Ruggiero Michael
Published: February 2022

The magnetic configuration of crystalline solids can have a profound impact on material properties, ranging from subtle structural effects to macroscopic phenomena. With the increased adoption of magnetic crystals for advanced applications, there is a significant need for tools that can characterize and predict the nature of magnetic ordering in solids. While there certainly exist techniques for acquiring such insight, those methods can be plagued by constraints (such as requiring certain elements), ultimately limiting their utility. Here, the strong-dependence of low-frequency (terahertz) vibrational dynamics on weak and long-range forces in crystals is leveraged to determine the spin state of iron phosphate -- a promising material for cathodes in lithium ion batteries. We highlight how terahertz time-domain spectroscopy -- coupled with quantum mechanical simulations -- can discern between various spin configurations in FePO4. Furthermore, the results of this work unambiguously show that the well-accepted space group symmetry for FePO4 is actually incorrect, and that low-frequency spectroscopic measurements provide a clearer picture of the correct structure over the gold-standard of X-ray diffraction. This work opens the door for characterizing, predicting, and interpreting crystalline magnetic ordering using low-frequency vibrational spectroscopy
Hydroboration of terminal alkenes and trans-1,2-diboration of terminal alkynes catalyzed by a Mn(I) alkyl complex
Authors: Weber Stefan , Zobernig Daniel , Stöger Berthold , Veiros Luis , Kirchner Karl
Published: February 2022

A Mn(I)-catalyzed hydroboration of terminal alkenes and the 1,2-diboration of terminal alkynes with pinacolborane (HBPin) is described. In the case of alkenes anti-Markovnikov hydroboration takes place, while in the case of alkynes the reaction proceeds with excellent trans-1,2-selectivity. The most active pre-catalyst is the bench-stable alkyl bisphosphine Mn(I) complex fac-[Mn(dippe)(CO)3(CH2CH2CH3)]. The catalytic process is initiated by migratory insertion of a CO ligand into the Mn-alkyl bond to yield an acyl intermediate which undergoes B-H bond cleavage of HBPin (in the case of alkenes) and rapid C-H bond cleavage (in the case of alkynes) forming the active Mn(I) boryl and acetylide catalysts [Mn(dippe)(CO)2(BPin)] and [Mn(dippe)(CO)2(CCR)], respectively, together with liberated butanal. The diboration is accompanied by dihydrogen liberation. A broad variety of aromatic and aliphatic alkenes and alkynes was efficiently and selectively borylated. Mechanistic insights are provided based on experimental data and DFT calculations revealing that an acceptorless reaction pathway involving dihydrogen release is operating.
Engineering a Cytidine Aminotransferase for Biocatalytic Production of the Antiviral Molnupiravir
Authors: Burke Ashleigh , Birmingham William , Zhuo Ying , Costa Bruna Zuculoto da , Crawshaw Rebecca , Thorpe Thomas , Rowles Ian , Finnigan James , Charnock Simon J. , Lovelock Sarah , Turner Nicholas , Green Anthony , Young Carl
Published: February 2022

The COVID-19 pandemic highlights the urgent need for cost-effective processes to rapidly manufacture antiviral drugs at scale. Here we report a concise biocatalytic process for Molnupiravir, a nucleoside analogue currently in phase 3 clinical trials as an orally available treatment for SARS-CoV-2. Key to the success of this process was the development of a cytidine aminotransferase for the production of N-hydroxy-cytidine through evolutionary adaption of the hydrolytic enzyme cytidine deaminase. This engineered biocatalyst performs >100,000 turnovers in less than 30 minutes, operates at 180 g/L substrate loading and benefits from in situ crystallization of the N-hydroxy-cytidine product (>90% yield), which can be converted to Molnupiravir by a selective 5’-acylation using Novozym® 435.
Reactant-Induced Photoactivation of a Gold-Catalyzed Csp2-Csp Cross-Coupling Leading to Indoles
Authors: Zhao Fen , Abdellaoui Mehdi , Berthet Jérome , Corcé Vincent , Delbaere Stéphanie , Dossmann Héloïse , Espagne Agathe , Forté Jérémy , Jullien Ludovic , Le Saux Thomas , Mouriès-Mansuy Virginie , Ollivier Cyril , Fensterbank Louis
Published: February 2022

A novel access to 2,3-disubstituted indoles from o-alkynyl aniline and iodoalkyne derivatives via a gold-catalyzed sequence under visible-light irradiation and in the absence of an exogenous photocatalyst was uncovered. A wide scope of the process was observed. Of note, 2-iodo-ynamides that have never been used in any organometallic cross-coupling reaction could be used as electrophiles. The resulting N-alkynyl indoles lend themselves to post-functionalization affording valuable scaffolds, notably benzo[a]carbazoles. Mechanistic studies converged on the fact that a potassium sulfonyl amide generates emissive aggregates in the reaction medium. Static quenching of these aggregates by a vinylgold(I) intermediate yields to an excited state of the latter, which can react with an electrophile via oxidative addition and reductive elimination to forge the key C-C bond. This reactant-induced photoactivation of an organogold intermediate opens rich perspectives in the field of cross-coupling reactions.
Reactions of Aluminium(I) with Transition Metal Carbonyls: Scope, Mechanism and Selectivity of CO Homologation
Authors: Kong Richard , Batuecas Maria , Crimmin Mark
Published: February 2022

Over the past few decades, numerous model systems have been discovered that create carbon–carbon bonds from CO. These reactions are of potential relevance to the Fischer-Tropsch (F-T) process, a technology that converts syngas mixtures (H2/CO) into mixtures of hydrocarbons. In this paper, a new homogeneous model system that constructs carbon chains from CO is reported. The system exploits the cooperative effect of a transition metal complex and main group reductant. An entire reaction sequence from C1 to C2 to C3 to C4 has been synthetically verified. The scope of reactivity is broad and includes a variety of transition metals (M = Cr, Mo, W, Mn, Re, Co), including those found in industrial heterogeneous F-T catalysts. Variation of the transition metal fragment impacts the relative rate of the steps of chain growth, allowing isolation and structural characterisation of a rare C2 intermediate. The selectivity of carbon chain growth is also impacted by this variable; two distinct isomers of the C3 carbon chain were observed to form in different ratios with different transition metal reagents. Based on a combination of experiments (isotope labelling studies, study of intermediates) and calculations (DFT, NBO, ETS-NOCV) we propose a complete mechanism for chain growth that involves defined reactivity at both transition metal and main group centres.
How two molecules self-assemble and what accelerates their assembly
Authors: Pang Yuan-Ping
Published: February 2022

Cram’s supramolecular capsule Octacid4 can irreversibly and noncovalently self-assemble with small- molecule guests at room temperature, but how they self-assemble and what accelerates their assembly are open questions that hold the key to developing noncovalent irreversible complexes. This article reports 72 distinct Octacid4•guest self-assembly pathways captured in unrestricted, unbiased, millisecond molecular dynamics simulations, revealing that the self-assembly process was initiated by the guest interaction with the cavity portal exterior of Octacid4 to increase the portal collisions that led to the portal expansion for guest ingress, accelerated by engaging populated host and guest conformations for the exterior interaction to increase the portal collision frequency, and completed by the portal contraction caused by the guest docking inside the cavity to impede guest egress. These revelations explain why the presence of a cryptic exterior binding site at the rim of the enzyme active site is a fundamental feature of fast enzymes such as acetylcholinesterase and why small molecules adopt local minimum conformations when binding to proteins. Furthermore, these revelations suggest that noncovalent irreversible complexes with fast assembly rates could be developed—by engaging populated host and guest conformations during the exterior interactions—for materials technology, data storage and processing, molecular sensing and tagging, and drug therapy.
Self-Supervised Learning for Molecular Property Prediction
Authors: Dillard Laurent
Published: February 2022

Predicting molecular properties remains a challenging task with numerous potential applications, notably in drug discovery. Recently, the development of deep learning, combined with rising amounts of data, has provided powerful tools to build predictive models. Since molecules can be encoded as graphs, Graph Neural Networks (GNNs) have emerged as a popular choice of architecture to tackle this task. Training GNNs to predict molecular properties however faces the challenge of collecting annotated data which is a costly and time consuming process. On the other hand, it is easy to access large databases of molecules without annotations. In this setting, self-supervised learning can efficiently leverage large amounts of non-annotated data to compensate for the lack of annotated ones. In this work, we introduce a self-supervised framework for GNNs tailored specifically for molecular property prediction. Our framework uses multiple pretext tasks focusing on different scales of molecules (atoms, fragments and entire molecules). We evaluate our method on a representative set of GNN architectures and datasets and also consider the impact of the choice of input features. Our results show that our framework can successfully improve performance compared to training from scratch, especially in low data regimes. The improvement varies depending on the dataset, model architecture and, importantly, on the choice of input feature representation.
Virtual teaching laboratories – hands-on at a distance
Authors: Kobayashi Rika , Goumans Theodorus P. M. , Carstensen N. Ole , Soini Thomas M. , Marzari Nicola , Timrov Iurii , Poncé Samuel , Linscott Edward B. , Sewell Christopher J. , Pizzi Giovanni , Ramirez Francisco , Bercx Marnik , Huber Sebastiaan P. , Adorf Carl S. , Talirz Leopold
Published: February 2022

The COVID-19 pandemic disrupted chemistry teaching practices globally as many courses were forced online necessitating adaptation to the digital platform. The biggest impact was to the practical component of the chemistry curriculum – the so-called wet lab. Naively, it would be thought that computer-based teaching labs would have little problem in making the move. However, this is not the case as there are many unrecognised differences between delivering computer-based teaching in-person and virtually: software issues, technology and classroom management. Consequently, relatively few “hands-on” computational chemistry teaching laboratories are delivered online. In this paper we describe these issues in more detail and how they can be addressed, drawing on our experience in delivering a third-year computational chemistry course as well as remote hands-on workshops for the Virtual Winter School on Computational Chemistry and the European BIG-MAP project.
A One-pot Access to Diastereoselective Benzo[5,6]oxepino[2,3-c]pyrroles via Formal (5+2)-Annulation of Donor-/Acceptor-Type Aryl Vinyl diazosuccinimide with Ketones Under Silver Catalysis
Authors: Bhat Dr. Ramakrishna G. , Laha Debasish , Meher Kajal B. , Bankar Onkar S.
Published: February 2022

A silver triflimide catalyzed one-pot protocol for the diastereoselective synthesis of dihydrobenzoxepines has been developed. Silver triflimide found to be an efficient catalyst for the formal (5+2)-cycloaddition to access dihydrobenzoxepines as a single diastereomer using vinyl diazo compounds as 5-C-synthons and ketones. An unmet challenge of utilizing the donor-/acceptor-type vinyl diazosuccinimides as 5-C-synthons under silver-catalysis is presented. This protocol found to be highly regio-, chemo- and diastereoselective, and works well with aliphatic as well as aromatic methyl ketones bearing electron deactivating as well as donating groups to afford dihydrobenzo[5,6]oxepino[2,3-c]pyrroles with a broad substrates scope. The control experiments and time dependent NMR studies revealed the plausible mechanism of this transformation. The protocol also proved to be scalable on the gram scale synthesis.
Study of Antibacterial effects on Indian Currency
Authors: Hore Aniruddha , Mitra Saptarshi , Ghosh Sandip , Ghosh Avijit , Bose Sujoy
Published: February 2022

Abstract Indian currency is the official currency of India. With the advancement of science and technology several modes of cashless transaction have been introduced to our country but still a large section of our society is dependent on the transaction through currency notes. The composition of the Indian currency generally comprises of cotton rags, balsam and parts of silk for the purpose of security threads. These currency notes are a hidden threat to us as they transmit bacteria, virus and fungus through touch and gets transmitted from one person to another. An Indian note changes hands in an average of 500 times a day therefore increasing the chances of contaminating the currency getting high and the transmission of harmful diseases through this currency also increases. When these highly contaminated Indian currencies comes in contact with the human touch it results in the transmission of harmful bacteria into the humans therefore causing several bacteria prone diseases such as food poisoning diarrhoea Gonorrhoea, meningitis, ulcers, and several other diseases. Therefore, it is important to make the Indian currency antibacterial. The main focus of the study is to develop an antibacterial chemical agent which comprises of certain natural as well as chemical components as a solution which will be used to activate the antibacterial properties of the natural fibres present in the currency. Several investigations were carried out on how the natural ingredients that is of lemon extracts, industrial vinegar and ginger extract would act on the surface of the currency notes. Bleach was used to chlorinate the note as the fibroin fibres gets activated of the silk thread when chlorine treatment is done and it kills about 99.9% of the bacteria including E. coli and S. aureus. The application of the natural extracts on the surface of the currency showed specific changes as it was instantly more clear than previous condition. The acidic and the antibacterial properties of the natural ingredients used, makes the currency note bacteria free as well as dirt free for a certain period of time which is a notifiable change. The treated currency were seen to be preventing the growth of bacteria for a certain period of time because of the activation of antibacterial properties of silk fibres due to the application of chlorine on silk and also the application of natural ingredients therefore preventing the growth of bacteria by persisting on the outer surface of the currency.
Role of ‘O’ Substitution in Expanded Porphyrins on Uranyl Complexation: Orbital and density based analyses
Authors: Chattaraj Saparya , Bhattacharyya Arunasis , Sadhu Biswajit
Published: February 2022

The need for efficient macrocyclic ligands that can sequester U(VI) has gained immense importance due to the increased applications of U(VI) in various sectors, including but not limited to nuclear energy. Structural attributes such as number and type of donor centers ("hard" and "soft") of ligands are essentially the key components for providing the adequate bonding scenario for uranyl. Beside hard or soft-donor-based binding cavity, the mixed-donor ligands are also finding popularity for achieving optimized performances. However, many aspects are still unknown about how and at what extent the ratio of hard-to-soft donor centers tune the bonding attributes with uranyl. Moreover, a consensus is yet to be reached on the nature and role of underlying covalent interaction between U and donors upon complexation, particularly in the mixed-donor ligand environment. In this work, using relativistic density functional theory (DFT), we attempted to address these important issues by systematically investigating the impact on the bonding characteristics of uranyl ion and an expanded porphyrin, viz. sapphyrin with increasing number of 'O' substitution at the cavity. Our results suggest that in the O-substituted sapphyrin variants, UO$_2^{2+}$ prefers to bind N over O donor sites, and decrease in N donor sites at the cavity prompts UO$_2^{2+}$ to have better interaction with the rest of N donor centers. Extended transition state (ETS) with natural orbital for chemical valences (NOCV) analysis shows that at equatorial plane N acts as better $\sigma$ donor to uranyl than O donor. Molecular orbital (MO) and density of states (DOS) analysis shows favorable bonding-interaction between U(d) and donor's p orbitals, the participation of U(f)-orbitals in bonding are of low-extent but non-negligible. Energy decomposition analysis (EDA), natural population analysis (NPA) along with thermodynamic analyses confirms the dominance of electrostatic interaction on the thermodynamic stability of the complexes. However, the U-N/O bonds at the equatorial plane do carry appreciable amount of covalent character. Analysis of quantum theory of atoms in molecules (QTAIM) descriptors in conjugation with MO analysis and overlap integral calculations confirms its nature as near-degeneracy driven type. Statistics of mixed-orbitals and overlap integral further suggest that the O donor does not act as adequate replacement of N for uranyl binding despite having more number of mixed MOs due to the variation in the amplitude of overlap.
Polyclonal aptamer libraries as binding entities on a graphene FET based biosensor for the discrimination of apo- and holo- retinol binding protein 4
Authors: Kissmann Ann-Kathrin , Andersson Jakob , Raber Heinz Fabian , Krämer Markus , Xing Hu , Kubiczek Dennis Horst , Bozdogan Anil , Aspermair Patrik , Knoll Wolfgang , Rosenau Frank
Published: February 2022

Oligonucleotide DNA aptamers represent an emergently important class of binding entities towards as different analytes as small molecules or even whole cells. Without the canonical isolation of individual aptamers following the SELEX process already the focused polyclonal libraries prepared by this in vitro evolution and selection can directly be used to label their dedicated analytes and to serve as binding molecules on surfaces. Here we report the first instance of a sensor able to discriminate between loaded and unloaded retinol binding protein 4 (RBP4), an important biomarker for the prediction of diabetes and kidney disease. The sensor relies purely on two aptamer libraries tuned such, that they discriminate between the protein isoforms, requiring no further sample labelling to detect RBP4 in both state. The evolution, binding properties of the libraries and the functionalization of graphene FET sensor chips are presented as well as the functionality of the resulting biosensor.
Luminol Anchors Improve the Electrochemical-Tyrosine-Click Labelling of Proteins
Authors: Depienne Sébastien , Alvarez-Dorta Dimitri , Croyal Mikael , Temgoua Ranil , Charlier Cathy , deniaud david , Boujtita Mohammed , gouin sebastien
Published: February 2022

New methodologies for the chemo-selective modifications of peptides and native proteins are of great importance in chemical biology and for the developm ent of therapeutic conjugates. Less abundant and uncharged amino-acid residues are interesting targets to form less heterogeneous conjugates and preserve biological functions. Phenylurazole (PhUr), N-methylphenylurazole (NMePhUr) and N-methylluminol (NMeLum) derivatives were described as tyrosine (Y) anchors after chemical or enzymatic oxydations. Recently, we developed the first electrochemical Y-bioconjugation method coined eY-click to activate PhUr in biocompatible media. In this work, we assessed the limitations, benefits and relative efficiencies of eY-click conjugations performed with a set of PhUr, NMePhUr and NMeLum derivatives. Results evidenced a high efficiency of NMeLum that showed a complete Y-chemoselectivity on polypeptides and biologically relevant proteins after soft electrochemical activation. Side reactions on nucleophilic or heteroaromatic amino-acids such as lysine or tryptophan were never observed during mass spectrometry analysis. Myoglobine, bovine serum albumin, a plant mannosidase, glucose oxidase and the therapeutically relevant antibody trastuzumab were efficiently labelled with a fluorescent probe in a two-step approach combining eY-click and strain-promoted azide-alkyne cyclization (SPAAC). The proteins conserved their structural integrity as observed by circular dichroism and the trastuzumab conjugate showed a similar binding affinity for the natural HER2 ligand as shown by bio-layer interferometry. Compared to our previously described protocol with PhUr, eY-click with NMeLum species showed faster reaction kinetics, higher (complete) Y-chemoselectivity and reactivity, and offer the interesting possibility for the double tagging of solvent-exposed Y.
Fluorine labeling of ortho-phenylenes to facilitate conformational analysis
Authors: Kirinda Viraj C. , Vemuri Gopi Nath , Kress Nicholas G. , Flynn Kaitlyn M. , Kumarage Nuwanthika Dilrukshi , Schrage Briana R. , Tierney David L. , Ziegler Christopher J. , Hartley C. Scott
Published: February 2022

¹H NMR spectroscopy is a powerful tool for the conformational analysis of ortho-phenylene foldamers in solution. However, as o-phenylenes are integrated into ever-more-complex systems, we are reaching the limits of what can be analyzed by ¹H- and ¹³C-based NMR techniques. Here, we explore fluorine labeling of o-phenylene oligomers for analysis by ¹⁹F NMR spectroscopy. Two series of fluorinated oligomers have been synthesized. Optimization of monomers for Suzuki coupling enables an efficient stepwise oligomer synthesis. The oligomers all adopt well-folded geometries in solution, as determined by ¹H NMR spectroscopy and X-ray crystallography. ¹⁹F NMR experiments complement these methods well. The resolved singlets of one-dimensional ¹⁹F{¹H} spectra are very useful for determining relative conformer populations. The additional information from two-dimensional ¹⁹F NMR spectra is also clearly valuable when making ¹H assignments. Comparison of ¹⁹F isotropic shielding predictions to experimental chemical shifts is not, however, currently sufficient by itself to establish o-phenylene geometries.
Ternary Kinetic Models for Rational Design of Molecular Glues
Authors: Douglass Jr. Eugene F. , Miller Chad J.
Published: February 2022

Recently, academic and industrial interest in molecular glue-based therapeutics has grown dramatically. Traditional drugs are designed to act on single targets, whereas molecular glues simultaneously bind two targets. By forming a ternary complex, molecular glues can create new therapeutic effects, such as rewiring cellular machinery to degrade specific proteins. Unfortunately, rational design of these therapies is challenging as current pharmacological theory is based on binary complex equilibria. Here, we extend our previous ternary-complex equilibrium work(JACS, 2013, 135, 6092) to derive a set of kinetic models highly analogous to Michaelis-Menten kinetics. We identify the weakest binding affinity as the most important engineerable parameter in the design of ternary-complex based therapeutics. Finally, we. have combined these equations with “big data” from new thermodynamic and kinetic databases to build interactive online tools that enable non-computational investigators to simulate their own experimental systems: • https://douglasslab.com/ternary_equilibrium/ • https://douglasslab.com/Btmax_kinetics/
Active Learning Configuration Interaction for Excited States Calculations of Polycyclic Aromatic Hydrocarbons
Authors: Jeong WooSeok , Gaggioli Carlo Alberto , Gagliardi Laura
Published: February 2022

We present the active learning configuration interaction (ALCI) method for multiconfigurational calculations based on large active spaces. ALCI leverages the use of an active learning procedure to find important electronic configurations among the full configuration space generated within an active space. We tested it for the calculation of singlet-singlet excited states of acenes and pyrene, by using different machine learning algorithms. The ALCI method yields excitation energies within 0.2–0.3 eV from those obtained by traditional complete active space configuration interaction (CASCI) calculations (affordable for active spaces up to 16 electrons in 16 orbitals), by including only a small fraction of the CASCI configuration space in the calculations. For larger active spaces (up to 26 electrons in 26 orbitals), not affordable with traditional CI methods, ALCI captures the trends of experimental excitation energies. Overall ALCI provides satisfactory approximations to large active-space wave functions with up to ten orders of magnitude fewer configurations. These ALCI wave functions are promising and affordable starting points for subsequent second order perturbation theory or pair-density functional theory calculations.
Proteoform-selective imaging of tissues using mass spectrometry
Authors: Yang Manxi , Hu Hang , Su Pei , Thomas Paul M. , Camarillo Jeannie M. , Greer Joseph B. , Early Bryan P. , Fellers Ryan T. , Kelleher Neil L. , Laskin Julia
Published: February 2022

Unraveling the complexity of biological systems relies on the development of new approaches for spatially resolved proteoform-specific analysis of the proteome. Top-down proteomics is a powerful tool, which has been used for the identification of thousands of proteoforms in biological samples. Herein, we present a first spatially resolved top-down proteomics analysis of biological tissues using nanospray desorption electrospray ionization mass spectrometry imaging (nano-DESI MSI). Nano-DESI generates multiply charged protein ions, which is advantageous for their structural characterization using tandem mass spectrometry (MS/MS). Proof-of-concept experiments demonstrate that the nano-DESI MSI combined with on-tissue top-down proteomics is ideally suited for the proteoform-selective imaging of thin tissue sections. Using rat brain tissue as a model system, we provide the first evidence of the differential proteoform expression in different regions of the brain.
Structural Basis for the Friedel-Crafts Alkylation in Cylindrocyclophane Biosynthesis
Authors: Wang Hua-Qi , Mou Shu-Bin , Xiao Wen , Zhou Huan , Hou Xu-Dong , Wang Su-Jing , Wang Qian , Gao Jiali , Wei Zhiyi , Liu Lijun , Xiang Zheng
Published: February 2022

The Lewis acid-catalyzed Friedel-Crafts alkylation of an aromatic ring with an alkyl halide is extensively used in organic synthesis. However, its biological counterpart was not reported until the elucidation of the cylindrocyclophane biosynthetic pathway in Cylindrospermum licheniforme ATCC 29412 by Balskus and co-workers. CylK is the key enzyme to catalyze the formation of the cylindrocyclophane scaffold through the Friedel-Crafts alkylation reactions with regioselectivity and stereospecificity. Further research demonstrates that CylK can accept other resorcinol rings and secondary alkyl halides as substrates. To date, the crystal structure of CylK has not been disclosed and the catalytic mechanism remains obscure. Herein we report the crystal structures of CylK in its apo form and its complexes with the analogues of its substrate and reaction intermediate. Combining the crystal structures, free energy simulations and the mutagenesis experiments, we proposed a concerted double-activation mechanism, which could explain the regioselectivity and stereospecificity. This work provides a foundation for engineering CylK as a biocatalyst to expand its substrate scope and applications in organic synthesis.
Screening for Group A Streptococcal disease via Solid-State Nanopore Detection of PCR Amplicons
Authors: King Simon , Briggs Kyle , Slinger Robert , Tabard-Cossa Vincent
Published: February 2022

Single molecule detection methods are becoming increasingly important for diagnostic applications. Practical Early detection of disease requires sensitivity down to the level of single copies of the targeted biomarkers. Of the candidate technologies that can address this need, solid-state nanopores show great promise as digital sensors for single-molecule detection. Here, we present work detailing the use of solid-state nanopores as downstream sensors for a PCR-based assay targeting group A streptococcus (strep A) which can be readily extended to detect any pathogen that can be identified with a short nucleic acid sequence. We demonstrate that with some simple modifications to the standard PCR reaction mixture, nanopores can be used to reliably identify strep A in clinical samples. We also discuss methodological best practices both for adapting PCR-based assays to solid-state nanopore readout as well as analytical approaches by which to decide on sample status.
An Efficient Synthesis of Tetrodotoxin
Authors: Konrad David , Ruehmann Peter , Ando Hiroyasu , Hetzler Belinda , Matsuura Bryan , Trauner Dirk
Published: February 2022

Tetrodotoxin (TTX) is an indispensable probe in neuroscience, a biosynthetic and ecological enigma, and one of the most celebrated targets of synthetic chemistry. Here, we present a stereoselective synthesis of TTX that proceeds in 22 steps starting from a readily available glucose derivative. The central cyclohexane ring of TTX and its α-tertiary amine moiety was established via the intramolecular 1,3-dipolar cycloaddition of a nitrile oxide, followed by alkynyl addition to the resultant isoxazoline. After some carefully chosen protecting group manipulations, a ruthenium-catalyzed hydroxylactonization set the stage for the formation of its dioxa-adamantane core. Installation of the guanidine, oxidation of a primary alcohol, and late-stage epimerization of the resultant aldehyde gave a mixture of TTX and anhydro TTX. Our synthesis represents one of the most effective of TTX reported to date and could give ready access to biologically active derivatives.
Charge Carrier Screening in Photoexcited Epitaxial Semiconductor Nanorods Revealed by Transient X-ray Absorption Linear Dichroism
Authors: Rossi Thomas , Dykstra Conner , Haddock Tyler , Wallick Rachel , Burke John , Gentle Cecilia , Doumy Gilles , March Anne Marie , van der Veen Renske
Published: February 2022

Understanding the electronic structure and dynamics of semiconducting nanomaterials at the atomic level is crucial for the realization and optimization of devices in solar energy, catalysis, and optoelectronic applications. We report here on the use of ultrafast X-ray linear dichroism spectroscopy to unravel the carrier dynamics in epitaxial ZnO nanorods after band-gap photoexcitation. By rigorously subtracting out thermal contributions and conducting ab initio calculations, we reveal an overall depletion of absorption cross sections in the transient X-ray spectra caused by photogenerated charge carriers screening the core-hole potential of the X-ray absorbing atom. At low laser excitation densities, we observe phase-space filling by excited electrons and holes separately. These results pave the way for carrier- and element-specific probing of charge transfer dynamics across heterostructured interfaces with ultrafast table-top and fourth generation X-ray sources.
Reconciling Imbalanced Transition State Effects with Nonadiabatic CPET Reactions
Authors: Schneider Joseph , Goetz McKenna , Anderson John
Published: February 2022

Recently there have been several experimental demonstrations of how concerted proton electron transfer (CPET) reaction rates are affected by off-main-diagonal energies, namely the stepwise thermodynamic parameters ΔG°PT and ΔG°ET. Semi-classical structure-activity relationships have been invoked to rationalize these asynchronous linear free energy relation-ships despite the widely acknowledged importance of quantum effects such as nonadiabaticity and tunneling in CPET reactions. Here we report variable temperature kinetic isotope effect data for the asynchronous reactivity of a terminal Co-oxo complex with C–H bonds and find evidence of substantial quantum tunneling which is inconsistent with semi-classical models even when including tunneling corrections. This indicates substantial nonadiabatic tunneling in the CPET reactivity of this Co-oxo complex and further motivates the need for a quantum mechanical justification for the in-fluence of ΔG°PT and ΔG°ET on reactivity. To reconcile this dichotomy, we include ΔG°PT and ΔG°ET in nonadiabatic models of CPET by having them influence the anharmonicity and depth of the proton potential energy surfaces, which we approximate as Morse potentials. With this model we independently reproduce the dominant trend with ΔG°PT + ΔG°ET as well as the subtle effect of ΔG°PT − ΔG°ET (or η) in a nonadiabatic framework. The primary route through which these off-diagonal energies influence rates is through vibronic coupling. Our results reconcile predictions from semiclassical transition state theory with models that treat proton transfer quantum mechanically in CPET reactivity and suggest that similar treatments may be possible for other nonadiabatic processes.
Hydration dynamics gives the distinctive brown color in the "brown ring" nitrate test
Authors: Banerjee Ambar , Coates Michael R. , Odelius Michael
Published: February 2022

The chemistry of the brown-ring test has been investigated for nearly a century. Though recent studies have focused on solid state structure determination and the measurement of spectra, mechanistic details and kinetics, the aspects of solution structure and dynamics remain unknown. From ab initio molecular dynamics simulations of the brown-ring complex in aqueous solution, we have identified that the classically established pseudo-octahedral [Fe(H2O)5(NO)]2+ complex is in equilibrium with a square-pyramidal [Fe(H2O)4(NO)]2+ complex through the exchange of one of the coordinated H2O molecules. We also find, using ab-initio multi-reference methods, that the mixture of these two complexes is what gives the distinctive brown coloration to the brown-ring test. We show that its UV-vis spectrum can be theoretically reproduced only by accounting these two species and not the [Fe(H2O)5(NO)]2+ complex alone. The energetics of the two complexes are also investigated with multi-reference methods.
Side-Chain Engineering of Aggregation-Induced Emission Molecules for Boosting Cancer Phototheranostics
Authors: song shanliang , Zhao Yue , Kang Miaomiao , Zhang Zhijun , Wu Qian , Fu Shuang , Li Youmei , Wen Haifei , Wang Dong , Tang Ben Zhong
Published: February 2022

The ingenious construction of versatile cancer phototheranostic agents involving FLI, PDT, and PTT concurrently has attracted great interest. By virtue of the plentiful freely rotated moieties and the inherent twisted structure, AIEgens have been proven a perfect template for development of phototheranostic system. The systematic regulation of the energy consumption pathways through altering the molecular structure of AIEgens based on side-chain engineering is of great significance for the simultaneous pursuit of controllable fluorescence, photodynamic and photothermal properties, but has rarely been reported. Herein, an AIE-active multifunctional phototheranostic system was reported through intentional control the side-chain structure. Bearing the longest alkyl chain, all of those three energy dissipation pathways were retained controllably. In vitro and in vivo evaluations verified that TBFT2 nanoparticles performed well in terms of FLI-guided PDT and PTT synergistic cancer therapy. This study provides a new insight into the exploration of superior versatile phototheranostics through side-chain engineering.
Enhancing thermally activated delayed fluorescence by fine-tuning the dendron donor strength
Authors: Duda Eimantas , Hall David , Bagnich Sergey , Carpenter-Warren Cameron L. , Saxena Rishabh , Wong Michael Y. , Cordes David B. , Slawin Alexandra M. Z. , Beljonne David , Olivier Yoann , Zysman-Colman Eli , Köhler Anna
Published: February 2022

Thermally activated delayed fluorescence (TADF) relies on a small energy gap between the emissive singlet and the non-emissive triplet state, obtained by reducing the wavefunction overlap between donor and acceptor moieties. Efficient emission, however, requires maintaining a good oscillator strength, which is itself based on sufficient overlap of the wavefunctions between donor and acceptor moieties. We demonstrate an approach to subtly fine-tune the required wavefunction overlap by employing donor-dendrons of changing functionality. We use a carbazolyl-phthalonitrile based donor-acceptor core, 2CzPN, as a reference emitter, and progressively localize the hole density through substitution at the 3,6-positions of the carbazole donors (Cz) with further carbazole, (4-tert-butylphenyl)amine (tBuDPA) and phenoxazine (PXZ). Using detailed photoluminescence studies, complemented with Density Functional Theory (DFT) calculations, we show that this approach permits a gradual decrease of the singlet-triplet gap, ΔEST, from 300 meV to around 10 meV in toluene, yet we also demonstrate why a small ΔEST alone is not enough. While sufficient oscillator strength is maintained with the Cz- and tBuDPA-based donor dendrons, this is not the case for the PXZ-based donor dendron, where the wavefunction overlap is reduced too strongly. Overall, we find the donor-dendron extension approach allows successful fine-tuning of the emitter photoluminescence properties.
The Effect of Particle Size on the Optical and Electronic Properties of MgO Nanoparticles
Authors: Zwijnenburg Martijn
Published: February 2022

The quasiparticle states, fundamental gaps, optical gaps, exciton binding energies and UV-Vis spectra for a series of cuboidal nanoparticles of the prototypical oxide magnesium oxide (MgO), the largest of which has 216 atoms and edges of 1 nm, were predicted using many-body perturbation theory (evGW-BSE). The evolution of the properties with particle size was explicitly studied. It was found that while the highest occupied and lowest unoccupied quasiparticle states and fundamental gap change with particle size, the optical gap remains essentially fixed for all but the smallest nanoparticles, in line with what was previously observed experimentally. The explanation for these observations is demonstrated to be that while the optical gap is associated with an exciton that is highly localised around the particle’s corner atoms, the highest occupied and lowest unoccupied quasiparticle states, while primarily localised on the oxygen corner atoms (hole) and magnesium corner atoms -(electron), show significant delocalisation along the edges. The strong localisation of the exciton associated with the optical gap on the corner atoms is argued to also explain why the nanoparticles have a much smaller optical gaps and red-shifted spectra than bulk MgO. Finally, it is discussed how this non-quantum confinement behaviour, where the properties of the nanoparticles arise from surface defects rather than differences in localisation of edge or exciton states, appears typical of alkaline earth oxide nanoparticles, and that the true optical gap of bulk crystals of such materials is also probably the result of surface defects, even if unobservable experimentally.
Non-Adiabatic Dynamics Simulations of a Light-Driven Molecular Motor in Solution
Authors: Wen Jin , Mai Sebastian , Gonzalez Leticia
Published: February 2022

Despite molecular motors have numerous potential applications in optoelectronics, where optical properties can be tuned to transform light into mechanical movements, finding relationships between molecular motion and the environment is challenging. Here, we report the first excited state dynamics study of an overcrowded alkene in solution using a hybrid quantum mechanics/molecular mechanics (QM/MM) approach combined with non-adiabatic molecular dynamics simulations. Using QM/MM surface-hopping trajectories, we calculate time-resolved emission and transient absorption spectra. These show the rise of a short-lived Frank-Condon state in the first 150 fs, followed by a formation of a dark state, before the motor relaxes to the ground state in about 1 ps. From the analysis of radial distribution functions we infer that the orientation of the solvent in the electronic excited state is similar to that in the ground state during the photoisomerization.