Chemical Literature Research Articles

MolScribe: Robust Molecular Structure Recognition with Image-to-Graph Generation.

Molecular structure recognition is the task of translating a molecular image into its graph structure. Significant variation in drawing styles and conventions exhibited in chemical literature poses a significant challenge for automating this task. In this paper, we propose MolScribe, a novel image-to-graph generation model that explicitly predicts atoms and bonds, along with their geometric layouts, to construct the molecular structure. Our model flexibly incorporates symbolic chemistry constraints to recognize chirality and expand abbreviated structures. We further develop data augmentation strategies to enhance the model robustness against domain shifts. In experiments on both synthetic and realistic molecular images, MolScribe significantly outperforms previous models, achieving 76-93% accuracy on public benchmarks. Chemists can also easily verify MolScribe's prediction, informed by its confidence estimation and atom-level alignment with the input image. MolScribe is publicly available through Python and web interfaces: https://github.com/thomas0809/MolScribe.

The most common linkers in bioactive molecules and their bioisosteric replacement network

Structures of the large majority of bioactive molecules are composed of several rings that are decorated by substituents and connected by linkers. While numerous cheminformatics studies focusing on rings and substituents are available, practically nothing has been published about the third important structural constituent of bioactive molecules - the linkers. The current study attempts to fill this gap. The most common linkers present in bioactive molecules are identified, their properties analyzed and a method for linker similarity search introduced. The bioisosteric replacement network of linkers is generated based on a large corpus of structure–activity data from medicinal chemistry literature. The results are presented in a graphical form and the underlying data are also made available for download. This analysis is intended to help medicinal chemists to better understand the role of linkers, particularly heterocyclic rings in bioactive molecules and to select an optimal set of linkers in their future project.

Superhydrophobic Sand Repels Water

A key concept in current fluid dynamics and its applications to biology and technology is a phenomenon known as wetting. Wetting is familiar from everyday life and is simply the ability of a liquid to stay in contact with a solid surface. The wettability depends on the properties of the liquid and the solid and can be characterized by the static equilibrium contact angle θ (the angle at which the liquid–gas interface meets the liquid–solid interface). A contact angle below 90° indicates favorable wetting such that a drop of the liquid would spread over a large amount of the flat solid surface, whereas a high contact angle indicates that very little of the solid is wetted (this can be seen in Fig. 1, which shows various stages of surface wetting in terms of the equilibrium contact angle). Nevertheless, this theory generally sounds quite dry or difficult to visualize when explained to students for the first time. The theory of the contact angle also contains some controversies and has undergone some recent developments. We propose a simple classroom demonstration with superhydrophobic sand that gives a concrete visualization of “superhydrophobicity” and outline how the phenomenon can be explained macroscopically with wetting theory. There are several interesting physical effects that are due to superhydrophobicity: experimental studies have found, for example, that superhydrophobic spheres always splash when they impact a body of liquid. In terms of applications, there are various possibilities for water storage with superhydrophobic sand outlined in the chemistry literature.

Building on the strengths of a double-hybrid density functional for excitation energies and inverted singlet-triplet energy gaps.

It is demonstrated that a double hybrid density functional approximation, ωB88PTPSS, that incorporates equipartition of density functional theory and the non-local correlation, however with a meta-generalized gradient approximation correlation functional, as well as with the range-separated exchange of ωB2PLYP, provides accurate excitation energies for conventional systems, as well as correct prescription of negative singlet-triplet gaps for non-conventional systems with inverted gaps, without any necessity for parametric scaling of the same-spin and opposite-spin non-local correlation energies. Examined over "safe" excitations of the QUESTDB set, ωB88PTPSS performs quite well for open-shell systems, correctly and fairly accurately [relative to equation-of-motion coupled-cluster singles and doubles (EOM-CCSD) reference] predicts negative gaps for 50 systems with inverted singlet-triplet gaps, and is one of the leading performers for intramolecular charge-transfer excitations and achieves near-second-order approximate coupled cluster (CC2) and second-order algebraic diagrammatic construction quality for the Q1 and Q2 subsets. Subsequently, we tested ωB88PTPSS on two sets of real-life examples from recent computational chemistry literature-the low energy bands of chlorophyll a (Chl a) and a set of thermally activated delayed fluorescence (TADF) systems. For Chl a, ωB88PTPSS qualitatively and quantitatively achieves DLPNO-STEOM-CCSD-level performance and provides excellent agreement with experiment. For TADF systems, ωB88PTPSS agrees quite well with spin-component-scaled CC2 (SCS-CC2) excitation energies, as well as experimental values, for the gaps between the S1 and T1 excited states.

Short review on mechanical activation in non-metallurgical alumina production

The terms mechano-chemistry and mechanical activation of solid materials were introduced in chemical literature by Ostwald at the beginning of the XX century. Both terms cover a whole range of interconnected phenomena taking place during the mechanical action on solids or their separate parts participating in chemical reactions, phase transitions, mixing and creating composite materials, alloying and crystal growth in the solid state, deformation and changing physical and thermal properties, all of them at low temperature. The common effects of the mechanical activation on solid material are fracturing and reduction of particle sizes, generation of new reactive surfaces, diffusion of atoms of the reactant phase through the product phase, and quite significantly, accumulating energy in crystalline or amorphous structure (enough twists in atomic and molecular networks, tensions in atomic bond and active sites to trigger the nucleation of new phases). Mechanical activation is very used to produce all clean alumina mineralogical phases with uniform particle size dimensions from nano to macro size. Also, mechanical activation may extend the specific surface of some minerals, enhancing the yields in the solid-liquid extraction process. With adequate precursors, all phase transitions from amorphous to alfa α-Al2O3 can be carried out on the same route as in thermally activated alumina, but some other routes, impossible by thermal activation, might be followed. The difference between the two activation ways is that mechanical activation is made at room temperature.

Ethnochemistry: Exploring the Potential of Sasak and Java Local Wisdom as a Teaching Materials

The lack of availability of learning resources in the form of teaching materials is one of the problems found in chemistry learning, both in secondary schools and in tertiary institutions, so it is very urgent to develop contextual chemistry teaching materials as an implementation of the ethnochemical approach in learning. The purpose of this study was to explore and develop chemistry teaching materials as learning resources by exploring the potential of local Sasak and Javanese wisdom. This research approach uses a qualitative approach with data collection techniques through literature, interviews, and documentation. The data obtained were analyzed using Miles & Huberman's qualitative analysis. The research subjects consisted of community leaders, chemical content experts, and chemical literature relevant to the research study. Based on the research findings, it can be concluded that Sasak and Javanese local wisdom can be used as a source of chemistry learning through integrating Sasak and Javanese local wisdom with chemical bonding materials and changes in elements, compounds, and mixtures. Thus, the implications of this research can be a source of reference in developing contextual chemistry teaching materials so as to make learning more meaningful.

Eponyms in Laboratory Equipment

In the chemistry laboratory, we can find plenty of tools that bear the name of their creator. Such names are called eponyms. The article presents 72 of the most commonly used representatives of eponymic names in the laboratory technique. Their primary sources (where possible) and actual creators were identified by excerpting historical chemical literature including rare and not easily accessible items. The article shows that some eponymic names are not based on the name of the discoverer, but rather on the names of the manufacturers (e.g., Griffin beaker), the names of those who popularized the device (e.g., Liebig condenser), or who were associated with it because of their fame (e.g., Willstätter needle). Eponymic names in the laboratory technique are not only a legacy of the past and an important means of communication in contemporary chemistry, but they can also be used to communicate chemistry to students and lay people, using interesting stories hidden behind them.
 Full text English translation is available in the on-line version.

ACS members honored with AIChE awards

Members of the American Chemical Society were recognized by the American Institute of Chemical Engineers (AIChE) at its 2022 annual meeting. Liang-Shih Fan , a Distinguished University Professor, C. John Easton Professor in Engineering, and professor of chemical and biomolecular engineering at the Ohio State University, received the Warren K. Lewis Award for Chemical Engineering Education. Timothy J. Hebrink , a senior staff scientist at 3M, received the Energy and Sustainability Award. Cato T. Laurencin , the University Professor and Albert and Wilda Van Dusen Distinguished Endowed Professor of Orthopaedic Surgery at the University of Connecticut, received AIChE’s highest honor, the Founders Award for Outstanding Contributions to the Field of Chemical Engineering. Eleftherios “Terry” Papoutsakis , the Unidel Eugene du Pont Professor at the University of Delaware, received the William H. Walker Award for Excellence in Contributions to Chemical Engineering Literature. Christopher J. Pope , an independent chemical engineering researcher

First Synthesis of 3-Glycopyranosyl-1,2,4-Triazines and Some Cycloadditions Thereof.

C-glycopyranosyl derivatives of six-membered heterocycles are scarcely represented in the chemical literature and the title 3-glycopyranosyl-1,2,4-triazines are completely unknown. In this paper, the first synthesis of this compound class is accomplished by the cyclocondensation of C-glycosyl formamidrazones and 1,2-dicarbonyl derivatives. In addition, the synthesis of C-glycopyranosyl 1,2,4-triazin-5(4H)-ones was also carried out by the transformation of the above formamidrazones with α-keto-carboxylic esters. Inverse electron demand Diels-Alder reactions of 3-glycopyranosyl-1,2,4-triazines with a bicyclononyne derivative yielded the corresponding annulated 2-glycopyranosyl pyridines.

Prediction uncertainty validation for computational chemists.

Validation of prediction uncertainty (PU) is becoming an essential task for modern computational chemistry. Designed to quantify the reliability of predictions in meteorology, the calibration-sharpness (CS) framework is now widely used to optimize and validate uncertainty-aware machine learning (ML) methods. However, its application is not limited to ML and it can serve as a principled framework for any PU validation. The present article is intended as a step-by-step introduction to the concepts and techniques of PU validation in the CS framework, adapted to the specifics of computational chemistry. The presented methods range from elementary graphical checks to more sophisticated ones based on local calibration statistics. The concept of tightness, is introduced. The methods are illustrated on synthetic datasets and applied to uncertainty quantification data issued from the computational chemistry literature.

Large-Scale Distributed Training of Transformers for Chemical Fingerprinting.

Transformer models have become a popular choice for various machine learning tasks due to their often outstanding performance. Recently, transformers have been used in chemistry for classifying reactions, reaction prediction, physiochemical property prediction, and more. These models require huge amounts of data and localized compute to train effectively. In this work, we demonstrate that these models can successfully be trained for chemical problems in a distributed manner across many computers—a more common scenario for chemistry institutions. We introduce MFBERT: Molecular Fingerprints through Bidirectional Encoder Representations from Transformers. We use distributed computing to pre-train a transformer model on one of the largest aggregate datasets in chemical literature and achieve state-of-the-art scores on a virtual screening benchmark for molecular fingerprints. We then fine-tune our model on smaller, more specific datasets to generate more targeted fingerprints and assess their quality. We utilize a SentencePiece tokenization model, where the whole procedure from raw molecular representation to molecular fingerprints becomes data-driven, with no explicit tokenization rules.

Analysis of Protein-Protein Interactions for Intermolecular Bond Prediction.

Protein-protein interactions often involve a complex system of intermolecular interactions between residues and atoms at the binding site. A comprehensive exploration of these interactions can help reveal key residues involved in protein-protein recognition that are not obvious using other protein analysis techniques. This paper presents and extends DiffBond, a novel method for identifying and classifying intermolecular bonds while applying standard definitions of bonds in chemical literature to explain protein interactions. DiffBond predicted intermolecular bonds from four protein complexes: Barnase-Barstar, Rap1a-raf, SMAD2-SMAD4, and a subset of complexes formed from three-finger toxins and nAChRs. Based on validation through manual literature search and through comparison of two protein complexes from the SKEMPI dataset, DiffBond was able to identify intermolecular ionic bonds and hydrogen bonds with high precision and recall, and identify salt bridges with high precision. DiffBond predictions on bond existence were also strongly correlated with observations of Gibbs free energy change and electrostatic complementarity in mutational experiments. DiffBond can be a powerful tool for predicting and characterizing influential residues in protein-protein interactions, and its predictions can support research in mutational experiments and drug design.

What makes a reaction network “chemical”?

BackgroundReaction networks (RNs) comprise a set X of species and a set mathscr {R} of reactions Yrightarrow Y', each converting a multiset of educts Ysubseteq X into a multiset Y'subseteq X of products. RNs are equivalent to directed hypergraphs. However, not all RNs necessarily admit a chemical interpretation. Instead, they might contradict fundamental principles of physics such as the conservation of energy and mass or the reversibility of chemical reactions. The consequences of these necessary conditions for the stoichiometric matrix mathbf {S}in mathbb {R}^{Xtimes mathscr {R}} have been discussed extensively in the chemical literature. Here, we provide sufficient conditions for mathbf {S} that guarantee the interpretation of RNs in terms of balanced sum formulas and structural formulas, respectively.ResultsChemically plausible RNs allow neither a perpetuum mobile, i.e., a “futile cycle” of reactions with non-vanishing energy production, nor the creation or annihilation of mass. Such RNs are said to be thermodynamically sound and conservative. For finite RNs, both conditions can be expressed equivalently as properties of the stoichiometric matrix mathbf {S}. The first condition is vacuous for reversible networks, but it excludes irreversible futile cycles and—in a stricter sense—futile cycles that even contain an irreversible reaction. The second condition is equivalent to the existence of a strictly positive reaction invariant. It is also sufficient for the existence of a realization in terms of sum formulas, obeying conservation of “atoms”. In particular, these realizations can be chosen such that any two species have distinct sum formulas, unless mathbf {S} implies that they are “obligatory isomers”. In terms of structural formulas, every compound is a labeled multigraph, in essence a Lewis formula, and reactions comprise only a rearrangement of bonds such that the total bond order is preserved. In particular, for every conservative RN, there exists a Lewis realization, in which any two compounds are realized by pairwisely distinct multigraphs. Finally, we show that, in general, there are infinitely many realizations for a given conservative RN.Conclusions“Chemical” RNs are directed hypergraphs with a stoichiometric matrix mathbf {S} whose left kernel contains a strictly positive vector and whose right kernel does not contain a futile cycle involving an irreversible reaction. This simple characterization also provides a concise specification of random models for chemical RNs that additionally constrain mathbf {S} by rank, sparsity, or distribution of the non-zero entries. Furthermore, it suggests several interesting avenues for future research, in particular, concerning alternative representations of reaction networks and infinite chemical universes.

Determination of absolute configuration of a new triterpenic acid in leaves of Ilex hainanensis

This study aimed to explore the triterpenic acid components in leaves of Ilex hainanensis. Alkaline water extraction, macroporous resin adsorption, and high performance liquid chromatography were used to separate and purify the triterpenic acid components in leaves of I. hainanensis. The physical and chemical property analysis, MS, NMR spectroscopy, and literature comparison were performed to identify the structures, and a new triterpene acid compound was discovered:(3S, 4R, 5R, 8R, 9R, 10R, 14S, 17S, 18S, 19R)-3,19-dihydroxyursa-12,20(30)-diene-24,28-dioic-acid, and named ilexhainanin F. In addition, according to its structural characteristics, the ~(19)F-NMR Mosher method was further employed to study its absolute configuration. By comparison of the ~(19)F-NMR chemical shifts of Mosher esters, it was determined that the absolute configuration of the 3-position chiral center of the compound was the S configuration.

RealOrganicChemistry.org: A Collection of Introductory-Appropriate Organic Chemistry Reactions

For most students, completing practice problems is an essential prerequisite for success in organic chemistry courses. Practice work, however, is sometimes perceived to be easier than or even not related to the types of chemistry that students see in assessments and “real-world” science. This negative view may contribute to a reduced level of engagement with course content and scientific learning practices. To combat this perception, a collection of introductory level-appropriate organic reactions bearing literature citations has been assembled and made available at RealOrganicChemistry.org. Portions of this collection were crowdsourced by introductory organic chemistry students through a three-part literature assignment intended for students reading the chemical literature for the first time. For students, RealOrganicChemistry.org is intended to provide a wealth of practice opportunities to complement conventional learning resources. For instructors, RealOrganicChemistry.org hosts a simple-to-complex range of reaction examples that are useful for literature-backed teaching efforts.

On k-regular edge connectivity of chemical graphs

Abstract Quantitative structure property research works, which are the essential part in chemical information and modelling, give basic underlying topological properties for chemical substances. This information enables conducting more feasible studies between theory and practice. Connectivity concept in chemical graph theory gives information about underlying topology of chemical structures, fault tolerance of molecules, and vulnerability of chemical networks. In this study we first defined two novel types of conditional connectivity measures based on regularity notion: k-regular edge connectivity and almost k-regular edge connectivity in chemical graph theory literature. We computed these new graph invariants for cycles, complete graphs, and Cartesian product of cycles. Our results will be applied to calculate k-regular edge connectivity of some nanotubes which are stated as Cartesian product of cycles. These calculations give information about fault tolerance capacity and vulnerability of these chemical structures.

Crystallize It before It Diffuses: Kinetic Stabilization of Thin-Film Phosphorus-Rich Semiconductor CuP2.

Numerous phosphorus-rich metal phosphides containing both P–P bonds and metal–P bonds are known from the solid-state chemistry literature. A method to grow these materials in thin-film form would be desirable, as thin films are required in many applications and they are an ideal platform for high-throughput studies. In addition, the high density and smooth surfaces achievable in thin films are a significant advantage for characterization of transport and optical properties. Despite these benefits, there is hardly any published work on even the simplest binary phosphorus-rich phosphide films. Here, we demonstrate growth of single-phase CuP2 films by a two-step process involving reactive sputtering of amorphous CuP2+x and rapid annealing in an inert atmosphere. At the crystallization temperature, CuP2 is thermodynamically unstable with respect to Cu3P and P4. However, CuP2 can be stabilized if the amorphous precursors are mixed on the atomic scale and are sufficiently close to the desired composition (neither too P poor nor too P rich). Fast formation of polycrystalline CuP2, combined with a short annealing time, makes it possible to bypass the diffusion processes responsible for decomposition. We find that thin-film CuP2 is a 1.5 eV band gap semiconductor with interesting properties, such as a high optical absorption coefficient (above 105 cm–1), low thermal conductivity (1.1 W/(K m)), and composition-insensitive electrical conductivity (around 1 S/cm). We anticipate that our processing route can be extended to other phosphorus-rich phosphides that are still awaiting thin-film synthesis and will lead to a more complete understanding of these materials and of their potential applications.

Pd-Catalyzed Cross-Couplings: On the Importance of the Catalyst Quantity Descriptors, mol % and ppm.

This Review examines parts per million (ppm) palladium concentrations in catalytic cross-coupling reactions and their relationship with mole percentage (mol %). Most studies in catalytic cross-coupling chemistry have historically focused on the concentration ratio between (pre)catalyst and the limiting reagent (substrate), expressed as mol %. Several recent papers have outlined the use of “ppm level” palladium as an alternative means of describing catalytic cross-coupling reaction systems. This led us to delve deeper into the literature to assess whether “ppm level” palladium is a practically useful descriptor of catalyst quantities in palladium-catalyzed cross-coupling reactions. Indeed, we conjectured that many reactions could, unknowingly, have employed low “ppm levels” of palladium (pre)catalyst, and generally, what would the spread of ppm palladium look like across a selection of studies reported across the vast array of the cross-coupling chemistry literature. In a few selected examples, we have examined other metal catalyst systems for comparison with palladium.

Digitization and validation of a chemical synthesis literature database in the ChemPU

Despite huge potential, automation of synthetic chemistry has only made incremental progress over the past few decades. We present an automatically executable chemical reaction database of 100 molecules representative of the range of reactions found in contemporary organic synthesis. These reactions include transition metal-catalyzed coupling reactions, heterocycle formations, functional group interconversions, and multicomponent reactions. The chemical reaction codes or χDLs for the reactions have been stored in a database for version control, validation, collaboration, and data mining. Of these syntheses, more than 50 entries from the database have been downloaded and robotically run in seven modular chemputers with yields and purities comparable to those achieved by an expert chemist. We also demonstrate the automatic purification of a range of compounds using a chromatography module seamlessly coupled to the platform and programmed with the same language.

Can New Series of Half-sandwich Lanthanum(III), Erbium(III), and Ytterbium(III) Complexes of Organometallic Ferrocenyl Schiff Base Ligands Display Biological Activities as Antibacterial and Anticancer Drugs?

ABSTRACT A new series of La(III), Er(III), and Yb(III) complexes were synthesized from ferrocenyl Schiff base ligands (2-(1-((8-aminonaphthalen-1-yl)imino)ethyl)cyclopenta-2,4-dien-1-yl) (cyclopenta-2,4-dien-1-yl)iron (L1) and (2-(1-((1-carboxyethyl)imino)ethyl) cyclopenta-2,4-dien-1-yl)(cyclopenta-2,4-dien-1-yl)iron (HL2). Complexes were designed, synthesized, and characterized using various spectroscopic techniques. Molar conductance data exposed that the complexes were electrolytes except La(III)-HL2 complex, which was non-electrolyte. IR spectra denoted that Schiff bases were coordinated with transition metal ions in a bidentate manner, N,N donor sites with L1 and N,O donor sites with HL2. All complexes were octahedral and prepared in a 1:1 molar ratio with the ligands. Thermal behavior of the complexes was studied. The in vitro antibacterial activities of these compounds were evaluated against eight bacterial species such as four Gram positive bacteria (Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Streptococcus faecalis), and four Gram negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Neisseria gonorrhoeae, Salmonella typhimurium) and results displayed that title compounds are biologically active. Also, they were assessed for their anticancer activities against cell line MCF-7 for breast cancer. Finally, molecular docking studies were tested for all prepared compounds with two different COVID-19 receptors (7BZ5 and 7C8J), also, against 3HB5 receptor of breast cancer. Molecular docking has shown favorable interaction between the title compounds and three protein receptors. This paper affords a manifestation of a novel tradition by which Comments on Inorganic Chemistry starts publishing original research content that, nonetheless, preserves the Journal’s identity as a niche for a critical discussion of contemporary literature in inorganic chemistry; for previous manifestations, see Comments Inorg. Chem. 2020, 40, 277–303, and references cited in the abstract thereof.