Molecular insight into endosulfan degradation by Ese protein from Arthrobacter: Evidence-based structural bioinformatics and quantum mechanical calculations.

Endosulfan is an organochlorine insecticide widely used for agricultural pest control. Many nations worldwide have restricted or completely banned it due to its extreme toxicity to fish and aquatic invertebrates. Arthrobacter sp. strain KW has the ability to degrade α, ß endosulfan and its intermediate metabolite endosulfate; this degradation is associated with Ese protein, a two-component flavin-dependent monooxygenase (TC-FDM). Employing in silico tools, we obtained the 3D model of Ese protein, and our results suggest that it belongs to the Luciferase Like Monooxygenase family (LLM). Docking studies showed that the residues V59, V315, D316, and T335 interact with α-endosulfan. The residues: V59, T60, V315, D316, and T335 are implicated in the interacting site with ß-endosulfan, and the residues: H17, V315, D316, T335, N364, and Q363 participate in the interaction with endosulfate. Topological analysis of the electron density by means of the Quantum Theory of Atoms in Molecules (QTAIM) and the Non-Covalent Interaction (NCI) index reveals that the Ese-ligands complexes are formed mainly by dispersive forces, where Cl atoms have a predominant role. As Ese is a monooxygenase member, we predict the homodimer formation. However, enzymatic studies must be developed to investigate the Ese protein's enzymatic and catalytic activity.

An Organocopper(III) Fluoride Triggering C-CF3 Bond Formation.

Copper(III) fluorides are catalytically competent, yet elusive, intermediates in cross-coupling. The synthesis of [PPh4 ][CuIII (CF3 )3 F] (2), the first stable (isolable) CuIII -F, was accomplished via chloride addition to [CuIII (CF3 )3 (py)] (1) yielding [PPh4 ][CuIII (CF3 )3 Cl(py)] (1⋅Cl), followed by treatment with AgF. The CuIII halides 1⋅Cl and 2 were fully characterized using nuclear magnetic resonance (NMR) spectroscopy, single crystal X-ray diffraction (Sc-XRD) and elemental analysis (EA). Complex 2 proved capable of forging C-CF3 bonds from silyl-capped alkynes. In-depth mechanistic studies combining probes, theoretical calculations, trapping of intermediate 4a ([PPh4 ][CuIII (CF3 )3 (C≡CPh)]) and radical tests unveil the key role of the CuIII acetylides that undergo facile 2e- reductive elimination furnishing the trifluoromethylated alkynes (RC≡CCF3 ), which are industrially relevant synthons in drug discovery, pharma and agrochemistry.

Quest for the Most Aromatic Pathway in Charged Expanded Porphyrins.

Despite the central role of aromaticity in the chemistry of expanded porphyrins, the evaluation of aromaticity remains difficult for these extended macrocycles. The presence of multiple conjugation pathways and different planar and nonplanar π-conjugation topologies makes the quantification of global and local aromaticity even more challenging. In neutral expanded porphyrins, the predominance of the aromatic conjugation pathway passing through the imine-type nitrogens and circumventing the amino NH groups is established. However, for charged macrocycles, the question about the main conjugation circuit remains open. Accordingly, different conjugation pathways in a set of neutral, anionic, and cationic expanded porphyrins were investigated by means of several aromaticity indices rooted in the structural, magnetic, and electronic criteria. Overall, our results reveal the predominance of the conjugation pathway that passes through all nitrogen atoms to describe the aromaticity of deprotonated expanded porphyrins, while the outer pathway through the perimeter carbon atoms becomes the most aromatic in protonated macrocycles. In nonplanar and charged macrocycles, a discrepancy between electronic and magnetic descriptors is observed. Nevertheless, our work demonstrates AVmin remains the best tool to determine the main conjugation pathway of expanded porphyrins.

The NCIWEB Server: A Novel Implementation of the Noncovalent Interactions Index for Biomolecular Systems.

It is well-known that the activity and function of proteins is strictly correlated with their secondary, tertiary, and quaternary structures. Their biological role is regulated by their conformational flexibility and global fold, which, in turn, is largely governed by complex noncovalent interaction networks. Because of the large size of proteins, the analysis of their noncovalent interaction networks is challenging, but can provide insights into the energetics of conformational changes or protein-protein and protein-ligand interactions. The noncovalent interaction (NCI) index, based on the reduced density gradient, is a well-established tool for the detection of weak contacts in biological systems. In this work, we present a web-based application to expand the use of this index to proteins, which only requires a molecular structure as input and provides a mapping of the number, type, and strength of noncovalent interactions. Structure preparation is automated and allows direct importing from the PDB database, making this server (https://nciweb.dsi.upmc.fr) accessible to scientists with limited experience in bioinformatics. A quick overview of this tool and concise instructions are presented, together with an illustrative application.

Conformational preference analysis in C2H6 using orbital forces and non-covalent interactions; comparison with related systems.

Dynamic Orbital Forces (DOF) and Non-Covalent Interactions (NCIs) are used to analyze the attractive/repulsive interactions responsible of the conformational preference of ethane and some related compounds. In ethane, it is found that the stabilization of the staggered conformation with respect to the adiabatic eclipsed one arises from both attractive and repulsive interactions in CH3⋯CH3. Attractive ones are predominant in a ratio 2 : 1, with an important role of a σ MO. On the contrary, the stabilization of the staggered conformation with respect to the vertical eclipsed one arises almost only from repulsive π interactions. Weak long-range H⋯H repulsions also favour the staggered conformation. From the sum of DOFs, yielding intrinsic bond energies, the rotation barrier can be decomposed into a weakening of the C-C bond (ca. 7 kcal mol-1), moderated by a strengthening of C-H ones (ca. 4 kcal mol-1). This evidences the decrease of hyperconjugation in the eclipsed conformation with respect to the staggered one. In the compounds CH3-SiH3, SiH3-SiH3, CH3-CF3 and CF3-CF3, the conformational preference is predominantly or exclusively due to repulsive interactions, with respect as well to adiabatic as to vertical eclipsed structures.

In silico design of bio-marker detection fluorescent probes.

Fluorescent probes capable of sensing the biological medium are of utmost importance in medical diagnostics. However, the optical spectrum of such probes needs to be tuned with care for compatibility with living tissues. More specifically, fluorescent bioprobes must be adjusted so as to avoid light interference with pigments (e.g. hemoglobin), tissue photodamage, scattering of the emitted light, and autofluorescence. This leads to two important conditions on the optical spectrum of the probes. On the one hand, the emission wavelength must be in an optical window of 650 to 950 nm. On the other hand, the Stokes shift must be large, ideally greater than 150 nm. In this paper, we showcase the in-silico design of potential fluorescent biomarkers fulfilling these two conditions by means of heteroatomic substitution and conjugation on a 1,2,4-triazole core initially far away from biological standards.

How do density functionals affect the Hirshfeld atom refinement?

In this work, the effect of mixing different amounts of Hartree-Fock (HF) exchange with hybrid density functionals applied to the Hirshfeld atom refinement (HAR) of urea and oxalic acid dihydrate is explored. Together, the influence of using different basis sets, methods (including MP2 and HF) and cluster sizes (to model bulk effects) is studied. The results show that changing the amount of HF exchange, no matter the level of theory, has an impact almost exclusively on the H atom refinement parameters. Contrary to pure quantum mechanical calculations where good geometries are obtained with intermediate HF exchange mixtures, in the HAR the best match with neutron diffraction reference values is not necessarily found for these admixtures. While the non-hydrogen covalent bond lengths are insensitive to the combination of method or basis set employed, the X-H bond lengths always increase proportionally to the HF exchange for the analysed systems. This outcome is opposite to what is normally observed from geometry optimisations, i.e., shorter bonds are obtained with greater HF exchange. Additionally, the thermal ellipsoids tend to shrink with larger HF exchange, especially for the H atoms involved in strong hydrogen bonding. Thus, it may be the case that the development of density functionals or basis sets suitable for quantum crystallography should take a different path than those fitted for quantum chemistry calculations.

Insight into the inclusion of heteroatom impurities in silicon structures.

The bonding properties of the tilt boundary in poly-silicon and the effect of interstitial impurities are investigated by first-principles. In order to obtain thorough information on the nature of chemical bondings in these solid systems, an accurate topological analysis is performed, through partitioning of the electron localization function. Although the mechanism of segregation of single light impurities, such as carbon, nitrogen, and oxygen, in Si-based systems is known, it is only in the presence of multiple segregations that the distinctive structures of the various interstitial impurities emerge. The structural analysis of the modified Si systems and the comparison with the corresponding molecular structure within these solid phases provide an adequate description of interesting properties, for which bond charges provide more insight than bond length. It is shown that, in the presence of isovalent carbon, all systems try to preserve the tetrahedral coordination; on the contrary, trivalent nitrogen induces a strong local distortion to fit in the tetrahedral Si matrix while oxygen is the impurity that segregates more easily and more regularly. This work shows that impurities lead to local distortions and shows how the electron distribution rearranges to smooth these distortions. Overall, it shows how the analysis of bonds and their correlation with energetics and electronic structure is of fundamental importance for the understanding of the defects induced properties and of the basic mechanisms that influence them.

New venues in electron density analysis.

We provide a comprehensive overview of the chemical information from electron density: not only how to extract information, but also how to obtain and how to assess the quality of the electron density itself. After introducing several indexes derived from electron density, which allow bonding to be revealed, we focus on the various potential sources of electron density, and also explain the error trends they show so that a judicious choice of methods and limitations are clearly laid on the table. Computational, experimental-computational combinations, and machine learning efforts are covered in this work.

Orbital energies and nuclear forces in DFT: Interpretation and validation.

The bonding and antibonding character of individual molecular orbitals has been previously shown to be related to their orbital energy derivatives with respect to nuclear coordinates, known as dynamical orbital forces. Albeit usually derived from Koopmans' theorem, in this work we show a more general derivation from conceptual DFT, which justifies application in a broader context. The consistency of the approach is validated numerically for valence orbitals in Kohn-Sham DFT. Then, we illustrate its usefulness by showcasing applications in aromatic and antiaromatic systems and in excited state chemistry. Overall, dynamical orbital forces can be used to interpret the results of routine ab initio calculations, be it wavefunction or density based, in terms of forces and occupations.

Kick-Fukui: A Fukui Function-Guided Method for Molecular Structure Prediction.

Here, we introduce a hybrid method, named Kick-Fukui, to explore the potential energy surface (PES) of clusters and molecules using the Coulombic integral between the Fukui functions in the first screening of the best individuals. In the process, small stable molecules or clusters whose combination has the stoichiometry of the explored species are used as assembly units. First, a small set of candidates has been selected from a large and stochastically generated (Kick) population according to the maximum value of the Coulombic integral between the Fukui functions of both fragments. Subsequently, these few candidates are optimized using a gradient method and density functional theory (DFT) calculations. The performance of the program has been evaluated to explore the PES of various systems, including atomic and molecular clusters. In most cases studied, the global minimum (GM) has been identified with a low computational cost. The strategy does not allow to identify the GM of some silicon clusters; however, it predicts local minima very close in energy to the GM that could be used as the initial population of evolutionary algorithms.

Designing boron and metal complexes for fluoride recognition: a computational perspective.

Fluoride anions (F-) may have beneficial or harmful effects on the environment depending on their concentration. Here, we shed light on F- recognition by compounds containing boron, tellurium and antimony, which were experimentally demonstrated to be capable of interacting with the F- ion in a partially aqueous medium. Boron and metal complexes recognize F- anions primarily using electrostatic energy along with important contributions from orbital interaction energy. The natural orbitals for chemical valence (NOCV) methodology indicates that the main orbital interactions behind fluoride recognition are σ bonds between the receptors and the F- anions. The charged receptors, which provide (i) two B atoms, (ii) one B atom and one Sb atom, or (iii) one B atom and one Te atom to directly interact with the F- ions, appear to be some of the best structures for the recognition of F- anions. This is supported by the combination of favorable electrostatic and σ bond interactions. Overall, the presence of electron donor groups, such as -CH3 and -OH, in the receptor structure destabilizes the fluoride recognition because it decreases the attractive electrostatic energy and increases the Pauli repulsion energy in the receptor⋯F- bonds. Notably, electron acceptor groups, for example, -CN and -NO2, in the receptor structure favor the interaction with the F- ions, due to the improvement of the electrostatic and σ bond interactions. This study opens the way to find the main features of a receptor for F- recognition.

The role of Si vacancies in the segregation of O, C, and N at silicon grain boundaries: An ab initio study.

Grain boundaries (GBs) are defects originating in multi-crystalline silicon during crystal growth for device Si solar cell fabrication. The presence of GBs changes the coordination of Si, making it advantageous for charge carriers to recombine, which brings a significant reduction of carrier lifetimes. Therefore, GBs can be highly detrimental for device performances. Furthermore, GBs easily form vacancies with deep defect electronic states and are also preferential segregation sites for various impurity species, such as C, N, and O. We studied from first principles the correlation between structural, energetics, and electronic properties of the Σ3{111} Si GB with and without vacancies, and the segregation of C, N, and O atoms. C and O atoms strongly increase their ability to segregate when vacancies are present. However, the electronic properties of the Σ3{111} Si GB are not affected by the presence of O, while they can strongly change in the case of C. For N atoms, it is not possible to find a clear trend in the energetics and electronic properties both with and without vacancies in the GB. In fact, as N is not isovalent with Si, as C and O, it is more flexible in finding new chemical arrangements in the GB structure. This implies a stronger difficulty in controlling the properties of the material in the presence of N impurity atoms compared to C and O impurities.

Energetics of Electron Pairs in Electrophilic Aromatic Substitutions.

The interacting quantum atoms approach (IQA) as applied to the electron-pair exhaustive partition of real space induced by the electron localization function (ELF) is used to examine candidate energetic descriptors to rationalize substituent effects in simple electrophilic aromatic substitutions. It is first shown that inductive and mesomeric effects can be recognized from the decay mode of the aromatic valence bond basin populations with the distance to the substituent, and that the fluctuation of the population of adjacent bonds holds also regioselectivity information. With this, the kinetic energy of the electrons in these aromatic basins, as well as their mutual exchange-correlation energies are proposed as suitable energetic indices containing relevant information about substituent effects. We suggest that these descriptors could be used to build future reactive force fields.

Understanding Topological Insulators in Real Space.

A real space understanding of the Su-Schrieffer-Heeger model of polyacetylene is introduced thanks to delocalization indices defined within the quantum theory of atoms in molecules. This approach enables to go beyond the analysis of electron localization usually enabled by topological insulator indices-such as IPR-enabling to differentiate between trivial and topological insulator phases. The approach is based on analyzing the electron delocalization between second neighbors, thus highlighting the relevance of the sublattices induced by chiral symmetry. Moreover, the second neighbor delocalization index, δi,i+2, also enables to identify the presence of chirality and when it is broken by doping or by eliminating atom pairs (as in the case of odd number of atoms chains). Hints to identify bulk behavior thanks to δ1,3 are also provided. Overall, we present a very simple, orbital invariant visualization tool that should help the analysis of chirality (independently of the crystallinity of the system) as well as spreading the concepts of topological behavior thanks to its relationship with well-known chemical concepts.

The "Inverted Bonds" Revisited: Analysis of "In Silico" Models and of [1.1.1]Propellane by Using Orbital Forces.

This article dwells on the nature of "inverted bonds", which refer to the σ interaction between two sp hybrids by their smaller lobes, and their presence in [1.1.1]propellane. Firstly, we study H3 C-C models of C-C bonds with frozen H-C-C angles reproducing the constraints of various degrees of "inversion". Secondly, the molecular orbital (MO) properties of [1.1.1]propellane and [1.1.1]bicyclopentane are analyzed with the help of orbital forces as a criterion of bonding/antibonding character and as a basis to evaluate bond energies. Triplet and cationic states of [1.1.1]propellane species are also considered to confirm the bonding/antibonding character of MOs in the parent molecule. These approaches show an essentially non-bonding character of the σ central C-C interaction in propellane. Within the MO theory, this bonding is thus only due to π-type MOs (also called "banana" MOs or "bridge" MOs) and its total energy is evaluated to approximately 50 kcal mol-1 . In bicyclopentane, despite a strong σ-type repulsion, a weak bonding (15-20 kcal mol-1 ) exists between both central C-C bonds, also due to π-type interactions, though no bond is present in the Lewis structure. Overall, the so-called "inverted" bond, as resulting from a σ overlap of the two sp hybrids by their smaller lobes, appears highly questionable.

Characterization and Decomposition of the Natural van der Waals SnSb2Te4 under Compression.

High pressure X-ray diffraction, Raman scattering, and electrical measurements, together with theoretical calculations, which include the analysis of the topological electron density and electronic localization function, evidence the presence of an isostructural phase transition around 2 GPa, a Fermi resonance around 3.5 GPa, and a pressure-induced decomposition of SnSb2Te4 into the high-pressure phases of its parent binary compounds (α-Sb2Te3 and SnTe) above 7 GPa. The internal polyhedral compressibility, the behavior of the Raman-active modes, the electrical behavior, and the nature of its different bonds under compression have been discussed and compared with their parent binary compounds and with related ternary materials. In this context, the Raman spectrum of SnSb2Te4 exhibits vibrational modes that are associated but forbidden in rocksalt-type SnTe; thus showing a novel way to experimentally observe the forbidden vibrational modes of some compounds. Here, some of the bonds are identified with metavalent bonding, which were already observed in their parent binary compounds. The behavior of SnSb2Te4 is framed within the extended orbital radii map of BA2Te4 compounds, so our results pave the way to understand the pressure behavior and stability ranges of other "natural van der Waals" compounds with similar stoichiometry.

Steric clash in real space: biphenyl revisited.

A textbook case of twisted structure due to hydrogen-hydrogen steric clash, the biphenyl molecule, has been studied in real space from a new perspective. Long-term discrepancies regarding the origin of the steric repulsion are now reconciled under the NCI (Non Covalent Interaction) method, which reflects in 3D the balance between attractive and repulsive interactions taking place in the region between the phenyl rings. The NCI method confirms that the steric repulsion does not merely come from the H-H interaction itself, but from the many-atom interactions arising from the Cortho-H region, therefore providing rigorous physical grounds for the steric clash. This method allows a continuous scan of all the subtle changes on the electron density on going from the planar to the perpendicular biphenyl structure. The NCI results agree with other topological approaches (IQA, ELF) and are in line with previous findings in the literature regarding controversial H-H interactions in steric clash situations: H-H interactions are attractive, but repulsion appears between (Cortho-H)(Cortho-H), raising the intraatomic energy of the ortho H. ELF is also used to support these conclusions. Indeed, deformations are observed in compressed basins that allow to visualize the intraatomic effect of steric repulsion. These results can be easily extrapolated to systems with similar topological features in which steric clash is claimed to be the reason for instability.

A Bond Charge Model Ansatz for Intrinsic Bond Energies: Application to C-C Bonds.

A simple bond charge model is proposed to predict intrinsic bond energies. Model parameters can be derived from the topology of the electron localization function and equilibrium geometries through classic considerations. Results for carbon-carbon covalent bonds are shown to be very accurate in different chemical environments. Insight can be extracted from the application of the model due to its elementary construction and simple mathematical formulation. The remarkable robustness of the fitted model highlights how different density functional approximations relate geometries, densities, and energies.

Real-Space Approach to the Reaction Force: Understanding the Origin of Synchronicity/Nonsynchronicity in Multibond Chemical Reactions.

In this article, we present a complementary analysis based on the reaction force F(ξ)/reaction force constant κ(ξ) and noncovalent interactions (NCI) index to characterize the energetics (kinetic and thermodynamics) and mechanistic pathways of two sets of multibond chemical reactions, namely, two double-proton transfer and two Diels-Alder cycloaddition reactions. This approach offers a very straightforward and useful way to delve into a deeper understanding of this type of process. While F(ξ) allows the partition of the whole pathway into three regions or phases, κ(ξ) describes how orchestrated are the bond-breaking and bond-formation events. In turn, NCI indicates how the inter- and intramolecular bonds evolve. The most innovative aspect is the inclusion of the formation of the reactant complex along the pathway, which, by means of NCI, unveils the early molecular recognition and the comprehension of its role in determining the degree of the synchronicity/nonsynchronicity of one-step processes. This approach should be a useful and alternative tool to characterize the energetics and the mechanism of general chemical reactions.