Bond Geometry Research Articles

Re-evaluation of protein neutron crystallography with and without X-ray/neutron joint refinement.

Protein neutron crystallography is a powerful technique to determine the positions of H atoms, providing crucial biochemical information such as the protonation states of catalytic groups and the geometry of hydrogen bonds. Recently, the crystal structure of a bacterial copper amine oxidase was determined by joint refinement using X-ray and neutron diffraction data sets at resolutions of 1.14 and 1.72 Å, respectively [Murakawa et al. (2020 ▸). Proc. Natl Acad. Sci. USA, 117, 10818-10824]. While joint refinement is effective for the determination of the accurate positions of heavy atoms on the basis of the electron density, the structural information on light atoms (hydrogen and deuterium) derived from the neutron diffraction data might be affected by the X-ray data. To unravel the information included in the neutron diffraction data, the structure determination was conducted again using only the neutron diffraction data at 1.72 Å resolution and the results were compared with those obtained in the previous study. Most H and D atoms were identified at essentially the same positions in both the neutron-only and the X-ray/neutron joint refinements. Nevertheless, neutron-only refinement was found to be less effective than joint refinement in providing very accurate heavy-atom coordinates that lead to significant improvement of the neutron scattering length density map, especially for the active-site cofactor. Consequently, it was confirmed that X-ray/neutron joint refinement is crucial for determination of the real chemical structure of the catalytic site of the enzyme.

Hyperconjugative Interactions of the Carbon-Halogen Bond that Influence the Geometry of Cyclic α-Haloacetals.

The analysis of the structures of low-energy conformers of different α-haloacetals reveals changes in bond lengths and geometries that correspond to stabilizing orbital interactions that contribute to the ground-state structures of these systems. Several factors, including the electron-donating and electron-accepting abilities of the substituents on the ring, affect the degree of the electronic interactions in these carbohydrate-like systems. The presence of an α-halogen atom that can participate in hyperconjugation has been shown to contribute to the structural characteristics of the low-energy conformer. The experimental evidence is supported by natural bond order (NBO) analysis to identify the types of interactions and to assess their relative importance.

The combination of RPLC-ESI-FTMS/MS and m-CPBA epoxidation for the location and geometry assignment of double bonds in unsaturated fatty acyl chains of drying oils

Abstract Oil painting is the process of painting with drying oils as binders. Such oils mainly consist of triacylglycerols characterized by high levels of unsaturated fatty acyl chains. For instance, poppy seed oils have received much attention for their use as oil paints since very ancient time. Upon exposure to oxygen, not only do drying oils harden to a densely cross-linked polymer network through radical reactions, but their fatty acids also interact with cations of some pigments forming the related carboxylate salts. These so-called metal soaps lead to severe degradation phenomena because they can migrate and aggregate, breaking through the surface of the paint. Since the fatty-acidome of a drying oil is involved in these processes, the current study is chiefly devoted to the identification of both free and total fatty acids in poppy seed oil by reversed-phase liquid chromatography coupled with high-resolution mass spectrometry by an electrospray ionization source (RPLC-ESI-FTMS). Total fatty acids (TFA) were investigated by enzymatic hydrolysis and comparisons were made between the free fatty acid (FFA) profile and the total one resulting from the digestion on the same poppy seed oil. A key component of our approach was the double bond (C=C) epoxidation reaction, which was carried out on unsaturated fatty acids by meta-chloroperoxybenzoic acid (m-CPBA). A chromatographic set up was developed to separate such oxidized lipids, that were identified as deprotonated molecules [epoM-H]− by accurate mass matching in full mass spectra. Their epoxide ring was subsequently cleaved upon tandem mass fragmentation to yield a pair of diagnostic product ions for C=C double bond localization. Interestingly, the double bond geometry (i.e., cis/trans) was also assigned based on the retention times of derivatized-FA. The present approach opens new avenues for the analysis of artworks whether affected by metal soap-related degradation phenomena.

Fast and Accurate Quantum Mechanical Modeling of Large Molecular Systems Using Small Basis Set Hartree-Fock Methods Corrected with Atom-Centered Potentials.

There has been significant interest in developing fast and accurate quantum mechanical methods for modeling large molecular systems. In this work, by utilizing a machine learning regression technique, we have developed new low-cost quantum mechanical approaches to model large molecular systems. The developed approaches rely on using one-electron Gaussian-type functions called atom-centered potentials (ACPs) to correct for the basis set incompleteness and the lack of correlation effects in the underlying minimal or small basis set Hartree-Fock (HF) methods. In particular, ACPs are proposed for ten elements common in organic and bioorganic chemistry (H, B, C, N, O, F, Si, P, S, and Cl) and four different base methods: two minimal basis sets (MINIs and MINIX) plus a double-ζ basis set (6-31G*) in combination with dispersion-corrected HF (HF-D3/MINIs, HF-D3/MINIX, HF-D3/6-31G*) and the HF-3c method. The new ACPs are trained on a very large set (73 832 data points) of noncovalent properties (interaction and conformational energies) and validated additionally on a set of 32 048 data points. All reference data are of complete basis set coupled-cluster quality, mostly CCSD(T)/CBS. The proposed ACP-corrected methods are shown to give errors in the tenths of a kcal/mol range for noncovalent interaction energies and up to 2 kcal/mol for molecular conformational energies. More importantly, the average errors are similar in the training and validation sets, confirming the robustness and applicability of these methods outside the boundaries of the training set. In addition, the performance of the new ACP-corrected methods is similar to complete basis set density functional theory (DFT) but at a cost that is orders of magnitude lower, and the proposed ACPs can be used in any computational chemistry program that supports effective-core potentials without modification. It is also shown that ACPs improve the description of covalent and noncovalent bond geometries of the underlying methods and that the improvement brought about by the application of the ACPs is directly related to the number of atoms to which they are applied, allowing the treatment of systems containing some atoms for which ACPs are not available. Overall, the ACP-corrected methods proposed in this work constitute an alternative accurate, economical, and reliable quantum mechanical approach to describe the geometries, interaction energies, and conformational energies of systems with hundreds to thousands of atoms.

Hydrogen Bonds with Fluorine in Ligand-Protein Complexes-the PDB Analysis and Energy Calculations.

Fluorine is a common substituent in medicinal chemistry and is found in up to 50% of the most profitable drugs. In this study, a statistical analysis of the nature, geometry, and frequency of hydrogen bonds (HBs) formed between the aromatic and aliphatic C–F groups of small molecules and biological targets found in the Protein Data Bank (PDB) repository was presented. Interaction energies were calculated for those complexes using three different approaches. The obtained results indicated that the interaction energy of F-containing HBs is determined by the donor–acceptor distance and not by the angles. Moreover, no significant relationship between the energies of HBs with fluorine and the donor type was found, implying that fluorine is a weak HB acceptor for all types of HB donors. However, the statistical analysis of the PDB repository revealed that the most populated geometric parameters of HBs did not match the calculated energetic optima. In a nutshell, HBs containing fluorine are forced to form due to the stronger ligand–receptor neighboring interactions, which make fluorine the “donor’s last resort”.

β-d-Galacto-pyranosyl-(1→4)-2-amino-2-de-oxy-α-d-gluco-pyran-ose hydro-chloride monohydrate (lactosamine).

The title compound, C12H24NO10 +·Cl-·H2O, (I), crystallizes in the monoclinic space group P21 and exists as a monohydrate of a monosubstituted ammonium chloride salt, with the reducing carbohydrate portion existing exclusively as the α-pyran-ose tautomer. The glycosidic bond geometry in (I) is stabilized by an intra-molecular hydrogen bond and is close to that found in crystalline α-lactose. All heteroatoms except gluco-pyran-ose ring O4 participate in an extensive hydrogen-bonding network, which propagates in all directions in the crystal structure of (I).

Reversible strain-induced magnetic phase transition in a van der Waals magnet.

Mechanical deformation of a crystal can have a profound effect on its physical properties. Notably, even small modifications of bond geometry can completely change the size and sign of magnetic exchange interactions and thus the magnetic ground state. Here we report the strain tuning of the magnetic properties of the A-type layered antiferromagnetic semiconductor CrSBr achieved by designing a strain device that can apply continuous, in situ uniaxial tensile strain to two-dimensional materials, reaching several percent at cryogenic temperatures. Using this apparatus, we realize a reversible strain-induced antiferromagnetic-to-ferromagnetic phase transition at zero magnetic field and strain control of the out-of-plane spin-canting process. First-principles calculations reveal that the tuning of the in-plane lattice constant strongly modifies the interlayer magnetic exchange interaction, which changes sign at the critical strain. Our work creates new opportunities for harnessing the strain control of magnetism and other electronic states in low-dimensional materials and heterostructures.

Unraveling excited state dynamics and photophysical properties for a series of phenol-quinoline derivatives by controlling hydrogen bond geometry

As a “site-specific” interaction, the hydrogen bonds play an important role in optical properties. Therefore, we used the time dependent density functional theory to study the excited state dynamics and photophysical properties of a series of phenol-quinoline derivatives (1-3 compounds) by controlling the hydrogen bond geometry. The calculated geometric parameters and reduced density gradient results show that the intramolecular hydrogen bond distance is inversely proportional to the hydrogen bond strength. Meanwhile, potential energy curves shows that the stronger the hydrogen bond strength, the smaller the energy barriers in the ground (S0) and excited (S1) states. In particular, we use not only the linear response solvation model but also the state-specific (SS) solvation model for the PES in the S1 state. The results show that the SS solvation model better establishes the relationship between the hydrogen bond strength and the energy barrier in the S1 state. In addition, increasing the dihedral angle of intramolecular hydrogen bond leads to more obvious intramolecular charge transfer during excitation transition. Moreover, we also found that the dihedral angle affects the excited state dynamics and the fluorescence emission properties. Our theoretical results indicate that the fluorescence quenching pathway of the 3 compound is caused by the photoinduced electron transfer process, which is different from the experimentally proposed non-radiative deactivation by conical intersections.

Investigation of structural, electronic and thermoelectric properties of two-dimensional graphdiyne/borophene monolayers and hetero-bilayers

The integration of dissimilar 2D materials is important for nanoelectronic and thermoelectric applications. Among different polymorphs and different bond geometries, borophene and graphdiyne (GDY) are two promising candidates for these applications. In the present paper, we have studied hetero-bilayers comprising graphdiyne–borophene (GDY–BS) sheets. Three structural models, namely S0, S1 and S2 have been used for borophene sheets. The optimum interlayer distance for the hetero-bilayers was obtained through binding energy calculations. Then, the structure and electronic properties of the monolayers and hetero-bilayers were individually examined and compared. GDY monolayer was shown to be a semiconductor with a band gap of 0.43 eV, while the borophene monolayers, as well as all studied hetero-bilayers showed metallic behavior. The thermoelectric properties of borophene and GDY monolayers and the GDY–BS bilayers were calculated on the basis of the semi-classical Boltzmann theory. The results showed signs of improvement in the conductivity behavior of the hetero-bilayers. Furthermore, considering the increase in Seebeck coefficient and the conductivity for all the structures after calculating figure of merit and power factor, a higher power factor and more energy generation were observed for bilayers. These results show that the GDY–BS hetero-bilayers can positively affect the performance of thermoelectric devices.

Isostructural Halogen Exchange and Halogen Bonds: The Case of N-(4-Halogenobenzyl)-3-halogenopyridinium Halogenides.

Six N-(4-halogenobenzyl)-3-halogenopyridinium cations were prepared by reacting meta-halogenopyridines (Cl, Br, and I) with (4-halogenobenzyl) bromides (Br and I) and were isolated as bromide salts, which were further used to obtain iodides and chlorides. Sixteen compounds (out of 18 possible cation/anion combinations) were obtained; two crystallized as hydrates and 14 as solvent free salts, 11 of which belonged to one isostructural series and 3 to another. All crystal structures comprise halogen-bonded chains, with the anion as an acceptor of two halogen bonds, with the pyridine and the benzyl halogen substituents of two neighboring cations. The halogen bonds with the pyridine halogen show a linear correlation between the relative halogen bond length and angle, which primarily depend on the donor halogen. The parameters of the other halogen bonds vary with all three halogens, indicating that the former halogen bond is the dominant interaction. This is also in accord with the calculated electrostatic potential in the σ-holes of the halogens and the thermal properties of the solids. The second isostructural group comprises combinations of the best halogen bond donors and acceptors, and features a more favorable halogen bond geometry of the dominant halogen bond, reaffirming its significance as the main factor in determining the structure.

Geometries of hydrogen bonds in water-ethanol mixtures from ab initio molecular dynamics simulations.

We outline a simple procedure to determine the geometry of hydrogen bonds between different molecular species in binary mixtures from ab initio molecular dynamics (AIMD) trajectories. Here we determine the geometry of the hydrogen bonds arising from intermolecular OH⋯O interactions between different H-bonded pairs, water-water, ethanol-ethanol and water-ethanol in water-alcohol mixtures at different compositions by plotting the intermolecular non-bonded OH⋯O and O⋯O distances, and the ∠HO⋯O (θ) angles for each of the possible pairs in the ensemble. Two regions separate out in each of the scatter-plots; the one with short OH⋯O and O⋯O intermolecular distances and almost linear ∠HO⋯O angles may be identified as the region where the intermolecular OH⋯O geometry would be favorable for hydrogen bonding. Using the different geometric criteria for each of the three possible H-bonded pairs we estimate the average number of water and ethanol molecules that are hydrogen bonded to a water molecule, and to an ethanol molecule, respectively, at different mole fractions of the mixture. We validate the results from values of the chemical shift of the two OH resonances (water and ethanol) in the proton NMR spectra of the mixtures at different concentrations as these values are known to be sensitive to the local chemical environment of the resonating nuclei.

Performance evaluation of flexible macrocycle docking in AutoDock.

Macrocycles represent an important class of ligands, both in natural products and designed drugs. In drug design, macrocyclizations can impart specific ligand conformations and contribute to passive permeation by encouraging intramolecular H-bonds. AutoDock-GPU and Vina can model macrocyclic ligands flexibly, without requiring the enumeration of macrocyclic conformers before docking. Here, we characterize the performance of the method for handling macrocyclic compounds, which is implemented and the default behaviour for ligand preparation with our ligand preparation pipeline, Meeko. A pseudoatom is used to encode bond geometry and produce an anisotropic closure force for macrocyclic rings. This method is evaluated on a diverse set of small molecule and peptide macrocycles, ranging from 7- to 33-membered rings, showing little accuracy loss compared to rigid redocking of the X-ray macrocycle conformers. This suggests that for conformationally flexible macrocycles with unknown binding modes, this method can be effectively used to predict the macrocycle conformation.

Surface-dependent band structure variations and bond deviations of GaN.

Density functional theory (DFT) calculations on a tunable number of GaN (0001) planes give an invariant band structure, density of states (DOS) diagram, and band gap of the GaN unit cell. Dissimilar band structures and DOS diagrams are obtained for 1, 3, 5, 7, and 9 layers of GaN (101̄0) planes, but the same band structure as that of the (0001) plane returns for 2, 4, 6, and 8 (101̄0) planes. Furthermore, 1 to 4 layers of GaN (101̄1) planes exhibit dissimilar band structures, but the GaN unit cell band structure is obtained for 5 (101̄1) planes. While there are no changes to the Ga-N bond length and bond geometry for the (0001) planes, the (101̄0) planes present bond length variation and bond distortion with odd numbers of layers. Bond length and bond direction deviations are also obtained for 1 to 4 (101̄1) planes. These results suggest that slight structural deviations may be present near the GaN surface to produce facet-dependent properties, and such atomic position deviations in the surface layer can be observed in various semiconductors.

Viscosity and transport in a model fragile metallic glass

How thermally activated structural excitations quantitatively mediate transport and microplasticity in a model binary glass at the microsecond timescale is revealed using atomistic simulation. These local excitations, involving a stringlike sequence of atomic displacements, admit a far-field shear-stress signature and underlie the transport of free-volume and bond geometry. Such transport is found to correspond to the evolution of a disclination network describing the spatial connectivity of topologically distinct bonding environments, demonstrating the important role of geometrical frustration in both glass structure and its underlying dynamics.

Preferential formation of mono‐dimethyl disulfide adducts for determining double bond positions of poly‐unsaturated fatty acids

AbstractDetermination of double bond positions of unsaturated lipids is fundamental for understanding their biofunctions and biosynthetic pathways. Derivatizing unsaturated lipids with dimethyl disulfide (DMDS) represents a convenient method to yield characteristic ions for determining double bond positions. However, DMDS adduction of poly‐unsaturated lipids often leads to the formation of poly‐ and/or cyclized DMDS adducts, which yield complex mass spectra that are difficult to interpret in terms of double bond positions. Here, we report a room‐temperature, convenient experimental procedure to preferentially form mono‐DMDS adducts for poly‐unsaturated fatty acid methyl esters (FAMEs) with two to five double bonds (c9, c12‐C18:2, t9, t12‐C18:2, c5, c9, c12‐C18:3, c7, c10, c13, c16‐C22:4 and c5, c8, c11, c14, c17‐C20:5). Electron‐impact ionization mass spectra of these mono‐DMDS adducts provide highly diagnostic ions for determining positions of all double bonds. Our approach overcomes the limit of traditional DMDS derivatization methods which are generally limited to mono‐unsaturated molecules. In addition, we show gas chromatography and gas chromatography–mass spectrometry analyses of mono‐DMDS adducts can also provide useful information about double bond geometry, as cis double bonds are prone to isomerize to trans isomers.

Discussion on the microscale geometry as the dominant factor for strength anisotropy in material extrusion additive manufacturing

This paper presents a discussion and interpretation of the findings in the review paper “Fused filament fabrication of polymer materials: A review of interlayer bond” by Xia Gao, Shunxin Qi, Xiao Kuang, Yunlan Su, Jing Li, Dujin Wang [Additive Manufacturing (2020): 101658]. This discussion draws different conclusions based on the microscale filament geometry of interlayer bonds as opposed to molecular-scale bonding (diffusion and entanglement of polymer chains), which is predominantly considered in the review. Four complementary arguments on the matter are proposed, demonstrating that microscale geometry rather than incomplete molecular bonding is the predominant cause of strength anisotropy in material extrusion additive manufacturing (MEAM). These arguments consider the evidence from studies that (i) factored microscale geometry into strength calculation; (ii) eliminated the influence of geometry; (iii) improved the geometry to reduce its impact on strength, and (iv) tested the effect of manually reproduced interlayer geometry in bulk material. Overall, this discussion suggests that the underlying cause of anisotropy in MEAM is filament-scale geometric features (grooves and voids between layers), not the deficient bonding as is often theorised. Drawing upon the evidence in the literature, this discussion proposes that specimens attain bulk material strength for a range of printing conditions and materials.

Fine tuning of hydrogen bond strength in crystals: a case study of O–H–O hydrogen bond in ammonium substituted potassium dihydrogen phosphate

Hydrogen bonds are one of the most enigmatic intermolecular interactions where the strength of interaction depends very intimately on the local environment of the bonded atoms. One can change the entire nature of the interactions by changing its local environment. Many of the enzymatic reactions work by this above-mentioned mechanism. Hence, it is important to understand how changes in the local environment can modify hydrogen bonds. In line with this, complete structural and vibrational investigations on ammonium ion substituted potassium dihydrogen phosphate mixed crystals K0.988(NH4)0.012H2PO4 and (K0.956(NH4)0.044H2PO4) are performed. The behaviour of O–H–O hydrogen bond in these crystals is very sensitive to changes in the local environment. A small change in the concentration of K+ ion has an observable effect on hydrogen bond geometry and hence on the double-well potential energy contour for these bonds. The dynamics of H atom depends on the potential barrier height. It changes gradually with decreasing temperature from predominantly inter-well to completely intra-well dynamics with an intermediate precursor region, where inter-well and intra-well dynamics are important.

Two-Dimensional Functionalized Germananes as Photoelectrocatalysts.

Succeeding graphene, monoelemental two-dimensional (2D) materials such as germanene and silicene, coined as "Xenes", have attracted vast scientific and technological interests. Adding covalently bonded hydrogen on both sides of germanene leads to germanane (i.e., hydrogen-terminated germanene, GeH). Further, the covalent functionalization of germanane allows the tuning of its physical and chemical properties. Diverse variants of germananes have been synthesized, but current research is primarily focused on their fundamental properties. As a case in point, their applications as photo- and electrocatalysts in the field of modern energy conversion have not been explored. Here, we prepare 2D germanene-based materials, specifically germanane and germananes functionalized by various alkyl chains with different terminal groups-germanane with methyl, propyl, hydroxypropyl, and 2-(methoxycarbonyl)ethyl-and investigate their structural, morphological, optical, electronic, and electrochemical properties. The bond geometries of the functionalized structures, their formation energies, and band gap values are investigated by density functional theory calculations. The functionalized germananes are tested as photoelectrocatalysts in the hydrogen evolution reaction (HER) and photo-oxidation of water. The performance of the germananes is influenced by the functionalized groups, where the germanane with -CH2CH2CH2OH termination records the lowest HER overpotentials and with -H termination reaches the highest photocurrent densities for water oxidation over the entire visible spectral region. These positive findings serve as an overview of organic functionalization of 2D germananes that can be expanded to other "Xanes" for targeted tuning of the optical and electronic properties for photo- and electrochemical energy conversion applications.

Liquid-Liquid Phase Separation of Short Histidine- and Tyrosine-Rich Peptides: Sequence Specificity and Molecular Topology.

The increasing realization of the prevalence of liquid-liquid phase separation (LLPS) across multiple length scales of biological constructs, from intracellular membraneless organelles to extracellular load-bearing tissues, has raised intriguing questions about intermolecular interactions regulating LLPS at the atomic level. Squid-beak derived histidine (His)- and tyrosine (Tyr)-rich peptides (HBpeps) have recently emerged as suitable short model peptides to precisely assess the roles of peptide motifs and single residues on the phase behavior and material properties of microdroplets obtained by LLPS. In this study, by systematically introducing single mutations in an HBpep, we have identified specific sticker residues that attract peptide chains together. We find that His and Tyr residues located near the sequence termini drive phase separation, forming interaction nodes that stabilize microdroplets. Combining quantum chemistry simulations with NMR studies, we predict atomic-level bond geometries and uncover inter-residue supramolecular interactions governing LLPS. These results are subsequently used to propose possible topological arrangements of the peptide chains, which upon expansion can help explain the three-dimensional network of microdroplets. The stability of the proposed topologies carried out through all-atom molecular dynamics simulations predicts chain topologies that are more likely to stabilize the microdroplets. Overall, this study provides useful guidelines for the de novo design of peptide coacervates with tunable phase behavior and material properties. In addition, the analysis of nanoscale topologies may pave the way to understand how client molecules can be trapped within microdroplets, with direct implications for the encapsulation and controlled release of therapeutics for drug delivery applications.

The Good, the Bad, and the Twisted Revisited: An Analysis of Ligand Geometry in Highly Resolved Protein-Ligand X-ray Structures.

An analysis of the rotatable bond geometry of drug-like ligand models is reported for high-resolution (<1.1 Å) crystallographic protein-ligand complexes. In cases where the ligand fit to the electron density is very good, unusual torsional geometry is rare and, most often, though not exclusively, associated with strong polar, metal, or covalent ligand-protein interactions. It is rarely associated with a torsional strain of greater than 2 kcal mol-1 by calculation. An unusual torsional geometry is more prevalent where the fit to electron density is not perfect. Multiple low-strain conformer bindings were observed in 21% of the set and, it is suggested, may also lie behind many of the 35% of single-occupancy cases, where a poor fit to the e-density was found. It is concluded that multiple conformer ligand binding is an under-recognized phenomenon in structure-based drug design and that there is a need for more robust crystallographic refinement methods to better handle such cases.