Interactions In Complexes Research Articles

Probing Noncovalent Interactions by Fast Magic-Angle Spinning NMR at 100 kHz and More.

Noncovalent interactions are the basis for a large number of chemical and biological molecular-recognition processes, such as those occurring in supramolecular chemistry, catalysis, solid-state reactions in mechanochemistry, protein folding, protein-nucleic acid binding, and biomolecular phase separation processes. In this perspective article, some recent developments in probing noncovalent interactions by proton-detected solid-state Nuclear Magnetic Resonance (NMR) spectroscopy at Magic-Angle Spinning (MAS) frequencies of 100 kHz and more are reviewed. The development of MAS rotors with decreasing outer diameters, combined with the development of superconducting magnets operating at high static magnetic-field strengths up to 28.2 T (1200 MHz proton Larmor frequency) improves resolution and sensitivity in proton-detected solid-state NMR, which is the fundamental requirement for shedding light on noncovalent interactions in solids. The examples reported in this article range from protein-nucleic acid binding in large ATP-fueled motor proteins to a hydrogen-π interaction in a calixarene-lanthanide complex.

Spectroscopic and computational investigations of isostructural phase transitions in urea 4-carboxyanilinium nitrate having trapped disordered-nitrate ions

Urea 4-carboxyanilinium nitrate (U4-CAN) and its functional groups deuterated counterpart dU4-CAN were studied using infrared vibrational spectroscopy and computational analysis. Using the known frequencies of the parent components the infrared vibrational frequencies of U4-CAN and dU4-CAN were assigned. FTIR study was carried out to understand how the intra-and inter-molecular interactions in the parent components are affected by U4-CAN co-crystal formation. U4-CAN undergoes isostructural phase transition at 359.1 K. Hence FTIR spectra of U4-CAN were also recorded at different temperature in the range 293 K to 368 K. The interesting observation seen with temperature dependent spectra was:(i) the spectral band intensity increased with increasing temperature and (ii) the peak position of almost all bands did not change in the entire temperature range studied. This results corroborate with the reported structural data of U4-CAN were in it is found that the structural phase transition is isostructural. Hence the crystal structure in the range 293 K to 368 K has same space group and differ only in few hydrogen bond interactions. In order to carry out various theoretical calculation of U4-CAN, the crystallographically obtained structure at 293 K was optimized by density functional theory (DFT) with B3LYP/6–311 G basis set. The theoretical calculated vibration spectra were similar to the experimentally obtained FTIR data. The fingerprint plot of U4-CAN obtained using CrystalExplorer 21 software indicated that the most prominent interaction corresponds to the short O···H contact. Noncovalent interaction (NCL) study indicated that the U4-CAN complex has steric, van der Waals and hydrogen bond interactions and the NH⋅⋅⋅⋅⋅O hydrogen bond interaction between NH3+/ NH2 moieties and NO3- was the strongest. From QTAIM calculation the strongest hydrogen bond interaction in U4-CAN complex was for NH.....O and NH.....N interactions.

Anticancer activity of Co(III) complex containing mixed ligand bis(5-phenyl-1,2,4-triazole)-3-sulfinamide and o-phen: Crystal structure, DFT, and Hirshfeld surface analysis

The cobalt complexes have demonstrated potential as antibacterial, antifungal, and anticancer agents, further enhancing their significance in the field of medicinal chemistry. Here, a cobalt(III) complex [Co(ptsm)H2O(o-phen)]·CH3OH containing in situ formed bis(5-phenyl-1,2,4-triazole)-3-sulfinamide (ptsm), 1,10-phenanthroline, and H2O molecule as ligand along with methanol molecule as crystallized solvent has been synthesized and characterized by various spectroscopic and X-ray crystallography techniques. The cobalt complex crystallizes in a triclinic system with space group P-1. The DFT and TD-DFT calculations were also performed to optimize geometry and better understand electronic transitions. The outcomes of quantum chemical calculations (TD-DFT and DFT) match the characteristics of the experiments. Various intermolecular interactions in complex 1 have been quantitively explained with Hirshfeld surface analysis. The MTT assay assessed the cytotoxicity of complex 1 against Dalton's lymphoma (DL) cells, yielding IC50 values of 40 µM. The AO/EtBr dual staining and DAPI staining further confirm the cytotoxic potential of the complex 1.

Structure and interactions of CO2 with reline (a 1:2 choline chloride – Urea mixture) according to quantum chemical calculations and molecular dynamics simulation

Quantum chemical DFT calculations [B3LYP+GD3/6-311++g(2d,2p)] of the structure and interactions in various complexes of CO2 molecule with a choline cation, a chloride anion, urea molecules, a choline chloride ion pair and a 1:2 choline chloride – urea complex were carried out. The contributions of Coulomb and van der Waals interactions were calculated. The QTAIM method was used to evaluate the strength of various bonds. A molecular dynamics simulation of CO2 molecules in reline in the NPT ensemble (1 atm, 298 K) was also carried out. The radial distribution functions of the particle centers of mass, local mole fraction functions, spatial distribution functions, and density profiles were calculated. Stronger interactions, compared to the other DES components, were observed in case of the chloride anion and the CO2 molecule according to the DFT calculations. However, in the system, stronger interactions were observed between the chloride anion and the system components, namely NHCl and OHCl hydrogen bonds. This made the chloride anion inaccessible and unable to interact with the CO2 molecule, according to the MD simulation results. Additionally, the presence of a fairly extensive surface layer containing DES and CO2 molecules was shown.

Modeling Ligands into Maps Derived from Electron Cryomicroscopy.

Deciphering the protein-ligand interactions in a macromolecular complex is crucial for understanding the molecular mechanism, underlying biological processes, and drug development. In recent years, cryogenic sample electron microscopy (cryoEM) has emerged as a powerful technique to determine the structures of macromolecules and to investigate the mode of ligand binding at near-atomic resolution. Identifying and modeling non-protein molecules in cryoEM maps is often challenging due to anisotropic resolution across the molecule of interest and inherent noise in the data. In this article, the readers are introduced to various software and methods currently used for ligand identification, model building, and refinement of atomic coordinates using selected macromolecules. One of the simplest ways to identify the presence of a ligand, as illustrated with the enolase enzyme, is to subtract the two maps obtained with and without the ligand. The extra density of the ligand is likely to stand out in the difference map even at a higher threshold. There are instances, as shown in the case of metabotropic Glutamate receptor mGlu5, when such simple difference maps cannot be generated. The recently introduced method of deriving the Fo-Fc omit map can serve as a tool for validating and demonstrating the presence of the ligand. Finally, using the well-studied β-galactosidase as an example, the effect of resolution on modeling the ligands and solvent molecules in cryoEM maps is analyzed, and an outlook on how cryoEM can be used in drug discovery is presented.

Insights into the DNA and RNA Interactions of Human Topoisomerase III Beta Using Molecular Dynamics Simulations.

Human topoisomerase III beta (hTOP3B) is the only topoisomerase in the human cell that can act on both DNA and RNA substrates. Recent findings have emphasized the physiological importance of hTOP3B and consolidated it as a valuable drug target for antiviral and anticancer therapeutics. Although type IA topoisomerases of different organisms have been studied over the years, the step-by-step interaction of hTOP3B and nucleic acid substrates is still not well understood. Due to the lack of hTOP3B-RNA structures as well as DNA/RNA covalent complexes, computational investigations have been limited. In our study, we utilized molecular dynamics (MD) simulations to study the interactions between hTOP3B and nucleic acids to get a closer look into the residues that play a role in binding DNA or RNA and facilitate catalysis, along with the differences and similarities when hTOP3B interacts with DNA compared to RNA. For this, we generated multiple models of hTOP3B complexed with DNA and RNA sequences using the hTOP3B crystal structure and 8-mer single-stranded DNA and RNA sequences. These models include both covalent and noncovalent complexes, which are then subjected to MD simulations and analyzed. Our findings highlight the complexes' stability, sequence preference, and interactions of the binding pocket residues with different nucleotides. Our work demonstrates that hTOP3B forms stable complexes with both DNA and RNA and provides a better understanding of the enzyme's interaction with different nucleic acid substrate sequences.

Identification of Potent SFRP1 Inhibitors for Colorectal Cancer using a Comprehensive Computational Approach.

The incidence of CRC has increased worldwide over the past decade. The statistics report from WHO highlights the increased severity and fatality rate of CRC among the populations. Wnt/β-catenin is recognized as the resource for cell regeneration and cancer signaling pathways driven by frizzled receptor cofactors. Aberrant regulation of Wnt/β- catenin suppression is an important challenge in treating CRC management. The SFRP1 comprises a cysteine-rich region that is homologous to the putative Wnt-binding sites of Frizzled proteins, with the potential to impede and alter the cascade of Wnt signaling. Indirect regulation, like targeting Wnt antagonist SFRP1, is an alternative strategy to suppress the cancer signals by enhancing the apoptotic activity. Hence, this study aimed to approach the SFRP1 protein as a therapeutic target to inhibit Wnt signaling in colorectal cancer. Further, it aimed to identify the lead compounds against the SFRP1 protein, which inhibit the oncogenic expression of CRC, which might be possible using computational approaches, recognizing the importance of the SFRP1 protein role in CRC. The homology-modeled SFRP1 structure was refined, and virtual screening was performed against the anti-cancer drugs and natural drug databases to find the best hit molecules. The molecular docking, MD, and MMGBSA analysis confirmed the firm binding of SFRP1 complexes to identify the potent CRC inhibitors. The amino acid residues Arg5, Arg11, Ala13, Lys 245, Lys274, Phe147, Pro99, and Ser277 are essential for ligand binding and show similar interactions for SFRP1 complexes. The ADME/T profile for top hits is acceptable in range and obtains the drug-likeness property. The 100ns run for MD simulation confirms the stability of protein complexes. Overall, the findings of this study reveal that the lead compounds screened are capable of inhibiting SFRP1 against CRC. Targeting SFRP1 paves the way for new platforms in the field of cancer and the therapeutic sector for new approachable finds.

Synergism of primary and secondary interactions in a crystalline hydrogen peroxide complex with tin

Despite the significance of H2O2-metal adducts in catalysis, materials science and biotechnology, the nature of the interactions between H2O2 and metal cations remains elusive and debatable. This is primarily due to the extremely weak coordinating ability of H2O2, which poses challenges in characterizing and understanding the specific nature of these interactions. Herein, we present an approach to obtain H2O2–metal complexes that employs neat H2O2 as both solvent and ligand. SnCl4 effectively binds H2O2, forming a SnCl4(H2O2)2 complex, as confirmed by 119Sn and 17O NMR spectroscopy. Crystalline adducts, SnCl4(H2O2)2·H2O2·18-crown-6 and 2[SnCl4(H2O2)(H2O)]·18-crown-6, are isolated and characterized by X-ray diffraction, providing the complete characterization of the hydrogen bonding of H2O2 ligands including geometric parameters and energy values. DFT analysis reveals the synergy between a coordinative bond of H2O2 with metal cation and its hydrogen bonding with a second coordination sphere. This synergism of primary and secondary interactions might be a key to understanding H2O2 reactivity in biological systems.

A computational workflow to determine drug candidates alternative to aminoglycosides targeting the decoding center of E. coli ribosome

The global antibiotic resistance problem necessitates fast and effective approaches to finding novel inhibitors to treat bacterial infections. In this study, we propose a computational workflow to identify plausible high-affinity compounds from FDA-approved, investigational, and experimental libraries for the decoding center on the small subunit 30S of the E. coli ribosome. The workflow basically consists of two molecular docking calculations on the intact 30S, followed by molecular dynamics (MD) simulations coupled with MM-GBSA calculations on a truncated ribosome structure. The parameters used in the molecular docking suits, Glide and AutoDock Vina, as well as in the MD simulations with Desmond were carefully adjusted to obtain expected interactions for the ligand-rRNA complexes. A filtering procedure was followed, considering a fingerprint based on aminoglycoside's binding site on the 30S to obtain seven hit compounds either with different clinical usages or aminoglycoside derivatives under investigation, suggested for in vitro studies. The detailed workflow developed in this study promises an effective and fast approach for the estimation of binding free energies of large protein-RNA and ligand complexes.

Design, Synthesis of 3-(Aryl)-1-(2-p-tolylthiazol-4-yl)prop-2-en-1-ones as Alpha(α)-Amylase Inhibitors.

α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-Vis., FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4 c (IC50=3.8 μM), 4 g (IC50=14.5 μM), and 4 f (IC50=17.1 μM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4 f and 4 h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.

Intermolecular interaction energies with AROFRAG-A systematic approach for fragmentation of aromatic molecules.

Intermolecular interactions with polycyclic aromatic hydrocarbons (PAHs) represent an important area of physisorption studies. These investigations are often hampered by a size of interacting PAHs, which makes the calculation prohibitively expensive. Therefore, methods designed to deal with large molecules could be helpful to reduce the computational costs of such studies. Recently we have introduced a new systematic approach for the molecular fragmentation of PAHs, denoted as AROFRAG, which decomposes a large PAH molecule into a set of predefined small PAHs with a benzene ring being the smallest unbreakable unit, and which in conjunction with the Molecules-in-Molecules (MIM) approach provides an accurate description of total molecular energies. In this contribution we propose an extension of the AROFRAG, which provides a description of intermolecular interactions for complexes composed of PAH molecules. The examination of interaction energy partitioning for various test cases shows that the AROFRAG3 model connected with the MIM approach accurately reproduces all important components of the interaction energy. An additional important finding in our study is that the computationally expensive long-range electron-correlation part of the interaction energy, that is,the dispersion component, is well described at lower AROFRAG levels even without MIM, which makes the latter models interesting alternatives to existing methods for an accurate description of the electron-correlated part of the interaction energy.

Theoretical studies for the detailed electronic structure of organotin(IV) derivatives of 4-fluoroanthranilic acid, X-ray structure of n-dibutyltin bis(4-fluoroanthranilate)

The present study describes the detailed DFT-based electronic structure calculations without any symmetry constraints being performed on di- and triorganotin derivatives of 4-fluoroanthranilic acid (AFA), viz. Me2SnL2 (1), n-Bu2SnL2 (2), Me3SnL (3), and Ph3SnL (4) (where L= monoanion of AFA). The structural and atomic charge analysis have confirmed the previously reported our experimental results, i.e. bicapped tetrahedral and distorted tetrahedral geometry for di- and triorganotin derivatives, respectively, and all the complexes 1–4 contain a positively charged central tin atom surrounded by a negatively charged system. The single crystal X-ray structure of complex 2 (n-Bu2SnL2) also suggests that AFA acts as a monoanion and bidentate ligand resulting a bicapped tetrahedral environment around tin. Various population analysis such as Mulliken (MPA), Hirshfeld (HPA), and natural population analysis (NPA) have been employed to calculate the charges at all the atoms. A finite difference approximation method has been used to explain the charge distribution within the studied complexes 1–4 based on the conceptual global and local reactivity DFT-based descriptions, frontier molecular-orbital analysis (FMOA), and molecular electrostatic potential maps (MEP). Further, the conceptual DFT-based global reactivity descriptors and frontier molecular orbital analysis show that the interactions between CT-DNA and complexes 1–4 may be groove binding or electrostatic. The integral equation formalism-polarizable continuum model (IEF-PCM) has been employed to calculate the UV–visible spectra of 1–4 in the solvent field, whereas the same in the gas phase has been obtained with the help of time-dependent DFT (TD-DFT) at the same level of theory. The intramolecular charge distribution in 1–4 has been investigated with the help of natural bond orbital (NBO) analysis. The topological and energetic parameters at the selected bond critical points in the coordination sphere of complexes 1–4 have been calculated using atoms-in-molecules (AIM) theory. The analysis of different kinds of non-covalent interactions (NCI) in complexes 1–4 has also been investigated.

Structural Diversity and Rare η1 Cu-C Interactions in CuI Complexes of 1,2,3-Triazole-Functionalized Bisphosphines.

This manuscript describes the synthesis of copper complexes of 1,2,3-triazolyl-phosphines: o-Ph2P(C6H4){1,2,3-N3CC6H5)C(PPh2)} (L1), (C6H5){1,2,3-N3C(C6H4(o-PPh2))-C(PPh2)} (L2), 3-Ph2P(C5H3N){1,2,3-N3C(C6H5)C(PPh2)} (L3), o-Ph2P(C6H4){1,2,3-N3C(C5H5N)C(PPh2)} (L4), and {(3,5-Ph2PC6H4-o)21,2,3-N3CCH} (L5). The reactions of L1-L3 with CuI salts afforded dimeric complexes having the general formula [Cu2(μ -X)2L2] (L = L1, X = Cl, Br and I: 1 - 3; L= L2, X = Cl, Br and I: 4- 6; L = L3; X = Cl, Br, and I: 7-9). The reaction of L4 with CuI in a 1:2 molar ratio afforded 1D-coordination polymer [{(CuI)2{o-Ph2P(C6H4){1,2,3-N3C(C5H5N)C(PPh2)}-μ-((k1-N)(k2-P,P))}}]n (10). The reaction of L5 with cuprous halides (CuX) (X = Br, I) yielded mononuclear complexes [CuX{(3,5-Ph2PC6H4-o)21,2,3-N3CCH}-κ2P,P] (X = Br, 12; I, 13). Crystal structures of complexes 12 and 13 showed close interactions between CuI and the triazole C7 carbon. These relatively short Cu···C7 separations may be due to the η1-C interaction (dπ-pπ bond) between the triazolic carbon atom (via pz orbital) and CuI or three-centered two-electron interaction between CuI and the triazolic C-H bond. The existence of the Cu···C interaction was further evinced by the QTAIM analysis in compounds 12 and 13.

Chiral Heterometallic Cu8Ln4 Complexes with Enantiopure Schiff Base Ligands: Synthesis, Structural, Spectroscopic and Magnetic Studies.

The enantiomerically pure Schiff base ligands H2L-S and H2L-R yield chiral heterometallic dodecanuclear complexes of the form [Cu8Ln4(OH)8(OMe)4(O2CBut)8(L-S or L-R)4(H2O)4] where LnIII=Gd (1S), Tb (2S), Dy (3S, 3R), Ho (4S, 4R), Er (5S) or Y (6S, 6R) and H2L=(S or R)-2-{[(1-hydroxypropan-2-yl)imino]methyl}-6-methoxyphenol. The complexes are isomorphous and crystallize in the non-centrosymmetric polar space group C2 in enantiomeric conformation. The chirality of the Schiff base ligands originates from the respective S- or R- enantiomer of 2-aminopropan-1-ol, is imparted to the complexes and to the crystals that belong to non-centrosymmetric space group. The chirality and enantiomeric conformation of all complexes are retained in dmso solutions as confirmed by Circular Dichroism spectra which consist of mirror images, expected for enantiomeric pairs. All complexes consist of four distorted cubane-like subunits [Cu2Ln2(μ3-OH)2(μ3-OMe)(μ3-OR)], which share the LnIII ions and result in a cyclic distorted tetragonal arrangement; each edge of the {LnIII 4} quadrilateral is occupied by two μ-OH- ions that further bridge to a CuII ion. Magnetic susceptibility measurements revealed ferromagnetic interactions for 3S with LnIII=Dy and antiferromagnetic interactions for all other complexes. AC susceptibility data of 3S under 1 kOe external dc field indicate slow magnetic relaxation phenomena below 2 K.

Membrane Heteroreceptor Complexes as Second-Order Protein Modulators: A Novel Integrative Mechanism through Allosteric Receptor-Receptor Interactions.

Bioluminescence and fluorescence resonance energy transfer (BRET and FRET) together with the proximity ligation method revealed the existence of G-protein-coupled receptors, Ionotropic and Receptor tyrosine kinase heterocomplexes, e.g., A2AR-D2R, GABAA-D5R, and FGFR1-5-HT1AR heterocomplexes. Molecular integration takes place through allosteric receptor-receptor interactions in heteroreceptor complexes of synaptic and extra-synaptic regions. It involves the modulation of receptor protomer recognition, signaling and trafficking, as well as the modulation of behavioral responses. Allosteric receptor-receptor interactions in hetero-complexes give rise to concepts like meta-modulation and protein modulation. The introduction of receptor-receptor interactions was the origin of the concept of meta-modulation provided by Katz and Edwards in 1999, which stood for the fine-tuning or modulation of nerve cell transmission. In 2000-2010, Ribeiro and Sebastiao, based on a series of papers, provided strong support for their view that adenosine can meta-modulate (fine-tune) synaptic transmission through adenosine receptors. However, another term should also be considered: protein modulation, which is the key feature of allosteric receptor-receptor interactions leading to learning and consolidation by novel adapter proteins to memory. Finally, it must be underlined that allosteric receptor-receptor interactions and their involvement both in brain disease and its treatment are of high interest. Their pathophysiological relevance has been obtained, especially for major depressive disorder, cocaine use disorder, and Parkinson's disease.

Computational analysis of affinity dynamics between the variants of SARS-CoV-2 spike protein (RBD) and human ACE-2 receptor

The novel coronavirus SARS-CoV-2 resulted in a significant worldwide health emergency known as the COVID-19 pandemic. This crisis has been marked by the widespread of various variants, with certain ones causing notable apprehension. In this study, we harnessed computational techniques to scrutinize these Variants of Concern (VOCs), including various Omicron subvariants. Our approach involved the use of protein structure prediction algorithms and molecular docking techniques, we have investigated the effects of mutations within the Receptor Binding Domain (RBD) of SARS-CoV-2 and how these mutations influence its interactions with the human angiotensin-converting enzyme 2 (hACE-2) receptor. Further we have predicted the structural alterations in the RBD of naturally occurring SARS-CoV-2 variants using the tr-Rosetta algorithm. Subsequent docking and binding analysis employing HADDOCK and PRODIGY illuminated crucial interactions occurring at the Receptor-Binding Motif (RBM). Our findings revealed a hierarchy of increased binding affinity between the human ACE2 receptor and the various RBDs, in the order of wild type (Wuhan-strain) < Beta < Alpha < Gamma < Omicron-B.1.1.529 < Delta < Omicron-BA.2.12.1 < Omicron-BA.5.2.1 < Omicron-BA.1.1. Notably, Omicron-BA.1.1 demonstrated the highest binding affinity of -17.4 kcal mol−1 to the hACE2 receptor when compared to all the mutant complexes. Additionally, our examination indicated that mutations occurring in active residues of the Receptor Binding Domain (RBD) consistently improved the binding affinity and intermolecular interactions in all mutant complexes. Analysis of the differences among variants has laid a foundation for the structure-based drug design targeting the RBD region of SARS-CoV-2.

Computational analysis of substituent effects on proton affinity and gas-phase basicity of TEMPO derivatives and their hydrogen bonding interactions with water molecules

The study investigates the molecular structure of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and its derivatives in the gas phase using B3LYP and M06-2X functional methods. Intermolecular interactions are analyzed using natural bond orbital (NBO) and atoms in molecules (AIM) techniques. NO2-substituted TEMPO displays high reactivity, less stability, and softer properties. The study reveals that the stability of TEMPO derivatives is mainly influenced by LP(e) → σ∗ electronic delocalization effects, with the highest stabilization observed on the oxygen atom of the nitroxide moiety. This work also considers electron density, atomic charges, and energetic and thermodynamic properties of the studied NO radicals, and their relative stability. The proton affinity and gas-phase basicity of the studied compounds were computed at T = 298 K for O-protonation and N-protonation, respectively. The studied DFT method calculations show that O-protonation is more stable than N-protonation, with an energy difference of 16.64–20.77 kcal/mol (22.80–25.68 kcal/mol) at the B3LYP (M06-2X) method. The AIM analysis reveals that the N–O…H interaction in H2O complexes has the most favorable hydrogen bond energy computed at bond critical points (3, − 1), and the planar configurations of TEMPO derivatives exhibit the highest EHB values. This indicates stronger hydrogen bonding interactions between the N–O group and water molecules.

Unveiling the underappreciated: The bonding features of C-H⋯S-S interactions observed from rotational spectroscopy.

The C-H⋯S-S interactions are fundamentally important to understand the stability of biomacromolecules and their binding with small molecules, but they are still underappreciated. Herein, we characterized the C-H⋯S-S interactions in model molecular complexes. The rotational spectra of the complexes of diethyl disulfide with CH2CH2 and CH2CHF were measured and analyzed. All the detected structures are mainly stabilized by a C-H⋯S-S hydrogen bond, providing stabilization energies of 2.3-7.2 kJ mol-1. Incidental C-H⋯π or C-H⋯F interactions enhance the stabilization of the complexes. London dispersion, which accounts for 54%-68% of the total attractions, is the main driving force of stabilization. The provided bonding features of C-H⋯S-S are crucial for understanding the stabilizing role of this type of interaction in diverse processes such as supramolecular recognition, protein stability, and enzyme activity.

Dispersion Control over Molecule Cohesion: Exploiting and Dissecting the Tipping Power of Aromatic Rings.

ConspectusWe have learned over the past years how London dispersion forces can be effectively used to influence or even qualitatively tip the structure of aggregates and the conformation of single molecules. This happens despite the fact that single dispersion contacts are much weaker than competing polar forces. It is a classical case of strength by numbers, with the importance of London dispersion forces scaling with the system size. Knowledge about the tipping points, however difficult to attain, is necessary for a rational design of intermolecular forces. One requires a careful assessment of the competing interactions, either by sensitive spectroscopic techniques for the study of the isolated molecules and aggregates or by theoretical approaches. Of particular interest are the systems close to the tipping point, when dispersion interactions barely outweigh or approach the strength of the other interactions. Such subtle cases are important milestones for a scale-up to realistic multi-interaction situations encountered in the fields of life and materials science. In searching for examples that provide ideal competing interactions in complexes and small clusters, aromatic systems can offer a diverse set of molecules with a variation of dispersion and electrostatic forces that control the dominant and peripheral interactions. Our combined spectroscopic and theoretical investigations provide valuable insights into the balance of intermolecular forces because they typically allow us to switch the aromatic substituent on and off. High-resolution rotational spectroscopy serves as a benchmark for molecular structures, as correct calculations should be based on correct geometries. When discussing the competition with other noncovalent interactions, obvious competitors are directional hydrogen bonds. As a second counterweight to aryl interactions, we will discuss aurophilic/metallophilic interactions, which also have a strong stabilization with a small number of atoms involved. Vibrational spectroscopy is most sensitive to interactions of light atoms, and the competition of OH hydrogen bonds with dispersion forces in a molecular aggregate can be judged well by the OH stretching frequency. Experiments in the gas phase are ideal for gauging the accuracy of quantum chemical predictions free of solvent forces. A tight collaboration utilizing these three methods allows experiment vs experiment vs theory benchmarking of the overall influence of dispersion in molecular structures and energetics.

Multi-omics analysis reveals novel loci and a candidate regulatory gene of unsaturated fatty acids in soybean (Glycine max (L.) Merr)

BackgroundSoybean is a major oil crop; the nutritional components of soybean oil are mainly controlled by unsaturated fatty acids (FA). Unsaturated FAs mainly include oleic acid (OA, 18:1), linoleic acid (LLA, 18:2), and linolenic acid (LNA, 18:3). The genetic architecture of unsaturated FAs in soybean seeds has not been fully elucidated, although many independent studies have been conducted. A 3 V multi-locus random single nucleotide polymorphism (SNP)-effect mixed linear model (3VmrMLM) was established to identify quantitative trait loci (QTLs) and QTL-by-environment interactions (QEIs) for complex traits.ResultsIn this study, 194 soybean accessions with 36,981 SNPs were calculated using the 3VmrMLM model. As a result, 94 quantitative trait nucleotides (QTNs) and 19 QEIs were detected using single-environment (QTN) and multi-environment (QEI) methods. Three significant QEIs, namely rs4633292, rs39216169, and rs14264702, overlapped with a significant single-environment QTN.ConclusionsFor QTNs and QEIs, further haplotype analysis of candidate genes revealed that the Glyma.03G040400 and Glyma.17G236700 genes were beneficial haplotypes that may be associated with unsaturated FAs. This result provides ideas for the identification of soybean lipid-related genes and provides insights for breeding high oil soybean varieties in the future.