Steric Interactions Research Articles

Atropisomerism Observed in Galactose-Based Monosaccharide Inhibitors of Galectin-3 Comprising 2-Methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione.

Galectin-3 (Gal-3) is a carbohydrate binding protein that has been implicated in the development and progression of fibrotic diseases. Proof-of-principal animal models have demonstrated that inhibition of Gal-3 is a potentially viable pathway for the treatment of fibrosis─with small molecule Gal-3 inhibitors advanced into clinical trials. We hereby report the discovery of novel galactose-based monosaccharide Gal-3 inhibitors comprising 2-methyl-4-phenyl-2,4-dihydro-3H-1,2,4-triazole-3-thione (compound 20) and 4-phenyl-4H-1,2,4-triazole (compound 15). Notably, hindered rotation caused by steric interaction between the 3-thione and ortho-trifluoromethyl group of compounds 20, 21 induced formation of thermodynamically stable atropisomers. Distinct X-ray cocrystal structures of 20 and 21 were obtained, which clearly demonstrated that the configuration of 21 proscribes a key halogen bonding σ-hole interaction of 3-chloro with carbonyl oxygen of Gly182, thereby leading to significant loss in potency. Ultimately, 20 and 15 were evaluated in mouse pharmacokinetic studies, and both compounds exhibited oral exposures suitable for further in vivo assessment.

Molecular dynamics modelling of interacting magnetic nanoparticles for investigating equilibrium and dynamic ensemble properties

Magnetic nanoparticles have the potential to be used in various biomedical applications, including magnetic drug targeting and hyperthermia for cancer treatment. In both cases, precise prediction of the local particle concentration is required to plan a successful therapy, which is a challenging task due to several complex flow phenomena. Computational macroscopic and microscopic models have been developed to support this process, but they have limitations in terms of interactions implementation, micromagnetic dynamics or computational costs. This study aims to develop a model that can represent micromagnetic dynamics and being employed to study equilibrium properties of particle ensembles in viscous media. Therefore, a kinetic Monte Carlo method in combination with Langevin equations is used. So, magnetization dynamics and mechanical motion can be simulated in combination very efficiently. The new model is validated with another model based on the stochastic Landau-Lifshitz-Gilbert equation. Various interaction potentials like Van der Waals, steric and electrostatic interactions are included to study their specific influence on structural properties. Also, methods to control the errors while integrating the equations of motion and using the Ewald method for calculating interaction quantities are implemented. As a validation we studied equilibrium and time dependent properties of non-interacting particle ensembles as well as errors made by the Ewald-method used for interaction quantities calculation. In all studies we found very good agreement of the simulation results with the theoretical predictions. The developed models can now be used for investigating equilibrium and dynamic properties of ferrofluids, or more general for biomedical research for magnetic drug targeting, hyperthermia, or imaging techniques. Furthermore, the new hybrid model can be also used for simulations in the range of milliseconds with reasonable computational effort.

Density functional theory and spectroscopic analysis of stigmasterol from Garcinia wightii: Deciphering its inhibitory potential against drug-resistant tuberculosis via insilico molecular docking and molecular dynamics simulations

This study investigates the molecular structure and electronic properties of stigmasterol, isolated from Garcinia wightii, using density functional theory (DFT) alongside experimental techniques including FT-IR, FT-Raman, UV–Vis, 1H and 13C NMR spectroscopy. Theoretical predictions are compared with experimental results, facilitated by vibrational energy distribution analysis for unambiguous vibrational wavenumber assignments. Natural bond orbitalanalyzes reveal donor-acceptor bond energies and electron densities, while Fukui functions identify reactive sites susceptible to electrophilic and nucleophilic attacks. Electronic properties are further explored through various analyzes, unveiling reactive surface sites. Non-covalent interactions are examined using reduced density gradient analysis. Assessment of absorption, distribution, metabolism, and excretion attributes aids in drug discovery efforts. Molecular docking studies against 20 target proteins for antitubercular screening show a stable glide score of -9.52 kcal/mol for the protein 4FDO (Mycobacterium tuberculosis DprE1 in complex with CT319). Molecular dynamics simulations over 100 ns indicate the stability of the ligand-protein complex, suggesting its potential as an antituberculosis agent. Stigmasterol's structural, vibrational, electronic, and topological properties are thoroughly investigated, revealing its ring skeleton with a flexible isooctyl side chain, adhering to C1 point group symmetry. Steric and stereo electronic interactions play crucial roles in conformation and binding to target proteins. Theoretical and experimental analyzes align, confirming the compound's bioactive properties. This comprehensive investigation underscores stigmasterol's potential as a tuberculosis treatment option, providing valuable insights into its structural characteristics and therapeutic possibilities.

Molecular Interactions Between Hexanal Schiff Bases and Boron Nanocages: A DFT Approach

This study explores the interactions between hexanal Schiff bases and a B12N12 nanocage, employing density functional theory (DFT) calculations to deepen our understanding of noncovalent bonds. Hexanal, a key component in tea, plays a vital role in prolonging the shelf-life of various plant-based products by inhibiting phospholipase-D. Our research initially focused on synthesizing Schiff bases through the condensation of hexanal with nucleobases and an amino acid. We then conducted a series of DFT calculations, including geometry optimizations, frontier molecular orbital (FMO), natural bond orbital (NBO) and noncovalent interactions (NCI) assays, using Gaussian 16 and ORCA 5.0.2 software packages. This study reveals that hexanal Schiff bases form stable complexes with the B12N12 nanocage, exhibiting notable dative coordinate bonding. The FMO analysis indicates a significant energy gap variation among the complexes, with CSB2 showing the lowest energy gap, hinting at its high reactivity. In the LED assay, CSB2 demonstrates the lowest decomposition energy, highlighting its potential stability. The AIMD simulations provide insights into the electronic motions of these complexes, underscoring their dynamic nature. Our NBO analysis offers a comprehensive view of the electron distribution within these complexes, emphasizing the significance of nitrogen and boron atoms in the bonding process. The NCI assay sheds light on the predominant van der Waals and steric interactions contributing to the stability of the complexes. This investigation provides a detailed account of the NCI between hexanal Schiff bases and the B12N12 nanocage. The findings not only contribute to the field of noncovalent bonding in inorganic-fullerene structures but also open avenues for future applications in material science and molecular engineering.

Ion steric interactions and electrostatic correlations on electro-osmotic flow in charged nanopores with multivalent electrolytes

Ion steric interactions and electrostatic correlations on electro-osmotic flow in charged nanopores with multivalent electrolytes

Extra-Annulated Chlorophyll Derivatives by Scholl Reaction.

The ferric chloride assisted Scholl reaction of methyl (3,5-dimethoxyphenyl)carbonyl-pyropheophorbide-a produced an extra-annulated, didehydrogenated chlorophyll derivative with a six-membered ring fused at the pyrrole A-ring. The steric interaction of the substituents on the additional tetralone and B-rings induced molecular helicity. The helically cyclized stereoisomers were separated by recrystallization, and their (P/M)-stereochemistry was confirmed by circular dichroism spectra. The distortion of their chlorin π-systems broadened electronic absorption bands to cover all visible regions and reach the near-infrared region.

2'-O-Alkyl-N 3-Methyluridine Functionalized Passenger Strand Improves RNAi Activity by Modulating the Thermal Stability.

Herein, we have demonstrated that the siRNA activity could be enhanced by incorporating the guide strand in the RISC complex through thermodynamic asymmetry caused by m3U-based destabilizing modifications. A nuclease stability study revealed that 2'-OMe-m3U and 2'-OEt-m3U modifications slightly improved the half-lives of siRNA strands in human serum. In the in vitro gene silencing assay, 2'-OMe-m3U modification at the 3'-overhang and cleavage site of the passenger strand in anti-renilla and anti-Bcl-2 siRNA duplexes were well-tolerated and exhibited improved gene silencing activity. However, gene silencing activity was attenuated when these modifications were incorporated at position 3 in the seed region of the antisense strand. The molecular modeling studies using these modifications at the seed region with the MID domain of hAGO2 explained that the 2'-alkoxy group makes steric interactions with the amino acid residues of the hAGO2 protein.

A holistic insight on stability and transport of hematite colloid: Role of various environmental factors

Hematite colloids (Hem) could carry pollutants into deep underground environments and its potential ecological risk needs to be evaluated. This study investigated the aggregation and transport behavior of Hem under different solution pH, electrolyte concentration and humic acid (HA) concentration. Rising the electrolyte concentration would shrink the double electric layer of Hem, weaken the electrostatic repulsion and promote the aggregation of Hem. The critical coagulation concentration (CCC) of Hem was higher at pH 5 (48.83 mM) than pH 10 (24.70 mM), implying that Hem were more stable under acidic conditions than under alkaline conditions. The addition of HA increased the negative charge of Hem and improved the electrostatic repulsion between colloid and sand surface, thus intensifying the stability and mobility of Hem. High HA concentration (≥ 0.5 mg/L) had little effect on the surface charge of Hem, indicating that electrostatic repulsion was not the dominant, however increasing HA significantly improve the stability and transport of Hem by stimulating the steric hindrance interaction. The effect of HA on the transport of Hem under acidic condition was significantly higher than that under alkaline condition because HA changed the surface charge of Hem from positive to negative under acidic condition, so that the electrostatic repulsion between the colloid and sand surface increased sharply and accompanied by a significant penetration. This study exhibited a holistic view on the aggregation and transport behavior of Hem in typical soil environment, and extended the understanding of co-transport potential mechanisms of colloids with contaminants and/or nutrients.

Unveiling the molecular insights of 2-(carboxymethyl) benzoic acid: A density functional theory approach towards structural and biological attributes

Nowadays density functional theory (DFT) is one of the best methods to explore the vibrational modes and structure of the biological system. Quantum mechanical calculations are performed using gas phase and different solvents (DMSO, methanol and water). The derived global reactive parameters, structural and topological study provides the clear insight of the 2-(Carboxymethyl) benzoic acid. Depth studies of DFT proves the existence of hydrogen bonds between donor and acceptor in the compound, which is supportive for the biological applications. In this paper, different experimental and computational simulated FT-IR, FT-Raman, UV–Vis spectral studies are used to explicate vibration assignments of the 2-(Carboxymethyl) benzoic acid. Experimentally observed vibrational frequency is compared with theoretically simulated spectrum. B3LYP method with 6–311++G (d, p) basis set is used in DFT to optimize the 2-(Carboxymethyl)benzoic acid structure. The most stable lower energy conformer is identified using potential energy surface (PES) analysis using Gaussian 16 W software. ESP, HOMO-LUMO, NBO, and QTAIM calculations have evinced an adequate electronic characterization of 2-(Carboxymethyl) benzoic acid. Further, van der Waals and steric interactions among 2-(Carboxymethyl) benzoic acid have been discussed with the help of RDG study. Hirshfeld surface studies establish the existing various interaction among molecules and total packing arrangement of the crystal structure. Due to the high biological activity score, 2-(Carboxymethyl) benzoic acid is a good therapeutic candidate. Lipophilicity analysis of 2-(Carboxymethyl)benzoic acid clearly explicates the bioactivity properties and its effective drug applications. Further, molecular docking investigates that the compound can be used as anticancer medication. The detailed DFT study of the 2-(Carboxymethyl) benzoic acid justified its biological applications of the present communication. The calculated NLO parameters of 2-(Carboxymethyl)benzoic acid evidenced for good efficacy in diverse filed application has been discussed.

POTRA domains of the TamA insertase interact with the outer membrane and modulate membrane properties

The outer membrane (OM) of gram-negative bacteria serves as a vital organelle that is densely populated with OM proteins (OMPs) and plays pivotal roles in cellular functions and virulence. The assembly and insertion of these OMPs into the OM represent a fundamental process requiring specialized molecular chaperones. One example is the translocation and assembly module (TAM), which functions as a transenvelope chaperone promoting the folding of specific autotransporters, adhesins, and secretion systems. The catalytic unit of TAM, TamA, comprises a catalytic β-barrel domain anchored within the OM and three periplasmic polypeptide-transport-associated (POTRA) domains that recruit the TamB subunit. The latter acts as a periplasmic ladder that facilitates the transport of unfolded OMPs across the periplasm. In addition to their role in recruiting the auxiliary protein TamB, our data demonstrate that the POTRA domains mediate interactions with the inner surface of the OM, ultimately modulating the membrane properties. Through the integration of X-ray crystallography, molecular dynamic simulations, and biomolecular interaction methodologies, we located the membrane-binding site on the first and second POTRA domains. Our data highlight a binding preference for phosphatidylglycerol, a minor lipid constituent present in the OM, which has been previously reported to facilitate OMP assembly. In the context of the densely OMP-populated membrane, this association may serve as a mechanism to secure lipid accessibility for nascent OMPs through steric interactions with existing OMPs, in addition to creating favorable conditions for OMP biogenesis.

Electrostatic Surface Potentials and Chalcogen-Bonding Motifs of Substituted 2,1,3-Benzoselenadiazoles Probed via 77Se Solid-State NMR Spectroscopy.

Chalcogen bonds (ChB) are moderately strong, directional, and specific non-covalent interactions that have garnered substantial interest over the last decades. Specifically, the presence of two σ-holes offers great potential for crystal engineering, catalysis, biochemistry, and molecular sensing. However, ChB applications are currently hampered by a lack of methods to characterize and control chalcogen bonds. Here, we report on the influence of various substituents (halogens, cyano, and methyl groups) on the observed self-complementary ChB networks of 2,1,3-benzoselenadiazoles. From molecular electrostatic potential calculations, we show that the electrostatic surface potentials (ESP) of the σ-holes on selenium are largely influenced by the electron-withdrawing character of these substituents. Structural analyses via X-ray diffraction reveal a variety of ChB geometries and binding modes that are rationalized via the computed ESP maps, although the structure of 5,6-dimethyl-2,1,3-benzoselenadiazole also demonstrates the influence of steric interactions. 77Se solid-state magic-angle spinning NMR spectroscopy, in particular the analysis of the selenium chemical shift tensors, is found to be an effective probe able to characterize both structural and electrostatic features of these self-complementary ChB systems. We find a positive correlation between the value of the ESP maxima at the σ-holes and the experimentally measured 77Se isotropic chemical shift, while the skew of the chemical shift tensor is established as a metric which is reflective of the ChB binding motif.

Structural Modification and Biological Evaluation of 2,8-Disubstituted Adenine and Its Nucleosides as A2A Adenosine Receptor Antagonists: Exploring the Roles of Ribose at Adenosine Receptors.

Building on the preceding structural analysis and a structure-activity relationship (SAR) of 8-aryl-2-hexynyl nucleoside hA2AAR antagonist 2a, we strategically inverted C2/C8 substituents and eliminated the ribose moiety. These modifications aimed to mitigate potential steric interactions between ribose and adenosine receptors. The SAR findings indicated that such inversions significantly modulated hA3AR binding affinities depending on the type of ribose, whereas removal of ribose altered the functional efficacy via hA2AAR. Among the synthesized derivatives, 2-aryl-8-hexynyl adenine 4a demonstrated the highest selectivity for hA2AAR (Ki,hA2A = 5.0 ± 0.5 nM, Ki,hA3/Ki,hA2A = 86) and effectively blocked cAMP production and restored IL-2 secretion in PBMCs. Favorable pharmacokinetic properties and a notable enhancement of anticancer effects in combination with an mAb immune checkpoint blockade were observed upon oral administration of 4a. These findings establish 4a as a viable immune-oncology therapeutic candidate.

Field theory of active chiral hard disks: a first-principles approach to steric interactions

A first-principles approach for active chiral hard disks is presented, that explicitly accounts for steric interactions on the two-body level. We derive an effective one-body equation for the joint probability distribution of positions and angles of the particles. By projecting onto the angular modes, we write a hierarchy for the lowest hydrodynamic modes, i.e. particle density, polarisation, and nematic tensor. Introducing dimensionless variables in the equations, we highlight the assumptions, which—though inherent—are often included implicit in typical closure schemes of the hierarchy. By considering different regimes of the Péclet number, the well-known models in active matter can be obtained through our consideration. Explicitly, we derive an effective diffusive description and by going to higher orders in the closure scheme, we show that this first-principles approach results in the recently introduced Active Model B +, a natural extension of the Model B for active processes. Remarkably, here we find that chirality can change the sign of the phenomenological activity parameters.

Unveiling the Nature of lignin's Interaction with Molecules: A Mechanistic Understanding of Adsorption of Methylene Blue Dye.

The valorization of lignin into advanced materials for water and soil remediation is experiencing a surge in demand. However, it is imperative that material research and manufacturing be sustainable to prevent exacerbating environmental issues. Meeting these requirements necessitates a deeper understanding of the role of lignin's functional groups in attracting targeted species. This research delves into the interaction mechanisms between lignin and organic molecules, using the adsorption of the cationic dye Methylene Blue (MB+) as a case study. Herein, we aim to quantitatively estimate the contribution of different interaction types to the overall adsorption process. While carbonyl groups were found to have no significant role in attraction, carboxylic groups (-COOH) exhibited significantly lower adsorption compared with hydroxyl groups (-OH). Through alternately blocking aliphatic and phenolic -OH groups, we determined that 61% of the adsorption occurred through hydrogen bonding and 38% via electrostatic interactions. Performance studies of modified lignin along with spectroscopic methods (XPS, FTIR) confirmed the negligible role of π-π interactions in adsorption. This study offers fundamental insights into the mechanistic aspects of MB adsorption on lignin, laying the groundwork for potential modifications to enhance the performance of lignin-based adsorbents. The findings underscore the importance of hydroxyl groups and provide a roadmap for future studies examining the influence of steric factors and interactions with other organic molecules.

Interfacial Behavior of Biodegradable Poly(lactic-co-glycolic acid)-Pluronic F127 Nanoparticles and Its Impact on Pickering Emulsion Stability.

Biodegradable nanoparticle-based emulsions exhibit immense potential in various applications, particularly in the pharmaceutical, cosmetic, and food industries. This study delves into the intricate interfacial behavior of Pluronic F127 modified poly(lactic-co-glycolic acid) (PLGA-F127) nanoparticles, a crucial determinant of their ability to stabilize Pickering emulsions. Employing a combination of Langmuir balance, surface tension, and diffusion coefficient measurements, we investigate the interfacial dynamics of PLGA-F127 nanoparticles under varying temperature and ionic strength conditions. Theoretical calculations are employed to elucidate the underlying mechanisms governing these phenomena. Our findings reveal a profound influence of temperature-dependent Pluronic layer behavior and electrostatic and steric interactions on the interfacial dynamics. Nonlinear changes in surface tension are observed, reflecting the interplay of these factors. Particle aggregation is found to be prevalent at elevated temperatures and ionic strengths, compromising the stability and emulsification efficiency of the formed emulsions. This work provides insights into the rational design of stable and efficient biodegradable nanoparticle-based Pickering emulsions, broadening their potential applications in various fields.

Molecular-Induced Steric Shape Separation of Nano Geometries

The separation of specific-shaped nanoparticles from particle mixtures is important for the construction of particle domains with shape-specific characteristics. On the other hand, shape-based particle separation techniques have not received as much attention as size-based techniques. The shape separation effect of molecule-coated nanoparticles is primarily dependent on short-range steric interaction. The surfactant’s geometrical arrangement determines the position of the nanoparticle’s various crystallographic facets; this also determines how the various shapes are organized throughout the nanoparticle self-assembly process. In addition to smooth surfaces with a fixed droplet contact line and a stable environment, the self-assembled shape separation effect has been observed on surfaces with wettability stripe patterns and fluctuating environments where the droplet contact line behaves stick–slip-like during the evaporation process. The shape separation of spheres and rods is strongly influenced by steric interactions. Since shape-dependent transport properties exist in such nano-crystalline domains, it is important to understand the shape separation effect.

Zr-BTB nanosheets assist in optimizing the structure of forward osmosis membranes to enhance the lithium concentration performance

Recently, low-energy forward osmosis (FO) technology has been employed in the lithium concentration stage during the extraction of lithium from brine sources. The interlayer FO membrane is renowned for its exceptional structural characteristics; however, challenges remain in selecting suitable interlayer materials and exploring their control mechanisms on amine monomers. As interlayer materials, traditional 3D nanomaterials are prone to detachment, while traditional 2D materials without micropores can increase the transmission resistance of water molecules. This study introduces a novel FO membrane utilizing Zr-BTB nanosheets with 5.4 Å micropores as the interlayer material. Based on detection and simulation calculations, it was found that the increase in steric hindrance and interaction forces jointly slowed the diffusion of amine monomers in the presence of the Zr-BTB interlayer. This results in a thinner separation layer, facilitating water transport. The interlayer also plays crucial roles in preventing defective pore formation in the separation layer and assisting in intercepting salt ions. The Zr-BTB interlayer membrane exhibited a water flux of 29.14 L m−2 h−1 and a reverse salt flux of 0.16 g m−2 h−1, which are superior to those of many FO membranes reported in the field. The prepared membrane also has excellent performance in lithium concentration applications, and its separation mechanism was explored by MD simulations.

Active transport of a passive colloid in a bath of run-and-tumble particles

The dispersion of a passive colloid immersed in a bath of non-interacting and non-Brownian run-and-tumble microswimmers in two dimensions is analyzed using stochastic simulations and an asymptotic theory, both based on a minimal model of swimmer-colloid collisions characterized solely by frictionless steric interactions. We estimate the effective long-time diffusivity D\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathscr {D}}$$\\end{document} of the suspended colloid resulting from its interaction with the active bath, and elucidate its dependence on the level of activity (persistence length of swimmer trajectories), the mobility ratio of the colloid to a swimmer, and the number density of swimmers in the bath. We also propose a semi-analytical model for the colloid diffusivity in terms of the variance and correlation time of the net fluctuating active force on the colloid resulting from swimmer collisions. Quantitative agreement is found between numerical simulations and analytical results in the experimentally-relevant regime of low swimmer density, low mobility ratio, and high activity.

Steric interaction of iridium sites towards efficient oxygen and hydrogen evolution

Transition metal materials that loaded with trace of Iridium (Ir) are widely accepted as effective catalysts for oxygen evolution (OER) and hydrogen evolution reaction (HER), in which the Ir atoms exposed on the surface can directly affect the electrocatalytic reaction. However, this neglects the Ir – Ir interaction of distinct locations, which may be benefit for the fine-tuning of electronic structure. Herein, we changed the locations (surface and inside) of Ir atoms in the cobalt oxide (Co3O4@NC), and investigated their alkaline OER and HER performances. Combined with X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS) and theoretical calculations, we infer that the steric interaction induced by the surface – internal Ir sites can weaken the Ir-O bond and optimize the adsorption of intermediates on catalyst surface with a negative shift of d-band center, enabling the surface-Ir sites with lower energy barrier for water dissociation and hydrogen adsorption for HER. Therefore, the as-prepared Irw-Co3O4@NC with surface − inside Ir distribution significantly improve the HER without degrading OER performance, with low overpotential of −173 / −71 mV for HER at −10 mA/cm2 in 0.1 M KOH / 1.0 M KOH, and 244 / 249 mV at 10 mA/cm2 for OER.

Distribution of Density of States in Organic Field–Effect Transistors Based on Polymer Dielectrics

AbstractThe distribution of density of states (DOS) holds fundamental importance in determining charge transport within organic field–effect transistors (OFETs). Herein, the modulation of DOS distribution in OFET devices is demonstrated by altering the chain conformation of the polymer dielectrics. A rapid film‐formation technique, specifically the spin‐casting method, is used to fabricate the dielectric layer using poly(methyl methacrylate) (PMMA). This method allows for the retention of some memory of the chain conformations from the solution to the resulting dry film. This memory effect is employed to prepare thin PMMA films with different local chain conformations by adjusting the quality of the solvent. Good solvent forms solidified films with a reduced amount of gauche conformer in the PMMA chain, resulting in a narrow DOS distribution width. Consequently, the device exhibited enhanced charge mobility and a reduced subthreshold swing. The observed change in the width of the DOS distribution can be attributed to the alteration of the local energy state of the semiconductor, induced by the local chain conformation of PMMA dielectrics through electrostatics and steric interactions.