Steric Hindrance Factors Research Articles

Tandem Electrochemical Oxidation of Polycyclic Aromatic Amines Towards Carbazoles and Phenazine-based Aza-helicenes.

Experimental and theoretical study of the regioselectivity and mechanism of polycyclic aromatic amine (PAA) electrochemical oxidation is important for designing nitrogen doped large π-conjugated functional molecules. Herein, we used binary-, ternary-, and quaternary-fused PAAs as electro-oxidative reaction substrates to investigate the yield changes of carbazole and phenazine based aza-helicene other than oligomers, which were obtained through pyrrole and pyrazine annulation pathways. Combined with the restrained electrostatic potential (RESP) and steric hindrance factor analysis of the substrate, the electron spin density distribution of free radical resonance hybrid and the spin population analysis of the atoms in the structure of each free radical tautomer indicate that the degree of delocalized dispersion of N free radical and the resulting change in the spin density distribution of C free radical tautomers determine the reaction regioselectivity. The potential charge of the K-region, Bay-region, and L-region adjacent to the C(α)-C(β1) bond is higher than that of other regions within the molecule, and the charge in these high RESP regions tends to delocalize more strongly toward electron-deficient N free radicals. Thus, the activity of N-C(α)-C(β1) region is increased, which supports the proposed free radical addition and free radical coupling mechanism for the electro-oxidative reaction of PAA.

Towards modeling of ZrO2 atomic layer deposition at reactor scale based on experimental kinetic approximation

In this study, the growth kinetics of ZrO2 via the atomic layer deposition (ALD) using a mixed alkylamido-cyclopentadienyl zirconium precursor are proposed based on experimental data to evaluate the film growth behavior using reactor-scale simulation. In the ALD process, the hydroxyl concentration on the targeted surface govern the saturated growth per cycle values. However, we found that the bulkiness of remaining ligands on adsorbed species hinders the adsorption of Cp-Zr molecules.Considering this phenomenon, we proposed a kinetic model by calculating the energetic terms to quantify the “steric hindrance effect” of the first elementary surface reaction of CpZr(N(CH3)2)3 precursor (Cp-Zr), which enables the film growth prediction with the reactor-scale computational fluid dynamic (CFD) model.According to the experimental ALD process, the film growth was found to be influenced by the steric hindrance factor, especially at the temperature range from 150 °C to 250 °C, but the hindrance effect decreases with increasing temperature and disappears at 300 °C. The effective activation energy of the adsorption of Cp-Zr molecules on Si substrate was estimated to be 0.175 eV. Further understanding of the kinetic of ZrO2 deposition in this study is estimated to contribute to the optimization of the high-k metal oxides ALD deposition processes.

COSMO-RS predictive screening of type 5 hydrophobic deep eutectic solvents for selective platform chemicals absorption

Platform chemicals are crucial to the development of designer chemicals in industry; however, the utilization of these chemicals is limited from requiring separation from an aqueous phase. Type 5 hydrophobic deep eutectic solvents (HDES) have recently proven their ability to extract various low concentration solutes from aqueous solution. However, identifying a suitable HDES experimentally is a daunting task due to the large number of hydrogen bond donors (HBD), hydrogen bond acceptors (HBA), and their mixing ratio, with the HDES being ever increasing. In this study, Conductor-like Screening MOdel for Real Solvents (COSMO-RS) was utilized for over one hundred HDES and their relative solubilization ability for sorbitol, 5-hydroxymethyl furfural, and levulinic acid. Moreover, energetic mechanisms of solubilization were analyzed through the prediction of sigma profiles, sigma potentials, activity coefficients, and excess enthalpy of absorption. COSMO-RS results show that HBAs with tetra alkyl chains and amino acid-based HBDs are suitable HDES components for absorbing sorbitol, 5-hydroxymethyl furfural, and levulinic acid through a combination of van der Waals and hydrogen bonding interactions. These interactions are quantitatively examined through calculated excess enthalpy predictions, for example tetrabutylammonium bromide and arginine with a compositional ratio of 8:1, respectively, had an excess enthalpy of mixing with HMF of −7.9 kcal/mol despite the steric hindrance factor valuing ∼ 4.0 kcal/mol.

Hydrogen Bond Donor and Unbalanced Ion Pair Promoter-Assisted Gold-Catalyzed Carbon–Oxygen Cross-Coupling of (Hetero)aryl Iodides with Alcohols

We have developed an efficient gold-catalyzed C–O cross-coupling reaction of (hetero)aryl iodides with primary and secondary alcohols via an AuI–AuIII catalytic cycle. This protocol featured moisture/air insensitivity, simple operation, and excellent functional group tolerance. Good yields were obtained regardless of steric hindrance and electronic factor (electron-rich or poor) of substrates, and the chirality of chiral alcohol starting materials could be preserved. Our protocol worked well for both intermolecular and intramolecular couplings. In addition, the RuPhos ligand was applied to gold-catalyzed cross-couplings. An unbalanced ion pair promoter and hydrogen bond donor solvent might be crucial in this transformation.

Single-Atom-Kernelled Nanocluster Catalyst.

To propose the concept of single-atom-kernelled nanocluster, we synthesized a Pd-based trimetal nanocluster with a single-Ag atom-kernel for the first time by introducing some steric hindrance factors and employing a joint alloying strategy that combines the coreduction with an antigalvanic reduction (AGR). Although the AGR-derived Pd-based trimetal nanoclusters with single-silver atom kernels have low contents of gold, they show higher activity and selectivity than those of the bimetal precursor nanocluster in the electrocatalytical reduction of CO2 to CO. Furthermore, it is revealed that the kernel single atoms from both Au4Pd6(TBBT)12 and Au3AgPd6(TBBT)12 are not the active sites for catalysis, but greatly influence the catalytical performance by effecting the electronic configuration. Thus, it is demonstrated that the single-atom-kernelled nanocluster can not only improve the precious metal utilization (even to 100%) but also better the properties and provide insight into the structure-property correlation for metal nanoclusters.

Soft‐wall ion transfer channel accurately predicts sterically hindered ion channel permeability

AbstractWe provide a simple and systematic computational model to study ion channel permeability using density functional theory. While existing permeability models with a hard‐wall steric hindrance factor work reasonably well for large ions, they severely inhibit the permeation of small ions through channel pores. Here, by introducing a steric hindrance factor that allows pore expansion due to intrinsically soft ion transfer channel walls, the new permeability model accurately describes the effect of steric hindrance stemming from the soft and flexible ion channel wall. Most importantly, the soft‐wall ion transfer channel model works for a wide range of ionic radii from fluoride to gluconate. In addition, we show that strong local electrostatic interaction between densely charged ions such as fluoride and bicarbonate and ion channels with ion binding sites significantly promotes the permeation processes.

Impacts of Polar Molecules of Crude Oil on Spontaneous Imbibition in Calcite Nanoslit: A Molecular Dynamics Simulation Study

Spontaneous imbibition is a crucial method for developing tight reservoirs. The interactions between fluid and solid are key to imbibition behavior. In this work, the molecular simulation method was used to study the occurrence state of polar molecules in calcite nanoslit and the mechanisms of their impacts on spontaneous imbibition. The results showed that both adsorption energy and molecular orientation were key parameters for characterization of the occurrence state of polar molecules. The temperature and average area controlled by each polar molecule affected the adsorption energy by changing the molecular orientation, and the quantitative relationship was established by the regression analysis method. During spontaneous imbibition, polar molecules affect imbibition by delaying the advance of water molecules in the first hydration layer, and the degree of delay depends on the synergistic effect of the adsorption energy and the molecular orientation. By coupling the adsorption energy and order parameters, a concept of a steric hindrance factor was proposed. The spontaneous imbibition process in calcite nanoslit can be divided into two periods, a linear period and a plateau period, but it experiences a short elastic period before spontaneous imbibition. The recovery degree of octane in the elastic period is only related to temperature and that in the linear period is related to the temperature and steric hindrance factors. Temperature promotes the diffusion of water molecules to the deep pore and reduces the steric hindrance factor, which further reduces the inhibiting effect on water molecules. Finally, a prediction model for the recovery degree of octane in calcite nanoslit with polar molecules is proposed, which provides theoretical guidance for improving the spontaneous imbibition recovery of tight carbonate reservoirs.

The density, viscosity, speed of sound, excess properties of binary mixtures of linear polydimethylsiloxane and various alkanes at temperatures in the range (288.15–328.15) K

This article describes the binary system composed of linear polydimethylsiloxane (PDMS) and diesel fuel main components n-decane, n-dodecane, n-tridecane and n-tetradecane at atmospheric pressure, and the density, viscosity and speed of sound were measured at 288.15 K, 298.15 K, 308.15 K, 318.15 K and 328.15 K, respectively. Their excess molar volume (VmE), excess viscosity (ηE), excess molar Gibbs free energy (ΔGEm), molar isobaric thermal expansion (EP,m) and excess molar isentropic compressibility (κEs,m) were calculated. The influence of the intermolecular force, steric hindrance, molecular stacking and other factors on the excessive properties of the binary system solution was discussed. The results indicate that with an increase in carbon chain length, the excess molar volume, excess viscosity, molar isobaric thermal expansion and excess molar isentropic compressibility increased and excess molar Gibbs free energy decreased, which probably ascribe to the increase in steric effect and the stronger interactions between homo-molecular than those of hetero-molecular interactions between PDMS and long-chain alkane molecules.

Прогнозирование реакционной активности сульфирующих агентов олеума при сульфировании карбамида

In this work, a research of the reactivity of sulfonating agents of oleum during sulfonation of carbamide was carried out. Cation HSO3+ and sulfur trioxide in monomeric, dimeric, and trimeric forms were chosen as sulfonating agents. The modeling was carried out by the density functional theory (B3LYP5/aug-cc-pVDZ) and the second-order Möller-Plesset perturbation theory (MP2/aug-cc-pVDZ). Simulation was carried out in a vacuum and a polar solvent, which was taken as 100% sulfuric acid. The solvent was taken into account using the COSMO model. The evaluation of the reactivity of sulfonating agents was carried out on the basis of molecular modeling of sulfonating agents and carbamide. The reactivity descriptors were chosen as the reactivity criteria, such as: energies and the location of the highest occupied molecular orbital and lowest unoccupied molecular orbital, charges on atoms, molecular electrostatic potential, absolute hardness and electrophilicity index. It was determined that carbamide is a fairly hard Lewis base, the absolute hardness in vacuum is 6.072, and in a solvent it is 6.635, so charge control is preferable for its sulfonation reaction. Based on this, the greatest preference in the analysis of reactivity indices was given to atomic charges and molecular electrostatic potential. According to the results of the analysis, it was revealed that the highest activity of the studied sulfonating agents is possessed by cation HSO3+, as it has the highest partial charges on atoms (+3.29 in vacuum, +3.38 in a solvent), has the highest electrophilicity (13.45 in a vacuum, 5.35 in a solvent) and does not have steric hindrance factor in contact with the carbamide molecule. Among the forms of sulfur trioxide, preference can be given to both monomeric (highest activity, but there are steric hindrance factor) and trimeric (least steric hindrance factor).

Stereoselective Allylic Alkylation of 1-Pyrroline-5-carboxylic Esters via a Pd/Cu Dual Catalysis.

The asymmetric allylation of 1-pyrroline-5-carboxylic esters has been accomplished through a synergistic Pd/Cu catalyst system under mild reaction conditions. The mechanistic studies suggested that (1) nucleophilic attack is the enantiodiscriminating step; (2) the cooperative action of two chiral reactive species, N-metalated azomethine ylides and π-allylpalladium, is most likely responsible for its high reactivity and excellent enantioselectivity (up to >99% ee); and (3) the steric hindrance and electronic factors of the allylic electrophiles and imino ester substrates are crucial for the formation of the linear products. A series of 3,4-2 H-pyrrole derivatives bearing a quaternary stereogenic center were easily synthesized in high yields and with high to excellent regioselectivity and enantioselectivity.

Kinetic Parameters of Biomass Pyrolysis by TGA

Pyrolysis processes of typical biomass, such as corn stalk and birch chips, were investigated by thermogravimetric analysis (TGA). The apparent activation energy and pre-exponential factor were calculated with the adoption of the improved Coats-Redfern integral method, 46 types of common mechanism functions, and the least square and iterative methods. By applying basic parameters of biomass pyrolysis, a reaction rate constant, activation entropy and activation enthalpy, activation Gibbs free energy, and the steric-hindrance factor were all calculated. Results showed that biomass pyrolysis can be divided into two primary reaction zones (Event 3 and Event 4). Event 3 is focused by cellulose and hemicellulose. Event 4 is oriented by lignin and cellulose. The thermogravimetric curves of the two biomass types under carbon dioxide and nitrogen atmospheres were roughly similar. The reaction mechanism function is 1 - alpha. It is possible to use activation entropy to represent the pre-exponential factor and to use the steric hindrance factor to predict the reaction rate.

Carbohydrate-Conjugated Amino Acid-Based Fluorescent Block Copolymers: Their Self-Assembly, pH Responsiveness, and/or Lectin Recognition.

An effective strategy has been documented to combine both carbohydrate and amino acid biomolecules in a single synthetic polymeric system via a reversible addition-fragmentation chain transfer (RAFT) polymerization technique. The resultant unique block copolymer was engineered to form uniform micelles with the desired projection of either selective or both amino acid/sugar residues on the outer surface with multivalency, providing pH-based stimuli-responsiveness and/or lectin recognition. The self-assembly process was studied in detail by field emission scanning electron microscopy (FE-SEM), dynamic light scattering (DLS), and UV-visible spectroscopy. The enhanced lectin binding behavior was observed for glyconanoparticles with both amino acid/sugar entities on the shell as compared to the only glycopolymer nanoparticle because of the higher steric hindrance factor in the case of only the glycopolymer nanoparticle. Fluorophore conjugation by postpolymerization functionalization was further exploited by fluorescence spectroscopy for evidencing the lectin recognition process.

Sustainable Electrochemistry: From Lignin Processing to Paired Electrolysis Reactions

When evaluating the sustainability of an electrochemical synthesis, the source and efficient use of electricity, the generation of waste byproducts, and the source of chemicals used should be considered in the development of a greener process. Constant current electrochemical oxidation reactions increase functionality of a molecule but are limited in scope based on oxidation potential. This shortcoming disappears when using a chemical oxidant, which can select based on steric hindrance, chirality, chelation control, and other factors. However, a major pitfall of any stoichiometric chemical oxidation reaction is the generation of a stoichiometric reduction byproduct, oftentimes a metal waste product. To circumvent this problem, chemical oxidants can be recycled directly at the anode while generating only H­2 gas at the cathode and can be powered by a simple photovoltaic power supply.1,2 From a green chemistry standpoint, the substrates used in anodic oxidations should have their origins from renewable feedstocks. Lignin, a biopolymer found in wood, has been disassembled into small monomers and converted into substrates for synthesis of heterocyles and quinones.3 Ideally, to maximize efficiency of these and other electrochemical processes, one wants to perform a useful oxidation at the anode simultaneously with a useful reduction at the cathode. Using this idea of a paired electrolysis, electrochemical oxidation of lignin-derived substrates has been coupled with CO2 reduction. In this presentation, the recycling of a variety of chemical oxidants at an electrode using simple photovoltaics as the source of electricity will be discussed. Furthermore, breakdown of lignocellulosic biomass into chemical building blocks for use in paired electrolyses will be explored (Figure 1).

Tuning the Neutral State Color of Blue, Cyan and Green PI-Conjugated Copolymers By Jointly Playing the Acceptor Strength and the Steric Hindrance

Due to their electronic structure, most of pi-conjugated polymers present visible coloration in their neutral state, hence possess a characteristic absorbance in the 400-800nm spectrum. Upon p-doping, this absorption shifts toward longer wavelengths leading to electrochromic properties. Among the colors accessible in the visible palette, the primary cyan is somewhat particular to obtain because two absorption bands are necessary, one around 400nm and a second near 670nm. This can be obtained by synthesizing donor-acceptor (D-A) pi-conjugated copolymers. Moreover during the switching of the material, these two bands have to be concomitantly shifted toward the infrared.1 In this presentation we will present the synthesis and characterizations of four pi-conjugated monomers having D-A-D structure (Scheme 1). The donating units are based on a fixed alkylated propylenedioxythiophenes and accepting units based on benzothiadiazole or quinoxaline units bearing variable substituents. The polymerization is conducted under mild conditions via oxidative coupling using iron III trichloride. The obtained copolymers have tunable optical properties that can be relied to the acceptor strength which control of D-A charge transfer (CT). The optical characterizations allow to extract the CIELAB colorimetric coordinates and experimental HOMO-LUMO energetic levels were obtained from electrochemical characterization. We also used computational chemistry (B3LYP and TD-B3LYP methods) to browse the structures of interesting candidates to achieve successful color control in D-A polymers using model compounds (monomers and trimers). Finally a color/structure relationships provides valuable insights on molecular design principles for this class of copolymers, putting forth the importance of jointly playing the steric hindrance factor and the electron-withdrawing/donating strength of carefully chosen substituents. Figure 1

M1 Protein from GAS Protects against Histone Killing

Histones are an essential element of chromatin structure and necessary for eukaryotic survival. Highly positively charged, histones resemble small, cationicantimicrobial peptides (AMPs) of the mammalian innate immune system. The broad‐spectrum bactericidal action of histones against a variety of bacteria was first described in 1958. More recently, a framework for histone function in host defense in vivo was revealed with the discovery of neutrophil extracellular traps (NETs), DNA and histone‐based structures extruded by neutrophils to entrap and kill bacteria. Here, we explore histone resistance of several Gram‐positive bacterial pathogens and observe that one important human pathogen, group A Streptococcus (GAS), is highly resistant to histone killing. A screen of isogenic GAS mutants lacking various virulence factor genes revealed that the surface‐anchored M1 protein is associated with high‐level histone resistance. Studies utilizing purified protein and heterologous gene expression showed M1 to be both necessary and sufficient to confer histone resistance. The capacity of M1 to sequester histones and promote accumulatation of host fibrinogen as a further steric hindrance factor, blocked histone access to the bacterial cell wall. M1‐mediated histone resistance was correlated with enhanced GAS survival in NETs. This is the first description of a Gram‐positive bacterial resistance mechanism to histone killing, which in turn contributes to NET resistance. Histone resistance is likely a contributing factor to the well‐established virulence role of M1 in invasive GAS infection.This research was supported by NIH grant (AI096837) to PG and VN.

Synthesis and Biological Evaluation of 4-Arylcoumarin Analogues of Combretastatins. Part 2

A series of A-ring variously methoxylated 4-(3-hydroxy-4-methoxyphenyl)coumarins related to combretastatin A-4 was prepared by cross-coupling reactions. Cytotoxicity studies indicated a potent activity against HBL100 cell line. Substitution patterns on A-ring had only a slight effect on antiproliferative activity. For most cytotoxic compounds, the activity as potential modulators of P-gp and BCRP efflux pumps was evaluated. The results show that compounds 2 and 7 were able to restore mitoxantrone accumulation (BCRP) at concentrations similar to that of cyclosporine A. Compound 7 was the most efficient to reverse P-gp activity. All compounds were found to potently inhibit in vitro microtubule formation via a substoichiometric mode of action for the most part. Compounds 1 and 2 were found to have an apparent affinity binding constant similar to that of combretastatin A-4, i.e., 1 × 10 (6) M(-1). The molecular modeling of coumarin derivatives was performed on the basis of the molecular structure of 7, as determined by single-crystal X-ray crystallography. The calculations suggested that the presence of a methoxy group out of the plane of the chromenone moiety is an important steric hindrance factor embedding the accessibility of those molecules inside the binding pocket on tubulin.

Modeling of Nanofiltration of Dye Using a Coupled Concentration Polarization and Pore Flow Model

Concentration polarization and transport through pores are used to explain the permeation of eosin dye through a nanofiltration membrane. Due to the ionic character of the dye, fixed charges in the membrane pores affect the permeation of the dye. Two transport coefficients, namely, hindered coefficients for diffusion and convection, steric hindrance factor of dye, and pore charge density are estimated by minimizing the error involved between the experimental and calculated permeate flux and concentration values. Contributions of electrical migration, convection, and diffusion towards the solute flux, have been quantified. It is found that more negative fixed charges on membrane pores leads to reduced dye concentration in the permeate.

Revealing Atropisomer Axial Chirality in Drug Discovery

An often overlooked source of chirality is atropisomerism, which results from slow rotation along a bond axis due to steric hindrance and/or electronic factors. If undetected or not managed properly, this time-dependent chirality has the potential to lead to serious consequences, because atropisomers can be present as distinct enantiomers or diastereoisomers with their attendant different properties. Herein we introduce a strategy to reveal and classify compounds that have atropisomeric chirality. Energy barriers to axial rotation were calculated using quantum mechanics, from which predicted high barriers could be experimentally validated. A calculated rotational energy barrier of 20 kcal mol(-1) was established as a suitable threshold to distinguish between atropisomers and non-atropisomers with a prediction accuracy of 86%. This methodology was applied to subsets of drug databases in the course of which atropisomeric drugs were identified. In addition, some drugs were exposed that were not yet known to have this chiral attribute. The most valuable utility of this tool will be to predict atropisomerism along the drug discovery pathway. When used in concert with our compound classification scheme, decisions can be made during early discovery stages such as "hit-to-lead" and "lead optimization," to foresee and validate the presence of atropisomers and to exercise options of removing, further stabilizing, or rendering the chiral axis of interest more freely rotatable via SAR design, thereby decreasing this potential liability within a compound series. The strategy can also improve drug development plans, such as determining whether a drug or series should be developed as a racemic mixture or as an isolated single compound. Moreover, the work described herein can be extended to other chemical fields that require the assessment of potential chiral axes.

Nanostructure and amphiphile self-assembly in polar molecular solvents: amides and the “solvophobic effect”

The ability of low molecular weight amides to support amphiphile self-assembly is shown to be a general feature for this class of solvents. This report extends the number of known polar solvents which can support amphiphile self-assembly by five new amides; more than doubling the number of known amides able to serve as amphiphile self-assembly media. The formation of lyotropic liquid crystalline phases by cationic and non-ionic surfactants in these liquid amides is reported. The ability of a solvent to promote amphiphile self-assembly is governed by the "solvophobic effect" and is linked to the solvent cohesiveness. The Gordon parameter which is a measure of the solvent cohesiveness was found to provide a guide to an amides capacity to support lyotropic liquid crystalline phase diversity and thermal stability ranges of those phases. The "solvophobic effect" and steric hindrance factors were compared between amide's and protic ionic liquids possessing analogous chemical structures and also being able to promote amphiphile self-assembly.

Coupled concentration polarization and pore flow modeling of nanofiltration of an industrial textile effluent

A coupled model of concentration polarization and transport of solutes through the pores was used to study the nanofiltration of two dye system and salt (NaCl) in a textile effluent. The transport coefficients, namely, hindered coefficient for diffusion and convection as well as steric hindrance factor of the dyes were estimated by minimizing the error involved between experimental and calculated permeate flux and permeate concentration under various operating conditions. Although the removal of dyes through the membrane was significant (more than 90%), the salt retention was less than 4% due to its very high concentration in the textile effluent. The contributions of electrical migration, convection and diffusion towards the flux of dyes through the pores were quantified. It was found that in case of bulkier dye molecules, diffusive flux was predominant mechanism, which was an order of magnitude higher than the flux due to convection and electrical migration. For smaller salt species, the convective flux was more dominant.