Steric Parameters Research Articles

Rigid and concave, 2,4-cis-substituted azetidine derivatives: A platform for asymmetric catalysis

A series of single enantiomer, 2,4-cis-disubstituted amino azetidines were synthesised and used as ligands for copper-catalysed Henry reactions of aldehydes with nitromethane. Optimisation of ligand substituents and the reaction conditions was conducted. The enantiomeric excess of the formed products was highest when alkyl aldehydes were employed in the reaction (>99% e.e.). The absolute stereochemistry of one representative azetidine derivative salt was determined by analysis of the Flack parameter of an XRD single crystal structure. The origin of selectivity in catalysis was investigated computationally, revealing the importance of the amino-substituent in determining the stereochemical outcome. A racemic platinum complex of a cis-disubstituted azetidine is examined by XRD single crystal structure analysis with reference to its steric parameters, and analogies to the computationally determined copper complex catalyst are drawn. A preliminary example of the use of a cis-disubstituted azetidine scaffold in thiourea H-bonding catalyst is noted in the supporting information.

From a Highly Disordered to a Metastable State: Uncovering Insights of α-Synuclein.

α-Synuclein (αS) is a major constituent of Lewy bodies, the insoluble aggregates that are the hallmark of one of the most prevalent neurodegenerative disorders, Parkinson's disease (PD). The vast majority of experiments in vitro and in vivo provide extensive evidence that a disordered monomeric form is the predominant state of αS in water solution, and it undergoes a large-scale disorder-to-helix transition upon binding to vesicles of different types. Recently, another form, tetrameric, of αS with a stable helical structure was identified experimentally. It has been shown that a dynamic intracellular population of metastable αS tetramers and monomers coexists normally; and the tetramer plays an essential role in maintaining αS homeostasis. Therefore, it is of interest to know whether the tetramer can serve as a means of preventing or delaying the start of PD. Before answering this very important question, it is, first, necessary to find out, on an atomistic level, a correlation between tetramers and monomers; what mediates tetramer formation and what makes a tetramer stable. We address these questions here by investigating both monomeric and tetrameric forms of αS. In particular, by examining correlations between the motions of the side chains and the main chain, steric parameters along the amino-acid sequence, and one- and two-dimensional free-energy landscapes along the coarse-grained dihedral angles γ and δ and principal components, respectively, in monomeric and tetrameric αS, we were able to shed light on a fundamental relationship between monomers and tetramers, and the key residues involved in mediating formation of a tetramer. Also, the reasons for the stability of tetrameric αS and inability of monomeric αS to fold are elucidated here.

Regioselectivity of Radical Addition of Thiols to 1‐Alkenes

The addition of dodecanethiol (1) to 1‐alkenes H2C=CHR that have substituents R = Hex, (CH2)8COOMe, Ph, Bn, cHex, CH2cHex, tBu (2a–2g) with different steric effects was studied. Some few percent of branched Markovnikov addition product 4 was formed in all cases with the exemption of styrene (2c) in addition to linear anti‐Markovnikov product 3 as the main product. The regioselectivities correlate well with the Taft steric parameter ES of the R‐substituent at the alkene. This gives evidence that the regioselective outcome of the radical addition of thiols to 1‐alkenes is mainly steered by the steric effect of the R‐substituent as it is well known for the addition of alkyl radicals to alkenes. In the case of thiol addition, however, the regioselectivity is strongly enhanced by the much faster fragmentation of the intermediate Markovnikov than of the anti‐Markovnikov adduct radical.

Hologram quantitative structure–activity relationship and topomer comparative molecular-field analysis to predict the affinities of azo dyes for cellulose fibers

A hologram quantitative structure–activity relationship (HQSAR) and topomer comparative molecular-field analysis (CoMFA) were performed on 51 molecules that belong to the azo dyes to determine their affinities to cellulose fiber. The best HQSAR model was obtained by using atoms. Hydrogen atoms as a fragment distinction and a fragment size of 3–6 showed a leave-one-out cross-validated correlation coefficient (q2LOO) of 0.849 and a non-cross-validated correlation coefficient (r2) of 0.927. The best topomer CoMFA model with steric and electrostatic field parameters based on three fragments gave satisfactory results (q2LOO = 0.821; r2 = 0.934). External predictions were made on a test set and compared with previously reported models. Topomer CoMFA steric, electrostatic, and HQSAR atomic contribution maps were generated to analyze the structural features of this data set that govern their affinity potency.

Spectral, structural and energetic study of acephate, glyphosate, monocrotophos and phorate: an experimental and computational approach

ABSTRACTIn the current study, experimental (UV–visible, Fourier transform infrared [FTIR], 1H-NMR and scanning electron microscope) and computational (UV–visible, FTIR, 1H-NMR, HOMO–LUMO, steric and geometric parameters) analyses of acephate, glyphosate, monocrotophos and phorate were performed for the first time. Computational studies were performed at the HF/6–311G(d,p) level of theory. It was found that experimental values of UV–visible, FTIR, 1H-NMR and geometric data were in very good agreement with the computational ones. The current study may assist future studies, like spectral analysis, pesticide(s) detection, surface behaviour and decomposition analysis of top selling titled pesticides of world market.

Mechanistic insights into the SN2-type reactivity of aryl-Co(iii) masked-carbenes for C-C bond forming transformations.

Herein we describe the synthesis and characterization of a family of C-metalated aryl-Co(iii) enolates, which can be considered as masked-carbenes, using diazoacetates as coupling partners. These species have been proved to be necessary intermediates in the C(sp2)-C(sp3) bond forming event to obtain cyclic amides, taming the elusive Co(iii)-carbene species. The scope of diazoacetates has been exhaustively examined, varying the nature of the ester and the α-substitution, and a clear preference for electron-poor carbene precursors is observed. Exhaustive experimental and theoretical studies indicate that an unprecedented intramolecular SN2-type process governs the formation of the newly formed C-C bond. Furthermore, the key role of several Lewis acids as carboxylate-activating reagents is further explored by DFT calculations.

Structure-activity modelling of essential oils, their components, and key molecular parameters and descriptors

Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r2 = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development.

Structural characterization and hydrogen sorption properties of the Mg50Ni45Cr5 alloy

The Mg50Ni45Cr5 alloy for hydrogen storage is prepared by mechanical alloying. First, using the X-ray diffraction (XRD) and the scanning electron microscopy (SEM) we examine the morphology and the structure of the substrate. The obtained results highlight the effectiveness of this alloy in loading hydrogen as it is a nanocrystalline and a ductile one. Second, we attempt to justify these expectations using the statistical physic, precisely the model monolayer with two levels of energy, in modeling a hydrogen absorption and desorption isotherms on Mg50Ni45Cr5 alloy at four temperatures T = 275 K, T = 300 K, T = 325 K and T = 350 K. The model has six physicochemical parameters deduced from the fitting of the isotherms, they are divided by two categories of steric and energetic parameters. Thanks to these parameters we compare the absorption and desorption processes, in order to highlight the hysteresis phenomenon encountered during the hydrogen sorption.

Alkane Carbon‐Hydrogen Bond Functionalization as a Tool Toward a Steric Parameter for Hydrotris(pyrazolyl)borate (Tpx) Ligands

AbstractThe effect of a series of hydrotris(pyrazolyl)borate ligands (Tpx) in the regioselectivity of the catalytic functionalization of the secondary carbon‐hydrogen bonds of hexane with ethyl diazoacetate and TpxCuL as the catalysts has led to the definition of the relative steric parameter SPR. The validity of the parameter has been assessed upon its correlation with the regioselectivity observed in several transformations (olefin cyclopropanation, C−H functionalization, C−H amidation), in all cases a good degree of fitting being observed.

Energetics of Saddling versus Ruffling in Metalloporphyrins: Unusual Ruffled Dodecasubstituted Porphyrins

Presented herein is a first major density functional theory (BP86/D3/STO-TZ2P) survey of the energetics of saddling versus ruffling for a wide range of dodecasubstituted metalloporphyrins with M = Ni, Cu, Zn, Pd, and Pt. For the majority of X8TPP (i.e., β-octasubstituted-meso-tetraphenylporphyrin), the calculations indicated a clear preference for the saddled conformation, consistent with a large body of experimental data. The preference for the saddled conformation relative to the ruffled conformation was found to vary from about ∼0.3–0.4 eV for Me8TPP derivatives up to 1 eV for I8TPP and (CF3)8TPP derivatives. For X = Ph, that is, dodecaphenylporphyrins, the saddled and the ruffled conformation are almost equienergetic, with even a slight preference for the ruffled conformation in some cases. This finding provides a satisfactory explanation for the X-ray crystallographic observation of both saddled and ruffled conformations for dodecaphenylporphyrin complexes as well as for spectroscopic evidence for conformational mobility of these complexes in solution. The calculations also indicate near-equienergetic saddled and ruffled conformations for meso-tetraacetylenyltetrabenzoporphyrins, again consonant with key crystallographic findings. By and large, both the energetics and nonplanar distortions of the metalloporphyrin derivatives correlated well with the Charton and Sterimol B1 steric parameters of the peripheral substituents.

Determination of volumetric, steric and excess properties of naphthyl hydroxamic acid derivatives in ethanol between 298.15 and 313.15 K

Densities and refractive indices of three naphthyl hydroxamic acids, N-1-naphthyl-o-ethoxybenzohydroxamic acid (NEBHA), N-1-naphthyl-o-methylbenzohydroxamic acid (N-o-MBHA) and N-1-naphthyl-p-methylbenzohydroxamic acid (N-p-MBHA) were determined in ethanol under atmospheric pressure at T=(298.15 to 313.15K). This study was undertaken to determine molar volume, V, specific molar volume, VS, apparent molar volume, Vϕ, apparent molar volume at infinite dilution, Vϕ0, and slope, SV⁎, based on the Masson's equation. The apparent molar expansibility at infinite dilution, ϕE0, thermal expansion coefficient, α2, and Hepler's constant, (∂2Vϕ0/∂T2)P, have also been calculated from temperature dependence of Vϕ0. The steric parameters such as molar refraction, RM, and polarizability, α, have been determined from the refractive index, n, data. Excess molar volume, VE, excess refractive index, nE, excess molar refraction, RME, and vander Waal constant, b, have also been estimated. These parameters have been used to understand the solute–solute and solute–solvent interactions qualitatively.

Fluorinated nucleosides as an important class of anticancer and antiviral agents.

Fluorine-containing nucleoside analogs (NAs) represent a significant class of the US FDA-approved chemotherapeutics widely used in the clinic. The incorporation of fluorine into drug-like agents modulates lipophilic, electronic and steric parameters, thus influencing pharmacodynamic and pharmacokinetic properties of drugs. Fluorine can block oxidative metabolism of drugs and the formation of undesired metabolites by changing H-bonding interactions. In this review, we focus our attention on chemical fluorination reagents and methods used in the NAs field, including positron emission tomography radiochemistry. We briefly discuss both the cellular biology and clinical properties of FDA-approved and fluorine-containing nucleoside/nucleotide analogs in development as well as common resistance mechanisms associated with their use. Finally, we emphasize pronucleotide strategies used to improve therapeutic outcome of NAs in the clinic.

Tunable, Chemo- and Site-Selective Nitrene Transfer Reactions through the Rational Design of Silver(I) Catalysts

Carbon-nitrogen (C-N) bonds are ubiquitous in pharmaceuticals, agrochemicals, diverse bioactive natural products, and ligands for transition metal catalysts. An effective strategy for introducing a new C-N bond into a molecule is through transition metal-catalyzed nitrene transfer chemistry. In these reactions, a metal-supported nitrene can either add across a C═C bond to form an aziridine or insert into a C-H bond to furnish the corresponding amine. Typical catalysts for nitrene transfer include Rh2Ln and Ru2Ln complexes supported by bridging carboxylate and related ligands, as well as complexes based on Cu, Co, Ir, Fe, and Mn supported by porphyrins and related ligands. A limitation of metal-catalyzed nitrene transfer is the ability to predictably select which specific site will undergo amination in the presence of multiple reactive groups; thus, many reactions rely primarily on substrate control. Achieving true catalyst-control over nitrene transfer would open up exciting possibilities for flexible installation of new C-N bonds into hydrocarbons, natural product-inspired scaffolds, existing pharmaceuticals or biorenewable building blocks. Silver-catalyzed nitrene transfer enables flexible control over the position at which a new C-N bond is introduced. Ag(I) supported by simple N-donor ligands accommodates a diverse range of coordination geometries, from linear to tetrahedral to seesaw, enabling the electronic and steric parameters of the catalyst to be tuned independently. In addition, the ligand, Ag salt counteranion, Ag/ligand ratio and the solvent all influence the fluxional and dynamic behavior of Ag(I) complexes in solution. Understanding the interplay of these parameters to manipulate the behavior of Ag-nitrenes in a predictable manner is a key design feature of our work. In this Account, we describe successful applications of a variety of design principles to tunable, Ag-catalyzed aminations, including (1) changing Ag/ligand ratios to influence chemoselectivity, (2) manipulating the steric environment of the catalyst to achieve site-selective C-H bond amination, (3) promoting noncovalent interactions between Ag/substrate or substrate/ligand to direct C-H functionalization, and (4) dictating the substrate's trajectory of approach to the Ag-nitrene. Our catalysts distinguish between the aminations of various types of C-H bonds, including tertiary C(sp3)-H, benzylic, allylic, and propargylic C-H bonds. Efforts in asymmetric nitrene transfer reactions catalyzed by Ag(I) complexes are also described.

Bioethanol production from fruit processing wastes

Many essential oil components are known to possess broad spectrum antimicrobial activity, including against antibiotic resistant bacteria. These compounds may be a useful source of new and novel antimicrobials. However, there is limited research on the structure-activity relationship (SAR) of essential oil compounds, which is important for target identification and lead optimization. This study aimed to elucidate SARs of essential oil components from experimental and literature sources. Minimum Inhibitory Concentrations (MICs) of essential oil components were determined against Escherichia coli and Staphylococcus aureus using a microdilution method and then compared to those in published in literature. Of 12 essential oil components tested, carvacrol and cuminaldehyde were most potent with MICs of 1.98 and 2.10 mM, respectively. The activity of 21 compounds obtained from the literature, MICs ranged from 0.004 mM for limonene to 36.18 mM for α-terpineol. A 3D qualitative SAR model was generated from MICs using FORGE software by consideration of electrostatic and steric parameters. An r2 value of 0.807 for training and cross-validation sets was achieved with the model developed. Ligand efficiency was found to correlate well to the observed activity (r2 = 0.792), while strongly negative electrostatic regions were present in potent molecules. These descriptors may be useful for target identification of essential oils or their major components in antimicrobial/drug development.

Study of Monomeric Copper Complexes Supported by N-Heterocyclic and Acyclic Diamino Carbenes

The thermal properties of a series of monomeric copper(I) hexamethyldisilazide complexes supported by N-heterocyclic and acyclic diamino carbenes were evaluated to study the impact of N-alkyl substituents and backbone character on volatility and thermal stability of copper amides. The series of complexes were either liquids or solids with melting points in the broad range of 45–184 °C. Vaporization rates were measured by stepped-isothermal TGA experiments and found to be between 110–170 °C. Enthalpies of vaporization were determined to be 63–90 kJ/mol. Temperatures for 1 Torr vapor pressure were estimated to be 143–172 °C, showing a general dependence on molecular weight. The imidazolylidene complexes were thermally unstable with convincing evidence indicating the unsaturated backbone as a point of weakness. The imidazolinylidene complexes showed excellent thermal stability with comparable results for the formamidinylidenes complexes. The steric parameter of the carbene, %VBur, was calculated for all comp...

3D quantıtatıve structure actıvıty relatıonshıp of tetrahydroımıdazo [1,2-a] pyrımıdıne as antımıcrobıal agents

A series 24 tetrahydroimidazo[1,2-a] pyrimidine derivatives were subjected to 3D quantitative structure activity relationship for antimicrobial activity. Partial least square methodology was utilized for the development of QSAR models. Six different QSAR models have been generated for antimicrobial efficiency of tetrahydroimidazo[1,2-a] pyrimidine derivatives against three human pathogens. QSAR models revealed positive influence of steric and electronic parameters on antimicrobial potential - of tetrahydroimidazo[1,2-a] pyrimidine derivatives.

Steric effects on electroosmotic flow in soft nanochannels

A numerical solution is derived of the mixed pressure and electroosmotically driven flow in a soft nanochannel considering the steric effect within electric double layer. The electric potential and the velocity distributions are described by the modified Poisson–Boltzmann equation and the modified Navier–Stokes equation under the conditions of boundary slip and constant charge density on the walls. By using the finite difference method, the numerical solutions of the electric potential, velocity and the volumetric flow rate are obtained. Results show that the electric potential increases with the steric parameter. The velocity decreases with the steric parameter for lower surface charge density, while opposite trend can be found for higher surface charge density. We compare the results of soft and rigid nanochannels and find the velocity in the soft nanochannel is larger than that in the rigid one except for the case of higher surface charge density.

Palladium-Catalyzed Cross-Coupling of Silyl Electrophiles with Alkylzinc Halides: A Silyl-Negishi Reaction.

We report the first example of a silyl-Negishi reaction between secondary zinc organometallics and silicon electrophiles. This palladium-catalyzed process provides direct access to alkyl silanes. The delicate balance of steric and electronic parameters of the employed DrewPhos ligand is paramount to suppressing isomerization and promoting efficient and selective cross-coupling.

Polyimidazolium Salts: Robust Catalysts for the Cycloaddition of Carbon Dioxide into Carbonates in Solvent-Free Conditions.

There is a growing interest in sustainable heterogeneous catalysts based on organic polymers. Here, we describe a series of polyimidazolium salt catalysts, prepared from the direct reaction of arene-bridged bis- and tris-alkyl halides with trimethylsilylimidazole. The polyimidazolium salts were characterized by spectroscopic and analytical techniques and it was found that their morphology and porosity could be controlled by adjusting the steric parameters of the spacer in the alkyl-halide starting materials. Moreover, the polymers are excellent heterogeneous organocatalysts for the cycloaddition of CO2 to epoxides to afford cyclic carbonates at atmospheric pressure under solvent-free conditions. The polymer catalysts exhibit long-term stability and may be recycled and reused at least 10 times.

A closer look at the reactivity between N-heterocyclic carbenes and fluoroalkenes

The fundamental reactivity leading to N-heterocyclic fluoroalkene adducts is explored in detail, featuring a total of 15 N-heterocyclic carbenes (NHCs) with various electronic and steric environments. The activity of these carbenes towards tetrafluoroethylene (TFE), hexafluoropropene (HFP), trifluoroethylene (HTFE) and vinylidene fluoride (VDF) is assessed in THF and toluene. Attempts were made to correlate the observed reactivity with electronic (Tolman Electronic Parameters) and steric (% buried volume) parameters unique to each NHC, but a trend has yet to be fully determined. However, the unique steric constraints of a cyclic (alkyl)(amino)carbene (CAAC) were shown to modify the initial point of nucleophilic attack on HTFE, providing selective transformation to a different adduct than has been observed to date with all reactions involving this fluoroalkene.