Steric Parameters Research Articles

Steric and Solvation Effects on Polymerization Kinetics, Dormancy, and Tacticity of Zr-Salan Catalysts

1-Hexene polymerization using four zirconium-based amine bis(phenolate) catalysts, Zr[2-R-4-tBu-ONNO]Bn2 (where R = methyl (1), ethyl (2), isopropyl (3), and tert-butyl (4)), was examined to establish the effect of ligand sterics on kinetics and stereocontrol of olefin polymerization. For each catalyst, a rich data set was obtained including monomer consumption, molecular weight evolution, end-group analysis, and active site counts. A set of reaction specific rate constants was determined for catalysts 2–4. In addition to the standard elementary reaction steps of initiation, propagation, mis-insertion, and chain transfer, these catalysts undergo isomerization leading to dormancy. This isomerization is particularly prominent in bromobenzene and for less sterically hindered complexes. Across the series 2–4, ligand steric properties have a systematic effect on both insertion and chain transfer rate constants. This relationship was rationalized using the Sterimol steric parameters. The rates of propagation an...

Uncovering Subtle Ligand Effects of Phosphines Using Gold(I) Catalysis.

Herein, we report the integration of simple linear regressions with gold(I) catalysis to interrogate the influence of phosphine structure on metal-catalyzed organic transformations. We demonstrate that observed product ratios in [4 + 3]/[4 + 2] cycloisomerization processes are influenced by both steric and electronic properties of the phosphine, which can be represented by the Au-Cl distance. In contrast, the observed selectivity of a similar [2 + 3]/[2 + 2] cycloisomerization is governed by L/B1, a steric parameter. Using this correlation, we were able to accurately predict the selectivity of a previously untested, Buchwald-type ligand to enhance selectivity for the same transformation. This ligand found further utility in increasing the selectivity of a previously reported gold-catalyzed cycloisomerization/arylation of 1,6-enynes by ~1 kcal/mol.

Theoretical Assessment of Low-Valent Germanium Compounds as Transition Metal Ligands: Can They Be Better than Phosphines or NHCs?

We analyze the key transition metal ligand properties, σ-donor and π-acceptor ability, ligand-to-metal charge transfer, and steric parameters, using theoretical methods in order to examine 144 synthesized low-valent germanium compounds as potential ligands in homogeneous transition metal catalysis. We compare these features to those of currently widely used ligands (carbenes, phosphines). We find that several low-valent germanium compounds discovered lately, especially Ge(0) and double-donor-stabilized Ge(II) compounds, can easily outperform phosphine ligands in σ-donor strength or reach the strength of NHCs. We set up a databank in which one can find the most suitable germanium-based ligand to promote different homogeneous catalytic steps. We present the factors behind the favorable features of low-valent germanium compounds, which may help to design new low-valent germanium compounds with enhanced properties in the future.

Synthesis and Characterization of 1,2‐Azaborine‐Containing Phosphine Ligands: A Comparative Electronic Structure Analysis

The synthesis and characterization of two 1,2‐azaborine‐containing phosphine ligands are described. The structural and electronic parameters of the two ligands were compared with those of their direct all‐carbon analogues using X‐ray crystallography and UV‐photoelectron and IR spectroscopy. Our results indicate that the azaborine‐containing ligands are significantly stronger electron donors than their corresponding carbonaceous counterparts, while the steric parameters remain similar.

Study on the Catalytic Behavior of Bifunctional Hydrogen-Bonding Catalysts Guided by Free Energy Relationship Analysis of Steric Parameters.

Free energy relationship (FER) studies to correlate steric parameters with the enantiocatalytic performance of bifunctional tertiary-amine hydrogen-bonding catalysts, including (S,S)-cyclohexane-1,2-diamine-derived thioureas, Cinchona alkaloid derived thioureas, and (S,S)-cyclohexane-1,2-diamine-derived squaramides, in Michael reactions revealed that the reactions are much favored by catalysts with less bulky N-substituents. The observed FERs are independent of the chiral scaffold and hydrogen-bond donor, and deepen the understanding of current bifunctional hydrogen-bonding catalysts. Moreover, DFT calculations were performed to interpret the observed high reactivities of thioureas with less bulky substituents. In particular, the computations demonstrated the advantage of a benzyl thiourea catalyst, in which an extra CH⋅⋅⋅π interaction between catalyst and substrate is the key factor.

Azolo[1,4]diazepines: the methods of synthesis and structural modification

The literature relating to the methods of synthesis and chemical transformations of azolo[1,4]diazepines (pyrazolo-, imidazo-, triazolo-, isoxazolo-, oxazolo-, isothiazolo- and thiazolodiazepines) currently known have been generalized and systematized. Their role as important substances for the design of compounds with a great pharmacological potential has been noted. The methods of synthesis of pyrazolo[3,4-e][1,4]diazepines, pyrazolo[4,3-e][1,4]diazepines and tri- and tetracyclic pyrazolo[1,4]diazepines based on formation of the diazepine ring in most cases due to transformations of multifunctional pyrazole derivatives have been described in detail. A significant emphasis is focused on the structural functionalization of pyrazolo[1,4]diazepines; this functionalization is a powerful tool to design attractive synthetic and biological derivatives. On the examples of 7-hydroxypyrazole[3,4-e][1,4]diazepines the effect of the reaction conditions, electronic and steric parameters, which control the processes of functionalization of the diazepine nucleus with SH-, NH- and C- nucleophilic reagents, is described. The synthetic potential of 7-arylpyrazole[4,3-e][1,4]diazepin-4-ones as key structures for their direct functionalization in position 4 with chloro-, methylthio-, amino- and hydrazino groups is shown. The methods of preparation and some chemical transformations of imidazo[1,4]diazepines, in particular imidazo[4,5-e][1,4]diazepin-8-ones and 5,8-diones, which in recent years attract great attention of researchers, have been analyzed.

Reactions of palladium(0) olefin complexes stabilized by some different hetero- and homo-ditopic spectator ligands with propargyl halides

Several new allenyl and propargyl complexes have been obtained by oxidative addition with propargyl chlorides of palladium (0) olefin complexes stabilized by N−N, P−P, N−P, N−S. and N−C homo− and hetero−ditopic spectator ligands. The oxidative addition of some of the isolated palladium(0) olefin derivatives with 3−chloro−1−propyne and 3−chloro−1− phenyl−propyne has been investigated and the ensuing tautomeric mixtures bearing propargyl and allenyl fragmenst η1− coordinated isolated. As a consequence of a detailed kinetic study, we have analyzed the influence of the electronic and steric parameters of the involved reactants and hypothesized the mechanism of reaction. The tautomeric rearrangement of one allenyl isomer into its propargyl counterpart was also investigated and in this case the complete determination of all the rate constants involved has been obtained. Beside these studies, two very rare η3−propargyl palladium derivatives have been isolated and characterized.

Redox properties of alkyl-substituted 4-aryl-2,4-dioxobutanoic acids

Redox properties of a set of aryldiketo acids (ADKs), small organic molecules that comprise 2,4-dioxobutanoic acid moiety, were studied. Along with well-known HIV-1 integrase (IN) inhibition, ADKs exert widespread biological activities. The aim of this work was to evaluate the effects of aryl substitutions on the properties of the dioxobutanoic moiety that is involved in key interactions with metal ions within the active sites of target enzymes. The effect of pH on the electronic properties of nine congeners was examined using cyclic voltammetry and differential pulse polarography. The compounds were chosen as a simple set of congeners bearing Me-groups on the phenyl ring, which should not be involved in electrochemical reactions, leaving the diketo moiety as the sole electrophore. The substitution pattern was systematically varied, yielding a set having different torsion between the phenyl ring and the aryl keto group (Ar?C(O)). The protonation state of the ADKs at different pH values was determined from the experimentally obtained pKa values. The results showed that an equal number of protons and electrons were involved in the oxidation and reduction reactions at the surface of the electrode. Quantitative linear correlations were found between the reduction potentials and the energies of the frontier orbitals, calculated for neutral, mono-anionic and the corresponding radical anionic species, and the steric parameter as two independent variables.

QSAR MODELLING OF NEW TRIAZOLOTHIADIAZOLE DERIVATIVES AS ANTIMICROBIALS

In this research, twenty nine analogues having variable inhibition of Escherichia coli were subjected to quantitative structure activity relationship analysis. Various thermodynamic, electronic and steric parameters were calculated using Chem 3D package of molecular modeling software Chem office 8.0. QSAR models were generated employing sequential multiple regression method using in-house statistical program VALSTAT. Statistically significant models with R-values 0.90 were obtained. Models were validated using leave one out and bootstrapping methods. Results obtained shows that stretch energy, dipole-dipole energy, HOMO energy and Non-1, 4 VDW Energy are contributing to biological activity. Findings of present study reveal that substituent those decrease the flexibility of molecule results in increase in antimicrobial potency, aryl substituent would enhance the antimicrobial activity of compounds and presence of electron withdrawing group in structure is favorable for antibacterial activity of triazolothiadiazoles.

Кислотно-основні рівноваги у системах «карбонова кислота – основа – оксиран».

The formation pathways of self- and heteroassociates in the “carboxylic acid – base (tertiary amine / tetraalkylammonium salt) – oxirane” system were investigated. The effect of the steric parameters and solvent characteristics was considered. It was shown that carboxylic acids are highly complexable. The hydrogen-bonded acid dimers, acid – oxirane, and acid – base associates are also capable to form secondary complexes. The dependence of processes of primary and secondary association on solvent polarity and acid-base properties of system components was established. It was stated that the inert aprotic solvents promote primary and secondary complex formation in the “carboxylic acid – base – oxirane” system, but the primary association is the dominant interaction process. The effect of the nucleophilic and base properties of organic nitrogen-containing base on the association degree of the system components was estimated. The decrease of steric hindrances at the nitrogen atom in the base results in decrease of concentration of the complex acid – base, and the temperature decrease has similarly effect. It was established that more nucleophilic and more polar then amines, quaternary ammonium salts tend to form ionic complexes, yet increase of system temperature shifts the equilibrium towards formation of molecular complexes. The existence of all the considered types of hydrogen-bonded complexes was confirmed by experimental spectral methods: IR and UV spectroscopy. The spectroscopic studies were carried in two solvents: non-polar aprotic carbon tetrachloride and polar aprotic epichlorohydrin. The quantitative characteristics of complexes: acid – acid, acid – oxirane, acid – base and their effect on reaction rate and its mechanism were analyzed.

Synthesis of 1,2-Dioxetanes as Thermochemiluminescent Labels for Ultrasensitive Bioassays: Rational Prediction of Olefin Photooxygenation Outcome by Using a Chemometric Approach.

Great interest in new thermochemiluminescent (TCL) molecules, for example, in bioanalytical assays, has prompted the design and synthesis of a small library of more than 30 olefins to be subjected to photooxygenation, with the aim of obtaining new 1,2-dioxetane-based TCL labels with optimized properties. Fluorine atoms on the acridan system remarkably stabilize 1,2-dioxetanes when they are located in the 3- and/or 6-position (4 h and 4 i). On the other hand, 2,7-difluorinated acridan dioxetane (4 j) showed a significantly enhanced fluorescence quantum yield with respect to the unsubstituted dioxetane (4 a). Some of the synthesized olefins did not undergo singlet oxygen addition and a rationale was sought to ease the photooxygenation step, leading to the TCL dioxetanes. A chemometric approach has been adopted to exploit principal component analysis and linear discriminant analysis of the structural and electronic molecular descriptors obtained by DFT optimizations of olefins 3. This approach allows the steric and electronic parameters that govern dioxetane formation to be revealed.

STRUCTURAL OPTIMIZATION OF 6 SUBSTITUTED 2-AMINOBENZOTHIAZOLE DERIVATIVES AS ANTIFUNGAL AGENTS

In the present research fifteen analogues of 6 substituted 2-aminobenzothiazole derivatives displaying variable inhibition of Candida albicans were subjected to quantitative structure activity relationship analysis. Various thermodynamic, electronic and steric parameters were calculated using Chem 3D package of molecular modeling software Chemoffice 8.0. QSAR models were generated employing sequential multiple regression method using in-house statistical program VALSTAT. Statistically significant models with R-values(0.984), R2-(0.9699) and Q2 (0.848) were obtained. Models were validated using leave one out and bootstrapping methods. Results obtained shows that partition coefficient, HOMO energy and VDW Energy are contributing to biological activity. Findings of present study reveals that substituents those alters partition coefficient, HOMO energy and VDW Energy of molecule results in increase in antifungal potency.

Olfactory response modeling of mouse muscone receptor MOR215-1 to binary muscone enantiomers odor by statistical physics models

In this paper, an adsorption modeling has been presented to describe the interactions of a binary mixture of ℓ-muscone and d-muscone with the mouse muscone receptor MOR215-1. The formulation of the 2-dimensional monolayer models with identical and two types of sites for the perceived response of odor binary mixture odor are based on statistical physics and some theoretical hypothesis, in order to model pure and binary mixture dose-response curves. Thanks to the grand canonical ensemble of statistical physics, some pertinent physico-chemical parameters describing the adsorption process were introduced in the analytical model expressions. The results showed a high correlation of the 2-dimensional monolayer model using two types of sites with binary mixture of ℓ-muscone and d-muscone response curve. In this model, six physico-chemical parameters derived from the fitting of the experimental data by a numerical simulation were discussed.Furthermore, these statistical physics models include physico-chemical parameters specific to the respective effects of each compound in the binary mixture, which may help to clarify the inhibitory effects that are often seen in ℓ-muscone and d-muscone mixture through the determination of the involved new steric parameters. In addition, the calculation of the molar adsorption energies showed that the two muscone enantiomers and their racemic were physisorbed onto cell surface neurons.

Enantioselective hydroformylation of 2- and 4-substituted styrenes with PtCl2[(R)-BINAP] + SnCl2 ‘in situ’ catalyst

Two sets of styrenes possessing various substituents either in ortho or para position were hydroformylated in the presence of ‘in situ’ catalyst formed from PtCl2[(R)-BINAP] and tin(II) chloride. The reversal of the absolute configuration of the preferred enantiomers was observed using both sets of substrates by the variation of the reaction temperature in the range of 40–100 °C. In case of the 4-substituted styrenes, the reversal temperature of the enantioselectivity shows correlation with the Hammett substituent constants, i.e., with the electron donor or electron acceptor properties of the para-substituents. This phenomenon was explained by the reversible formation of the Pt-branched alkyl intermediates, leading to the corresponding (R)- and (S)-enantiomers of 2-arylpropanals.Strong substituent effect on the regioselectivity was observed in the hydroformylation of 2-substituted styrenes: the presence of substituents characterised by larger steric parameter resulted in the highly favoured formation of the linear aldehyde. For instance, regioselectivities of 45%, 22% and 7% towards branched aldehyde were obtained with styrene, 2-fluoro- and 2-bromostyrene, respectively, at 80 °C reaction temperature. In addition to the characteristic change of regioselectivity, the reversal of absolute configuration as a function of reaction temperature was also observed.

4-Aminosubstituted 1,6-dyhidropyrazolo[3,4-e][1,4] diazepines: the synthesis, NMR-spectral and quantum-chemical study

The role of the structural modification of 1,4-benzodiazepine systems with dialkylamino groups previously used successfully for a number of important derivatives possessing a complex of specific biological properties has been noted. This paper significantly expands the variety of hetero-annelated diazepines by developing a preparatively convenient synthetic route of new amino substituted pyrazol[3,4-e][1,4]diazepines. For this purpose, the reaction of 4-chloro-1,6-dihydropyrazolo[3,4-e][1,4]diazepines with the primary alkyl (aryl) amines and the secon- dary cycloalkylamines has been studied in detail. It has been found that this interaction occurs under 8-10 hour reflux in ethanol and for the primary and secondary alkylamines it leads to 4-amino-1,6-dihydropyrazolo[3,4-e] [1,4]diazepine hydrochlorides, and in case of aryl amines – to their corresponding free bases with high yields. The reaction of the secondary amines has been shown to be very sensitive to their steric parameters: dietyl- or diisopropylamines do not interact with 4-chloro derivatives of 1,6-dihydropyrazolo[3,4-e][1,4]diazepines. The structure of the compounds synthesized is consistent with the results of elemental analysis, LS/MS-, IR- and NMR-spectra. The COSY and EXSY methods were used for reliable identification of signals of cycloalkylamino substituents of 1,6 dihydropyrazolo[3,4-e][1,4]diazepines. Changes in NMR-spectra during protonation of 5-cycloalkylaminopyrazolodiazepines correspond to the results of quantum chemical simulations, according to them the preferred structure is the one with the protonated nitrogen atom in position 5 of the pyrazolodiazepine system.

ChemInform Abstract: Asymmetric Conjugate Addition of Benzofuran‐2‐ones to Alkyl 2‐Phthalimidoacrylates: Modeling Structure—Stereoselectivity Relationships with Steric and Electronic Parameters.

AbstractThe 3,5‐bis(trifluoromethyl)benzyl substituted compound (THU) and the analogous methyl derivative are found to be suitable catalysts for the Michael addition of 3‐substituted benzofurans and alkyl 2‐phthalimidoacrylates.

Evaluation of the Substrate Scope of Benzoic Acid (De)carboxylases According to Chemical and Biochemical Parameters

The enzymatic carboxylation of phenolic compounds has been attracting increasing interest in recent years, owing to its regioselectivity and technical potential as a biocatalytic equivalent for the Kolbe-Schmitt reaction. Mechanistically the reaction was demonstrated to occur through electrophilic aromatic substitution/water elimination with bicarbonate as a cosubstrate. The effects of the substituents on the phenolic ring have not yet been elucidated in detail, but this would give detailed insight into the substrate-activity relationship and would provide predictability for the acceptance of future substrates. In this report we show how the kinetic and (apparent) thermodynamic behavior can be explained through the evaluation of linear free energy relationships based on electronic, steric, and geometric parameters and through the consideration of enzyme-ligand interactions. Moreover, the similarity between the benzoic acid decarboxylases and the amidohydrolases superfamily is investigated, and promiscuous hydrolytic activity of the decarboxylase in the context of the hydrolysis of an activated ester bond has been established.

Equilibrium modeling of single and binary adsorption of Food Yellow 4 and Food Blue 2 on modified chitosan using a statistical physics theory: new microscopic interpretations

For a good understanding of the single and binary adsorption systems, the use of statistical physics models is paramount. In this research, the monolayer model with two energies and the extended monolayer model with two energies were applied to interpret the single and binary adsorption isotherms of Food Yellow 4 (FY4) and Food Blue 2 (FB2) on modified chitosan at different temperatures. The equilibrium isotherms were constructed experimentally in batch systems at 298, 308, 318 and 328K. The statistical physics models were developed using the grand canonical ensemble containing different steric and energetic physicochemical parameters, which allow the microscopic interpretation of the adsorption process. The adsorption isotherms were interpreted according to these parameters, which were obtained by numerical simulation. The main contribution of this work is to attribute new microscopic interpretations for the adsorption of FY4 and FB2 on modified chitosan, in single and binary systems at different temperatures. A multimolecular and multianchorage process in single and binary system respectively was described by the study of the number of molecules per site. The investigation of the adsorption energy indicated that the electrostatic interaction and hydrogen bond interactions are the dominant contribution describing the adsorption of these dyes for the single and binary adsorption.

Cyclic (Alkyl)(Amino)Carbene Complexes of Rhodium and Nickel and Their Steric and Electronic Parameters.

N-heterocyclic carbenes (NHCs) and cyclic (alkyl)(amino)carbenes (CAACs) are of great interest, as their electronic and steric properties provide a unique class of ligands and organocatalysts. Herein, substitution reactions involving novel carbonyl complexes of rhodium and nickel were studied to provide a deeper understanding of the fundamental electronic factors characterizing CAAC(methyl) , which were compared with the large array of data available for NHC and sterically more demanding CAAC ligands.

Characterization of substituted aryl meroterpenoids from red seaweed Hypnea musciformis as potential antioxidants

The ethyl acetate fraction of red seaweed Hypnea musciformis was purified to yield three substituted aryl meroterpenoids, namely, 2-(tetrahydro-5-(4-hydroxyphenyl)-4-pentylfuran-3-yl)-ethyl-4-hydroxybenzoate (1), 2-2-[(4-hydroxybenzoyl)-oxy]-ethyl-4-methoxy-4-2-[(4-methylpentyl)oxy]-3,4-dihydro-2H-6-pyranylbutanoic acid (2) and 3-((5-butyl-3-methyl-5,6-dihydro-2H-pyran-2-yl)-methyl)-4-methoxy-4-oxobutyl benzoate (3). The structures of these compounds, as well as their relative stereochemistries, were confirmed by exhaustive NMR spectroscopic data analyses. Compound 1 exhibited similar 2,2′-diphenylpicrylhydrazyl radical inhibiting and Fe2+ ion chelating activities (IC50 25.05 and 350.7μM, respectively) as that of commercial antioxidant gallic acid (IC50 32.3 and 646.6μM, respectively), followed by 3 (IC50 231.2 and 667.9μM, respectively), and 2 (IC50 322.4 and 5115.3μM, respectively), in descending order of activities. Structure-activity relationship analysis revealed that the antioxidant activities of these compounds were directly proportional to the steric and hydrophobic parameters. The seaweed derived aryl meroterpenoids might serve as potential lead antioxidative molecules for use in pharmaceutical and food industries.