Steric Substituent Constants Research Articles

Remote Steric and Electronic Effects of N-Heterocyclic Carbene Ligands on Alkene Reactivity and Regioselectivity toward Hydrocupration Reactions: The Role of Expanded-Ring N-Heterocyclic Carbenes.

The remote groups in N-heterocyclic carbene (NHC) ligands have a significant influence on metal-catalyzed reactions. We examine how remote bulkiness, electronic groups, and expanded-ring NHCs (ER-NHCs) influence alkene reactivity and regioselectivity toward hydrocupration using density functional theory calculations. The impact of remote steric bulkiness on the Cu-H insertion rate is analyzed, revealing a strong correlation between the steric substituent constant and rate ratio, where a bulky group increases the rate due to reduced steric effects in the transition state (TS). The steric properties of the examined catalysts (with a remote group R2 = CPh3, CHPh2, CH2Ph, CH3, and H) and their corresponding TSs are found to be modulated greatly by the remote steric substitution group and the ring size of the NHC ligand. Enhanced bulkiness enhances the nucleophilic Cu-H moiety. The remote electronic groups have a smaller impact on insertion barrier compared to that of steric hindrance. Furthermore, ER-NHC exploration indicates that NHCs with over five-membered rings have a significantly negative influence on the reaction rate. Finally, with a highly bulky group (R2 = CPh3), anti-Markovnikov insertion preference is attributed to high interaction energy and improved steric properties. Overall, our findings here provide valuable insights for the development of a more effective catalyst in metal-catalyzed reactions.

Thermal Decomposition Kinetics of Bis-Gem-Dinitroethyl Derivatives of N-Nitraminoacetic Acid

Thermal decomposition kinetics of bis-gem-dinitroethyl substituted compounds based on N-nitraminoacetic acid is studied. Structural and kinetic patterns are revealed and a chemical mechanism of decomposition reaction is established, including the primary homolysis of C-NO2 bond in the gem-dinitroethyl fragment. The activation parameters are defined for the initial reaction. The reactivity of the studied compounds was analyzed and quantitative correlations between the logarithms of the rate constant, the activation energies and the steric constants of substituents in the gem-dinitroethyl group were found

Catalytic Pyrolysis of Aliphatic Carboxylic Acids into Symmetric Ketones over Ceria-Based Catalysts: Kinetics, Isotope Effect and Mechanism

Ketonization is a promising way for upgrading bio-derived carboxylic acids from pyrolysis bio-oils, waste oils, and fats to produce high value-added chemicals and biofuels. Therefore, an understanding of its mechanism can help to carry out the catalytic pyrolysis of biomass more efficiently. Here we show that temperature-programmed desorption mass spectrometry (TPD-MS) together with linear free energy relationships (LFERs) can be used to identify catalytic pyrolysis mechanisms. We report the kinetics of the catalytic pyrolysis of deuterated acetic acid and a reaction series of linear and branched fatty acids into symmetric ketones on the surfaces of ceria-based oxides. A structure–reactivity correlation between Taft’s steric substituent constants Es* and activation energies of ketonization indicates that this reaction is the sterically controlled reaction. Surface D3-n-acetates transform into deuterated acetone isotopomers with different yield, rate, E≠, and deuterium kinetic isotope effect (DKIE). The obtained values of inverse DKIE together with the structure–reactivity correlation support a concerted mechanism over ceria-based catalysts. These results demonstrate that analysis of Taft’s correlations and using simple equation for estimation of DKIE from TPD-MS data are promising approaches for the study of catalytic pyrolysis mechanisms on a semi-quantitative level.

Ring-Chain Tautomerism of the Condensation Products of 2-Mercaptobenzohydrazide with Aliphatic and Aromatic Aldehydes: Influence of Electronic and Steric Factors

It has been shown by 1H and 13C NMR spectroscopy that 2-mercaptobenzoyl-hydrazones of aliphatic and aromatic aldehydes exist in solution as tautomeric mixtures of linear and cyclic benzo-1,3,4-thiadiazepine forms. The linear hydrazone form is represented by (E,E')-and (E,Z')-conformational isomers, differing in the disposition relative to the amide C–N bond. Growing bulk of the alkyl substituent at the C=N bond of the aliphatic aldehydes derivatives decreases the fraction of the cyclic tautomer; therewith the logarithms of the constants of the chain-ring tautomeric equilibrium correlate with the ES steric constants of the alkyl substituents. In the series of the aromatic aldehydes 2-mercaptobenzoylhydrazones the linear tautomer prevails, and the logarithms of the tautomeric equilibrium constants KT correlate with the σ-constants of the substituents in the aromatic nucleus.

ChemInform Abstract: Strategy for Molecular Design of Photochromic Diarylethenes Having Thermal Functionality

AbstractReview: [31 refs.

Strategy for Molecular Design of Photochromic Diarylethenes Having Thermal Functionality.

Thermal reactivities of photochromic diarylethene closed-ring isomers can be controlled by the introduction of substituents at the reactive positions. Diarylethenes having bulky alkyl groups undergo thermal cycloreversion reactions. When bulky alkoxy groups are introduced, the diarylethenes have both thermal cycloreversion reactivities and low photocycloreversion quantum yields. Such photochromic compounds can be applied to thermally reusable photoresponsive-image recordings. The thermal cycloreversion reactivity of the closed-ring isomers can be evaluated using specific steric substituent constants and be correlated with the parameters. By introduction of trimethylsilyl or methoxymethyl groups at the reactive positions, the diarylethene closed-ring isomers undergo thermal irreversible reactions to produce by-products at high temperatures. These diarylethenes may be useful for secret-image recordings. Furthermore, thiophene-S,S-dioxidized diarylethenes having secondary alkyl groups at the reactive positions undergo thermal by-product formation reactions, in addition to the photostability of the colored closed-ring isomers. Such materials may be used for light-starting thermosensors. The thermal by-product formation reactivity can be evaluated by the specific substituent constants and theoretical calculations of quantum chemistry. These results supply the strategy for the molecular design of the photochromic diarylethenes having thermal functionality.

Alkyl substituent effects in photochemical and thermal reactions of photochromic thiophene-S,S-dioxidized diarylethenes

Thiophene-S,S-dioxidized diarylethenes introducing various alkyl groups at the reactive positions were newly synthesized. The diarylethenes showed reversible photochromism, whereas the photocycloreversion reaction was suppressed by thiophene-oxidation. The diarylethene closed-ring isomers with secondary alkyl groups at the reactive positions were found to undergo thermal bleaching reactions to produce byproducts. The thermal bleaching reactions were accelerated by introducing a more bulky substituent at the reactive positions. The relationship between the rate constant of the thermal bleaching reactions and the bulkiness of the substituent at the reactive positions can be correlated using a steric substituent constant. Moreover, it was noted that introduction of a methyl group at the 4-position of the thiophene in the oxidized diarylethenes accelerates the thermal byproduct formation. The rate of the thermal bleaching reactions was found to depend on the difference in the ground state energy between the closed-ring isomer and one of the byproducts, as can be estimated by theoretical calculation of the energy level. Such materials can be used in application such as light-starting irreversible thermosensors.

Evaluation of the Reactivity of L-tyrosine in the T-for-H Exchange Reaction at Low Temperature

In order to quantitatively evaluate the internal exposure of tritium(3H or T), both the reactivity of exchangeable and non‐exchangeable Organically Bound Tritium(OBT) must be observed at body temperature. In this study, we assumed the model of exchangeable OBT, and the hydrogen isotope exchange reaction(T-for-H exchange reaction) between L-tyrosine and HTO vapor was observed at 25 and 36 ℃ in the gas-solid system. Applying the A″-McKay plot method to the data obtained in the reaction, the rate constants(k) of the functional groups in the material were obtained and Arrhenius plots were also drawn. In addition, from the Arrhenius plots in the range of 50 - 70 ℃, the estimated rate constants(kex) of 36 and 25 ℃ were obtained by using extrapolation method. Comparing k and kex, following three matters have been found in the T-for-H exchange reaction. (1)Because the value of k was similar to kex, extrapolation method is useful. (2)Applying Taft's equation, polar and steric substituent constants of C7H7O were obtained. (3)The method used in this work is useful for quantitative clarification of the reactivity of the T-for-H exchange reaction, and for the estimation of the internal exposure of exchangeable OBT.

Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors

A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, 1H, 13C and 19F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure–activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.

Systematic study on the thermal cycloreversion reactivity of diarylethenes with alkoxy and alkyl groups at the reactive carbons

The relationship between the thermal cycloreversion reactivity of diarylethenes and the bulkiness of the substituents at the reactive carbons was systematically investigated. Two photochromic diarylethenes, 1,2-bis(2-isobutoxy-5-phenyl-3-thienyl)perfluorocyclopentene (1a) and 1,2-bis(2-neopentoxy-5-phenyl-3-thienyl)perfluorocyclopentene (2a), were newly synthesized and their optical properties and thermal cycloreversion reactivity were examined, because there is insufficient data for diarylethenes with alkoxy groups at the reactive carbons. The steric substituent constant was employed to correlate the relationship between the thermal cycloreversion reactivity of diarylethenes with alkyl and alkoxy groups at the reactive carbons and the bulkiness of the substituent. A good correlation was obtained for the substituent constant using CH2 instead of oxygen in the alkoxy groups. The results indicate that this is a very useful strategy for the design of novel diarylethenes with desired thermal cycloreversion reactivity.

Kinetics and Mechanism of the Oxidation of Some Secondary Alcohols by Benzimidazolium Dichromate

Benzimidazolium dichromate (BIDC), in dimethylsulfoxide, oxidizes secondary alcohols to the corresponding ketones. The reaction is first order with respect to BIDC. The order with respect to alcohol is more than one but less than two. Michaelis - Menten type kinetics were observed with respect to alcohol. The formation constants of the alcohol-BIDC complexes and the rates of their decomposition were determined at different temperatures. The oxidation of deuterated 2-propanol indicated the presence of a substantial primary kinetic isotope effect. The reaction exhibited a second order dependence on hydrogen-ion concentration. The reaction was studied in nineteen organic solvents. The solvent effect was analyzed using multiparametric equations. It was found that the cation-solvating power of the solvent played the major role. The rates of oxidation exhibited an excellent correlation with polar and steric substituent constants. A suitable mechanism has been proposed.

Correlation between Steric Substituent Constants and Thermal Cycloreversion Reactivity of Diarylethene Closed-Ring Isomers

Abstract Two kinds of diarylperfluorocyclopentenes having 5-phenyl-2-propyl-3-thienyl and 2-isobutyl-5-phenyl-3-thienyl group as the aryl groups were newly synthesized, and the thermal stability of their closed-ring isomers was investigated. The bulkiness of the substituent (R) at the reacting positions in photochromic diarylethenes plays an important role in the thermal cycloreversion reactivity of the photogenerated closed-ring isomers. The steric substituent constant was introduced to investigate the relationship between the steric hindrance of the substituent R and the thermal cycloreversion reactivity. We employed three steric substituent constants, Es(R), Esc(R), and v(R) values. We found that there is a good correlation between the Esc(R) value and the thermal cycloreversion reactivity. Furthermore, the Es(CH2R) value has also a good correlation with the thermal cycloreversion reactivity, while Es(R) has no correlation. These results indicate that the steric hindrance has an effect on the thermal cycloreversion and there is no hyperconjugation of the α-hydrogen on the 2-substituent on the thiophene ring. Moreover, the activation energy was also found to be related to the steric substituent constant. These findings would give a new useful strategy to design novel diarylethenes having desired thermal stability.

Remarkable Substituent Effects on the Activation Energy of Silylene Insertion into Silicon–Chlorine Bonds

Insertion reactions of dimethylsilylene (Me(2)Si:) into the silicon-chlorine bond of various substituted chlorosilanes have been computationally studied by using DFT calculations with a 6-31++G(d,p) basis set. All of the insertions investigated herein were exothermic (more than 40 kcal mol(-1)) and proceeded via three-membered cyclic transition states (TS) with one substituent of a chlorosilane in the ring plane and two other substituents out of the plane. Among the two possible concerted insertion pathways, the pathway via a TS with a silylene lone-pair orbital approaching a chlorosilane silicon atom was preferred. Important nucleophilic interactions of silylene lone-pair orbitals with anti-bonding sigma orbitals of Si-Y (in plane) were supported by carrying out a natural bond orbital (NBO) analysis of the reaction. A radical pathway through the initial abstraction of chlorine from chlorosilane by the silylene cannot compete with the preferred concerted pathway. Systematic calculations for SiMe(2) insertion into various chlorosilanes (YR(2)SiCl; Y (in-plane substituent) = H, Me, NH(2), OH, F, SiH(3), PH(2), SH and Cl; R (out-of-plane substituent) = H, Me, iPr and tBu) have revealed remarkable substituent effects on activation free energies (DeltaG(double dagger)). In-plane (Y) substituent effects were mostly electronic. Electron-withdrawing substituents accelerate the insertion through enhanced nucleophilic interaction between silylene lone-pair orbitals with the sigma*(Si-Y) orbital at the TS. The DeltaG(double dagger) values correlate with the sigma(I) constants as a scale of the inductive effect of Y. Out-of-plane (R) substituent effects are mainly steric, and bulky substituents increase the activation free energy . Correlation of the DeltaG(double dagger) values with Taft's steric substituent constants (E(s)) was observed. There was no significant difference in the out-of-plane substituent effects between the electron-withdrawing Cl and the electron-donating Me groups.

Tautomerism and conformational isomerism of mercaptoacetylhydrazones of aliphatic and aromatic aldehydes

Mercaptoacetylhydrazones of aliphatic and aromatic aldehydes exist in the solutions as tautomeric mixtures of open-chain and cyclic 1,3,4-thiadiazine forms. The linear hydrazone form consists of a set of isomers due to the configurational and conformational isomerism. At growing bulk of the alkyl substituent at the C=N bond of the aliphatic aldehydes derivatives decreases the fraction of the cyclic tautomer; therewith the logarithms of the constants of the chain-ring tautomeric equilibrium correlate with the steric constants of the alkyl substituents. In the series of the aromatic aldehydes mercaptoacetylhydrazones the linear tautomer prevails, and the equilibrium position is insignificantlyt affected at variation of the electronic characteristics of the substituents in the aromatic ring.

Artificial neural network modeling of peptide mobility and peptide mapping in capillary zone electrophoresis

Recently, we have developed an artificial neural network model, which was able to predict accurately the electrophoretic mobilities of relatively small peptides. To examine the robustness of this methodology, a 3-3-1 back-propagation artificial neural network (BP-ANN) model was developed using the same inputs as the previous model, which were the Offord's charge over mass term (Q/M 2/3), corrected steric substituent constant ( E s,c) and molar refractivity (MR). The data set consisted of 102 peptides with a larger range of size than that of our earlier report – up to 42 amino acid residues as compared to 13 amino acids in the initial study – that also included highly charged and hydrophobic peptides. The entire data set was obtained from the published result by Janini and co-workers. The results of this model are compared with those obtained using multiple linear regressions (MLR) model developed in this work and the multi-variable model released by Janini et al. Better predictive ability of the BP-ANN model over the MLR indicates the non-linear characteristics of the electrophoretic mobility of peptides. The present model exhibits better robustness than the MLR models in predicting CZE mobilities of a diverse data set at different experimental conditions. To explore the utility of the ANN model in simulation of the CZE peptide maps, the profiles for the endoproteinase digests of melittin, glucagon and horse cytochrome C is studied in the present work.

Kinetic study of hydrolysis of benzoates. Part XXIV—Variation of the ortho substituent effect with solvent in the alkaline hydrolysis of substituted phenyl benzoates

AbstractThe second‐order rate constants k2 (M−1 s−1) for the alkaline hydrolysis of meta‐, para‐ and ortho‐substituted phenyl benzoates, C6H5CO2C6H4X, in aqueous 0.5 M n‐Bu4NBr were measured spectrophotometrically. The dependence of substituent effects, especially ortho inductive, resonance and steric terms on different solvent parameters, was studied using the following equation: where Δlog k=log kX−log kH, σI, σR0 and EsB are the inductive, resonance and steric substituent constants and E, Y and P are the solvent electrophilicity, polarity and polarizability parameters, respectively. In data treatment $\Delta E = E_{\rm S} - E_{{\rm H}_2 {\rm O}}, \ \Delta Y = Y_{\rm S} - Y_{{\rm H}_2 {\rm O}} \ {\rm and} \ \Delta P = P_{\rm S} - P_{{\rm H}_2 {\rm O}}$ were used. The solvent electrophilicity was found to be the main factor responsible for changes in the ortho, para and meta polar substituent effects with medium. The variation of the ortho inductive term with the solvent electrophilicity ES was found to be ca threefold smaller than that for para substituents, whereas the ortho resonance term appeared to vary with solvent very similarly to that for para substituents. The steric term of ortho substituents was found to be approximately independent of solvent parameters. The ortho effect caused by the supplementary inductive effect from ortho position was found to disappear in a solvent whose electrophilic solvating power is comparable to that of 60% aqueous ethanol (E ≈ 13.3). Copyright © 2005 John Wiley & Sons, Ltd.

Prediction of electrophoretic mobilities of peptides in capillary zone electrophoresis by quantitative structure-mobility relationships using the offord model and artificial neural networks

The aim of this work was to explore the usefulness of empirical models and multivariate analysis techniques in predicting electrophoretic mobilities of small peptides in capillary zone electrophoresis (CZE). The data set consists of electrophoretic mobilities, measured at pH 2.5, for 125 peptides ranging in size between 2 and 14 amino acids. Among the existing empirical models, the Offord model (i.e., mu identical with Q/M(2/3)) gave the best correlation for the data set. A quantitative structure-mobility relationship (QSMR) was developed using the Offord's charge-over-mass term (Q/M(2/3)) as one descriptor combined with the corrected steric substituent constant (E(s, c)) and molar refractivity (MR) descriptors to account for the steric effects and bulkiness of the amino acid side chains. The multilinear regression (MLR) of the data set showed an improvement in the predictive ability of the model over the simple Offord's relationship. A 3-4-1 back propagation artificial neural networks (BP-ANN) model resulted in a significant improvement in the predictive ability of the QSMR over the MLR treatment, especially for peptides of higher charges that contain basic amino acids arginine, histidine, and lysine. The improved correlations by the BP-ANN analysis suggest the existence of nonlinear characteristic in the mobility-charge relationships.

Re-examination of Steric Substituent Constants by Molecular Mechanics

Statistical analysis employing the set of the steric constants Ωj,k(Rc) is shown to be very effective in characterizing the substituent steric effect on organic reactions. Ωj,k(Rc) contains several variable parameters which are useful for the diagnosis of the character of steric effect. The parameters controlling the angular, or directional, weight (j,k) and the size of reaction center atom X(Rc) are varied in order to elucidate the characteristics of several steric substituent constants.

Tautomeric and Conformational Isomerism of Mercaptoacetylhydrazones of Methyl Alkyl Ketones

Mercaptoacetylhydrazones of methyl alkyl ketones (Alk = Me, Et, Pr, i-Pr, i-Bu, s-Bu, t-Bu) exist in solutions as a tautomeric mixture of linear and cyclic 1,3,4-thiadiazine forms.The linear hydrazone form exists as a set of conformers caused by restricted rotation of the amide group relative to the C–N bond. It is shown that tautomeric equilibrium constants correlate with the steric constants of the alkyl substituents, ES.

Inductive Electronegativity Scale. Iterative Calculation of Inductive Partial Charges

A number of novel QSAR descriptors have been introduced on the basis of the previously elaborated models for steric and inductive effects. The developed "inductive" parameters include absolute and effective electronegativity, atomic partial charges, and local and global chemical hardness and softness. Being based on traditional inductive and steric substituent constants these 3D descriptors provide a valuable insight into intramolecular steric and electronic interactions and can find broad application in structure-activity studies. Possible interpretation of physical meaning of the inductive descriptors has been suggested by considering a neutral molecule as an electrical capacitor formed by charged atomic spheres. This approximation relates inductive chemical softness and hardness of bound atom(s) with the total area of the facings of electrical capacitor formed by the atom(s) and the rest of the molecule. The derived full electronegativity equalization scheme allows iterative calculation of inductive partial charges on the basis of atomic electronegativities, covalent radii, and intramolecular distances. A range of inductive descriptors has been computed for a variety of organic compounds. The calculated inductive charges in the studied molecules have been validated by experimental C-1s Electron Core Binding Energies and molecular dipole moments. Several semiempirical chemical rules, such as equalized electronegativity's arithmetic mean, principle of maximum hardness, and principle of hardness borrowing could be explicitly illustrated in the framework of the developed approach.