Hammett Σp Constants Research Articles

Zooming in on the hydrated imidazoline ring expansion: Factors influencing the rate of N → N′ aroyl migration in N-aroyl-N-(hetero)aryl ethylenediamines

The influence of electronic factors on the rates of N → N′ aroyl migration in N-aroyl-N-(hetero)aryl ethylenediamines has been examined. Electron-withdrawing substituents on the aroyl group were found to weakly accelerate the reaction (in linear correlation with the Hammett σp constants). Much stronger influence came from the nitrogen-bound aromatic group which gave a strong linear correlation with the Hammett σp− constants. For electron-deficient heteroaromatics and nitroaromatics, the migration was nearly instantaneous in basic medium. These findings will significantly impact the planning of mechanistically related transformations of N-(2-aminoethyl) lactams through the hydrated imidazoline ring expansion (HIRE) process.

Effect of substituents in hydroxyl radical-mediated degradation of azo pyridone dyes: Theoretical approaches on the reaction mechanism

Understanding the degradation behavior of azo dyes in photocatalytic wastewater treatment is of fundamental and practical importance for their application in textile-processing and other coloration industries. In this study, quantum chemistry, as density functional theory, was used to elucidate different degradation pathways of azo pyridone dyes in a hydroxyl radical (HO•)-initiated photocatalytic system. A series of substituted azo pyridone dyes were synthesized by changing the substituent group in the para position of the benzene moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The effect of dye molecular structure on the photocatalytic degradation reaction mechanism was analyzed and quantification of substituent effects on the thermodynamic and kinetics parameters was performed. Potential energy surface analysis revealed the most susceptible reaction site for the HO• attack. The calculated reaction barriers are found to be strongly affected by the nature of substituent group with a good correlation using Hammett σp constants and experimentally determined reaction rates. The stability of pre-reaction complexes and transition state complexes were analyzed applying the distortion-interaction model. The increased stability of the transition state complexes with the distancing from the substituent group has been established.

Rotational barrier and electron-withdrawing substituent effects: Theoretical study of -conjugation in para-substituted anilines

The rotational barrier RB around C–NH2 bond between the minimum and maximum states of 84 electron-withdrawing groups at para-position in aniline were studied at the density functional wB97X-D/6-31G** level. The rotational barrier was found to correlate strongly with shortening of the C–NH2 bond, increase of flattening of NH2 group, decrease in negative natural charge on amino nitrogen, increase in minimum ionization potential around lone pair of amino nitrogen, increase in maximum (positive) electrostatic potential on amino hydrogens, increase in NH2 stretching frequencies, and increase in stabilization energy. The rotational barrier was also found to correlate well with empirical pKa and Hammett σp constants. The rotational barrier is shown to be a reliable quantum mechanical approach to measure p-conjugation in para-substituted anilines. Based on RB a quantitative scale is constructed for the ability of electron-withdrawing substituents to resonate with aniline. A quinone-like structure has been proposed for stronger electron-withdrawing substituents where an extension of resonance stabilization requires the simultaneous presence of electron donor (NH2) and electron-withdrawing groups.

Synthesis and emissive properties of a series of tetrahydro (imidazo[1,5-a]pyrid-3-yl)phenols: a new class of large Stokes shift organic dyes

A series of 2-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-3-yl)phenols with different substituents (R) in the para position with respect to the hydroxyl group, was synthesized. The photophysical properties of these species have been investigated in dichloromethane solution: they displayed intense fluorescence when excited with UV light (310–340 nm), with λmax of emission varying in the range 430–530 nm and lifetime decay of few nanoseconds. A very large Stokes shift (up to 189 nm) and high absolute quantum yields (up to 0.72) were recorded for most of the compounds. Moreover, good tuning of the emission is observed according to the electronic features of the substituent R, and a linear correlation was found between the emission maxima of the compounds and the Hammett σp constants of R. Two of these (tetrahydroimidazo[1,5-a]pyridin-3-yl)phenols were then chosen for preliminary measurements of their photophysical properties when dispersed in a host polymeric matrix (PMMA).

The Influence of para Substituents in Bis(N-Heterocyclic Carbene) Palladium Pincer Complexes for Electrocatalytic CO2 Reduction.

The effect of modifying the pyridyl para position of lutidine-linked bis(N-heterocyclic carbene) Pd pincer complexes is studied both experimentally (R = OMe, H, Br, and COOR) and computationally, showing a strong effect on the first reduction potential of the complex and allowing the reduction potential to be tuned over a wide range in relation to the Hammett σp constant of the para substituent. The effect of the pyridyl para substituent on electron density of the metal center, frontier orbital energies, and dissociation energy of the trans ligand are also investigated in the context of reactivity with CO2 through electrochemical characterization of the complexes under N2 and CO2 and controlled potential electrolysis experiments where CO2 is reduced to CO.

Further structure-activity relationships study of substituted dithiolethiones as glutathione-inducing neuroprotective agents.

BackgroundParkinson’s disease is a neurodegenerative disorder associated with oxidative stress and glutathione depletion. The induction of cellular glutathione levels by exogenous molecules is a promising neuroprotective approach to limit the oxidative damage that characterizes Parkinson’s disease pathophysiology. Dithiolethiones, a class of sulfur-containing heterocyclic molecules, are known to increase cellular levels of glutathione; however, limited information is available regarding the influence of dithiolethione structure on activity. Herein, we report the design, synthesis, and pharmacological evaluation of a further series of dithiolethiones in the SH-SY5Y neuroblastoma cell line.ResultsOur structure–activity relationships data show that dithiolethione electronic properties, given as Hammett σp constants, influence glutathione induction activity and compound toxicity. The most active glutathione inducer identified, 6a, dose-dependently protected cells from 6-hydroxydopamine toxicity. Furthermore, the protective effects of 6a were abrogated by the inhibitor of glutathione synthesis, buthionine sulfoximine, confirming the importance of glutathione in the protective activities of 6a.ConclusionsThe results of this study further delineate the relationship between dithiolethione chemical structure and glutathione induction. The neuroprotective properties of analog 6a suggest a role for dithiolethiones as potential antiparkinsonian agents.

Modification of optoelectronic properties of conjugated oligomers due to donor/acceptor functionalization: DFT study

A comprehensive DFT study of a set of oligo(p-phenylene vinylene) molecules is performed to understand the structural and electronic changes upon functionalization. These changes are rationalized within a model considering frontier molecular orbitals of the π-conjugated system and σ-bonding orbital by which the functional group is attached to the host molecule. Two simple scalar quantum chemical descriptors are shown to correlate with optoelectronic properties of the functionalized molecule: the electronegativity and the relative electric dipole moment of the smallest π-closed shell subsystem containing the functional group and the terminal segment of the host molecule (phenyl). Both descriptors correlate linearly with the empirical Hammett σp constant for a set of 24 functional groups. Comparison with available experimental data on UV–vis absorption and cyclic voltammetry is made. Observed structural changes reflect changes in the electronic density.

Quantitative structure-activity relationship analysis of substituted arylazo pyridone dyes in photocatalytic system: Experimental and theoretical study

A series of arylazo pyridone dyes was synthesized by changing the type of the substituent group in the diazo moiety, ranging from strong electron-donating to strong electron-withdrawing groups. The structural and electronic properties of the investigated dyes was calculated at the M062X/6-31+G(d,p) level of theory. The observed good linear correlations between atomic charges and Hammett σp constants provided a basis to discuss the transmission of electronic substituent effects through a dye framework. The reactivity of synthesized dyes was tested through their decolorization efficiency in TiO2 photocatalytic system (Degussa P-25). Quantitative structure-activity relationship analysis revealed a strong correlation between reactivity of investigated dyes and Hammett substituent constants. The reaction was facilitated by electron-withdrawing groups, and retarded by electron-donating ones. Quantum mechanical calculations was used in order to describe the mechanism of the photocatalytic oxidation reactions of investigated dyes and interpret their reactivities within the framework of the Density Functional Theory (DFT). According to DFT based reactivity descriptors, i.e. Fukui functions and local softness, the active site moves from azo nitrogen atom linked to benzene ring to pyridone carbon atom linked to azo bond, going from dyes with electron-donating groups to dyes with electron-withdrawing groups.

A combined experimental and density functional study of 1-(arylsulfonyl)-2-R-4-chloro-2-butenes reactivity towards the allylic chlorine

Nucleophilic substitution and dehydrochlorination reactions of a number of the ring-substituted 1-(arylsulfonyl)-2-R-4-chloro-2-butenes are studied both experimentally and theoretically. The developed synthetic procedures are characterized by a general rapidity, cheapness, and simplicity providing moderate to high yields of 1-arylsulfonyl 1,3-butadienes (48–95%), 1-(arylsulfonyl)-2-R-4-(N,N-dialkylamino)-2-butenes (31–53%), 1-(arylsulfonyl)-2-R-2-buten-4-ols (37–61%), and bis[4-(arylsulfonyl)-3-R-but-2-enyl]sulfides (40–70%). The density functional theory B3LYP/6-311++G(2d,2p) calculations of the intermediate allylic cations in acetone revealed their high stability occurring from a resonance stabilization and hyperconjugation by the SO2Ar group. The reactivity parameters estimated at the bond critical points of the diene/allylic moiety display a high correlation (R2 > 0.97) with the Hammett (σp) constants. 1-Arylsulfonyl 1,3-butadienes are characterized by a partly broken π conjugated system, which follows from analysis of the two-centered delocalization (δ) and localization (λ) index values. The highest occupied molecular orbital energies of 1-arylsulfonyl 1,3-butadienes are lower than those of 1,3-butadiene explaining their low reactivity towards the Diels–Alder condensation. Copyright © 2015 John Wiley & Sons, Ltd.

Hammett Analysis of a Family of Carbene−Carbene Complex Equilibria

p-X-substituted phenylchlorocarbenes (X = NO(2), CF(3), Cl, H, Me, and MeO) form π-type complexes with trimethoxybenzene in pentane. The carbenes and complexes are in equilibrium, and logarithms of the measured equilibrium constants are well correlated by Hammett σ(p) constants with ρ = 2.48. The carbene complexes are characterized by UV-vis spectroscopy, and computational analysis is afforded by DFT calculations.

Absorption and photoluminescence properties of 4-substituted Alq3 derivatives and tris-(4-hydroxypyridinoanthrene)aluminum

A series of 4-substituted Alq3 derivatives have been synthesized. Photophysical properties of the complexes in solution have been studied in detail. The results show that Hammett σp constants of the substituents have a linear correlation with the emission maximum values of the aluminum complexes. Substitution at the 4-position improves the color purity of the emission and it has also a strong influence on the quantum yields. A new type of Alq3 derivative, tris-(4-hydroxypyridinoanthrene)aluminum, has a good quantum yield and high emission color purity.

Mo‐Catalyzed Cross‐Metathesis Reaction of Propynylferrocene

AbstractCatalysts formed in situ from [Mo(CO)6] and halophenols in dichloromethane efficiently promote cross metathesis reactions of (prop‐1‐yn‐1‐yl)ferrocene with various functionalized alkynes to give the corresponding alkynylferrocenes with good selectivity and yields. Optimization of the reaction conditions by changing the phenol component has been carried out, revealing a critical influence of the phenol structure on the reaction yield. The structures of selected compounds were determined by single‐crystal X‐ray diffraction, and the results (particularly the crystal packing) were correlated with DFT calculations. In addition, the series of alkynes 4‐XC6H4C≡CFc (Fc = ferrocenyl) differing by the substituent X was studied by electrochemical methods, manifesting a good correlation between the redox potential of the ferrocene/ferrocenium couple and the Hammett σp constants of the remote substituents X. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Potent and Selective α-Ketoheterocycle-Based Inhibitors of the Anandamide and Oleamide Catabolizing Enzyme, Fatty Acid Amide Hydrolase

A study of the structure-activity relationships (SAR) of 2f (OL-135), a potent inhibitor of fatty acid amide hydrolase (FAAH), is detailed, targeting the 5-position of the oxazole. Examination of a series of substituted benzene derivatives (12-14) revealed that the optimal position for substitution was the meta-position with selected members approaching or exceeding the potency of 2f. Concurrent with these studies, the effect of substitution on the pyridine ring of 2f was also examined. A series of small, nonaromatic C5-substituents was also explored and revealed that the K(i) follows a well-defined correlation with the Hammett sigma(p) constant (rho = 3.01, R2 = 0.91) in which electron-withdrawing substituents enhance potency, leading to inhibitors with K(i)s as low as 400 pM (20n). Proteomic-wide screening of the inhibitors revealed that most are exquisitely selective for FAAH over all other mammalian proteases, reversing the 100-fold preference of 20a (C5 substituent = H) for the enzyme TGH.

Estimation of Hammett sigma constants of substituted benzenes through accurate density‐functional calculation of core‐electron binding energy shifts

AbstractFor substituted benzenes such as (p‐F‐C6H4‐Z), Linderberg et al. 1 demonstrated the validity of an equation similar to: ΔCEBE ≈ κσ, where ΔCEBE is the difference in core‐electron binding energies (CEBEs) of the fluorinated carbon in p‐F‐C6H4‐Z and that in FC6H5, the parameter κ is a function of the type of reaction, and σ is the Hammett substituent (σ) constant. In this work, CEBEs of ring carbon atoms for a series of para disubstituted molecules p‐F‐C6H4‐Z were first calculated using Density Functional Theory (DFT) with the scheme ΔEKS (PW86‐PW91)/TZP+Crel//HF/6‐31G*. An average absolute deviation of 0.13 eV from experiment was obtained for the CEBEs. Then we performed a linear regression analysis in the form of Y = A+B*X for a plot of Hammett σp constants against calculated shifts ΔCEBEs (in eV) for the fluorinated carbon. The results were: A = –0.08 and B = 1.01, with correlation coefficient R = 0.973, standard deviation = 0.12, and P < 0.0001. The intercept A of the fitted line, close to zero, shows that the Hammett σp constant is proportional to the calculated ΔCEBEs. On the other hand, the slope B of the straight line gives an estimate of the parameter κ. Similar statistical correlations were obtained for the carbon atoms ortho and meta to the substituent Z. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

Acid-base interactions in some isoquinoline and quinazoline amino derivatives

Few groups of substituted 1-aminoisoquinoline, 4-amino- and 2,4-diaminoquinazoline derivatives have been examined in order to find general relationships between the basicity and a kind of substituent. pKa Values have been determined for these compounds and correlated with the original Hammett σm and σp constants. They clearly showed that the steric effects of the bulky substituents neighbouring the protonated ring nitrogen atom influence the electron transfer in such arrangements. Different tendencies in the electron transfer caused by the same groups in the position 1 of isoquinoline and position 4 of quinazoline have been also disscused. The ρ value, single crystal X-ray analysis, 15 N-NMR spectra and MNDO calculations give evidence about the electronic effects and the preferential site of protonation in such arrangements.

Substituent effects in columnar β-diketonate metallomesogens

A systematic study of the mesomorphic properties of two homologous series of copper(II) and palladium(II) complexes 1a–b derived from unsymmetrical β-diketonate derivatives 2 containing a variety of functional substituents (X = H, CH3, C2H5, OCH3, Cl, Br, I, CN) on the phenyl ring is reported. These disc-like molecules all contain eight n-octyloxy chains, required for the formation of columnar phases appended to the central β-diketonate core. All complexes exhibited columnar phases studied by differential scanning calorimetry, polarized optical microscopy and powder X-ray diffraction. The mesomorphic results indicated that all compounds formed stable enantiotropic columnar mesophases, and the formation of columnar phases was strongly dependent on the electronic and/or the steric factors of the substituents. For compounds containing bulky substituents (i.e. X = Me, Et) a rectangular columnar phase (Colr) was observed, however, other compounds containing electron-withdrawing substituents (i.e. X = Cl, Br, I) exhibited a hexagonal columnar phase (Colh). Most of the palladium(II) complexes, except for X = CH3 and OCH3 derivatives, have lower clearing temperatures than those of the copper(II) analogues, and this is probably due to a weaker molecular interaction between the cores in the palladium(II) complexes. Lattice constants for these two types of compound obtained by powder X-ray diffraction were found to be insensitive to the metal center incorporated. These values were all relatively close in magnitude, which indicated that the two structures were quite similar. A satisfactory linear relationship with a correlation coefficient of 0.974 between the clearing temperatures and the Hammett σp constants of substituents was obtained only for the copper complexes.

Revisiting Markovnikov addition to alkenes via molecular electrostatic potential.

Molecular electrostatic potentials (MESP) surrounding the pi-region of several substituted ethylenes (CH(2)CHR) have been characterized by locating the most negative-valued point (V(min)) in that region. The substituents have been classified as electron donating and withdrawing on the basis of the increase or decrease in the negative character of V(min) in these systems as compared to ethylene. The values of V(min) show a good linear correlation with the Hammett sigma(p) constants, suggesting that the substituent electronic effects in substituted ethylenes and substituted benzenes are basically similar. With electron-donating substituents, the position of MESP minimum is closer to the unsubstituted carbon facilitating the pi-complex formation of it with HCl at this site. Such a regiospecific pi-complex formation is found to favor the formation of Markovnikov-type transition state for the addition of HCl to CH(2)CHR. For the electron-withdrawing substituents, the V(min) location is almost equidistant and farther from the ethylenic carbon atoms. This and the less negative V(min) values account for the less regiospecific CH(2)CHR...HCl pi-complexes as well as the transition states for the HCl addition to CH(2)CHR when R is an electron-withdrawing group. The interaction energy (E(int)) between CH(2)CHR and HCl for the formation of the CH(2)CHR...HCl pi-complex shows a good linear correlation with the corresponding V(min) value.

Thermal Racemization of Substituted Indolinobenzospiropyrans: Evidence of Competing Polar and Nonpolar Mechanisms

A series of 6-substituted indolinobenzospiropyrans were resolved by chiral stationary phase HPLC and rate constants krac for their thermal racemization were measured by circular dichroism spectropolarimetry at 60 °C in three different solvents: cyclohexane, 90:10 hexanes/2-propanol, and acetonitrile. Results show that the spiropyrans undergo thermal racemization most rapidly in acetonitrile, with krac values ranging from 9.3 × 10-5 to >5.0 × 10-3 s-1, and least rapidly in cyclohexane, with krac values ranging from 6.8 × 10-6 to 4.6 × 10-4 s-1. V-shaped plots of log krac vs Hammett σp constants in 90:10 hexanes/2-propanol and acetonitrile suggest that thermal racemization of the 6-substituted spiropyrans proceed via two competing mechanisms: a polar mechanism involving heterolytic C(sp3)−O bond cleavage with anchimeric assistance from the indoline nitrogen and a nonpolar electrocyclic ring opening mechanism with no anchimeric assistance from the indoline nitrogen. The outcome of this competition appears ...

Determination and Structural Correlation of PkA Values of P-Substituted Trans-β-Aroylacrylic Acids

For a series of 10 p-substituted trans-β-aroylacrylic acids, pKa values were determined spectrophotometrically in water at 25°C and at ionic strength 0.1 M (NaCl). The thermodynamic pKa values were correlated with Hammett σp constants.

103Rh Chemical Shifts in Complexes Bearing Chelating Bidentate Phosphine Ligands

Experimental and theoretical methods have been employed to investigate the influence of the chelating phosphine ligand on the 103Rh chemical shift in complexes containing the [(P2)Rh] fragment (P2 = chelating bidentate phosphine). The δ(103Rh) values obtained by 2D(31P,103Rh{1H}) NMR spectroscopy for a series of neutral rhodium complexes [{R2P(CH2)nPR2}Rh(hfacac)] (R = Ar, Ph, Cy, Me, n = 1−4, hfacac = hexafluoroacetylacetonate) have been compared. Systematic variation of the phosphine ligand has allowed separation of electronic and geometrical effects. The purely electronic influence of para substituents in complexes [{(p-XC6H4)2P(CH2)4P(p-XC6H4)2}Rh(hfacac)] correlates directly with the Hammett σP constants of X, but leads to variations in the chemical shift of less than 80 ppm between X = CF3 and X = OMe. In contrast, geometrical changes in complexes [(P2)Rh(hfacac)] lead to variations in the chemical shift over a range of approximately 800 ppm. The individual contributions of various structural parame...