Hammett Substituent Constants Research Articles

Deep eutectic solvent as an operative media on structure‐reactivity relationships

AbstractDeep eutectic solvents seem to be environmentally friendly solvents, particularly because they are prepared easily and have very low‐vapor pressures under ambient conditions. They are suitable candidates as green solvents for reaction media with special properties. To present this behavior, substitution reactions of some para‐ and meta‐substituted anilines with 1‐fluoro‐2,4‐dinitrobenzene have been spectrophotometrically investigated in varying mole fractions of ethaline as a deep eutectic solvent in dimethyl sulfoxide (DMSO). The measured rate coefficients of the reaction demonstrated a noticeable variation with the increasing mole fraction of ethaline in ethaline‐DMSO mixtures. The linear free energy relationship (LFER) of second‐order rate coefficients based on Hammett's substituent constants demonstrates a reasonably linear straight line with a negative slope in different mole fractions of ethaline‐DMSO mixtures. Another LFER investigation based on the polarity parameters of the media showed a good agreement with hydrogen bond donor and acceptor abilities of the solvent. Non‐LFER assay according to the preferential solvation model confirmed differences between the microsphere solvation of the solute molecules and the bulk composition of the solvents.

Syntheses of Chalcone-Type Chlorophyll Derivatives Possessing a Bacteriochlorin, Chlorin or Porphyrin π-System and Their Optical Properties.

C3-(Trans-2-arylethenyl)carbonylated chlorophyll derivatives possessing a bacteriochlorin or chlorin π-system were synthesized by cross-aldol (Claisen-Schmidt) condensation of methyl pyrobacteriopheophorbide-a or 3-acetyl-3-devinyl-pyropheophorbide-a bearing the C3-acetyl group with p-(un)substituted benzaldehydes under basic conditions. The corresponding porphyrin-type chlorophyll derivatives were prepared by the oxidation (17,18-didehydrogenation) of the chlorin-type. Their Qy absorption and fluorescence emission maxima in dichloromethane correlated well with Hammett substituent constants of the p-substituents. Several electron-withdrawing p-substituents suppressed the emission due to photoinduced electron transfer quenching in a molecule. The substitution sensitivities for their maxima and fluorescence quantum yields decreased in the order of bacteriochlorin-, chlorin- and porphyrin-type derivatives.

Trans-kinetic effects in ligand substitution processes of ruthenium polypyridyl complexes

A concerted mechanism is disclosed when studying trans-kinetic effects in substitution processes of complexes of formula [Ru(trpy)(4,4′-(X)2-bpy)(H2O)]2+, with trpy = 2,2′:6′,2″-terpyridine, bpy = 2,2′-bipyridine and X = H, CH3, OCH3, NH2 and N(CH3)2. The second order rate constants k2 for substitution of water by acetonitrile increase with increasing donor ability of the X group. The correlation between ln k2 and Hammett substituent constants σp of X gives a slope of near 1, indicating high sensitivity of the kinetic parameters for water replacement to the donor ability of the para-substituent attached to a bipyridine trans- to the water ligand and considerably separated from it. Besides, the activation enthalpies decrease with increasing pKa values of the 4,4′-(X)2-bpy ligands and the activation entropies have negative values almost one order of magnitude higher than those reported before in similar processes. These data indicate a concerted ligand interchange mechanism, infrequently found in substitution reactions of octahedral complexes which can be explained by the fact that H-bonds between the leaving ligand (H2O) and the entering ligand (CH3CN) will favor an intermediate transition state of increased order respect to the initial state. These results are pertinent for finding the best candidates in the quantitative detection of CH3CN, an important contaminant in radiopharmaceuticals used in PET (positron emission tomography) studies.

Mechanistic investigations on asymmetric N-H insertion of amines catalyzed by palladium-chiral guanidine complex

The mechanism and stereoselectivity of the asymmetric N-H insertion reactions between α-diazocarbonyl compounds and amines mediated by palladium-chiral guanidine complexes were investigated at the BP86-D3(BJ)/def2TZVP (SMD, CH2Cl2)//BP86-D3(BJ)/def2SVP (SMD, CH2Cl2) level at 303 K. The non-catalytic reaction occurred through a stepwise mechanism, with a high activation barrier of 56.4 kcal mol−1. Good linear correlations between the global nucleophilicity index (N) of amine, Hammett substituent constants (σP), and the activation energy barriers (ΔG≠) were found. The Pd(0)-guanidine-catalyzed reaction consisted of three continuous steps, including: (i) generation of Pd-carbene intermediate by dinitrogen loss from α-diazoesters substrate, (ii) formation of CN bond, and (iii) 1,2-H transfer by metal-associated ylide, accompanying with the regeneration of catalyst. A water molecule accelerated the final H-transfer by constructing hydrogen bonding network. The cyclohexyl group in ligand provided sufficient steric shielding around Pd-carbene intermediate from the re-face attack by amines. The combination of the hydrogen bonding orientation of amide moiety of guanidine ligand, as well as the steric repulsion between the ester group of α-diazoester substrate and bulky CH(Ph)2 group in ligand played an important role in controlling the stereoselectivity, affording the predominant S-configuration product observed in experiment. Introducing one aromatic ring to chiral backbone of the guanidine ligand enhanced the enantiodifferentiation of products by increasing the difference of strain energy (ΔΔEstrain) of Pd-carbene moiety along two competing pathways. Different from Pd(0)-catalyst, the Pd(II)-chiral guanidine complex accelerated N-H insertion reaction via Lewis acid catalysis. In this process, the formation of free ylide in the reaction led to low ee. These results were in good agreement with experimental observations.

Spin-Crossover Temperature Predictable from DFT Calculation for Iron(II) Complexes with 4-Substituted Pybox and Related Heteroaromatic Ligands.

Spin-crossover (SCO) is a reversible transition between low and high spin states by external stimuli such as heat. The SCO behavior and transition temperature (T1/2) of a series of [FeII(X-pybox)2](ClO4)2 were studied to establish a methodology for ligand-field engineering, where X-pybox stands for 2,6-bis(oxazolin-2-yl)pyridine substituted with X at the 4-position of the pyridine ring. We utilized X = MeO, Me, 3-thienyl, Ph, H, MeS, 2-thienyl, N3, Cl, Br, 3-pyridyl, and 4-pyridyl. The solution susceptometry on five new derivatives with X = Me, 2-thienyl, N3, Br, and 3-pyridyl was performed in acetone, giving the SCO temperatures of 220, 260, 215, 280, and 270 K, respectively. The density-functional-theory molecular orbital (MO) calculation was performed on the ligands with geometry optimization. The atomic charge on the pyridine nitrogen atom [ρ(Npy)] was extracted from the natural orbital population analysis. Positive correlation appeared in the T1/2 versus ρ(Npy) plot with R2 = 0.734, being consistent with the analysis using the Hammett substituent constants (σp and σp+). This finding well agrees with the mechanism proposed: the rich electron density lifts the t2g energy level through the dπ–pπ interaction, resulting in a narrow t2g–eg energy gap and favoring the high-spin state and low T1/2. The MO method was successfully applied to the known SCO-active iron(II) compounds involving 4-substituted 2,6-bis(pyrazol-1-yl)pyridines. A distinct positive correlation appeared in the T1/2 versus ρ(Npy) plot. The comparison of correlation coefficients indicates that ρ(Npy) is a more reliable parameter than σp or σp+ to predict a shift of T1/2. Furthermore, this method can be more generalized by application to another known SCO family having 3-azinyl-4-p-tolyl-5-phenyl-1,2,4-triazole ligand series, where azinyl stands for a 2-azaaromatic ring. A good linear correlation was found in the T1/2 versus ρ(NA) plot (NA is the ligating nitrogen atom in the azaaromatic ring). Finally, we will state a reason why the present treatment is competent to predict the SCO equilibrium position only by consideration on the electronic perturbation.

MICROWAVE ASSISTED SYNTHESIS, SPECTRAL CORRELATION AND ANTIMICROBIAL EVALUATION OF SOME ARYL IMINES

A series of aryl imines have been synthesized by SiO2-H3PO4 catalyzed microwave assisted condensation of amine and aldehyde under solvent-free conditions. The yield of the imines has been found to be more than 80%. The purity of all imines has been checked using their physical constants and spectral data as published earlier in literature. The UV λmax(nm), infrared νC=N(cm-1), NMR δ(ppm) of C-H and C=N spectral data have been correlated with Hammett substituent constants and F and R parameters using single and multi-linear regression analysis. From the results of statistical analysis, the effect of substituents on the above spectral data has been studied. The antimicrobial activities of all imines have been studied using Bauer-Kirby method.

Substituent effect on the acid-induced isomerization of spiropyran compounds

Spiropyran compounds are well known as an isomeric system, the closed spiropyran (SP) could be converted into the open merocyanine (MC) via acid-induced because stable protonated merocyanine (MCH) were formed by combination of MC and H+. In order to understand how the substituent affect the isomerization of spiropyran. A series of the chromene 7-subsituted spiropyran compounds were designed and synthesized. The photophysical properties of them were studied comparatively by UV-absorption and fluorescence spectra in different pH. The results demonstrated that the various substituents influenced not only the photophysical properties of SP, MC and MCH forms, but also the pKa of the MC-MCH transformation. There was a good linearity relationship between the pKa and the Hammett constant of substituent, the pKa was smaller when the Hammett constant of substituent was larger.

Synthesis and properties of π-conjugated donor–acceptor macrocycles derived from phenanthrylene building blocks

Phenanthrylene-ethynylidene macrocycles combining electron donor and electron acceptor subunits in their shape-persistent fully conjugated core were synthesized. The donor subunits consisted of two 9,10-dialkoxyphenanthrenes linked either with 1,2-ethynylidene or 2,5-thienylene bridge. The acceptors were 9,10-phenanthroquinone and dibenzoquinoxaline and dibenzophenazines derived from it. Solvatochromic photoluminescence from intramolecular-charge-transfer (ICT) excited state was observed mainly in non-polar solvents. In more polar solvents, the excited states favor non-radiative relaxation. DFT calculated HOMO/LUMO energies of the macrocycles correlate well with spectroscopic and electrochemical data. In the series of substituted dibenzophenazine acceptors a good correlation with Hammett substituent constants σp– was found.

In-silico analysis of substituent effect on the static first order hyperpolarizability of electron donating mono substituted Chalcone derivatives.

Noncentrosymmetric π conjugated systems with suitable electron donor acceptor groups play a crucial role in material NLO activity. The influence of an electron donating mono substituent at the para position of the phenylene ring of chalcone was investigated as a resource for second harmonic generation. The geometrical optimization of 11 electron donating group substituted chalcones were performed using density functional theory at the B3LYP/6-311G(d,p) level and compared with experimental geometrical parameters of five reported chalcones. All the derivatives are transparent to visible radiation as shown by the electronic absorption spectra investigated by the TDDFT-CAM B3LYP/6-311G(d,p) method, and the maximum absorption wavelength was due to the πPhB → π* transition. The first order hyperpolarizability βtot, calculated using the CAM B3LYP/6-311G(d,p) method, increases with the electron donating ability of the substituent, and the largest βtot was observed for dimethylamino substituent. The Hammett substituent constant (σp) shows good linear correlation with β, λmax, and Egap in the ground state. The Brown constant (σp+) was better correlated indicating the polarization of carbonyl group in the excited state. Frontier molecular orbitals also reveal the valence electron excitation. Correlation of σp with various parameters was analyzed to assess the property interrelationship with electronic reorganization in the molecule. The electronic structures of molecular fragments were described in terms of natural bond orbital analysis, which shows intramolecular interactions.

(Invited) Substituted Aryl Structure Effects on Photoluminescence Properties of Locally Functionalized Single-Walled Carbon Nanotubes

Sp3 defect doping to semiconducting single-walled carbon nanotubes (SWNTs) provides fascinating near infrared photoluminescence (NIR PL) properties, in which, compared to PL (E 11) of pristine SWNTs, redshifted PL with enhanced quantum yields (E 11*) is observed by local functionalization through the doping.[1-6] In the locally functionalized SWNTs (lf-SWNTs), chemical structures of the modified molecules on the doped sites play an important role to determine and control the E 11* PL wavelengths. For example, we have succeeded in generation of remarkably redshifted PL on the basis of a proximal modification approach [5] and development of dynamic wavelength shift systems driven by molecular recognition at the doped sites [6]. Here, we report recent findings of the chemical structure factors that modulate the E 11* PL properties of aryl functionalized lf-SWNTs. When positional isomeric structures of the substituted aryl groups are introduced for the doped sites of lf-SWNTs (Figure), significantly different PL is observed from that of typical para-aryl modified lf-SWNTs.[3] Namely, the meta-aryl modified lf-SWNTs show deviation from the reported liner relationship between the Hammett substituent constants and ΔE = E 11*-E 11 of the para-aryl modified lf-SWNTs. For the ortho-aryl modified lf-SWNTs, two PL peaks generate by the functionalization and one of them appears in the largely redshifted region compared to typically observed E 11* PL. The present findings, therefore, are expected to provide new designs for the molecule-based PL modulation of lf-SWNTs. In this presentation, more details about the structural factors will be discussed.

Interactions of Substituted Nitroaromatics with Model Graphene Systems: Applicability of Hammett Substituent Constants To Predict Binding Energies.

Applicability of Hammett parameters (σm and σp) was tested in extended π-systems in gas phase. Three different model graphene systems, viz. 5,5-graphene (GR), 3-B-5,5-graphene (3BGR), and 3-N-5,5-graphene (3NGR), were designed as extended π-systems, and interactions of various nitrobenzene derivatives (mainly m- and p-substituted together with some multiple substitutions) on such platforms were monitored using density functional theory (M06/cc-pVDZ, M06/cc-pVTZ, M06/sp-aug-cc-pVTZ) and Møller–Plesset second-order perturbation (MP2/cc-pV-DZ) theory. Offset face to face (OSFF) stackings were found to be the favored orientations, and reasonable correlations were found between binding energies (ΔEB) and the ∑|σm| values of the substituted nitrobenzenes. It was proposed previously that |σm| contains information about the substituents’ polarizability and controls electrostatic and dispersion interactions. The combination of ∑|σm| and molar refractivity (as ∑Mr) or change in polarizability (Δα: with respect to benzene) of nitrobenzene derivatives generated statistically significant correlation with respect to ΔEB, thereby supporting the hypothesis related to the validity of |σm| correlations. The |σp| parameters also maintain similar correlations for the various p-substituted nitrobenzene derivatives together with several multiply-substituted nitrobenzene derivatives. The correlation properties in such cases are similar to the |σm| cases, and the energy partition analysis for both the situations reveled importance of electrostatic and dispersion contributions in such interactions. The applicability of Hammett parameters was observed previously on the restricted parallel face to face orientation of benzene···substituted benzene systems, and the present results show that such an idea could be used to predict ΔEB values in OSFF orientations, if the scaffolds are designed in such a way that substituted benzene systems cannot escape their π-clouds.

Rational design of FLP catalysts for reversible H2 activation: A DFT study of the geometric and electronic effects

Frustrated Lewis pairs (FLPs) emerge as a new type of bifunctional metal-free catalysts for reversible H2 activation, which is important for the storage and liberation of H2 or further controllable utilizing chemical fuels via hydrogenation/dehydrogenation. Herein, a DFT study was conducted to understand the geometric factors and electronic effects of FLPs on reversible H2 activation. The Lewis base group mainly contributes to the proton attachment, and influences the kinetics of the H2 activation. The Lewis acid group mainly relates to the hydride attachment, and affects more significantly on the thermodynamics of H2 activation. The dimer and quenched structure of FLPs also have a degree of influence on the performance of catalyzed H2 activation. A series of FLPs with para-substituted phenyl derivatives as LA groups were designed and evaluated. The results indicate that the variation of LA groups has significant impact on thermodynamic energy of dihydrogen adducts but insignificant effect on kinetics. Moreover, we found the thermodynamic energy of products has a good linear relationship with Hammett substituent constants. The solvent effect on H2 activation was also studied, and polar solvent is beneficial for zwitterionic products. These results should provide deeper insight to understand the relation between FLPs structure and reactivity, which is critical for rational design of more efficient FLPs catalysts for reversible H2 activation.

Informing Efforts to Develop Nitroreductase for Amine Production.

Nitroreductases (NRs) hold promise for converting nitroaromatics to aromatic amines. Nitroaromatic reduction rate increases with Hammett substituent constant for NRs from two different subgroups, confirming substrate identity as a key determinant of reactivity. Amine yields were low, but compounds yielding amines tend to have a large π system and electron withdrawing substituents. Therefore, we also assessed the prospects of varying the enzyme. Several different subgroups of NRs include members able to produce aromatic amines. Comparison of four NR subgroups shows that they provide contrasting substrate binding cavities with distinct constraints on substrate position relative to the flavin. The unique architecture of the NR dimer produces an enormous contact area which we propose provides the stabilization needed to offset the costs of insertion of the active sites between the monomers. Thus, we propose that the functional diversity included in the NR superfamily stems from the chemical versatility of the flavin cofactor in conjunction with a structure that permits tremendous active site variability. These complementary properties make NRs exceptionally promising enzymes for development for biocatalysis in prodrug activation and conversion of nitroaromatics to valuable aromatic amines. We provide a framework for identifying NRs and substrates with the greatest potential to advance.

Synthesis and Characterisation of Substituted 2-benzofuranyl Chalcones

A series of substituted Stryl 2- benzofuranyl ketones have been synthesized by Crossed Aldol condensation of substituted benzaldehyde and 2- acetyl benzofuran using Ultrasonicator. The synthesized chalcones have been characterized by Physical constant, Mass spectra, IR, 1H NMR and 13C NMR. The spectral data are correlated with Hammett substituent constants and Swain – Lupton parameters. From the regression analysis, the effect of substituent on the group of frequencies has been predicted. The structure activity relationship (SAR) have been studied by screening of anti biological activity over a representative panel at bacterial and fungal strain using disc diffusion(zone of inhibition) method. All these synthesized chalcones exhibited significant activities against all bacterial and fungal strain.

Mechanism and kinetics of electrocarboxylation of aromatic ketones in ionic liquid

The electrochemical carboxylation of a range of substituted benzophenones was studied in 1-butyl-1-methyl-pyrrolidinium bis(trifluoromethylsulfonyl)imide ionic liquid (IL, ([Bmpy][NTf2])). As expected, the aromatic carbonyls exhibited electrochemical reversibility for the first reduction to the radical anion at potentials which were a function of the sum of their Hammett substituent constants (Σσ). However, in the presence of CO2, the electrochemical reversibility was lost and positive shifts in reduction potentials were observed which were indicative of post-electron transfer chemical reaction which has been attributable to the nucleophilic radical anion/CO2 coupling reaction.Analysis of the positive potential shift a function of sweep rate (ν) indicated that the mechanism is either ECE or DISP1, or mixed ECE/DISP1. Also from the potential shift with ν, an apparent rate constant (kapp), and a pseudo-first order rate constant (k1), for the coupling reaction was determined and compared to molecular solvent where the rate is over two orders of magnitude lower in IL compared to dimethylformamide (DMF). The low polarity of the IL compared to DMF appears to be the cause of slow kinetics. Finally, plots of kapp vs. Σσ were strictly linear indicating that IL does not preferentially interact with any of the electrogenerated radical anions thus implying that the electrocarboxylation reaction may be a useful probe of IL environments and structure on radical anion reactions.

Theoretical exploring of the substituent effect on the NQR and NMR parameters in a platinum-based anticancer drug, trans-(NHC) PtI2 (para-NC5H4X) complex

In this study, quantum chemical calculations using MPW1PW91 method were applied to analyze substituent effect on the 14N NQR and NMR parameters in trans-(NHC) PtI2 (para-NC5H4X); (X = H, F, CHO, COOH, CN, NO2, Me, OH, NH2) complex. The substituent effect was examined in the presence of electron withdrawing groups (EWG) and electron donor groups (EDG). The chemical shifts (δ) and spin-spin coupling constants (J and K) were evaluated with the gauge including atomic orbital (GIAO) approach. Significant factors contributing to the magnitude of coupling constants (Fermi contact (FC), spin-dipolar (SD) terms, the diamagnetic spin orbital (DSO), and the paramagnetic spin orbital (PSO) terms) were elucidated. 14N NQR frequencies, quadrupole coupling constants, and the asymmetry parameters were calculated. The linear correlations between 14N NQR and NMR parameters with Hammett constants of substituents were studied. Also, NBO analysis was used for calculation of the p character value of lone pair electrons of nitrogen of para-NC5H4X ligand and the related occupancies. These parameters were effective on nuclear quadrupole coupling constant.

Theoretical investigation of the π+-π+ stacking interactions in substituted pyridinium ion

The interaction between positively charged aromatic groups (π+-π+) is characterized by stacked pyridinium ion derivatives X-PyH+||X-PyH+ (XH, NH2, OH, CN, F, Br and Cl) at the M06-2X/6-311++G(d,p) level of theory in the presence of three solvents. The results indicate the formation of π+-π+ stacking in a dielectric solvent can be due to the significant stability of the charge–charge repulsion forces. The trend in the absolute value of stacking interaction energy |ΔEπ+⋯π+| with respect to the solvent is formamide>water>acetone. In all complexes, the π+-π+ stacking interactions increase with the electron-donating substituents (EDSs) and decrease with the electron-withdrawing substituents (EWSs). Excellent correlations were found between the ΔEπ+⋯π+ values of the complexes and a combination of Hammett substituent constants. The results obtained from the atoms in molecules (AIM) and natural bond orbital (NBO) analysis show that the sum of electron densities calculated at BCPs and CCPs between the rings (∑rBCP and ∑ρCCP) and the sum of donor-acceptor interaction energies (∑E2) from one ring to other can be used as useful descriptors in the prediction of ΔEπ+⋯π+ values in the complexes.

Effect of substituent groups (R= [sbnd]CH3, [sbnd]Br and [sbnd]CF3) on the structure, stability and redox property of [Cr(R-pic)2(H2O)2]NO3·H2O complexes

Complexes [Cr(3-CH3-pic)2(H2O)2]NO3·H2O (1), [Cr(5-Br-pic)2(H2O)2]NO3·H2O (2) and [Cr(5-CF3-pic)2(H2O)2]NO3·H2O (3) were synthesized (pic = pyridine-2-carboxylic acid) and characterized by X-ray crystal diffraction. Crystal structure indicates that two bidentate ligands occupy equatorial position and two H2O occupy axial positions in trans-configuration. (i) Decomposition of complexes 1, 2 and 3 in different medium (phosphate buffered saline (PBS), apo-ovotransferrin (apootf) and EDTA) indicates that decomposition rate constants of these complexes follow the sequence of 1 < 2 < 3. (ii) The redox potential of Cr(III)/Cr(II) by cyclic voltammetry follows the sequence of 1 (−1.20 V) > 3 (−1.29 V) > 2 (−1.31 V). (iii) In addition, ·OH-generation of the new synthesized complexes was determined by Fenton-like reaction in comparison with Cr(pic)3, and it may be related to the reduction potential of the complexes. (iv) Moreover, Hammett substituent constants σp (inductive) and σm (resonance) (R = 3-CH3, 5-Br, 5-CF3) were introduced to evaluate the impact of substituent groups on the bond length and decomposition kinetics. The substituent group on the ligand has great effect on the properties of the complexes.

An Acidity Scale of Triazolium-Based NHC Precursors in DMSO.

An acidity scale of triazolium-based N-heterocyclic carbene precursors was established by measuring 25 compounds' (10a-15b) equilibrium acidities in dimethyl sulfoxide (DMSO) solution using overlapping indicator method. The pKa values ranged from 12.08 to 15.5, responding not only to the N-aryl motif, but also to the core structure. Excellent correlation was observed between the pKa values and the Hammett substituent constants (σp).

Intermolecular hydrogen bonds between 1,4-benzoquinones and HF molecule: Synergetic effects, reduction potentials and electron affinities

Some biological activities of quinones can be attributed to the H-bonding ability of acceptor oxygen atoms. According to the results obtained from the quantum mechanical calculations performed on a wide variety of complexes between the 1,4-benzoquinone (BQ) derivatives and HF molecules, the interplay between H-bonds and individual H-bond interaction energies (EHB) can be affected by the substituents placed on the six-membered ring of BQ. The total binding energies of complexes become more negative by the electron donating substituents (EDSs) while the changes are reversed by the electron withdrawing substituents (EWSs). The mutual interplay between the X-BQ⋯(HF)n (n=1–3) interactions has been investigated using the geometrical parameters, synergetic energies (SE) and the EHB values. Hydrogen bonding decreases the reduction potentials (E0red) and increases the electron affinities (EA) of X-BQ derivatives. Linear relationships have been observed between the E0red (and EA) values and the Hammett constants of substituents.