Polar Substituent Effects Research Articles

BIOLOGICAL ACTIVITY CALCULATED BY THE PASS METHOD AND EXPERIMENTAL ASSESSMENT OF THE ACIDITY OF NH GROUPS IN SULPHONAMIDE POLYCHLOROETHYLATED ARENES AND GLYCINE DERIVATIVES IN DIMETHYL SULPHOXIDE MEDIUM

The acidity of NH-groups of a number of sulphonamides and glycine derivatives in a dimethyl sulphoxide medium has been investigated using the potentiometric method. Dissociation constants of these compounds are determined from titration curves. It is shown that the acidity of NH groups in the studied sulphonamides is controlled by the polar effect of substituents. The possibility of quantitative potentiometric analysis of glycine derivatives has been established for the first time. Biological activity has been predicted with the help of PASS software. The correlation of NH group acidity with the biological potential of the compounds has been established.

Changes in Mechanism and Transition State Structure for Solvolysis Reactions of Ring Substituted Benzyl Chlorides in Aqueous Solution.

Rate and product data are reported for the solvolysis reactions of twenty-seven mono, di (3,4) and tri (3,4,5) ring-substituted benzyl chlorides. The first order rate constant for solvolysis in 20% acetonitrile in water decrease from k solv = 2.2 s-1 for 4-methoxybenzyl chloride to 1.1 x 10-8 s-1 for 3,4-dinitrobenzyl chloride. The product rate constant ratios k MeOH/k TFE for solvolysis in 70/27/3 (v/v/v) HOH/TFE/MeOH range from a minimum of k MeOH/k TFE = 8 to a maximum of 110. The rate data were fit to a four-parameter Hammett equation that separates the resonance and polar effects of the aromatic ring substituents on the reaction rate. Increases in the values of the Hammett reaction constants and are observed as the substituent constants or are increased. A sharp decrease in the product selectivity k MeOH/k TFE = 26 for stepwise solvolysis of 4-methoxybenzyl chloride is observed as electron-withdrawing meta-substituents are added to 4-methoxybenzyl ring due to a Hammond-effect on the position of the transition state for solvent addition to the substituted 4-methoxybenzyl carbocation reaction intermediates. Sharp increases in the selectivity k MeOH/k TFE are observed with decreasing reactivity of other 3,4,5-subsituted benzyl chlorides due to anti-Hammond shifts on a two-dimensional More-O'Ferrall reaction coordinate diagram in the position of the transition state for a concerted solvolysis reaction.

A new method for determining the intrinsic resistance energy of H‐atom transfer reaction and structure–activity relationship of H‐donating ability

AbstractThe intrinsic resistance energy ΔG≠XH/X of H‐donor XH in hydrogen atom transfer (HAT) reaction is usually used to evaluate the kinetic H‐donating ability. In this article, a new method for determining ΔG≠XH/X of H‐donor in HAT reaction was proposed by the definition of thermo‐kinetic parameter ΔG≠o (XH) = 1/2[ΔG≠XH/X + ΔGo (XH)]. ΔG≠o (XH) is the characteristic physical parameter of XH to describe the H‐donating ability in a chemical reaction during a certain reaction time, ΔGo (XH) is the bond dissociation free energy. The kinetic studies of HATs between 20 alcohols, ethers, alkanes and amines (XH) with cumyloxyl radical [PhC (CH3)2O•, CumO•] were researched, and ΔGo (XH), ΔG≠XH/X, and ΔG≠o (XH) were used to investigate the H‐donating abilities of the studied substrates in thermodynamics, kinetics, and HAT reaction. The effect of structures of XH on these three parameters, the structure–activity relationship, such as the influence of electronic, steric, polar and stereoelectronic effects of substituents, heteroatoms insertion in cycloalkanes, and cis–trans configurational isomerism on the H‐donating abilities were discussed in detail. This study not only provides a new method for determining ΔG≠XH/X but also systematically studies the factors affecting the H‐donating ability, laying a foundation for the selection, design, and synthesis of more efficient antioxidants.

Prediction of the biological activity of a compound depending on its NH-acidity

Abstract: Acetamides are building blocks for the synthesis of compounds containing pharmacophores in their structure, manifesting a diverse range of biological activity. The drugs based on these substances possess antidiabetic effect and inhibit blood coagulation. Some of them act as chemosensitizers (i.e., cancer cell inhibitors). However, the full potential of these compounds remains to be fully accomplished. In a previous study, we synthesised acetamides with the RCONHCH (R´) CCl3 general formula (where R = CH3, CH2Cl; R´ = C6H5, C6H4CH3, C6H4OCH3, C6H4OH) and studied their acid-base behaviour. The NH-acidity of the studied acetamides is controlled by the polar effects of substituents. In this paper, the potential biological activity of the previously obtained acetamides is calculated, and the dependence of their biological potential on the NH-acidity values is elucidated. Prediction of biological activity was carried out using the PASS software. An analysis of the types of biological activity occurring in all compounds allowed us to determine a linear dependence between the probability of biological potential and the value of dissociation constant.

Crystal structure, 1H and 13C NMR spectral studies of 1,2,4,5-oxadiazaborole derivatives

Substituent effects on 1H and 13C NMR chemical shifts of 5-substituted phenyl-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaboroles (1a-r) were studied respectively. Single and duel substituent parameters were used for the correlation analysis of substituent-induced chemical shifts with σ, F and R constants. The calculations have shown the polar and resonance substituent effects on N-H proton and C=N carbon atoms. The ρ value was found positive for compounds (1a-r), which means that the substituent effect is normal. Additionally, crystal structure of compound (1i) was also studied. Density functional theory (DFT) calculations were carried out to calculate the theoretical chemical shifts, bond distances and bond angles.

Effects of Polar Substituents and Media on the Performance of N,N′‐Di‐tert‐Butoxycarbonyl‐Indigos as Photoswitches

AbstractThe N,N′‐di‐tert‐butoxycarbonylindigo parent compound and four symmetrically substituted derivatives alternatively containing methoxy and nitro substituents in positions 5 and 6 were synthesized. The photochromic behavior was studied in solvents ranging in polarity from toluene to acetonitrile/water mixtures and characterized in terms of trans and cis isomer spectra, conversion quantum yields and thermal half‐lives of the metastable cis isomers. The half‐lives at 21 °C varied from a few seconds (5‐nitro in polar solvents) to several days (6‐methoxy in apolar media) and can be described by the substituents’ Hammett constants. Spectroscopic and photochemical parameters, in contrast, are governed largely by the substituents’ resonance effects according to a scheme well known from thioindigos and these are termed here favorable and unfavorable resonance effects (FRE and URE, respectively). The title photoswitches show little propensity to quenching by protons and may be operated in aqueous media.

NH-кислотность замещенных трихлорэтилацетамидов в среде диметилсульфоксида

In this work, we synthesized a series of N-(2,2,2-trichloroethyl) amides with the general formula of RCONHCH (R´) CCl 3 (where R = CH 3 , CH 2 Cl; R´ = C 6 H 5 , C 6 H 4 CH 3 , C 6 H 4 OCH 3 , C 6 H 4 OH) and investigated their acid/base properties in dimethyl sulfoxide (DMSO). For the first time, the curves and constants for the NH-acidity of the acetamides have been drawn using titration data. Under the potentiometric titration of the acetamides, curves with a pronounced jump in the potential of the indicator electrode were obtained in all the studied cases. The NH-acidity of the acetamides under study is shown to depend on the polar effects of substituents. The possibility of quantitative potentiometric analysis of individual acetamides, as well as double and ternary mixtures under their joint presence with sulfonamides in DMSO, was established. The metrological characteristics of the results obtained during a potentiometric determination of the constants under consideration were evaluated. These characteristics are demonstrated to possess a fairly high laboratory precision, with the coefficient of variation ranging from 0,04% to 0,52%. The obtained results were verified using the “introduced-found” method.

Kinetics of Biochemical Transformation of Aniline and Its Derivatives in Natural Water: Quantitative Estimation of the Substituent Effect

Substituent effect on the rate of biochemical transformation of substituted anilines in natural water has been studied. The process can be described by the Hammett equation. The direction of polar substituent effect suggests participation of the amino group in the rate-limiting step.

Synergistic effect of opposite polar substituents on selected properties of disperse yellow 119 dye

By theoretically exploring the synergistic effects of electron donating (ED) and electron withdrawing (EW) substituents on intramolecular charge movement in disperse yellow (DY)119 dye, series of new azopyridone disperse dyes with improved aqueous solubility and chemical reactivity have been predicted using VWN-BP/DNP model. Aqueous solubility and reactivity of DY119 were found to be greatly dependent on the nature and position of substituent(s) on the primary DY119 structure. Momentous increase in solubility was observed with CN and NH2 substituents compared to other substituents. The new derivatives of DY119 showed appreciable thermodynamic stability. TiO2 and ZnO were predicted to be the most promising photocatalysts for the dyes.

Synthesis and mesomorphic properties of benzoxazole derivatives with lateral multifluoro substituents

ABSTRACTFluorinated aromatics is generally chosen as mesogenic cores to design novel liquid crystal compounds. Here, a series of benzoxazole derivatives with laterally multifluorinated biphenyl units, 2-(3′,3-difluoro −4′-alkoxy-1,1′-biphenyl-4-yl)-benzoxazole derivatives (coded as nPF(3)PF(3)Bx), are synthesized and characterized, where methyl and nitro moieties are selected as terminal groups to investigate the effects of different polar substituents on the liquid crystal properties. The compounds nPF(3)PF(3)Bx show enantiotropic mesophases with mesophase ranges of 0–40°C and 0–63°C on heating and cooling for hydrogen-terminated derivatives (nPF(3)PF(3)BH), 43–93°C and 54–123°C for methyl-terminated ones (nPF(3)PF(3)BM), 60–108°C and 74–152°C for nitro terminated ones (nPF(3)PF(3)BN), respectively. They exhibit photoluminescence emission peaks at 390–392 nm and UV–vis absorption bands with maxima at 327–330 nm, respectively. The results reveal that lateral multifluoro substituents lead to a decrease in melting/clearing points, while electron-withdrawing terminal nitro moiety results in increases in both melting point and mesophase range.

Effects of polar substituents on the biological activity of thiosemicarbazone metal complexes

In this paper, citronellal, vanillin and pyridoxal thiosemicarbazones were modified with polar substituents, namely ethylmorpholine and glucose, to increase their polarity and compare the effects of these moieties on their biological activity. Altogether, nine ligands were synthesized and for each of them also their copper(II) and nickel(II) complexes were prepared and used for the biological tests. Eventually, assays on proliferation inhibition were conducted using leukemic cell line U937, already used as a model for previous citronellal thiosemicarbazone tests. Biological tests were also performed on solid tumor cell line HT29. From the first screenings, two of the metal complexes showed remarkable interesting properties, and, therefore, were also tested for histosensitivity.

Substituent effects on gas‐phase homolytic Fe–O and Fe–S bond energies of m‐G‐C6H4OFe(CO)2(η5‐C5H5) and m‐G‐C6H4SFe(CO)2(η5‐C5H5) studied using Hartree–Fock and density functional theory methods

The thermochemistry of organometallic complexes in solution and in the gas phase has been an area of increasing research interest. In this paper, the Fe–O and Fe–S homolytic bond dissociation energies [ΔHhomo(Fe–O)'s and ΔHhomo(Fe–S)'s] of two series of meta‐substituted phenoxydicarbonyl(η5‐cyclopentadienyl) iron [m‐G‐C6H4OFp (1)] and (meta‐substituted benzenethiolato)dicarbonyl(η5‐cyclopentadienyl) iron [m‐G‐C6H4SFp (2)] were studied using Hartree–Fock and density functional theory methods with large basis sets. In this study, Fp is (η5‐C5H5)Fe(CO)2, and G are NO2, CN, COMe, CO2Me, CF3, Br, Cl, F, H, Me, MeO, and NMe2. The results show that Tao–Perdew–Staroverov–Scuseria and Minnesota 2006 functionals can provide the best price/performance ratio and accurate predictions of ΔHhomo(Fe–O)'s and ΔHhomo(Fe–S)'s. The polar effects of the meta substituents show that the dominant role to the magnitudes of ΔΔHhomo(Fe–O)'s or ΔΔHhomo(Fe–S)'s. σα·, σc· values for meta substituents are all related to polar effects. Spin‐delocalization effects of the meta substituents in ΔΔHhomo(Fe–O)'s and ΔΔHhomo(Fe–S)'s are small but not necessarily zero. Molecular effects rather than ΔΔHhomo(Fe–O)'s and ΔΔHhomo(Fe–S)'s are more suitable indexes for the overall substituent effects on ΔHhomo(Fe–O)'s and ΔHhomo(Fe–S)'s. The meta substituent effects of meta‐electron‐withdrawing groups on the Fe–S bonds are much stronger than those on the Fe–O bonds. For meta‐electron‐donating groups, the meta substituent effects have the comparable magnitudes between series 1 and 2. ΔΔHhomo(Fe–O)'s (1) and ΔΔHhomo(Fe–S)'s (2) conform to the captodative principle. Insight from this work may help the design of more effective catalytic processes. Copyright © 2015 John Wiley & Sons, Ltd.

Preparation and properties of lateral monofluoro-substituted benzoxazole-based mesogenic compounds

A series of 2-(3ʹ-fluoro-4ʹ-alkoxy-1,1ʹ-biphenyl-4-yl)-benzoxazole liquid crystals (coded as nPF(3)PBx) were prepared, where a lateral fluorine substituent, as well as methyl, chlorine and nitro terminal groups, was introduced into the molecules to investigate the effects of different polar substituents on the liquid crystal properties. The mesomorphic and photophysical properties were investigated. The results show that compounds nPF(3)PBx have enantiotropic mesophases; meanwhile, they exhibit UV–vis absorption bands with maxima at 323–326 nm and photoluminescence emission peaks at 389–395 nm, respectively. It is noted that nPF(3)PBx with terminal polar groups or electron-withdrawing groups (NO2, Cl) display higher clearing temperatures and wider mesophase range than those of the corresponding homologues with terminal non-polar groups or electron-donating groups (CH3, H). Meanwhile, compared with two lateral fluorine-substituted analogues containing 3,5-difluorophenyl unit, lateral monofluoro-substituted nPF(3)PBx display enhanced mesophase range both in heating and cooling except for terminal methyl-substituted compounds, as well as show obvious red-shifted UV–vis absorption bands and photoluminescence emission, which are attributed to the enhanced dipole–dipole interaction caused by increased dipole moment.

Synthesis and optical properties of the isomeric pyrimidine and carbazole derivatives: Effects of polar substituents and linking topology

A series of nonlinear oligoarylenes with a pyrimidine unit as central core and carbazole containing aryl branches in positions 2, 4 and 4, 6 of the pyrimidine ring were successfully synthesized by sequential Suzuki coupling of the corresponding 2,4- or 4,6-dichloropyrimidines. Optical properties of the compounds were thoroughly investigated in the media of different polarity. Owing to pronounced electron-accepting properties of pyrimidine core, the compounds with donating carbazole groups showed expressed intramolecular charge transfer (ICT) character of the excited states, which was proved by solvatochromic dynamics and supported by DFT calculations. ICT resulted in the dramatic enhancement of excited state lifetime (up to 5 times) with increased solvent polarity. The competition of constantly decreasing radiative and nonradiative relaxation rates resulted in non-monotonous variation of fluorescence quantum yield from 24% to 74%. The tailoring of fluorescence quantum yield of the pyrimidine derivatives via altering linking topology and polarity of the substituents is discussed.

Maximizing the dielectric response of molecular thin films via quantum chemical design.

Developing high-capacitance organic gate dielectrics is critical for advances in electronic circuitry based on unconventional semiconductors. While high-dielectric constant molecular substances are known, the mechanism of dielectric response and the fundamental chemical design principles are not well understood. Using a plane-wave density functional theory formalism, we show that it is possible to map the atomic-scale dielectric profiles of molecule-based materials while capturing important bulk characteristics. For molecular films, this approach reveals how basic materials properties such as surface coverage density, molecular tilt angle, and π-system planarity can dramatically influence dielectric response. Additionally, relatively modest molecular backbone and substituent variations can be employed to substantially enhance film dielectric response. For dense surface coverages and proper molecular alignment, conjugated hydrocarbon chains can achieve dielectric constants of >8.0, more than 3 times that of analogous saturated chains, ∼2.5. However, this conjugation-related dielectric enhancement depends on proper molecular orientation and planarization, with enhancements up to 60% for proper molecular alignment with the applied field and an additional 30% for conformations such as coplanarity in extended π-systems. Conjugation length is not the only determinant of dielectric response, and appended polarizable high-Z substituents can increase molecular film response more than 2-fold, affording estimated capacitances of >9.0 μF/cm2. However, in large π-systems, polar substituent effects are substantially attenuated.

Phosphine‐Catalyzed Annulations between Modified Allylic Derivatives and Polar Dienes and Substituent Effect on the Annulation Mode

AbstractIn this work, the phosphine‐catalyzed annulation reactions between modified allylic derivatives and polar 1,1‐dicyano‐1,3‐dienes have been studied. In the catalysis of PPh3 (20 mol%), a [4+1] annulation reaction is realized between a series of 1,1‐dicyano‐2,4‐diaryl‐1,3‐dienes and ethoxycarbonyl‐activated allylic acetate, producing polysubstituted cyclopentenes in modest to excellent yields. It is also observed that the substituents of both 1,3‐dienes and allylic derivatives have a significant influence on the annulation mode: under the catalysis of PPh3 or PBu3 (20 mol%), regioselective [3+2] annulation products are formed from differently substituted substrates.

Linear free energy relationships of 13C NMR chemical shifts in 4-substituted phenyl-4,5-dihydrobenzo[f][1,4]oxazepin-3(2H)-ones(thiones)

Linear free energy relationships (LFER) were applied to the 13C NMR chemical shifts in 4-substituted phenyl-4,5-dihydrobenzo[f][1,4]oxazepin-3(2H)-ones(thiones). The correlation analysis for the substituent-induced chemical shifts (SCS) with inductive and resonance parameters (σ, F and R) were carried out by using SSP (single substituent parameter) and DSP (dual substituent parameter). The presented calculation accounts satisfactorily for the polar and resonance substituent effects operating at benzoxazepine carbon atoms. Negative ρ values were found for several correlations (reverse substituent effect). For a better understanding of the results, density functional theory (DFT) calculations were performed to determine the preferred geometry and to calculate the theoretical 13C NMR chemical shifts.

Combined Effect of Polar Substituents on the Electronic Flows in the Carotenoid Molecular Wires

Carrot wires: Carotenoid molecular wires containing a pair of polar aromatic substituents have been synthesized to probe the combined effect of electron-withdrawing and -donating groups as conductance modulators (see figure). The total conductance values of the carotenoid wires are mostly controlled by electron-withdrawing substituents, whereas fine tuning is possible by way of the electron-donating substituent. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Experimental and theoretical study of substituent effect on 13C NMR chemical shifts of 5-arylidene-2,4-thiazolidinediones

The electronic structure of 5-arylidene-2,4-thiazolidinediones has been studied by using experimental and theoretical methodology. The theoretical calculations of the investigated 5-arylidene-2,4-thiazolidinediones have been performed by the use of quantum chemical methods. The calculated 13C NMR chemical shifts and NBO atomic charges provide an insight into the influence of such a structure on the transmission of electronic substituent effects. Linear free energy relationships (LFERs) have been further applied to their 13C NMR chemical shifts. The correlation analyses for the substituent-induced chemical shifts (SCS) have been performed with σ using SSP (single substituent parameter), field (σF) and resonance (σR) parameters using DSP (dual substituent parameter), as well as the Yukawa–Tsuno model. The presented correlations account satisfactorily for the polar and resonance substituent effects operative at Cβ, and C7 carbons, while reverse substituent effect was found for Cα. The comparison of correlation results for the investigated molecules with those obtained for seven structurally related styrene series has indicated that specific cross-interaction of phenyl substituent and groups attached at Cβ carbon causes increased sensitivity of SCS Cβ to the resonance effect with increasing of electron-accepting capabilities of the group present at Cβ.

Calculated polar substituent effects on the stability of 3-substituted(X) bicyclo[1.1.1]pent-1-yl cations and 4-substituted(X) bicyclo[2.2.1]hept-1-yl cations: a DFT study

The effects of substituents on the stability of 3-substituted(X) bicyclo[1.1.1]pent-1-yl cations (3) and 4-substituted(X) bicyclo[2.2.1]hept-1-yl cations (4), for a set of substituents (X = H, NO2, CN, NC, CF3, CHO, COOH , F, Cl, HO, NH2, CH3, SiH3, Si(CH3)3, Li, O−, and NH3+) covering a wide range of electronic substituent effects were calculated using the DFT theoretical model at the B3LYP/6-311 + G(2d,p) and B3LYP/6-31 + G (d) levels of theory, respectively. Linear regression analysis was employed to explore the relationship between the calculated relative hydride affinities (ΔE, kcal/mol) of the appropriate isodesmic reactions for 3/4 and polar field/group electronegativity substituent constants (σF and σχ, respectively). The analysis reveals that the ΔE values for both systems are best described by a combination of both substituent constants. The result highlights the importance of the σχ dependency of charge delocalization in these systems. Copyright © 2012 John Wiley & Sons, Ltd.