Hammett Substituent Constants Research Articles

Bulk stereoselective cationic polymerization of vinyl ethers by the coordination of ZrCl4 with tunable spirocyclic phosphoric acids.

Control over stereochemistry in poly(vinyl ether)s leads to a notable change in their physical properties, yet remains a grand challenge. Here, we demonstrate the bulk stereoselective cationic polymerization of vinyl ethers using ZrCl4 coordinated with a spirocyclic phosphoric acid (SPA). The widely variable substituents in SPAs exert a profound impact on the stereochemical and activity outcome of the polymerization: the % m of poly(vinyl ether)s linearly increases with the Hammett substituent constant (σ) of SPAs; the catalytic activity increases with the σ; the large steric hindrance groups lead to decreased polymerization activity. Mechanism studies suggest that the coordination of ZrCl4 with three equivalents of SPAs generates the chiral complex. The complex can abstract chlorine from the initiator/chain end to form the chiral ion pair allowing the selective facial addition of incoming monomers. The catalyst system features characteristics of no solvent, low loads, high tacticity control, high monomer scope, and recyclability.

Defining the Synthetic Scope of ortho-Quinone Methides by Quantifying Their Electrophilicity.

A series of aryl-substituted ortho-quinone methides (oQMs) was synthesised and structurally characterised. Kinetic studies of the nucleophilic additions of carbanions (reference nucleophiles) to oQMs were used to determine second-order rate constants k2 for the carbon-carbon bond forming reactions (20°C, DMSO) at the oQMs' exocyclic π-bond. Analysing the kinetic data by the linear free energy relationship lg k2 = sN(N+E) revealed the Mayr electrophilicities E of the oQMs. The electrophilicities E of oQMs correlate linearly with Hammett substituent constants and experimentally determined reduction potentials Epred as well as with quantum-chemically calculated methyl anion affinities (MAAs), which provides valuable tools for prediciting the reactivity of further types of oQMs. Embedding the oQMs in Mayr's reactivity scales enables to predict novel nucleophilic reaction partners for oQMs and can productively be used to prepare simple Michael adducts as well as 4+2 or 4+1 cyclisation products as demonstrated in this work by several novel reactions with neutral or negatively charged C-, N-, and S-nucleophiles.

A new perspective on contaminants as "activators": Aromatic amine groups promoted degradation of tetracycline by ferrate(VI)

Occasionally, our group found that the degradation of tetracycline by ferrate(VI) could be promoted by four co-exist contaminants, containing aromatic amines (ofloxacin, diatrizoic acid, sulfadiazine and alachlor). This study investigated the promotion of aromatic amine groups on tetracycline degradation by ferrate(VI) by using aniline as a model compound. The results implied that the presence of aniline increased the degradation rate of tetracycline by 2.76 times, and the enhancement was weakened gradually with the decrease of pH from 10 to 7.5. The generation of Fe(IV) and·OH by the reaction between ferrate(VI) and aniline was proposed to enhance the degradation of tetracycline, supported by quenching experiments, electron paramagnetic resonance (EPR) and theoretical calculations. A positive correlation was found between the rate constant of tetracycline degradation and the electron-donating ability of the substituted amines (quantified by the Hammett substituent constants). In addition, the degradation of tetracycline was remarkably inhibited by HA and some inorganic ions such as NO3-, SO42-, Cl-, Ca2+, and Mg2+, and the inhibition also happened in the Songhua River water and the secondary effluent. The present study provided an insight into the complex oxidation process for the degradation of micropollutants containing aromatic amine by ferrate in water treatment.

Dissociative Electron Transfer to N‐(Arylthio)phthalimides: Factors Affecting the Formation and Dissociation of Radical Anions

AbstractA series of chemically and biologically relevant N‐(arylthio)phthalimides is synthesized and its electrochemical reduction investigated. The results of the electrochemical study are analysed through application of Savéant's dissociative electron transfer theory and with the assistance of theoretical calculations. Reduction of all investigated N‐(arylthio)phthalimides leads to the corresponding radical anions, followed by the ejection of the phthalimide anion resulting from the dissociation of the N−S chemical bond. This stepwise electron transfer mechanism is evidenced by the electrochemical data which allow determination of the standard reduction potentials of all compounds. In the formation of the N‐(arylthio)phthalimide radical anions, the theoretical calculations show that the incoming electron, is hosted by the phthalimidyl group indicating a homolytic dissociation mechanism. The dissociation rate constants of the radical anions are deduced and show that upon changing the substituent from the MeO, to Me, H, F, Cl and Br the dissociation becomes faster. A good correlation with the Hammett substituent constants is also obtained. Application of Savéant's theory through determination of the associated driving force and the intrinsic barrier energies help rationalize the observed results and show that the change in the dissociation rate constant depends mainly on the standard reduction potential of the parent compounds.

Unravelling the effects of functional groups on the adsorption of 2-mercaptobenzothiazole on a copper surface: a DFT study.

The adsorption of organic compounds onto metal surfaces holds significant importance across various applications, where understanding the intricate interactions between the compounds and the metal surfaces is indispensable. By using density functional theory calculations, this study investigated the impact of functional groups on the interaction between the thione form of 2-mercaptobenzothiazole (MBT) and the Cu(111) surface. The results indicated that substituting functional groups at the C6 position exerts a dual influence on the covalent and non-covalent interactions (NCI). Electron-donating groups enhanced both covalent and non-covalent interactions, whereas electron-withdrawing groups decreased covalent while increasing non-covalent interactions. The covalent interaction between MBTs and Cu(111) is mainly governed by the electron donation from the occupied orbitals of the molecules to the conduction band of copper, with the absolute interaction energies (eV) increasing in the order of MBT-NO2 (0.629) < MBT-COOH (0.660) < MBT-Cl (0.699) < MBT (0.715) < MBT-SH (0.727) < MBT-OH (0.733) < MBT-CH3 (0.735) < MBT-OCH3 (0.749) < MBT-NH2 (0.781) < MBT-NHCH3 (0.792). The influence of functional groups on covalent interactions is clarified by examining changes in the molecule's electronic structure, revealing a linear relationship between covalent interaction energy and HOMO energy, or the Hammett substituent constant. However, the impact of functional groups on non-covalent interactions is more complex and cannot be described by changes in the electronic structure. A novel parameter, the substitution interaction energy, was proposed to capture the effect of functional groups on the NCI-included adsorption energy of MBT derivatives on the Cu(111) surface. The stronger the substitution interaction, the stronger the NCI-included interaction of MBTs on Cu(111). The absolute NCI-included interaction energies follow the order of MBT (2.141) < MBT-Cl (2.213) < MBT-COOH (2.266) < MBT-CH3 (2.294) < MBT-OH (2.331) < MBT-OCH3 (2.379) < MBT-NO2 (2.461) = MBT-NH2 (2.461) < MBT-SH (2.530) < MBT-NHCH3 (2.565). These insights offer valuable guidance for manipulating the adsorption of organic substances on metal surfaces through functional groups in diverse applications.

Effect of the Hammett substituent constant of para-substituted benzoic acid on the perovskite/SnO2 interface passivation in perovskite solar cells.

It is critical to design bifunctional passivation molecules to simultaneously passivate the charge transport layer and perovskite layer at the charge transport layer/perovskite interface in perovskite solar cells (PSCs). In this study, we investigate the effect of para-substituted benzoic acid with different Hammett constants (σ) on the photovoltaic performance of PSCs. Two passivation molecules 4-aminomethylbenzoic acid (4-AMBA) and 4-sulfamoylbenzoic acid (4-SABA) are used to passivate the SnO2 surface with carboxylic acid and the perovskite with para-substituent electron-donating -CH2NH2 (σ = ca. -0.02) and electron-withdrawing -SO2NH2 (σ = ca. +0.60). Compared with non-passivated PSC, the passivation improves the power conversion efficiency (PCE) mainly due to the increased open-circuit voltage (VOC) and fill factor (FF), where the -SO2NH2 substituent is better in improving the photovoltaic performance than the -CH2NH2 one. The trap density is more reduced and the charge extraction ability is more improved by 4-SABA than by 4-AMBA, which indicates that the weak electron-withdrawing nature of a para-substituent such as -SO2NH2 is better for the passivation of the bottom perovskite than a weak electron-donating -CH2NH2 substituent. Consequently, the passivation with 4-SABA enhances the PCE from 22.27% to 23.64%, along with improved long-term stability. This work highlights for the first time the role of the Hammett constant in the surface passivation of PSCs.

The molecular structure of 4-substituted pyridine N-oxides–boron trifluoride triel bonded complexes: Peculiarities and regularities

Pyridine N-oxides are widely used in medicine, organic synthesis and design of functional coordination compounds and supramolecular systems. However, at present, issues related to the complex formation and stereochemistry of pyridine N-oxide molecular complexes as well as the nature of the complexing bond and the substituent effect remain relevant. In this paper the substituent effect on geometric, electronic, thermodynamic and spectral properties was established by quantum chemical calculations (DFT/M062-X/aug-cc-pvTZ) for the series of 4-substituted pyridine N-oxides with boron trifluoride as model complexes. Theoretical insights into the nature of OB triel bond was considered in terms of QTAIM and NBO analysis. A conformational analysis has been performed to resolve the contradictions in the literature data concerning the stereochemistry of such complexes. The calculated structural parameters, as well as complex formation energy, binding energy, thermodynamic characteristics, vibrational frequencies and chemical shifts reveal high correlation with the empirical Hammett substituent constants.

Unraveling the promoter effect and the roles of counterion exchange in glycosylation reaction.

The stereoselectivity of glycosidic bond formation continues to pose a noteworthy hurdle in synthesizing carbohydrates, primarily due to the simultaneous occurrence of SN1 and SN2 processes during the glycosylation reaction. Here, we applied an in-depth analysis of the glycosylation mechanism by using low-temperature nuclear magnetic resonance and statistical approaches. A pathway driven by counterion exchanges and reaction byproducts was first discovered to outline the stereocontributions of intermediates. Moreover, the relative reactivity values, acceptor nucleophilic constants, and Hammett substituent constants (σ values) provided a general index to indicate the mechanistic pathways. These results could allow building block tailoring and reaction condition optimization in carbohydrate synthesis to be greatly facilitated and simplified.

Improved Catalytic Performance toward Selective Oxidation of Benzyl Alcohols Originated from New Open-Framework Copper Molybdovanadate with a Unique V/Mo Ratio.

A new organic-inorganic hybrid open-framework molybdovanadate with mixed-valences of vanadium (V4+ /V5+ =4/3) and molybdenum (Mo5+ /Mo6+ =8/2) cations has been synthesized. The complex possesses the unique V/Mo ratio (7/10), fascinating 8-C topological network and 1D 4-MR channels (7.793 Å×6.699 Å). Importantly, its catalytic activities for the selective oxidation of benzyl alcohol to benzaldehyde (oxidant: H2 O2 , 30 wt %) have been well evaluated. The results indicated that it exhibited improved catalytic activities (conv.: 96.8 %) compared with the catalyst (Cpyr)5 PV2 Mo5 W5 O40 [conv.: 88.51 %, Cpyr=(C16 H32 C5 H4 N)+ )], high recyclability and structural stability. Moreover, the conversions and selectivities (conv.: 82.4-92.5 %; sele.: 91.5-95.7 %) of the substrates containing electron donating groups (-OH, -CH3 , -OCH3 and -Cl) were significantly higher than those of the substrate containing electron withdrawing group (-NO2 ) (conv. 67.4 %; sele.: 80.8 %). This is due to the fact that the -NO2 with a large Hammett substituent constant is not conducive to the generation of transition state products. The studies revealed the complex could act as a highly efficient heterogeneous catalyst in selective oxidation of benzyl alcohols.

Sheltering Mono-P-Ligated Metal Complexes in Porous Polystyrene Monolith: Effect of Aryl Pendant Stabilizers on Catalytic Durability.

Metal centers that can generate coordinatively unsaturated metals in accessible and stable states have been developed using synthetic polymers with sophisticated ligand and scaffold designs, which required synthetic efforts. Herein, we report a simple and direct strategy for producing polymer-supported phosphine-metal complexes, which stabilizes mono-P-ligated metals by modulating the electronic properties of the aryl pendant groups in the polymer platform. A three-fold vinylated PPh3 was copolymerized with a styrene derivative and a cross-linker to produce a porous polystyrene-phosphine hybrid monolith. Based on the Hammett substituent constants, the electronic properties of styrene derivatives were modulated and incorporated into the polystyrene backbone to stabilize the mono-P-ligated Pd complex via Pd-arene interactions. Through NMR, TEM, and comparative catalytic studies, the polystyrene-phosphine hybrid, which induces selective mono-P-ligation and moderate Pd-arene interactions, demonstrated high catalytic durability for the cross-coupling of chloroarenes under continuous-flow conditions.

Copper-Catalyzed Enantioselective Difluoromethylation-Alkynylation of Olefins by Solving the Dilemma between Acidities and Reduction Potentials of Difluoromethylating Agents.

Molecules containing a difluoromethyl group or a propargylic stereocenter are widely used in pharmaceuticals and agrochemicals, and 1,2-functionalization of olefins is an important method for introducing the two groups into molecules simultaneously. The construction of the propargylic stereocenter with terminal alkynes usually requires bases. However, difluoromethylating agents with high reduction potentials often decompose in the presence of bases because of their acidities, and those with low reduction potentials are stable but difficult to undergo the desired single electron transfer (SET) reduction. Using the linear relationship between reduction potential differences (ΔE) and Hammett substituent constants (σ) of difluoromethyl aryl sulfones, we solved the dilemma between acidities and reduction potentials of difluoromethylating agents. Herein, we report the first enantioselective difluoromethylation-alkynylation of olefins with difluoromethyl 4-chlorophenyl sulfone with high enantioselectivity (>90 % ee). We also extended this asymmetric fluoroalkylation-alkynylation reaction with other fluoroalkyl sulfones, which enabled efficient installation of trifluoromethyl, difluoroalkyl, difluorobenzyl, (benzenesulfonyl)-difluoromethyl and monofluoromethyl groups into products.

Copper‐Catalyzed Enantioselective Difluoromethylation‐Alkynylation of Olefins by Solving the Dilemma between Acidities and Reduction Potentials of Difluoromethylating Agents

AbstractMolecules containing a difluoromethyl group or a propargylic stereocenter are widely used in pharmaceuticals and agrochemicals, and 1,2‐functionalization of olefins is an important method for introducing the two groups into molecules simultaneously. The construction of the propargylic stereocenter with terminal alkynes usually requires bases. However, difluoromethylating agents with high reduction potentials often decompose in the presence of bases because of their acidities, and those with low reduction potentials are stable but difficult to undergo the desired single electron transfer (SET) reduction. Using the linear relationship between reduction potential differences (ΔE) and Hammett substituent constants (σ) of difluoromethyl aryl sulfones, we solved the dilemma between acidities and reduction potentials of difluoromethylating agents. Herein, we report the first enantioselective difluoromethylation‐alkynylation of olefins with difluoromethyl 4‐chlorophenyl sulfone with high enantioselectivity (&gt;90 % ee). We also extended this asymmetric fluoroalkylation‐alkynylation reaction with other fluoroalkyl sulfones, which enabled efficient installation of trifluoromethyl, difluoroalkyl, difluorobenzyl, (benzenesulfonyl)‐difluoromethyl and monofluoromethyl groups into products.

Tuning the pH of Activation of Fluorinated Hydrazone-Based Switches─A Pathway to Versatile 19F Magnetic Resonance Imaging Contrast Agents.

Molecular switches have become an area of great interest in recent years. They are explored as high-density data storage and organic diodes in molecular electronics as well as chemosensors due to their ability to undergo a transition between well-defined structures under the action of external stimuli. One of the types of such switches is hydrazones. They work by changing the configuration from E to Z under the influence of pH or light. The change in configuration is accompanied by a change in the absorption band and changes in the nuclear magnetic resonance (NMR) spectrum. In this publication, the structure-property relationship of fluorinated hydrazone switches was established. A linear relationship between the Hammett substituent constants and the pH where the switching occurs was found. Introduction of strong electron-donating groups allowed obtaining a hydrazone switch of pKa = 6 suitable for application in 19F MRI as contrast agents.

Synthesis and Characterization of Hypervalent Pentacoordinate Carbon Compounds Bearing a 7-6-7-Ring Skeleton.

To stabilize SN 2 transition state-like penta-coordinate carbon species, triaryl-substituted cationic carbon compounds bearing a moderately flexible 7-6-7-ring skeleton with sulfur donors were synthesized and characterized. Electronic effects of para substituents (R=Cl, F, H, CH3 , SMe, OMe) of the two equatorial aryl groups bound to the cationic central carbon were investigated systematically along with a planar bidentate thioxanthene derivative. X-ray analysis on their solid-state structures showed that the parent (R=H), chloro-, fluoro- and methyl-derivatives were tetracoordinate carbon (sulfonium) structures, while the p-MeO and thioxanthenyl system were pentacoordinate carbocation structures. The Hammett substituent constants for the para substituents (σp + ) correlates well with the bonding in these compounds. The methylthio-derivative with intermediate Hammett substituent constants (p-MeS; σp + =-0.60) showed a tetracooridnate solid-state structure, though solution UV-Vis properties suggested the presence of a penta-coordinate structure. These findings amount to the first unambiguous solution evidence of the hypervalent apical 3c-4e interactions in pentacoordinate carbon compounds.

Correlation between Absorption and Substitution of Photochromic 1,2‐Bis(thienyl)ethenes (BTEs) Using Modified Spectroscopic Hammett Equations

AbstractSeries of photochromic 1,2‐bis(thienyl)ethenes possessing perfluorocyclopentene backbones, either hydrogen or methyl groups at the β‐positions of the thiophenes, and a variety of substituents in their α'‐positions were prepared, which cover the range from electron‐donating to electron‐withdrawing (Me, −CH2OH, −OTBS, −TMS, −Br, 1,3‐dioxan‐2‐yl, pyridin‐4‐yl, −CH2OH, −COOH). As a linear free energy relationship the spectroscopic Hammett equation gives fair to excellent fits to the excitation energy of the absorption maxima of the ring‐opened as well as the ring‐closed forms of the BTEs, when Hammett substituent constants σp were replaced by Brown's modified substituent constants σp+ and σp−. Vice versa, hitherto unknown Hammett‐Brown substituent constants can be estimated from the UV spectra. Furthermore, we compared the experimentally measured absorption maxima with values which we calculated by three different methods (DFT STEOM‐DLPNO‐CCSD/def2‐TZVPP, TD‐DFT ωB97X‐D3/6‐31G*, TD‐DFT ωB97X‐D3/6‐311++G**).

A G4 approach to computing the Hammett substituent constants σp, σm, σ−, σ+, and σ+m

AbstractBy performing appropriate empirical scaling of G4 energy differences, it is possible to calculate Hammett substituent constants σp, σm, σ−, σ+, and σ+m with a typical accuracy (mean absolute error) of ±0.1. The procedure is straightforward and easily carried out by non‐experts using the Gaussian software package. Values are provided for 41 substituents of widely varying electronic character, including some reactive species for which experimental values are unavailable. Additionally, comparison of calculated and experimental values suggests that some previously published numbers might be significantly in error, particularly for some ionic, acidic, and/or basic substituents. Values are also provided for a newly defined substituent constant, σ−m.

A tunable pH probe scaffold based on sulfonamide rhodamine and its application in mitochondrial pH research

The mitochondrial pH is a vital microenvironment factor of mitochondria. Whether the mitochondria can play their unique function in a cell largely depends on what the mitochondrial pH is. Most of the influence factors of mitochondrial pH remain unclear because of the lack of pH sensitive probes for quantitative measurement of mitochondrial pH changes in vivo. Here, we report a pH fluorescence probe scaffold by which we can modify and accurately predict the pKa of the probe just according to the Hammett substituent constants. To verify the adjustability of the scaffold, 4-fluorophenylsulfonyl rhodamine was inspected as a test sample. The research showed that the predicted pKa value of the sample (5.586) was consistent with the measured value (5.584). Based on the scaffold, a two-photon ratio fluorescent pH probe 8 was designed, which can well target mitochondria and precisely measure the changes of mitochondrial pH. Probe 8 was successfully applied to study the effect of glucose content and oxidative stress on mitochondrial pH. For the first time, we measured the huge difference in mitochondrial pH between normal cells and cancer cells under a high glucose concentration with oxidative stress. The difference implied that cancer cells have lower adaptability to oxidative stress than normal cells under high glucose concentration.

Improved Synthesis Strategy for N‐Methoxy‐1,3‐oxazinane Nucleic Acids (MOANAs)

AbstractDependence of the hydrolysis rate of a series of N‐methoxy‐2‐phenyl‐1,3‐oxazinanes on the Hammett substituent constant of the substituent of the phenyl ring was determined, yielding a reaction constant ρ=−1.40±0.05. Based on this information, 4‐(benzoyloxy)benzaldehyde was selected as a protecting group for a new (2R,3S)‐4‐(methoxyamino)butane‐1,2,3‐triol phosphoramidite building block. The yield of the preparation of this building block as well as its coupling in automated oligonucleotide synthesis were greatly improved compared to the method reported previously. The 2‐[4‐(benzoyloxy)phenyl]‐1,3‐oxazine protection persisted throughout the synthesis of short oligonucleotides but was rapidly removed when the oligonucleotides were released from solid support and dissolved in water.

A Distinctive Pattern for Substituent Effects on Transition Metal Centers: Enhanced Electron-Donating Capacity of Cationic Palladium Species

A Distinctive Pattern for Substituent Effects on Transition Metal Centers: Enhanced Electron-Donating Capacity of Cationic Palladium Species

Comparison of the kinetics of aldehyde sensing by covalent bond formation with hydrazines and hydroxylamines

Analytical techniques for the detection of aldehydes often involve reaction with either a hydrazine or hydroxylamine derivative, resulting in the formation of a hydrazone or oxime, respectively. While there are various examples for the use of either type of derivatization reagent, there have been only few reports with data suitable to answer which of the two types of probes allows faster and more selective detection of aldehydes. Addressing this question, this work used 1H NMR spectroscopy to study the kinetics of the reactions of aromatic and aliphatic aldehydes with two derivatization probes, phenylhydrazine or O-phenylhydroxylamine, in tetrahydrofuran and in presence of an excess of acid catalyst. A fitting procedure was developed to determine the rate constants of these second order reactions while avoiding use of either aldehyde or probe in a large excess. Hydrazone formation was found to be on average 71 times faster than oxime formation. The rate constants for the reaction of aromatic aldehydes with the phenylhydrazine follow largely the trend predicted by Hammett substituent constants, with the notable exception of the hydrogen bond forming 2-hydroxybenzaldehyde. Unlike in studies with water as solvent, aliphatic aldehydes were not found to react faster than aromatic ones.