Electronic Nature Of Substituents Research Articles

Dual-Emissive Monoruthenium Complexes of N(CH3)-Bridged Ligand: Synthesis, Characterization, and Substituent Effect.

Three monoruthenium complexes 1(PF6)2-3(PF6)2 bearing an N(CH3)-bridged ligand have been synthesized and characterized. These complexes have a general formula of [Ru(bpy)2(L)](PF6)2, where L is a 2,5-di(N-methyl-N'-(pyrid-2-yl)amino)pyrazine (dapz) derivative with various substituents, and bpy is 2,2'-bipyridine. The photophysical and electrochemical properties of these compounds have been examined. The solid-state structure of complex 3(PF6)2 is studied by single-crystal X-ray analysis. These complexes show two well-separated emission bands centered at 451 and 646 nm (Δλmax = 195 nm) for 1(PF6)2, 465 and 627 nm (Δλmax = 162 nm) for 2(PF6)2, and 455 and 608 nm (Δλmax = 153 nm) for 3(PF6)2 in dilute acetonitrile solution, respectively. The emission maxima of the higher-energy emission bands of these complexes are similar, while the lower-energy emission bands are dependent on the electronic nature of substituents. These complexes display two consecutive redox couples owing to the stepwise oxidation of the N(CH3)-bridged ligand and ruthenium component. Moreover, these experimental observations are analyzed by computational investigation.

Synthesis of Spirolactones and Functionalized Benzofurans via Addition of 3-Sulfonylphthalides to 2-Formylaryl Triflates and Conversion to Benzofuroisocoumarins.

A convenient protocol for the synthesis of spirobenzofuran-isobenzofurans and substituted benzofurans via a modified Hauser-Kraus reaction of 3-sulfonylphthalide with 2-formylaryl triflates is reported here. The initial reaction involved 1,2-addition of phthalide to the formyl group and intramolecular cyclization via substitution of triflate followed by a cascade of rearrangements leading to spirolactone or benzofuran derivatives. The electronic nature of substituents on aryl triflates affected the course and outcome of the reaction. The mechanism was supported by successful characterization of one of the intermediates by mass spectrometry. A medicinally relevant influenza virus type B inhibitor, benzofuroisocoumarin, was synthesized in a single step from the spiro compound, thus demonstrating the synthetic utility of our methodology.

Imidazo[4,5-b]pyridine derived iminocoumarins as potential pH probes: Synthesis, spectroscopic and computational studies of their protonation equilibria

We describe the synthesis, spectroscopic characterization and computational analysis of the protonation equilibria of several newly designed imidazo[4,5-b]pyridine derived iminocoumarins to confirm their potential as pH sensing molecules in different solvents. The photophysical characterization and acid/base properties of these chromophores have been carried out in several polar and non-polar organic solvents as well as buffered aqueous solution with different pH values using UV–Vis and fluorescence spectroscopies. Obtained results revealed that both the solvent polarity and the electronic nature of substituents placed at the iminocoumarin and imidazo[4,5-b]pyridine cores significantly influence spectral responses of studied systems. An excellent agreement in experimentally measured and computationally determined pKa values and electronic excitations suggests that all systems are monoprotonated cations at neutral pH, while their transition to diprotonated forms occurs at pH values between 3.4 and 4.4, whereas they get reverted to neutral unionized molecules between 10.4 and 13.7. These small differences in narrow ranges of borderline pH values are predominantly brought about by variations in a single substituent on the iminocoumarin core, thereby allowing a simple strategy to further modify the observed sensing features and easily tune them for a specific application.

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol O -Nucleophiles

Chiral Sulfide/Phosphoric Acid Cocatalyzed Enantioselective Intermolecular Oxysulfenylation of Alkenes with Phenol and Alcohol <i>O</i> -Nucleophiles

Microwave‐Assisted 1,3‐Dioxa‐[3,3]‐Sigmatropic Rearrangement of Substituted Allylic Carbamates: Application to the Synthesis of Novel 1,3‐Oxazine‐2,4‐dione Derivatives

AbstractIn a first instance, the effect of the microwave irradiation on the 1,3‐Dioxa‐[3,3]‐sigmatropic rearrangement of aryl allylic carbamates was investigated. Under these new conditions, the reaction acceleration was clearly highlighted compared to conventional heating conditions. Depending on the electronic nature of substituents on the aromatic group, this type of rearrangement can be faster with similar or improved yields. Due to this experimental improvement, the diversity of aryl allylic carbamates able to undergo this rearrangement in a reasonable reaction time (30 min.) and with acceptable to high yields was greatly extended. Finally, an original synthetic way involving this microwave‐assisted process to access new six‐membered heterocyclic structures such as (E)‐5‐arylidene‐1,3‐oxazinane‐2,4‐diones was developed from Morita‐Baylis‐Hillman (MBH) adducts showing the interest of this molecular rearrangement approach. DFT and Fragment Distortion studies showed in general polar transition structures and connected high deformation and interaction energies with lower activation barriers.

Differential Chromogenic Response towards F− and H2PO4−: Hydrogen Bonding vs Deprotonation

AbstractHighly colored oxidized 3,3/‐di(indolyl)arylmethanes (DIAM) based probes have been synthesized in good yield using modified single‐step synthesis. The internal charge transfer state of the molecules as well as protonation equilibrium of indolyl units are dominated by the electronic nature of substituents (R=−CH3, −NMe2, −NO2 etc) present on the central aryl moiety. However, irrespective to the nature of the substituents, all compounds (HL) show selective chromogenic response towards basic anions, like F− and H2PO4− etc in CH3CN. At low concentration, both analytes induce hypsochromic shifts in absorption maximum owing to the formation of H‐bonded complex (HL….A). However, only F− ion at high concentration results in a large bathochromic shift (▵λ∼90 nm) at λmax, probably due to the formation of deprotonated receptor (L−), attributed by higher stability of H‐bonded [HF2−] dimer. Thus, one can easily discriminate between these ions via color‐changing response. On the other hand, HSO4− being an acidic anion results in protonation of indolyl nitrogen center (H2L+) even at low concentration in CH3CN‐H2O (1 : 1) mixture medium, leading to bathochromic shift of absorption maxima.

On the Effect of the Nature of Substituents on the Antimicrobial Activity of Water-Soluble Acylhydrazones on the Isatin Scaffold

The dependence of the level of antimicrobial activity of some ammonium isatin-3-acylhydrazones on the sterical hindrance and electronic nature of substituents in the benzyl moiety was elucidated using simple molecular descriptors and quantum chemical calculations. The structure and electronic nature of substituents in position 1 and the lipophilicity of compounds of this series were shown to be the key factors determining the activity.

Mechanistic Insight into Palladium‐Catalyzed Enantioselective Remote meta‐C−H Arylation and Alkylation by Using Density Functional Theory (DFT) Calculations

AbstractSteric hindrance is usually the only determining factor in controlling the enantioselectivity of a reaction. Here, we disclose a different way in which steric hindrance and electronic properties cooperate to control the transformation enantioselectivity. In this study, palladium‐catalyzed enantioselective remote meta‐C−H arylation and alkylation via a chiral transient mediator was investigated to elucidate the mechanistic details and essence of the excellent enantioselectivity by using density functional theory methods. The calculations indicate that the deprotonation process is the rate‐determining step of the reaction, whereas norbornene insertion is most likely the enantioselectivity‐determining step. Although transition state structure analysis indicates that steric hindrance indeed contributes to this enantioselectivity, its individual action is insufficient to account for the excellent S‐configuration selectivity. The electronic nature of substituents on the C=C double bond of norbornene as a chiral transient mediator plays a crucial role in this enantioselective conversion. A weak electron‐withdrawing group is favorable for enantioselectivity, whereas strong electron‐withdrawing and electron‐donating groups are exactly the opposite. Computations reveal that a weak electron‐withdrawing group slightly lowers the charge density of the chiral norbornene C=C double bond, resulting in a decrease in reactivity. Especially, for the R‐configuration, the insertion reaction energy barrier increases to approximately 29.3 kcal/mol. Such a high barrier is commensurate with that of the S‐configuration rate‐determining step (28.2 kcal/mol), thereby preventing the formation of R‐configuration products and ultimately determining the enantioselectivity of the protocol.magnified image

Experimental and theoretical exploration of photophysics and trans-cis photoisomerization of styrylbenzene conjugated terpyridine complexes of Ru(II): Strong effect of deprotonation from second coordination sphere

We report herein synthesis, characterization, photophysics, and photo-isomerization behaviors of a new class of heteroleptic Ru(II) complexes incorporating styrylbenzene conjugated terpyridine and 2,6–bis(benzimidazole–2–yl)pyridine ligands. All the complexes display moderately strong luminescence at room temperature with appreciably long lifetime varying in the range between 7.2 and 62.2 ns, depending upon the electronic nature of substituent as well as the solvent. The styrylbenzene moiety induces trans to cis isomerization resulting in remarkable changes in absorption and both steady state and time-resolved luminescence spectral characteristics upon irradiating with UV light. Reversal of cis to trans isomerization were also achieved on interacting with visible light as well as UV light of specific wavelength. Removal of two benzimidazole NH protons from the secondary coordination sphere of the complexes were made possible upon treatment with strong base accompanying with substantial modulation of their absorption and emission spectral properties. Interestingly, rate constant as well as quantum yield of photoisomerization dramatically increases upon deprotonation of the imidazole NH protons. Computational studies employing density functional theory (DFT) and time-dependent density functional theory (TD-DFT) were also executed for understanding the electronic charge distribution within the complex backbone and appropriate assignment of the observed spectral bands. In addition, observed spectral trend upon NH deprotonation as well as deprotonation-induced photoisomerization processes were also compared with the calculated results.

N-Phenyl substituent controlled diastereoselective synthesis of β-lactam-isatin conjugates

Unprecedented diastereoselective synthesis of novel β-lactam-isatin conjugates via a Staudinger [2+2] cycloaddition is described. The electronic nature of substituents on the imine N-phenyl moiety induced high levels of stereocontrol and plausibly controlled the competition between direct ring closure (conrotatory) and isomerization of the azabutadiene intermediate. The presence of electron-donating groups (OCH3 and CH3) at the para-position of the imine N-phenyl moiety increases the electron density of the imine nitrogen atom. This in turn increases direct conrotatory ring closure favoring the cis-isomer. On the other hand, electron-withdrawing groups (NO2 and CF3) at the para-position gave the thermodynamically more stable trans-isomer as the major products by promoting isomerization of the azadiene zwitterionic intermediate presumably due to a decrease in the electron density on the imine nitrogen atom. A varied diastereoselective behavior was observed for meta-position substituents, where OCH3, CH3 and NO2 groups favored the cis-isomer, hence indicating the additional role of steric hindrance in the observed diastereoselectivity. Additionally, the transition states of these reactions computed at the density functional theory (DFT) level were in accordance with the experimental results.

Hydrogen bonding in dicyclohexylmethane – or diphenylmethane based urea compounds and their polymer counterparts investigated by NMR spectroscopy: Interplay of electronic and geometrical factors

We investigated the H-bonding behavior of urea compounds with different electronic nature of substituents and different spatial organization. Variable-temperature 1H NMR spectroscopy studies were performed in polar solvents which are capable (DMSO‑d6 and DMF-d7) or not (CDCl3) to form the intermolecular hydrogen bonds and non-polar solvent (toluene-d8) at the temperature range from 25 to 70 °C. Our results indicates that in the investigated systems the geometrical factors dominated over electronic effects of substituents at formation of intra- and intermolecular H-bonds. By the reaction between isocyanate and heavy water was synthesized the polymers with selectively deuterated urea groups and recorded their high-resolution solid-state 2H NMR spectra and measured their 2H quadrupole interaction parameters (i.e., the quadrupole coupling constant χ and asymmetry parameter η). Quite unexpectedly, the intermolecular hydrogen bonds are weaker in phenyl based urea polymers than in their cyclohexane based counterparts.

Controlled Evolution of the Cope Rearrangement: Transition from Concerted to Interrupted and Aborted Pericyclic Reactions Regulated by a Switch Built from an Intramolecular Frustrated Lewis Pair.

We show how synergy between properly placed acceptor and donor groups allows rational design of interrupted and aborted pericyclic reactions, using the Cope rearrangement as a model process. When placed at C2 and C5 carbons of 1,5-hexadienes, a frustrated Lewis pair made of two complementary groups assures that the C-C bond formation is assisted by the flow of electron density from a donor at C5 into an acceptor at C2 through the formation of the C1-C6 bond. If the electron excess at the accepting group is strongly stabilized by the electronic nature of substituents, the pericyclic transition state can become an energy minimum, leading to a switch from a concerted sigmatropic shift to its aborted or interrupted versions. Depending on the electronic nature of acceptors at C5 and the donor groups at C2, a range of possibilities from concerted to aborted pathways is accessible, including the first example of an aborted Cope rearrangement in the absence of a metal catalyst. Furthermore, the zwitter-ionic strategy stabilizes the usually unfavorable boat TS that can potentially evolve into rarely accessible bicyclohexane products.

An approach on the comparative behavior of chloro / nitro substituted phenols photocatalytic degradation in water

The study of position and number of substituents on the photocatalytic removal of some mono-, di- and tri-, chloro- and nitrophenols, as well as more known initial TOC concentration effect, has revealed the noteworthy impact on the process efficiency. Despite the complex effect of multiple substituents directing the HO attack to their preferential positions, Hammett constant could be used to predict photocatalytic degradation performance. TiO2 P25 was able to mineralize initial TOC concentrations up to 25–50 mg·L−1. Higher TOC concentrations constitute a drawback and drive to residual parent pollutants and organic by-products, which become more important when raising the starting TOC loading. Increasing the number of chloro- or nitro- groups in the aromatic ring does not imply higher ecotoxiticy values; contrarily, the position of the substituent can lead to significant differences. TOC conversion values are hardly affected by the substituent position, but by the number of groups in the organic molecule, probably due to steric hindrance. The formation of chloride and nitrogen inorganic ions, inherent to photocatalytic degradation, fulfills the Cl and N mass balances. Finally, the effect of number, position and electronic nature of substituents on contaminant initial photocatalytic degradation rates was studied by corresponding Hammett constant correlations.

Pd(II)-Catalyzed Carbonyl-Directing Activation of Alkenes: Selective Fluorosulfonylation and Aminosulfonylation of 1,7-Enynes.

A new Pd(II)-catalyzed carbonyl-directing activation of alkenes has been established, enabling radical-induced selective fluorosulfonylation and aminosulfonylation of carbonyl-tethered 1,7-enynes with sulfinic acids and N-fluorobenzenesulfonimide (NFSI) under mild and redox neutral conditions to access densely functionalized ( E)-3,4-dihydronaphthalen-1(2 H)-ones with generally good yields and high stereoselectivity. The selectivity of these bifunctionalizations relies on the electronic nature of substituents on both aryl rings of 1,7-enynes.

Substituent effect of side chains on the photochemical behavior of a new generation 1,4-dihydropyridine: Lercanidipine

Lercanidipine (LERCA) is a third generation antihypertensive drug belonging to the 1,4-dihydropyridine’s family, which has been reported to induce photoallergic and/or phototoxic effects in patients with long term treatment. The electronic nature of substituents on the 4-aryl moiety bonded to the 1,4-dihydropyridine ring has been described to strongly affect the photophysical and photochemical behavior of this family of compounds, which displays a typical absorption band around 360nm. LERCA undergoes photodegradation after excitation, with a first order kinetic, in significant competition to the radiative path. The photodegradation quantum yields for LERCA are higher than for its homologue nimodipine (NIMO), thus indicating that the substituents on the 1,4-dihydropyridinic ring also affect their photophysical and photochemical properties. The media where the photodegradation takes place impacts on the product profile, in a homogeneous one the photoproducts obtained appear to be more polar than those obtained for a micro-heterogeneous one (micelles or bilayers mimicking biological media).

Synthesis and structure elucidation of allyl Pd(II) complexes of NHC ligands derived from substituted imidazo[1,5-a]quinolin-1(2H)-ylidene

Nine Pd(II) complexes involving N-heterocyclic carbenes (NHCs) derived from 2-substituted and 2- and 7-substituted imidazo[1,5-a]quinolin-1(2H)-ylidene with auxiliary allylic ligands were synthesized and characterized. The structure and configuration of the complexes were elucidated on the basis of combination of dynamic NMR and DFT studies. Conformational studies in respect of hindered rotation around Pd-C bond and η3-η1-η3 pseudo allyl rotation were performed. The results from dynamic NMR and DFT studies confirmed the mechanism of selective η3-η1-η3 isomerization, whose energy barriers are affected by steric hindrance of substituents at nitrogen atom. Energy barriers of isomerization (16.7–18.8 kcal/mol) are slightly influenced by the electronic nature of substituents at seventh position in imidazo[1,5-a]quinolin-1(2H)-ylidene moiety. The results from DFT calculations were in good agreement with the experimental energy barriers.

Multiparameter kinetic analysis of alkaline hydrolysis of a series of aryl diphenylphosphinothioates: models for P=S neurotoxins

Alkaline hydrolysis of a series of X-substituted-phenyl diphenylphosphinothioates (2a-i) in 80 mol%/20 mol% DMSO at 25.0 ± 0.1°C has been studied kinetically and assessed through a multiparameter approach. Substrates 2a to 2i are approximately 12 to 22 times less reactive than their P=O analogues 1a to 1i (ie, the thio effect). The Bronsted-type plot for the reactions of 2a to 2i is linear with βlg = −0.43, consistent with a concerted mechanism. Hammett plots correlated with σo and σ− constants also support a concerted mechanism; the Yukawa-Tsuno plot results in an excellent linear correlation with ρX = 1.26 and r = 0.30, indicating that expulsion of the leaving group occurs in the rate-determining step (RDS). The ΔH‡ value increases from 10.5 to 11.7 and 13.9 kcal/mol as substituent X in the leaving group changes from 3,4-(NO2)2 to 4-NO2 and H, in turn, while TΔS‡ remains constant at −6.0 kcal/mol. The strong dependence of ΔH‡ on the electronic nature of substituent X also indicates that the leaving group departs in the RDS. The reaction mechanism and origin of the thio effect are discussed by comparison of the current kinetic results with those reported for the reactions of 1a to 1i. The results suggest that for useful OP neurotoxins the mechanism of abiotic hydrolysis is concerted (with varying degrees of asynchronicity) when the substrate bears good leaving groups.

Enantiospecific cis-trans isomerization in chiral fulleropyrrolidines: hydrogen-bonding assistance in the carbanion stabilization in H2O@C60.

The stereochemical outcome of cis-trans isomerization of optically pure [60], [70], and endohedral H2O@C60 fulleropyrrolidines reveals that the electronic nature of substituents, fullerene size, and surprisingly the incarcerated water molecule plays a crucial role in this rearrangement process. Theoretical DFT calculations are in very good agreement with the experimental findings. On the basis of the experimental results and computational calculations, a plausible reaction mechanism involving the hydrogen-bonding assistance of the inner water molecule in the carbanion stabilization of endofullerene is proposed.

Exploring the influence of steric hindrance and electronic nature of substituents in the supramolecular arrangements of 5-(substituted phenyl)-2-formylpyrroles

The supramolecular arrangements of 5-(substituted phenyl)-2-formylpyrroles display the core formation of dimers, tetramers or polymers, depending on the phenyl substituents.

Aromaticity and amyloid formation: Effect of π-electron distribution and aryl substituent geometry on the self-assembly of peptides derived from hIAPP22–29

A comprehensive investigation of peptides derived from the 22–29 region of human islet amyloid polypeptide (hIAPP) that contain phenylalanine analogs at position 23 with a variety of electron donating and withdrawing groups, along with heteroaromatic surrogates, has been employed to interrogate how π-electron distribution effects amyloid formation. Kinetic aggregation studies using turbidity measurements indicate that electron rich aromatic ring systems consistently abolish the amyloidogenic propensity of hIAPP22–29. Electron poor systems modulate the rate of aggregation. Raman and Fourier transform infrared spectroscopy confirm the parallel β-sheet secondary structure of aggregates derived from peptides containing electron poor phenylalanine analogs and provide direct evidence of ring stacking. Transmission electron microscopy confirms the presence of amyloid fibrils. The effect of aryl substituent geometry on peptide self-assembly reveals that the electronic nature of substituents and not their steric profile is responsible for failure of the electron donating group peptides to aggregate. Non-aggregating hIAPP22–29 peptides were found to inhibit the self-assembly of full-length hIAPP1–37. The most potent inhibitory peptides contain phenylalanine with the p-amino and p-formamido functionalities. These novel peptides may serve as leads for the development of future aggregation inhibitors. A potential mechanism for inhibition of amylin self-assembly by electron rich hIAPP22–29 peptides is proposed.