Electron-withdrawing Substitution Research Articles

A comparative DFT study of monosubstituted silabenzene and benzene structures: Effects of Si atom incorporation in benzene ring

In the present study, monosubstituted structures with 16 substitutions in the ortho, meta, and para positions of silabenzene have been comprehensively compared with similar structures in benzene. This study aimed to investigate the effect of Si atom incorporation in the benzene ring. This comparison investigated the chemical properties, including structural geometries of molecules, molecular orbitals and reactivity, ring aromaticity, and excitation energy of each monosubstituted silabenzene and benzene structure. The density functional theory (DFT) at the B3LYP/6–311G++(d,p) level of theory was used to perform all relevant calculations. In addition to changes in ring geometry values and electron donating, the results showed that the Si atom incorporation in benzene ring and its monosubstituted derivatives in different positions caused a significant decrease in LUMO, chemical hardness, ring aromaticity, excitation energy, and a significant increase in HOMO, electrophilicity, nucleophilicity, and NMR chemical shift values. Among the positions of the substituents concerning the Si atom in the ring, the ortho and para positions exhibited the most optimal values. In contrast, the meta position displayed different values compared to the ortho and para positions. This difference is attributed to the electron-withdrawing effects of the substituents. Also, among substitutions, electron-donating substitutions especially -NH2 compared to electron-withdrawing substitutions especially -NO2 decreased HOMO, electrophilicity, excitation energy, and increased LUMO, chemical hardness, nucleophilicity, and ring aromaticity.

Exploring electron donor and acceptor effects: DFT analysis of ESIPT/GSIPT in 2-(oxazolinyl)-phenols for photophysical and luminophore enhancement.

Understanding excited-state intramolecular proton transfer (ESIPT) is essential for designing organic molecules to enhance photophysical and luminophore properties in the development of optoelectronic devices. In this context, an attempt has been made to understand the impact of substituents on the ESIPT process of 2-(oxazolinyl)-phenol. Electron donating (EDG: -NH2, -OCH3, and -CH3) and electron withdrawing (EWG: -Cl, -Br, -COOH, -CF3, -CN, and -NO2) substitutions have been computationally designed and screened through density functional theory (DFT) and time-dependent density-functional theory (TDDFT) calculations. Furthermore, the ground state intramolecular proton transfer and ESIPT mechanisms of these designed luminophores are explored using the transition state theory. The results reveal that molecules with EDG show higher absorption and emission peaks than molecules with EWG and also indicate that the mobility of charge carriers in 2-(oxazolinyl)-phenol derivatives is significantly influenced by substituents. We found that the EWGs decrease the reorganization energy and increase the vertical ionization potential and electron affinity values, as well as the highest occupied molecular orbital-lowest unoccupied molecular orbital gap, compared to the EDG substituted molecules. Significantly, the excited state (S1) of the keto emission (K) form shows notably larger values for the EDG substitutions. The intersystem crossing pathway efficiency weakens with reduced spin-orbit coupling matrix element in the enol form with electron-donating substituents and vice versa in the keto form during S1-T3 transitions. Our research links intramolecular proton transfers and triplet generation, making these substituted molecules appealing for optoelectronic devices. Introducing EDGs, such as -NH2, boosts the ESIPT reaction in 2-(oxazolinyl)-phenol. This study guides designing ESIPT emitters with unique photophysical properties.

Re(I)[2-aryl-1H-imidazo[4,5-f][1,10]phenanthroline] tricarbonyl chloride complexes for selective cancer therapy via a potential DNA damage mechanism.

Recently, achieving selective cancer therapy with trifling side effects has been a great challenge in the eradication of cancer. Thus, to amplify the cytoselective approach of complexes, herein, we developed a series of Re(I)[2-aryl-1H-imidazo[4,5-f][1,10]phenanthroline] tricarbonyl chloride complexes and screened their potency against HeLa and MCF-7 cell lines together with the evaluation of their toxicity towards a normal kidney cell line (HEK-293). On meticulous investigation, complex [ReI(CO)3Cl(K2-N,N-(2c))] (3c) was found to be the most potent anticancer entity among other complexes. Complex 3c also showed competency to induce apoptosis in MCF-7 cells through G2/M phase cell-cycle arrest in association with the generation of ample reactive oxygen species (ROS), eventually leading to DNA intercalation and internucleosomal cleavage. The order of the cytotoxicity of these complexes depended on their lipophilic character and the electron-withdrawing halogen substitution at the para-position of the phenyl ring in the imidazophenanthroline ligand.

Cobalt-Catalyzed Asymmetric Reductive Alkenylation and Arylation of Heterobiaryl Tosylates: Kinetic Resolution or Dynamic Kinetic Resolution?

Herein, we report a cobalt-catalyzed atroposelective reductive cross-coupling of racemic heterobiaryl tosylates with a C(sp2)-X type electrophile. Both aryl and alkenyl halides are competent precursors for this reaction, providing a variety of heterobiaryls as the products in a highly enantioselective manner with high functionality tolerance. The related asymmetric arylation and alkenylation are discovered to proceed with divergent mechanisms. The reaction pathway changes from kinetic resolution (KR) when alkenyl bromides and aryl iodides bearing strong electron-withdrawing substitution on the para-position are employed as the starting materials to an enantioconvergent transformation via dynamic KR of configurationally labile cobaltacycles when relatively electron-rich aryl iodides are used. The change of the reaction mechanisms turns out to arise from the relative rates of two competing elementary steps, which are the epimerization of the cyclic Co(I) intermediates and their trapping by the coupling electrophiles of the C(sp2)-type via oxidative addition.

Design, Synthesis, Characterization, and Anti-Cancer Activity Evaluation of Novel Thiosemicarbazide Analogs

Abstract: Aim/Background: Across the world disease of cancer is one of the factors of death and to identify the emerging role of thiosemicarbazide analogs for the cancer disease it was decided to design, and synthesize novel thiosemicarbazide derivatives (5a-i) with in-vitro anticancer activity evaluation. Materials and Methods: Substituted benzoic acid, thionyl chloride, hydrazine hydrate, and ammonium thiocyanate were used to create a new series of thiosemicarbazide derivatives (5a-i). The final derivatives were characterized using 13C and 1H NMR, FTIR, and mass spectroscopy. The compounds were then analyzed for anticancer action with the in-vitro MTT assay method as well as by measuring the percentage of tumor growth on the B16F10 melanoma cell line, a clone of B16 cells. Results: Compounds 5a, 5b, and 5e outperformed and were comparable to the reference drug, doxorubicin. All three compounds have an electron-withdrawing group substitution and have shown remarkable anticancer effects. When compared to other substituted derivatives, the drug-likeness score evaluated by Swiss ADME online software confirmed the same fact that thiosemicarbazides with electronwithdrawing groups substitution like halogens, and nitro groups at different positions could work as excellent and promising anticancer agents. Conclusion: The study and the result of the study revealed that thiosemicarbazide moiety represents an important core and could be used as a template for further development of analogs having promising anti-cancer effects. Keywords: Anticancer, B16F10 cell line, Melanoma, Thiosemicarbazide, MTT assay.

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Chiral Lewis Acid-Catalyzed Norrish Type II Cyclization to Synthesize α-Oxazolidinones via Enantioselective Protonation

Real-Time Fluorescence Screening Platform for Meat Freshness

Meat's freshness is closely related to food safety and human health and has received increasing attention nowadays. To on-site visually screen meat freshness in a fast and non-destructive manner, we rationally constructed a series of fluorescent probes (JDCN, JDNS, and JDPY) with distinct electron-withdrawing substitution groups based on julolidine-fused coumarin. These probes underwent an aza-Michael addition followed by an elimination reaction with cadaverine to generate a colorimetric and ratiometric fluorescence response, and their sensing performance was rationally enhanced by improving the electron-withdrawing strength of substitution groups. Particularly, JDCN with a dicyanovinyl group as the reaction site exhibited outstanding sensing performance including rapid response (∼60 s), high selectivity, and low detection limit (14 nM). Furthermore, JDCN was fabricated into test kits to detect cadaverine vapor with a high-contrast fluorescence change from red to green. Based on two-color visualization of cadaverine vapor, on-site non-contact and non-destructive monitoring of meat freshness was successfully achieved. The good sensing performance rendered JDCN test kits a promising real-time fluorescence screening platform for rapid, non-destructive, and accurate evaluation of meat freshness.

Preparation and DFT studies of chiral Cu (I)-complexes of biphenyl bisoxazolines and their application in enantioselective Kharasch–Sosnovsky reaction

Effect of a range of t-butyl perbenzoates bearing electron-withdrawing and electron-donating substitutions on the phenyl ring and HZSM-5 as a porous additive at 0 °C in enantioselective allylic C–H bond oxidation of cyclic and acyclic olefins in the presence of Cu (I)-(S,aS,S) complexes of biphenyl bisoxazoline ligands, produced easily through the chelation-induced process, were investigated. The enantioenriched allylic esters were obtained in reasonable times with excellent enantioselectivities and yields using electron-withdrawing substituted peresters in the presence of Cu (I)-(S,aS,S)-1a complex, containing phenyl groups at the stereogenic centers of the oxazoline moieties. To reach a better insight on geometry, chemical activity, enantioselectivity, and thermodynamic stability of the Cu (I)-BOX complexes, DFT calculations with B3LYP-D3/6-31G (d, p) level of theory were applied to them. Moreover, NBO analysis was used to illustrate interactions between orbitals.

Kinetics and mechanisms for sulfamethoxazole transformation in the phenolic acid-laccase (Trametes versicolor) system.

Oxidation of phenolic acids (PCs) by laccase could produce various kinds of reactive oxygen species (ROS), which is expected to have substantial impact on the transformation of antibiotics like sulfamethoxazole (SMX) in soil and aquatic environments. In this study, the formation of semiquinones radical (SQ●-), superoxide anion radical (O2●-), hydrogen peroxide (H2O2), hydroxyl radical (●OH), and singlet oxygen (1O2) in a laccase-gallic acid (GA) reaction system was confirmed. Meanwhile, GA would be transformed to its monomeric quinone and quinones of di- and tri-polymers. Transformation of SMX by laccase alone is negligible, while which was greatly enhanced in the presence of GA at the optimal pH of 5.5. The dissolved O2 was the requisite for transformation of SMX due to its fundamental role in the formation of SQ●-, the key species initializing the chain reactions for the generation of other ROS. The quenching experiments indicated O2●- and 1O2 were the main ROS responsible for SMX transformation. A total of thirteen products were proposed for the SMX transformation, with the pathways including the breaking of S-N bond, the cleavage of oxazole ring, electrophilic substitution, Michael addition, and condensation reactions. Moreover, the existence of electron-withdrawing substitution group on the benzene ring of PCs and less stability of SQ●- was believed to be favorable for the transformation of SMX. The results above expand our understanding on the role of oxidation of PCs by laccase in the SMX transformation in environments and are of significance in relation to use of laccase in dealing with SMX pollution.

Examining the Role of Aryldiazonium Salts in Surface Electroinitiated Polymerization.

Historically, the irreversible reduction of aryldiazonium salts has provided a reliable method to modify surfaces, demonstrating a catalogue of suitable diazonium salts for targeted applications. This work expands the knowledge of diazonium salt chemistry to participate in surface electroinitiated emulsion polymerization (SEEP). The influence of concentration, electronic effects, and steric hindrance/regiochemistry of the diazonium salt initiator on the production of polymeric films is examined. The objective of this work is to determine if a polymer film can be tailored, controlling the thickness, density, and surface homogeneity using specific diazonium chemistry. The data presented herein demonstrate a significant difference in polymer films that can be achieved when selecting a variety of diazonium salts and vinylic monomers. A clear trend aligns with the electron-rich diazonium salt substitution providing the thickest films (up to 70.9 ± 17.8 nm) with increasing diazonium concentration and electron-withdrawing substitution achieving optimal homogeneity for the surface of the film at a 5 mM diazonium concentration.

Tuning Catalyst-Free Photocontrolled Polymerization by Substitution: A Quantitative and Qualitative Interpretation.

Catalyst-free photocontrolled reversible addition-fragmentation chain transfer (RAFT) polymerization avoids the side effects of photocatalysts but has the accompanying slow kinetics, thereby warranting more efficient photolysis and faster chain transfer. To understand the underlying mechanisms, both quantitative and qualitative interpretations are needed. Such a goal can be achieved by the iCAS (imposed automatic selection and localization of complete active spaces) approach [J. Chem. Theory Comput. 2021, 17, 4846], which maintains the same CAS and meanwhile provides localized orbitals along the whole reaction. Taking dithiobenzoate as a representative of RAFT agents, it is found here that electron-donating substitution (by methoxy) clearly outperforms both electron-standing (by methyl) and electron-withdrawing (by cyano) substitutions in facilitating photo-RAFT polymerization, by narrowing the gap between the π* and σ* orbitals, so as to facilitate the π* → σ* charge transfer dominating both the photolysis and chain transfer processes. Such findings are of general values.

Substituent Effects Impact Surface Charge and Aggregation of Thiophenol-Labeled Gold Nanoparticles for SERS Biosensors.

SERS immunoassay biosensors hold immense potential for clinical diagnostics due to their high sensitivity and growing interest in multi-marker panels. However, their development has been hindered by difficulties in designing compatible extrinsic Raman labels. Prior studies have largely focused on spectroscopic characteristics in selecting Raman reporter molecules (RRMs) for multiplexing since the presence of well-differentiated spectra is essential for simultaneous detection. However, these candidates often induce aggregation of the gold nanoparticles used as SERS nanotags despite their similarity to other effective RRMs. Thus, an improved understanding of factors affecting the aggregation of RRM-coated gold nanoparticles is needed. Substituent electronic effects on particle stability were investigated using various para-substituted thiophenols. The inductive and resonant effects of functional group modifications were strongly correlated with nanoparticle surface charge and hence their stability. Treatment with thiophenols diminished the negative surface charge of citrate-stabilized gold nanoparticles, but electron-withdrawing substituents limited the magnitude of this diminishment. It is proposed that this phenomenon arises by affecting the interplay of competing sulfur binding modes. This has wide-reaching implications for the design of biosensors using thiol-modified gold surfaces. A proof-of-concept multiplexed SERS biosensor was designed according to these findings using the two thiophenol compounds with the most electron-withdrawing substitutions: NO2 and CN.

Homoleptic Ir(III) Phosphors with 2-Phenyl-1,2,4-triazol-3-ylidene Chelates for Efficient Blue Organic Light-Emitting Diodes

In this report, we synthesized two series of deep-blue-emitting homoleptic iridium(III) phosphors bearing 1,2,4-triazol-3-ylidene and 5-(trifluoromethyl)-1,2,4-triazol-3-ylidene cyclometalate. Compared with reported synthetic routes using Ag2O as the promoter, herein, we adopted a different strategy to furnish these complexes in high yields. Also, the meridional to facial isomerization was executed in the presence of trifluoroacetic acid. These phosphors were examined using NMR spectroscopies, single-crystal X-ray diffraction studies, and photophysical methods. The results revealed that electron-withdrawing trifluoromethyl substitution on the N-heterocyclic carbene fragment only gave a minor variation of photoluminescence peak wavelengths and a decrease in radiative lifetime but notable reduction in thermal stabilities. The parent 1,2,4-triazol-3-ylidene complexes have been demonstrated to be suitable for use as deep-blue phosphors, with structured emission with the peak max. located at ∼420 nm and with photoluminescence quantum yields in a range of 34.8-42.5% in degassed THF solution at RT. Fabrication of both the phosphorescent organic light-emitting diodes (OLEDs) and phosphor-sensitized OLEDs (or hyperphosphorescence) was successfully conducted, from which the OLED device based on m-tz1 showed a max. external quantum efficiency (EQE) of 10% with CIEx,y coordinates of 0.15, 0.06, while the corresponding hyperphosphorescent OLED using m-tz2 as a sensitizer and t-DABNA as a terminal emitter afforded a significantly improved max. EQE of 19.7%, EL λmax of 468 nm, and FWHM of 31 nm with CIEx,y coordinates of 0.12, 0.13.

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

Nickel-Catalyzed Reductive Asymmetric Aryl-Acylation and Aryl-Carbamoylation of Unactivated Alkenes

The Chemistry and Applications of Heteroisoindigo Units as Enabling Links for Semiconducting Materials.

ConspectusBecause of their low-temperature processing properties and inherent mechanical flexibility, semiconducting materials are promising candidates for enabling flexible displays, renewable energy, biological sensors, and healthcare. Progress has been made in materials performance by developing judicious materials design strategies. For example, improvements in electron transport have required new electron-deficient aromatics. Among them, isoindigo (IID) is an important functional group utilized in conjugated aromatics, where the structure combines two sets of five-membered electron-withdrawing lactam rings, exhibiting enhanced solubility, excellent chemical and thermal stabilities, broad absorption, and intriguing electron affinity.In the past decade, researchers have mainly focused on IID-based materials. However, the effect of heteroatom modification of the IID core has rarely been systemically investigated. In conventional conjugated polymers, single bonds connect the monomers, leading to energetic disorder and torsion defects, while ladder-type polymers are often intractable because of their fused nature. In this regard, the molecular design of new π scaffolds based on IID is central to the development of high-performance semiconductor polymers. Especially, a complete refresh of molecular design strategies and novel conjugated polymers with unique structures are needed to circumvent the disadvantages of the conventional ladder-type polymers.In this Account, we systematically summarize our recent progress in the design, synthesis, and structure-property relationships of IID- and particularly hetero-IID-based functional materials. More specifically, starting with molecular engineering of hetero-IIDs with variable electronic effects, conjugation lengths, and numbers of heterorings, we discuss the effect of the heteroring on the absorption spectra and energy levels. Additionally, we investigate a series of electron-withdrawing substitution of IIDs and hetero-IIDs and their molecular self-assembly behavior and the device performance. Furthermore, we discuss a series of IID-bis(EDOT) copolymers with hydrophilic ethylene glycol side chains for accumulation-mode organic thin-film electrochemical transistors, in which the relationships among the molecular structure, operational stability, film morphology, and device performance were revealed. Compared with IID polymers, the HOMO levels and optical band gaps of the thiophene and thienothiophene IID copolymers markedly decrease, and these polymers exhibit ambipolar charge transport. When we further expanded the IID core to a thieno[3,2-b][1]benzothiophene isoindigo (TBTI) core, such as in TBTIT, bulk-heterojunction solar cells employing this polymer class as the electron donor achieved good efficiency for additive- and annealing-free device conditions. When we introduced electron-deficient pyridine on the IID core, both the LUMO and HOMO energy levels of the copolymers markedly decreased, which significantly improved the electron mobility. In addition, we compare the correlation between the polymer structures of IID and hetero-IID copolymers with thiophene and benzothiophene as comonomers and their absorption spectra and energy levels. In particular, we evaluate the planarity and the dihedral angle between the repeat units, with systematic analysis by theoretical calculations to support our design concepts. We discuss polymer designs arising from simple aldol condensation, where the rigid backbone conformation has been locked by the double bonds. Our polymers display broad absorption from the visible to the NIR-II region, and more importantly, the high electron affinities of these polymers provide a platform to realize ambient-stable electron transport in solution-processed organic thin-film transistors. These exciting results are expected to open doors to new horizons of semiconducting materials in terms of other charming applications and the design and synthesis of superior materials.

Rational Design of Azothiophenes-Substitution Effects on the Switching Properties.

A series of substituted azothiophenes was prepared and investigated toward their isomerization behavior. Compared to azobenzene (AB), the presented compounds showed red‐shifted absorption and almost quantitative photoisomerization to their (Z) states. Furthermore, it was found that electron‐withdrawing substitution on the phenyl moiety increases, while electron‐donating substitution decreases the thermal half‐lives of the (Z)‐isomers due to higher or lower stabilization by a lone pair–π interaction. Additionally, computational analysis of the isomerization revealed that a pure singlet state transition state is unlikely in azothiophenes. A pathway via intersystem crossing to a triplet energy surface of lower energy than the singlet surface provided a better fit with experimental data of the (Z)→(E) isomerization. The insights gained in this study provide the necessary guidelines to design effective thiophenylazo‐photoswitches for applications in photopharmacology, material sciences, or solar energy harvesting applications.

Theoretical study on cycloaddition reaction of epoxides with CO2 catalyzed by metal-porphrin complexes: Reaction mechanisms and structure impacts on catalytic activity

The detailed reaction mechanisms for the coupling reaction of epoxides with CO2 catalyzed by metal-porphyrin complexes were investigated using density functional theory methods. A new concerted insertion process was proposed in this work and in comparison with the insertion step supported by the previous four-step mechanism. On the basis of the coupling reaction mechanisms, the potential relevance of structure and catalytic activity was also discussed. Our theoretical results show that the co-catalyst DMAP has significant effects on the free energy barriers of rate-determining steps by changing the electronic properties of metal centers, it suggested the co-catalyst could promote the catalytic activity as observed experimentally. As for the different metal centers (Co, Al, Mn), the rank of catalytic activity for metal-porphyrin catalysts was predicted to be Co > Al > Mn, which encouraged us to develop more catalytic systems with active metal center. Moreover, the electron-withdrawing substitutions in the meso-position also affect the energy barriers, the catalytic activity of metal-porphyrin catalysts were reduced along with more Br-substitutions in meso-position.

Nature-inspired pyrrolo[2,3-d]pyrimidines targeting the histamine H3 receptor.

Inspired by marine compounds the derivatization of the natural pyrrolo[2,3-d]pyrimidine lead scaffold led to a series of novel compounds targeting the histamine H3 receptor. The focus was set on improved binding towards the receptor and to establish an initial structure-activity relationship for this compound class based on the lead structure (compound V, Ki value of 126 nM). As highest binding affinities were found with 1,4-bipiperidines as basic part of the ligands, further optimization was focused on 4-([1,4'-bipiperidin]-1'-yl)-pyrrolo[2,3-d]pyrimidines. Related pyrrolo[2,3-d]pyrimidines that were isolated from marine sponges like 4-amino-5-bromopyrrolo[2,3-d]pyrimidine (compound III), showed variations in halogenation pattern, though in a next step the impact of halogenation at 2-position was evaluated. The chloro variations did not improve the affinity compared to the dehalogenated compounds. However, the simultaneous introduction of lipophilic cores with electron-withdrawing substitution patterns in 7-position and dehalogenation at 2-position (11b, 12b) resulted in compounds with significantly higher binding affinities (Ki values of 7 nM and 6 nM, respectively) than the initial lead structure compound V. The presented structures allow for a reasonable structure-activity relationship of pyrrolo[2,3-d]pyrimidines as histamine H3 receptor ligands and yielded novel lead structures within the natural compound library against this target.

Achieving Balanced Charge Transport and Favorable Blend Morphology in Non-Fullerene Solar Cells via Acceptor End Group Modification

Generally, the electron-withdrawing substitution on the end-capping group of the acceptor–donor–acceptor type small-molecule acceptor (SMA) narrows the optical bandgap, and the electron-donating group lifts the lowest unoccupied molecular orbital (LUMO) energy level of nonfullerene SMA, which increase the short-circuit current density (JSC) and open circuit voltage (VOC) of the organic solar cells (OSCs), respectively; however, their synergistic effect on the properties of SMA has remained elusive. Here, we first report a new end-capping group (EG), namely, 5-fluoro-6-methyl-3-dicycanovinylindan-1-one (CFDCI), that concurrently possesses an electron-withdrawing fluorine substitute and an electron-donating methyl group. A prototype SMA (namely, ITCF) based on CFDCI and its two control counterparts were prepared to fully understand the structure–property relationship that the new EG exerts on the resultant SMA. The ITCF demonstrated a moderately crystalline morphology in pristine film and more balanced char...

Docking studies of tetra substituted pyrazolone derivatives as potential antiviral agents

In an attempt to find potential antiviral agents, a series of pyrazolones (PA1-PA6& PC1-PC6) were designed and evaluated for their  DENVNS5 (RNA-dependent RNA polymerase) inhibitory activity. Molecular docking studies of all the designed compounds into the binding site of DENVNS5 (PDB Code: 4C11) were performed to gain a comprehensive understanding into rational binding modes. These compounds were also screened for in silico drug-likeliness properties on the basis of the absorption, distribution, metabolism and excretion (ADME) prediction. Among all the synthesized compounds, analogue  PA6showed superior inhibitory activity against RNA dependent RNA polymerase. SAR  study indicated that the presence of an electron withdrawing substitution on pyrazolone derivatives significantly improves its binding interaction with the protein.Results of ADME prediction revealed that most of these compounds showed in silico drug-likeliness.