Strong Electron-withdrawing Group Research Articles

Mechanistic study on the intramolecular oxa-[4 + 2] cycloaddition of substituted o-divinylbenzenes.

This paper reports a detailed computational study of the mechanisms of formation of oxacyclic derivatives from substituted o-divinylbenzenes by a photoinduced intramolecular oxa-[4 + 2] cycloaddition. The reaction mechanism and chemoselectivity of trans, trans- and cis, trans-substituted ortho-divinylbenzene were studied. Detailed density functional theory calculations show that the reaction system proceeds through two main steps: light-active intramolecular cyclization and Diels-Alder reactions of C=O. Trans, trans-products of cycloaddition of substituted o-divinylbenzenes are more favored than cis, trans-products. Compared with different substituents, the cycloaddition reaction of phenyl ketone has a relatively low activation barrier, and the strong electron-withdrawing group on the benzene ring is more favorable for the intramolecular cycloaddition reaction of substituted o-divinylbenzenes.

A Turn-On Optoacoustic Probe for Imaging Metformin-Induced Upregulation of Hepatic Hydrogen Sulfide and Subsequent Liver Injury.

Metformin is currently the most prescribed oral agent for diabetes treatment; however the overdose or long-term use may cause some severe side effects such as liver injury. Researches indicate that metformin-induced liver injury is closely related to upregulation of hepatic H2S. Hence, monitoring hepatic H2S generation induced by metformin could be an effective approach for evaluating hepatoxicity of the drug.Methods: We present a novel turn-on and dual-mode probe for detecting and imaging metformin-induced liver injury by specifically tracking the upregulation of hepatic H2S with fluorescent and optoacoustic methods. After reaction with H2S, the strong electron-withdrawing group dinitrophenyl ether (which acts as both the recognition moiety and the fluorescence quencher) was cleaved and replaced by an electron-donating group hydroxyl. This correspondingly leads to the changes of the probe's electronic state and absorption red-shifting as well as the subsequent turn-on fluorescent and optoacoustic signals.Results: The probe was applied to the colon tumor-bearing mice model and the metformin-induced liver injury mice model to achieve tumor imaging and liver injury assessment. The biosafety of the probe was verified by histological analysis (hematoxylin and eosin staining) and serum biochemical assays.Conclusion: The probe responds quickly to H2S in tumors and the liver, and MSOT imaging with the probe offers cross-secitonal and 3D spatial information of liver injury. This study may provide an effective approach for accessing medication side effects by tracking drug-metabolism-related products.

Aryl-urea fatty acids that activate the p38 MAP kinase and down-regulate multiple cyclins decrease the viability of MDA-MB-231 breast cancer cells

We recently developed a novel aryl-urea fatty acid (CTU; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that impaired the viability of MDA-MB-231 breast cancer cells in vitro and in mouse xenograft models in vivo. At present there is a deficiency of information on the structural requirements for the activity of CTU. Our initial study suggested that electron withdrawing groups were required on the aryl ring, and in this study we further evaluated the influence of the electronic properties of aromatic substitution on the capacity of CTU analogues to decrease MDA-MB-231 breast cancer cell viability. Analogues that contained strong electron-withdrawing groups in the meta- and para-positions of the aryl ring exhibited improved activity over CTU. Effective analogues down-regulated the cyclins D1, E1 and B1, and the cyclin-dependent kinases (CDKs) 4 and 6, that form complexes to coordinate cell cycle progression. Active CTU analogues also stimulated the phosphorylation and activation of the p38 MAP kinase signalling pathway in cells and both decreased proliferation (5-bromo-2′-deoxyuridine (brdU) incorporation) and activated apoptosis (executioner caspase-3/7 activity). These agents offer a new approach to target the cell cycle at multiple phases in order to efficiently prevent cancer cell expansion. Inclusion of the present structural information in drug design approaches could enhance the development of optimal analogues of aryl-urea fatty acids as potential anti-cancer agents.

Synthesis and fluorescence studies of selected N-aryl-2-aminoquinolines: Effect of hydrogen bonding, substituents and ESIPT on their fluorescence quantum yields

N-aryl-2-aminoquinolines have been widely synthesised and used in biological applications. However, their luminescence properties have not been studied in detail. Herein a series of N-aryl-2-aminoquinolines was synthesised from substitution reaction between 2-chloroquinoline and anilines with different substituent groups gave sufficient yield from 72–90%. The fluorescence behaviour was investigated in toluene, ethyl acetate and ethanol. The result shows that fluorescence quantum yield of N-aryl-2-aminoquinolines was the highest in toluene, followed by in ethyl acetate and the lowest in ethanol. Quenched emission observed in ethanol is caused by site-specific fluorophore-solvent hydrogen bonding interactions, inducing deactivation of the quinolinyl ring system. The bell-shaped Hammett plot of various substituted compounds suggested that both strong electron donating and electron withdrawing groups caused significant quenching in the fluorescence quantum yields. Therefore, most types of substituent groups on the phenyl moiety, hydrogen bonding between the fluorophore and solvent, and excited-state intramolecular proton transfer (ESIPT) were found as crucial contributors to fluorescence quenching of N-aryl-2-aminoquinolines.

Significant Influence of a Single Atom Change in Auxiliary Acceptor on Photovoltaic Properties of Porphyrin-Based Dye-Sensitized Solar Cells.

The rational design of porphyrin sensitizers is always crucial for dye-sensitized solar cells (DSSCs), since the change of only a single atom can have a significant influence on the photovoltaic performance. We incorporated the pyridothiadiazole group, as a stronger electron-withdrawing group, into the commonly well-established skeleton of D-porphyrin-triple bond-acceptor sensitizers by a single atom change for a well-known strong electron-withdrawing benzothiadiazole (BTD) unit as an auxiliary acceptor. The impact of the pyridothiadiazole group on the optical; electrochemical; and photovoltaic properties of D–π–A porphyrin sensitizers was investigated with comparison for a benzothiadiazole-substituted SGT-020 porphyrin. The pyridothiadiazole-substituted SGT-024 porphyrin dye was red-shifted so that the absorption range might be expected to achieve higher light harvest efficiency (LHE) than the SGT-020 porphyrin. However, all the devices were fabricated by utilizing SGT-020 and SGT-024, evaluated and found to achieve a cell efficiency of 10.3% for SGT-020-based DSSC but 4.2% for SGT-024-based DSSC under standard global AM 1.5G solar light conditions. The main reason is the lower charge collection efficiency of SGT-024-based DSSC than SGT-020-based DSSC, which can be attributed to the tilted dye adsorption mode on the TiO2 photoanode. This may allow for faster charge recombination, which eventually leads to lower Jsc, Voc and power conversion efficiency (PCE).

A Fluorescent Probe with Aggregation-Induced Emission for Detecting Alkaline Phosphatase and Cell Imaging.

Alkaline phosphatase (ALP) is associated with many diseases, and its accurate detection is of great significance. Fluorescent compounds with aggregation-induced emission (AIE) feature show beneficial advantages for serving as fluorescent probes. Herein, an AIE-active "turn on" probe for ALP detection was synthesized through incorporating a strong electron-withdrawing group (cyano) in the middle and the recognition moiety phosphate group at the end, thereby rendering a D-A-D structure with a relatively high conjugation degree and good water solubility. It was found that the probe TPE-CN-pho is highly sensitive to ALP in aqueous solution. In the presence of ALP, the hydrophilic phosphate group on the probe is rapidly removed, resulting in a decrease in water solubility and subsequent formation of aggregates, thereby achieving aggregation-induced emission. Moreover, the probe TPE-CN-pho has also been successfully applied to imaging ALP in living cells.

Efficient solution-processed red organic light-emitting diode based on an electron-donating building block of pyrrolo[3,2-b]pyrrole

Abstract An electron-rich moiety, pyrrolo[3,2-b]pyrrole, has been used as a new donor block in organic lighting-emitting diodes (OLEDs). Combined with a strong electron-withdrawing group of 2,1,3-benzothiadiazole, a novel red fluorophore BTZPP was synthesized. The solution-processed red-emitting device based on BTZPP showed encouraging performances with external quantum efficiency of up to 3.4%. This evidently indicates that the pyrrolo[3,2-b]pyrrole group can be a promising electron-donating moiety for enriching the material types and promoting the development of OLEDs.

Cationic red emitting fluorophore: A light up NIR fluorescent probe for G4-DNA

Guanine (G) quadruplexes (G4) are nucleic acid secondary structures formed by G-rich sequences, commonly found in human telomeric and oncogene-promoter regions, have emerged as targets for regulation of multiple biological processes. Considering their importance, targeting the G-quadruplex structure with small molecular binders is extremely pertinent. In this work, red emitting water soluble fluorophores bearing push-pull substituents were synthesized and examined for their interaction with human telomeric G4 and duplex (ds) -DNAs. The presence of a strong electron donating (dimethylamino) and electron withdrawing (cationic pyridinium) groups linked through a conjugated double bond helps in water solubility and enabling the emission in the near IR region (>700–nm). Binding of this cationic dye to the G4-DNA yields multiple-fold emission enhancement (~70 fold with G4-DNA vs. ~7 fold with ds-DNA) along with hypsochromic wavelength shifts (35 nm with G4-DNA and 8 nm with ds-DNA). The remarkable emission changes, ~2–4 fold enhanced binding efficiency noted with the antiparallel conformation of G4-DNA indicates preferential selectivity over ds-DNA. The molecular docking and dynamics studies of the ligands with duplex and G4-DNA were performed, and they provide insights into the mode of binding of these dyes with G4-DNA and supplement the experimental observations.

Recent Progress in Fused-Ring Based Nonfullerene Acceptors for Polymer Solar Cells.

The progress of bulk-heterojunction (BHJ) polymer solar cells (PSCs) is closely related to the innovation of photoactive materials (donor and acceptor materials), interface engineering, and device optimization. Especially, the development of the photoactive materials dominates the research filed in the past decades. Photoactive materials are basically classified as p-type organic semiconductor donor (D) and an n-type organic semiconductor acceptor (A). In the past two decades, fullerene derivatives are the dominant acceptors for high efficiency PSCs. Nevertheless, the limited absorption and challenging structural tunability of fullerenes hinder further improve the efficiency of PSCs. Encouragingly, the recent progresses of fused-ring based A-D-A type nonfullerene acceptors exhibit great potential in enhancing the photovoltaic performance of devices, driving the power conversion efficiency to over 13%. Such kind of nonfullerene acceptors is usually based on indacenodithiophene (IDT) or its extending backbone core and end-caped with strong electron-withdrawing group. Owing to the strong push-pulling effects, the acceptors possess strong absorption in the visible-NIR region and low-lying HOMO (highest occupied molecular orbital) level, which can realize both high open-circuit voltage and short-circuit current density of the devices. Moreover, the photo-electronic and aggregative properties of the acceptors can be flexibly manipulated via structural design. Many strategies have been successfully employed to tune the energy levels, absorption features, and aggregation properties of the fused-ring based acceptors. In this review, we will summarize the recent progress in developing highly efficient fused-ring based nonfullerene acceptors. We will mainly focus our discussion on the correlating factors of molecular structures to their absorption, molecular energy levels, and photovoltaic performance. It is envisioned that an analysis of the relationship between molecular structures and photovoltaic properties would contribute to a better understanding of this kind of acceptors for high-efficiency PSCs.

The investigation on the N[sbnd]H reactivity of pentacoordinate spirophosphoranes by H/D exchange and NMR experiments

Different pentacoordinate spirophosphoranes were investigated by H/D exchange and NMR tracking experiments. The H/D exchanged site of spirophosphoranes was confirmed to be the NH bond instead of the PH bond according to the integration of the signal changes in proton-decoupled, proton-coupled 31P NMR and 1H NMR tracking experiments. The reactivity of NH bond at the spiroring of spirophosphoranes was explored by the rate constant of H/D exchange of different spirophosphoranes. The results demonstrated that the reactivity of NH bond of spirophosphoranes was influenced by steric hindrance and the species of substituent at phosphorus atom, and the electronic effect of the substituent was the main effect factor on the reactivity of the NH bond. The strong electron-withdrawing group at phosphorus resulted in more reactive NH bond of spirophosphoranes. These results are beneficial to further understand and explore the characteristics of pentacoordinate spirophosphoranes.

Superacidity of P(OH)3 and SO(OH)2 derivatives of cyclopentadiene and vinylcyclopentadiene in the gas phase: A computational DFT analysis

Strong Brønsted acids were designed using a simple strategy of replacing double-bonded oxygen atoms in mineral acids H3PO4 and H2SO4 with cyclopentadiene and vinylcyclopentadiene moieties, followed by a substitution with strong electron-withdrawing cyano groups. Their intrinsic gas-phase acidity was assessed by the B3LYP density functional theory calculations employing the 6-311++G(d,p) basis set, and many highly potent superacids were identified. The pronounced acidity of these conjugates is due to two predominant factors, namely, (i) an increase in the aromaticity of the five-membered ring on deprotonation, as evaluated through the NICS parameters, and (ii) an extension of the conjugated π-network enabled by the cyano groups that efficiently distribute an excess negative charge over a large number of atoms in conjugate bases. The SO(OH)2 derivatives are generally more acidic than the corresponding P(OH)3 counterparts so that the ΔHacid values for the SO(OH)2 and P(OH)3 derivatives with CN substituents evaluated here are 260-266 and 263-272 kcal mol−1, respectively. Given the growing interest in highly acidic molecules together with related acidic catalysts and metal complexing agents, the results presented here should direct the attention toward utilizing proposed systems as improved organic materials, and their synthesis is highly recommended.

Similarity and Differences in the Regioselectivities of Thermal and Acid-Catalyzed van Alphen–Hüttel Rearrangements in the Series of 3,3-Diphenyl-3H-pyrazoles Containing Electron-Withdrawing Substituents on C4 and C5

3,3-Diphenyl-3H-pyrazoles containing an electron-withdrawing substituent in the 5-position undergo van Alphen–Huttel rearrangement with migration of one phenyl group to C4 on heating in an aprotic solvent (benzene, toluene), as well as on keeping at 20°C in acetic acid in the presence of a catalytic amount of concentrated sulfuric acid. Under similar conditions, 3,3-diphenyl-3H-pyrazoles with a strong electronwithdrawing group (sulfo or cyano) on C4 isomerize to 1H-pyrazoles via migration of one phenyl group to N2. If a moderate electron-withdrawing substituent (alkoxycarbonyl or acetyl group) is present in the 4-position, the acid-catalyzed phenyl group migration is directed mainly to the C4 atom, while thermal migration, toward N2. Probable reasons for the observed similarity and differences in the regioselectivities of the thermal and acidcatalyzed van Alphen–Huttel rearrangements have been proposed.

The Anticancer Activities of Some Nitrogen Donor Ligands Containing bis-Pyrazole, Bipyridine, and Phenanthroline Moiety Using Docking Methods.

The anticancer study of nitrogen-chelating ligands can be of tremendous help in choosing ligands for the anticancer metal complexes design especially with ruthenium(II). The inhibitory anticancer activities of some nitrogen-chelating ligands containing bis-pyrazole, bipyridine, and phenanthroline were studied using experimental screening against cancer cell and theoretical docking methods. In vitro anticancer activities showed compound 11 as the most promising inhibitor, and the computational docking further indicates its strong inhibitory activities towards some cancer-related receptors. Among the twenty-one modelled ligands, pyrazole-based compounds 7, 11, and 15 are the most promising inhibitors against the selected receptors followed by 18 and 21 which are derivatives of pyridine and phenanthroline, respectively. The presence of the carboxylic unit in the top five ligands that displayed stronger inhibitory activities against the selected receptors is an indication that the formation of noncovalent interactions such as hydrogen bonding and a strong electron-withdrawing group in these compounds are very important for their receptor interactions. The thermodynamic properties, the polarizabilities, and the LUMO energy of the compounds are in the same patterns as the observed inhibitory activities.

Acid-induced isomerization of ticagrelor: Systematic exploration on reaction condition and mechanism

N1N2 bond in molecules containing 1, 2, 3-triazoles framework is weakened and readily cleaved when N1 is attached to a strong electron-withdrawing group. However, ticagrelor, a pyrimidine-fused triazole without a strong electron-withdrawing group on N1 site still went through isomerization reaction via N1N2 bond rupture in the presence of acid to produce an impurity T3. Its structure was precisely obtained via NMR spectral analysis, MS spectroscopy and X-ray crystallography. The optimal condition of the isomerization reaction was systematically studied. Moreover, the isomerization mechanism was investigated and it is likely that ticagrelor and its analogues go through isomerization reaction when the 4-NH group and electron-deficiency ring exist in their structures. Besides, the steric hindrance of the substituent on 4-NH has an effect on the reactivity of equilibrium. Under mimic in vivo condition, the isomerization reaction of ticagrelor also generated, indicating ticagrelor may be not stable in stomach.

Quinoxaline-based organic dyes for efficient dye-sensitized solar cells: Effect of different electron-withdrawing auxiliary acceptors on the solar cell performance

Three novel metal-free organic dyes IT, IPT and IQT, containing a dipentyldithieno[3,2-f:2′,3′-h]quinoxaline (DPQ) unit as the π-bridge were synthesized and the impacts of the auxiliary acceptors on the photovoltaic performances were studied. IQT with 2,3-dipentylquinoxaline as the auxiliary acceptor exhibited the highest efficiency of 7.98%, with a short-circuit photocurrent density of 16.87 mA cm−2, an open-circuit photovoltage of 0.71 V, and a fill factor of 0.67, under standard global AM 1.5G solar light condition. IPT with the strongest electron-withdrawing group (2,3-dipentylpyridopyrazine) as the auxiliary acceptor could red-shift the absorption range, but showed the weakest performance, which might be due to the electron trap of the 2,3-dipentylpyridopyrazine unit. The results show that incorporating auxiliary acceptor with moderate electron-deficient ability can extend the absorption range and adjust the molecular orbital energy levels, improving the photovoltaic performance.

Solar collectors based on luminescent 2,5-diarylimidazoles

We report on the synthesis of new fluorescent symmetrical 2,5-diaryl-1-methylimidazoles obtained in good yields by using direct C-H arylation synthetic strategies. Spectroscopic investigations in THF solution evidenced that the 2,5-diarylimidazole bearing the strong electron-withdrawing cyanoacrylate groups achieved the best trade-off between fluorescence maximum (518 nm), Stokes shift (115 nm) and a quantum yield of 25%. Highly homogeneous dispersions of the selected fluorophore in poly(methyl methacrylate) (PMMA) thin films (25 ± 5 μm of thickness) perfectly maintained the optical features in solution, thus providing a brilliant green emission and a markedly enhanced quantum yield of 55%. Photocurrent measurements of the PMMA collectors supported the use of 2,5-diaryl-1-methylimidazoles as accessible alternatives to perylene backbones for the development of LSC with optical efficiencies close to 7%.

Synthesis, anionophoric activity and apoptosis-inducing bioactivity of benzimidazolyl-based transmembrane anion transporters

In this paper we show that a series of 1,3-bis(benzimidazol-2-yl)benzene (m-Bimbe) derivatives exhibit excellent performance as transmembrane anion transporters with anticancer activity. The transport efficiency of m-Bimbe and its derivatives has been firstly optimized by adding a strong electron-withdrawing nitro group at the 5-position of the central phenyl subunits to enhance the CH···anion interactions. Evidences for the interactions were obtained from ESI MS, spectrophotometric and 1H NMR titrations. These compounds exhibit potent anionophoric activity in both liposomal models and live cells. In particular, the 5-nitrated derivatives having nitro or trifluoromethyl groups at the benzimidazoloyl subunits exhibit 2370- and 1721-fold enhanced anionophoric activity with the EC50 values as low as 36 and 50 nM, respectively. These compounds can disturb the cellular homeostasis of chloride anions, modify the intracellular pH and induce the basification of acidic organelles. Most of this series of m-Bimbe derivatives exhibit potent cytotoxicity toward the tested human solid tumor cell lines, and the 5-nitrated derivative bearing trifluoromethyl groups at the benzimidazoloyl subunits is the most active with the IC50 value in the low micromolar range. Mechanistic studies suggest that the transport of chloride anions across the cellular membranes plays a critical role in the cytotoxic effect and these compounds induce cell death probably via an apoptotic process.

Effect of electron-withdrawing terminal group on BDT-based donor materials for organic solar cells: a theoretical investigation

Rational end group modification has been found as an effective strategy to improve power conversion efficiencies (PCEs) for photovoltaic materials. However, due to different electronic processes competition, various interaction factors must be taken into account to make materials design. Through density functional theory (DFT) and time-dependent DFT (TD-DFT), the effect of electron-withdrawing substitution on benzodithiophene-based donor materials from the open circuit voltage ( $$ V_{\text{OC}} $$ ), light absorption, exciton dissociation to charge transport in bulk materials has been investigated. The results point to that strong electron-withdrawing end group remarkably (1) enhances $$ V_{\text{OC}} $$ due to lowered HOMO energy level; (2) induces photon absorption redshift due to narrow optical gap (Eg); (3) facilitates exciton dissociation because of enhanced intramolecular charge transfer character. However, there is no direct correlation between electron-withdrawing ability and charge transport properties, since steric hindrance, noncovalent interaction and electrostatic interaction altogether have large impact on intermolecular stacking and then charge mobility. Comprehensive factors should be considered to improve PCEs for photovoltaic materials. Impressively, the designed molecule SM8 with dicyanovinyl-capped reveals excellent optical-electron properties, which may be a promising donor for high performance SM-OSCs.

Synthesis of synergetic phosphorus and cyano groups ([sbnd]C[tbnd]N) modified g-C3N4 for enhanced photocatalytic H2 production and CO2 reduction under visible light irradiation

Graphitic carbon nitride (g-C3N4) has become an attractive photocatalyst for solar energy conversion owing to its numerous advantages. Due to insufficient solar-light absorption and fast photogenerated carriers recombination, the photocatalytic activity of traditional g-C3N4 material is unsatisfactory. In this work, P element and cyano groups (CN) incorporated into the g-C3N4 framework is successfully fabricated by heat treatment of the mixed g-C3N4 and NaH2PO2. The cyano groups (CN) originated from the de-protonation of CNH2 can enhance the light absorption and act as strong electron-withdrawing groups, which can promote the efficient separation of photo-generated electron-hole pairs. The P element doping can enhance the visible light absorption, shorten the band gap and suppress the recombination of photo-induced carriers. The synergistic effect of CN functional groups and P element doping results in a 6.7 times enhanced photocatalytic H2 production activity and 1.58 times enhanced photocatalytic CO2 reduction activity than that of pristine g-C3N4. Experimental analysis indicates that the enhanced photocatalytic performance is mainly attributed to the enhanced light absorption and charge separation. Our work provides a new thought to design other high performance and low-cost g-C3N4-based photocatalytic materials for solar energy conversion.

Synthesis of inulin derivatives with quaternary phosphonium salts and their antifungal activity

Inulin is a kind of renewable and biodegradable carbohydrate with good water solubility and numerous physiological functions. For further utilization of inulin, chemical modification can be applied to improve its bioactivities. In this paper, five novel inulin derivatives were synthesized via chemical modification with quaternary phosphonium salt. Their antifungal activity against three kinds of plant pathogens including Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum was assessed with radial growth assay in vitro. Results revealed that all the inulin derivatives exhibited improved antifungal activity compared with inulin. Particularly, inulin modified with triphenylphosphine (TPhPAIL) exhibited the best antifungal activity with inhibitory indices of 80.0%, 78.8%, and 87.4% against Colletotrichum lagenarium, Phomopsis asparagi, and Fusarium oxysporum at 1.0mg/mL respectively. The results clearly showed that chemical modification of inulin with quaternary phosphonium salt could efficiently improve derivatives' antifungal activity. Further analysis of results indicated that the antifungal activity was influenced by alkyl chain length or electron-withdrawing ability of the grafted quaternary phosphonium salts. Longer alkyl chain lengths or the stronger electron-withdrawing groups would lead to enhanced antifungal efficacy.