Showing papers on "Substituent published in 2021"

Toward the Copolymerization of Propylene with Polar Comonomers.

Abstract: Polyolefins are produced in vast amounts and are found in so many consumer products that the two most commonly produced forms, polyethylene (PE) and polypropylene (PP), fall into the rather sparse category of molecules that are likely to be known by people worldwide, regardless of their occupation. Although widespread, the further upgrading of their properties (mechanical, physical, aesthetic, etc.) through the formation of composites with other materials, such as polar polymers, fibers, or talc, is of huge interest to manufacturers. To improve the affinity of polyolefins toward these materials, the inclusion of polar functionalities into the polymer chain is essential. The incorporation of a functional group to trigger controlled polymer degradation is also an emerging area of interest. Currently practiced methods for the incorporation of polar functionalities, such as post-polymerization functionalization, are limited by the number of compatible polar monomers: for example, grafting maleic anhydride is currently the sole method for practical functionalization of PP. In contrast, the incorporation of fundamental polar comonomers into PE and PP chains via coordination insertion polymerization offers good control, making it a highly sought-after process. Early transition metal catalysts (which are commonly used for the production of PE and PP) display poor tolerance toward the functional groups within polar comonomers, limiting their use to less-practical derivatives. As late transition metal catalysts are less-oxophilic and thus more tolerant to polar functionalities, they are ideal candidates for these reactions. This Account focuses on the copolymerization of propylene with polar comonomers, which remains underdeveloped as compared to the corresponding reaction using ethylene. We begin with the challenges associated with the regio- and stereoselective insertion of propylene, which is a particular problem for late transition metal systems because of their propensity to undergo chain walking processes. To overcome this issue, we have investigated a range of metal/ligand combinations. We first discuss attempts with group 4 and 8 metal catalysts and their limitations as background, and then focus on the copolymerization of propylene with methyl acrylate (MA) using Pd/imidazolidine-quinolinolate (IzQO) and Pd/phosphine-sulfonate (PS) precatalysts. Each generated regioregular polymer, but while the system featuring an IzQO ligand did not display any stereocontrol, that using the chiral PS ligand did. A further difference was found in the insertion mode of MA: the Pd/IzQO system inserted in a 1,2 fashion, while in the Pd/PS system a 2,1 insertion was observed. We then move onto recent results from our lab using Pd/PS and Pd/bisphosphine monoxide (BPMO) precatalysts for the copolymerization of propylene with allyl comonomers. These P-stereogeneic precatalysts generated the highest isotacticity values reported to date using late transition metal catalysts. This section closes with our work using Earth-abundant nickel catalysts for the reaction, which would be especially desired for industrial applications: a Ni/phosphine phenolate (PO) precatalyst yielded regioregular polypropylene with the incorporation of some allyl monomers into the main polymer chain. The installation of a chiral menthyl substituent on the phosphine allowed for moderate stereoselectivity to be achieved, though the applicable polar monomers currently remain limited. The Account concludes with a discussion of the factors that affect the insertion mode of propylene and polar comonomers in copolymerization reactions, beginning with our recent computational study, and finishing with work from ourselves and others covering both comonomer and precatalyst steric and electronic profiles with reference to the observed regioselectivity.

Enhancing a Molecular Electrocatalyst’s Activity for CO2 Reduction by Simultaneously Modulating Three Substituent Effects

Abstract: The electrocatalytic activity for CO2 reduction is greatly enhanced for Co complexes with pyridyldiimine-based ligands through the stepwise integration of three synergistic substituent effects: extended conjugation, electron-withdrawing ability, and intramolecular electrostatic effects. The stepwise incorporation of these effects into the catalyst structures results in a series of complexes that show an atypical inverse scaling relationship for CO2 reduction-the maximum activity of the resulting catalysts increases as the onset potentials are driven positive due to the ligand electronic substituent effects. Incorporating all three effects simultaneously into the catalyst structure results in a Co complex [Co(PDI-PyCH3+I-)] with dramatically enhanced activity for CO2 reduction, operating with over an order of magnitude higher activity (TOFcat = 4.1 × 104 s-1) and ∼0.2 V more positive catalytic onset (Eonset = -1.52 V vs Fc+/0) compared to the parent complex, an intrinsic activity parameter TOF0 = 6.3 × 10-3 s-1, and >95% Faradaic efficiency for CO production in acetonitrile with 11 M water. This makes [Co(PDI-PyCH3+I-)] among the most active molecular catalysts reported for the CO2 reduction reaction. Our work highlights a promising catalyst design strategy for molecular CO2RR catalysts in which catalytic ability is enhanced by tuning three synergistic substituent effects simultaneously in a single catalyst structure.

Designing fluorene-based conjugated microporous polymers for blue light-driven photocatalytic selective oxidation of amines with oxygen

Abstract: Conjugated microporous polymers (CMPs) have been showcased with a brilliant prospect in organic semiconductor photocatalysis, attributing to accessible molecular design, chemical stability and environmental friendliness. Here, two novel fluorene-based CMPs were designed and conveniently synthesized with carbazole as an electron donor. Importantly, subtle variation of substituent at the methylene bridge (9-position) of fluorene precursor results in different performances in which dimethyl substituent was proven to be more efficient than difluoro substituent for blue light photocatalysis. MFC [9,9'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis(9H-carbazole)]-CMP has a much larger specific surface area, a more favourable redox position, and resultantly a superior photocatalytic performance during blue light-driven selective oxidation of amines into imines with oxygen (O2) in an environmentally benign solvent ethanol (C2H5OH). This work suggests that subtle tweaking in electron acceptors could give rise to superior photocatalytic activity for CMPs in selective chemical conversions.

Radical Addition Enables 1,2-Aryl Migration from a Vinyl-Substituted All-Carbon Quaternary Center

Abstract: An efficient method for photocatalytic perfluoroalkylation of vinyl-substituted all-carbon quaternary centers involving 1,2-aryl migration has been developed. The rearrangement reactions use fac-Ir(ppy)3 , visible light and commercially available fluoroalkyl halides and can generate valuable multisubstituted perfluoroalkylated compounds in a single step that would be challenging to prepare by other methods. Mechanistically, the photoinduced alkyl radical addition to an alkene leads to the migration of a vicinal aryl substituent from its adjacent all-carbon quaternary center with the concomitant generation of a C-radical bearing two electron-withdrawing groups that is further reduced by a hydrogen donor to complete the domino sequence.

Substituent effects of nitro group in cyclic compounds

Abstract: Numerous studies on nitro group properties are associated with its high electron-withdrawing ability, by means of both resonance and inductive effect. The substituent effect of the nitro group may be well described using either traditional substituent constants or characteristics based on quantum chemistry, i.e., cSAR, SESE, and pEDA/sEDA models. Interestingly, the cSAR descriptor allows to describe the electron-attracting properties of the nitro group regardless of the position and the type of system. Analysis of classical and reverse substituent effects of the nitro group in various systems indicates strong pi-electron interactions with electron-donating substituents due to the resonance effect. This significantly affects the pi-electron delocalization of the aromatic ring decreasing the aromatic character, evidenced clearly by HOMA values. Use of the pEDA/sEDA model allows to measure the population of electrons transferred from the ring to the nitro group.

Theoretical investigations on the HOMO–LUMO gap and global reactivity descriptor studies, natural bond orbital, and nucleus-independent chemical shifts analyses of 3-phenylbenzo[d]thiazole-2(3H)-imine and its para-substituted derivatives: Solvent and substituent effects

Abstract: Natural bond orbital analysis, salvation, and substituent effects of electron-releasing (–CH3, –OH) and electron-withdrawing (–Cl, –NO2, –CF3) groups at para positions on the molecular structure of

New Nitro-Laterally Substituted Azomethine Derivatives; Synthesis, Mesomorphic and Computational Characterizations.

Abstract: Two new homologues series, based on two rings of the azomethine central group bearing the terminal alkoxy group of various chain lengths, were prepared. The alkoxy chain length varied between 6 and 16 carbons. The other terminal wing in the first series was the F atom, and the compound is named N-4-florobenzylidene-4-(alkoxy)benzenamine (In). The second group of compounds included a lateral NO2 substituent in addition to the terminal F atom, named N-(4-fluoro-3-nitrobenzylidene)-4-(alkyloxy)aniline (IIn). Mesomorphic and optical properties were carried out via differential scanning calorimetry (DSC) and polarized optical microscopy (POM). Elemental analyses, FT-IR, and NMR spectroscopy were carried out to elucidate the molecular structures of the synthesized groups. Mesomorphic investigations indicated that all the synthesized homologues (In) were monomorphic, possessing the smectic A (SmA) phase monotropically, while the second group (IIn) members were non-mesomorphic. The experimental data indicated that the formation of the mesophase is affected by the protrusion of the lateral nitro group. The disruption of the mesophase in the second group was attributed to the increase of its molecular width, which affects its lateral intermolecular interactions. The computational simulations were in agreement with the experimental data. On the other hand, the location of NO2 group within the molecular geometry increased the melting temperature of the molecule, and thus, affected their thermal and physical properties. By discussing the estimated parameters, it was found that the molecular architecture, the dipole moment, and the polarizability of the investigated compounds are highly affected by the electronic nature and position of the terminal and lateral substituents as well as their volumes.

Quinoline Functionalized Schiff Base Silver (I) Complexes: Interactions with Biomolecules and In Vitro Cytotoxicity, Antioxidant and Antimicrobial Activities

Abstract: A series of fifteen silver (I) quinoline complexes Q1-Q15 have been synthesized and studied for their biological activities. Q1-Q15 were synthesized from the reactions of quinolinyl Schiff base derivatives L1-L5 (obtained by condensing 2-quinolinecarboxaldehyde with various aniline derivatives) with AgNO3, AgClO4 and AgCF3SO3. Q1-Q15 were characterized by various spectroscopic techniques and the structures of [Ag(L1)2]NO3Q1, [Ag(L1)2]ClO4Q6, [Ag(L2)2]ClO4Q7, [Ag(L2)2]CF3SO3Q12 and [Ag(L4)2]CF3SO3Q14 were unequivocally determined by single crystal X-ray diffraction analysis. In vitro antimicrobial tests against Gram-positive and Gram-negative bacteria revealed the influence of structure and anion on the complexes' moderate to excellent antibacterial activity. In vitro antioxidant activities of the complexes showed their good radical scavenging activity in ferric reducing antioxidant power (FRAP). Complexes with the fluorine substituent or the thiophene or benzothiazole moieties are more potent with IC50 between 0.95 and 2.22 mg/mL than the standard used, ascorbic acid (2.68 mg/mL). The compounds showed a strong binding affinity with calf thymus-DNA via an intercalation mode and protein through a static quenching mechanism. Cytotoxicity activity was examined against three carcinoma cell lines (HELA, MDA-MB231, and SHSY5Y). [Ag(L2)2]ClO4Q7 with a benzothiazole moiety and [Ag(L4)2]ClO4Q9 with a methyl substituent had excellent cytotoxicity against HELA cells.

Electrochemical Selenylative Carbannulation of Biaryl Ynones to Seleno-Dibenzocycloheptenones/Spiro[5.5]Trienones.

Abstract: Electrooxidative-induced synthesis of structurally diverse seleno-dibenzocyclohepten-5-ones and seleno-spiro[5.5]trienones by selenylative carbannulation of biaryl ynones with diaryl diselenide has been developed. The switchable reactivity, intramolecular ortho-annulation or dearomative ipso-annulation, is directed by the substituent present on the ortho-aryl group of aryl-ynone. The prominent features of this method include metal-free, external chemical oxidant-free conditions, and readily accessible substrates.

A Fluorinated Carbanionic Substituent for Improving Water Solubility and Lipophilicity of Fluorescent Dyes.

Abstract: Installation of a carbanionic substituent, that is strongly stabilised by two (trifluoromethyl)sulfonyl (Tf = SO 2 CF 3 ) groups, into several fluorescence dyes including boron-dipyrromethenes (BODIPYs), fluoresceins, and aminocoumarins has been achieved by the 2,2-bis(triflyl)ethylation reaction of the dye frameworks with highly electrophilic Tf 2 C=CH 2 , followed by neutralisation with NaHCO 3 . Despite the contradiction between water-solubility and lipophilicity, the carbanion-decorated dyes thus obtained showed significant enhancement of not only water-solubility but also lipophilicity. This work clearly demonstrates that the fluorinated, highly stabilised carbanionic substituent is a new option for controlling the macroscopic property of chemical materials.

Pyridine Scaffolds, Phenols and Derivatives of Azo Moiety: Current Therapeutic Perspectives.

Abstract: Synthetic heterocyclic compounds have incredible potential against different diseases; pyridines, phenolic compounds and the derivatives of azo moiety have shown excellent antimicrobial, antiviral, antidiabetic, anti-melanogenic, anti-ulcer, anticancer, anti-mycobacterial, anti-inflammatory, DNA binding and chemosensing activities. In the present review, the above-mentioned activities of the nitrogen-containing heterocyclic compounds (pyridines), hydroxyl (phenols) and azo derivatives are discussed with reference to the minimum inhibitory concentration and structure–activity relationship, which clearly indicate that the presence of nitrogen in the phenyl ring; in addition, the hydroxyl substituent and the incorporation of a diazo group is crucial for the improved efficacies of the compounds in probing different diseases. The comparison was made with the reported drugs and new synthetic derivatives that showed recent therapeutic perspectives made in the last five years.

Improving Ethane/Ethylene Separation Performance of Isoreticular Metal-Organic Frameworks via Substituent Engineering.

Abstract: The preferential capture of ethane (C2H6) over ethylene (C2H4) presents a very cost-effective and energy-saving means applied to adsorptive separation and purification of C2H4 with a high product purity, which is however challenged by low selectivity originating from their similar molecular sizes and physical properties. Substituent engineering has been widely employed for selectivity regulation and improvement, but its effect on C2H6/C2H4 separation has been rarely explored to date. In this work, four isoreticular coordination framework compounds based on 5-(pyridin-3-yl)isophthalate ligands bearing different substituents were rationally constructed. As revealed by isotherm measurements, thermodynamic studies, and IAST computations, they exhibited promising utility for C2H6/C2H4 separation with moderate adsorption heat and a high uptake amount at a relatively low-pressure domain. Furthermore, the C2H6/C2H4 separation potential can be finely tuned and optimized via purposeful substituent alteration. Most remarkably, functionalization with a nonpolar methyl group yielded an improved separation efficiency compared to its parent compound. This work offers a good reference value for enhancing the C2H6/C2H4 separation efficiency of MOFs by engineering the pore microenvironment and dimensions via substituent manipulation.

Fine-Tuning Miscibility and π-π Stacking by Alkylthio Side Chains of Donor Molecules Enables High-Performance All-Small-Molecule Organic Solar Cells.

Abstract: Optimization of morphology and precise control of miscibility between donors and acceptors play an important role in improving the power conversion efficiencies (PCEs) of all-small-molecule organic solar cells (SM-OSCs). Besides device optimization, methods such as additives and thermal annealing are applied for finely tuning bulk-heterojunction morphology; strategies of molecular design are also the key to achieve efficient phase separation. Here, a series of A-D-A-type small-molecule donors (SM4, SM8, and SM12) based on benzodithiophene units were synthesized with different lengths of alkylthio side chains to regulate crystallinity, and their miscibility with the acceptor (BO-4Cl) was investigated. Consequently, SM4 with a short alkylthio substituent had a high crystallization propensity, leading to the oversized molecular domains and the poor morphology of the active layer. Meanwhile, SM12 with a longer alkylthio substituent showed weak crystallinity, causing a relatively looser π-π stacking and thus adversely affecting charge-carrier transport. The SM-OSC based on the small-molecule donor SM8 with a mid-length alkylthio substituent achieved a better PCE over 13%, which was attributed to a more harmonious blend miscibility without sacrificing carrier-charge transport. Eventually, the modulation of phase separation and miscibility via controlling the lateral side chains has proven its potential in optimizing the blend morphology to aid the development of highly efficient SM-OSCs.

Synthesis of 1,2,3-triazolyl nucleoside analogues and their antiviral activity.

Abstract: Based on the fact that a search for influenza antivirals among nucleoside analogues has drawn very little attention of chemists, the present study reports the synthesis of a series of 1,2,3-triazolyl nucleoside analogues in which a pyrimidine fragment is attached to the ribofuranosyl-1,2,3-triazol-4-yl moiety by a polymethylene linker of variable length. Target compounds were prepared by the Cu alkyne-azide cycloaddition (CuAAC) reaction. Derivatives of uracil, 6-methyluracil, 3,6-dimethyluracil, thymine and quinazolin-2,4-dione with ω-alkyne substituent at the N1 (or N5) atom and azido 2,3,5-tri-O-acetyl-D-β-ribofuranoside were used as components of the CuAAC reaction. All compounds synthesized were evaluated for antiviral activity against influenza virus A/PR/8/34/(H1N1) and coxsackievirus B3. The best values of IC50 (inhibiting concentration) and SI (selectivity index) were demonstrated by the lead compound 4i in which the 1,2,3-triazolylribofuranosyl fragment is attached to the N1 atom of the quinazoline-2,4-dione moiety via a butylene linker (IC50 = 30 μM, SI = 24) and compound 8n in which the 1,2,3-triazolylribofuranosyl fragment is attached directly to the N5 atom of the 6-methyluracil moiety (IC50 = 15 μM, SI = 5). According to theoretical calculations, the antiviral activity of the 1,2,3-triazolyl nucleoside analogues 4i and 8n against H1N1 (A/PR/8/34) influenza virus can be explained by their influence on the functioning of the polymerase acidic protein (PA) of RNA-dependent RNA polymerase (RdRP).

A Catalyst-Controlled Enantiodivergent Bromolactonization.

Abstract: A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed. Quinine-derived amino-amides bearing the same chiral core but different achiral aryl substituents were used as the catalysts. Switching the methoxy substituent in the aryl amide system from meta- to ortho-position results in a complete switch in asymmetric induction to afford the desired lactone in good enantioselectivity and yield. Mechanistic studies, including chemical experiments and density functional theory calculations, reveal that the differences in steric and electronic effects of the catalyst substituent alter the reaction mechanism.

A Series of Metal-Organic Framework Isomers Based on Pyridinedicarboxylate Ligands: Diversified Selective Gas Adsorption and the Positional Effect of Methyl Functionality.

Abstract: Solvothermal assembly of copper(II) cations and 5-(pyridine-3-yl)isophthalate linkers bearing different position-substituted methyl groups afforded four ligand-induced metal-organic framework (MOF) isomers as a platform for investigating diverse selective gas adsorption properties and understanding the positional effect of methyl functionality. Single-crystal X-ray diffraction (SCXRD) analyses showed that, when the methyl substituent is at the para position with respect to the pyridinic N atom, the resultant framework compound ZJNU-27 features an eea-type topology, while the other three solids possess an isoreticular structure with an rtl-type topology when the methyl group is situated at the other positions. As revealed by N2 physi-adsorption measurements at 77 K, they exhibit moderate specific surface areas ranging from 584 to 1182 m2 g-1 and distinct degrees of framework flexibility, which are heavily dependent on the methyl position. Comprehensive gas adsorption studies show that they are capable of effectively separating three pairs of binary gas mixtures including C2H2-CH4, CO2-CH4, and CO2-N2 couples. Moreover, their uptake capacities and adsorption selectivities can be tailored by altering the methyl position. In addition, their framework hydro-stability is also influenced by the methyl position. Compared to ZJNU-27 and ZJNU-28, ZJNU-26 and ZJNU-29 exhibit poorer stability against H2O, although the methyl group is more close to inorganic secondary building units (SBUs), which are believed to originate from the steric effect of the methyl group. Overall, the four MOFs display the methyl position-dependent network architectures, framework flexibilities, and selective gas adsorption properties as well as hydrostabilities. The findings observed in this work not only demonstrate the importance of the positional effect of the functional group but also highlight that engineering the substituent position is a potential strategy for achieving the modulation of MOF structures and properties.

Preparation of Near‐Infrared Emissive π‐Conjugated Polymer Films Based on Boron‐Fused Azobenzene Complexes with Perpendicularly Protruded Aryl Substituents

Abstract: Most organic luminescent dyes usually show poor emission in solid due to aggregation-caused quenching due to nonspecific intermolecular interaction, such as π-π stacking. Furthermore, since commodity molecules having near-infrared (NIR) emission properties tend to have extended π-conjugated systems, development of luminescent organic materials with solid-state NIR emission has been still challenging. Herein, the series of the azobenzene complexes with the perpendicularly-protruded aryl derivative at the boron atom toward π-conjugated system is synthesized. From the optical measurements, it is shown that these complexes can show crystallization-induced emission enhancement behaviors. The donor-acceptor type π-conjugated polymers composed of the azobenzene complexes are also synthesized. Highly-efficient NIR emission from the phenyl-substituted polymers both in solution (λPL = 742 nm, ΦPL = 15%) and film states (λPL = 793 nm, ΦPL = 9%) is obtained. Furthermore, emission wavelengths can be tuned by changing the substituent at the boron atom to the modified aryl groups. From mechanistic studies including theoretical calculations, it is shown that electronic interaction is allowable between the aryl substituent to the π-conjugated system through the tetradentate boron.

Inhibition Mechanism of SARS-CoV-2 Main Protease with Ketone-Based Inhibitors Unveiled by Multiscale Simulations: Insights for Improved Designs*.

Abstract: We present the results of classical and QM/MM simulations for the inhibition of SARS-CoV-2 3CL protease by a hydroxymethylketone inhibitor, PF-00835231. In the noncovalent complex the carbonyl oxygen atom of the warhead is placed in the oxyanion hole formed by residues 143 to 145, while P1-P3 groups are accommodated in the active site with similar interactions to those observed for the peptide substrate. According to alchemical free energy calculations, the P1' hydroxymethyl group also contributes to the binding free energy. Covalent inhibition of the enzyme is triggered by the proton transfer from Cys145 to His41. This step is followed by the nucleophilic attack of the Sγ atom on the carbonyl carbon atom of the inhibitor and a proton transfer from His41 to the carbonyl oxygen atom mediated by the P1' hydroxyl group. Computational simulations show that the addition of a methylchloride substituent to the P1' group may lower the activation free energy for covalent inhibition.

Tunable anticancer activity of furoylthiourea‐based Ru(II)‐arene complexes and their mechanism of action

Abstract: Fourteen new RuII -arene (p-cymene/benzene) complexes (C1-C14) have been synthesized by varying the N-terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure-activity relationships of the Ru-p-cymene and Ru-benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR-32 cancer cells, with C5 (Ru-p-cymene complex containing C6 H2 (CH3 )3 as N-terminal substituent) and C13 (Ru-benzene complex containing C6 H4 (CF3 ) as N-terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim-1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.