Phenyl Side Chain Research Articles

Retraction Note: Sulfonated polysulfone containing phenyl side chain as proton exchange membrane

Retraction Note: Sulfonated polysulfone containing phenyl side chain as proton exchange membrane

Design, Synthesis, Anti-Proliferative Effects, and Mechanistic Details of Fluorine-Containing Biguanide Derivatives with Various Carbon Rings

Introduction/Objective: Biguanide derivatives are small molecules with promising antitumor activity. However, the effect of different carbon rings at the end of one guanide group of these compounds on anti-proliferation activity is unknown. Therefore, we synthesized novel fluorine- containing biguanide compounds with various carbon rings, evaluated their anticancer activities, and explored their anti-proliferative mechanisms. Methods: Guanidine derivatives containing trifluoromethoxy or 3,4-difluorophenyl with nine different carbon rings were synthesized using established chemical methods. The phenyl side chain was fixed to trifluoromethoxy or 3,4-difluorophenyl with changes in the number of cyclic aminocyclic carbons. The effects of these derivatives were evaluated using MTT and clonogenic assays, while the underlying mechanisms were investigated by analyzing protein expression levels via western blotting. Results: This study analyzed the effects of new biguanide derivatives on cell growth in three different cell lines: HepG2, Ovcar3, and T24. The results showed that T24 cells were the most sensitive cell line to these biguanides. All biguanide derivatives significantly inhibited the growth of T24 cells, while compound 4b exhibited the strongest inhibition in all three cell lines by MTT assay. The inhibitory effects of 4b were further confirmed using colony formation experiments. Western blotting results indicated that the representative biguanide derivative, 4b, inhibited the EGFR signaling pathway, thereby inhibiting tumor growth. Conclusion: 1a-5a and 1b-4b, the cyclooctyl-containing 3,4-difluorophenyl biguanide analogs, have demonstrated significant potential in developing novel anticancer drugs. The 3,4- difluorophenyl biguanide containing cyclooctyl showed the best antitumor activity among the nine derivatives. This finding offers a novel perspective in developing anticancer drugs and a further improvement in biguanide activity in the future.

Discovery of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives as tubulin polymerization inhibitors for anticancer therapy: The in vitro and in vivo biological evaluation

A series of novel 2-substituted 2, 3-dihydroquinazolin-4(1H)-one derivatives were designed, synthesized and estimated for their in vitro antiproliferative activities against HepG2, U251, PANC-1, A549 and A375 cell lines. Among them, compound 32 was the most promising candidate, and displayed strong broad-spectrum anticancer activity. The mechanism studies revealed that compound 32 inhibited tubulin polymerization in vitro, disrupted cell microtubule networks, arrested the cell cycle at G2/M phase, and induced apoptosis by up-regulating the expression of cleaved PARP-1 and caspase-3. Furthermore, molecular docking analysis suggested that compound 32 well occupied the binding site of tubulin. In addition, compound 32 exhibited no significant activity against 30 different kinases respectively, indicating considerable selectivity. Moreover, compound 32 significantly inhibited the tumour growth of the HepG2 xenograft in a nude mouse model by oral gavage without apparent toxicity. These results demonstrated that some 2-substituted 2, 3- dihydroquinazolin-4(1H)-one derivatives bearing phenyl, biphenyl, naphthyl or indolyl side chain at C2-position might be potentially novel antitumor agents as tubulin polymerization inhibitors.

Computational Design and Experimental Validation of an Orthogonal X-bond/H-bond System to Improve the Binding Affinity and Recognition Specificity between Anesthetic Protein Kinase Cι and its Pseudosubstrate Peptide

Protein kinase C isoform [Formula: see text] (PKC[Formula: see text]) is an essential regulator of diverse neurobiological signaling pathways, which has been implicated in general anesthetic action and a variety of nervous neoplasms. Traditional efforts have been primarily addressed on the development of small-molecule inhibitors to target the catalytic or regulatory domain of this kinase. Instead, we herein reported a rational chemical modification of Par3 pseudosubstrate peptide to target the kinase domain with improved affinity and specificity. Structural and energetic analysis suggested that the Par3 peptide can be divided into two binding-independent sections; they are separately anchored to the substrate-binding pocket of PKC[Formula: see text] with two aromatic anchor residues Phe818 and Phe823. The side-chain phenyl group of these two aromatic residues was systematically substituted by different halogen moieties at [Formula: see text]-, [Formula: see text]- and [Formula: see text]-positions of the phenyl group. It is revealed that the [Formula: see text]-bromination of Par3 Phe818 and the [Formula: see text]-iodinization of Par3 Phe823 residue can separately form two geometrically and energetically satisfactory orthogonal halogen (X)-bond/hydrogen (H)-bond [ortX/H] motifs across Par3 complex interface with PKC[Formula: see text]; they co-define a so-called ortX/H system and were demonstrated to improve both the binding affinity and recognition specificity of the kinase–peptide interaction by integrating in silico analysis and in vitro assay. The peptide affinity promotes 23.5-fold and 6.6-fold upon the formation of ortX/H motif-I and motif-II, respectively, which further increases to 43.5-fold by forming the complete ortX/H system, indicating cooperativity between the two motifs in the system. In addition, we also demonstrated that the ortX/H system can considerably enhance the peptide selectivity for its cognate PKC[Formula: see text] and noncogante isoforms PKC[Formula: see text] and PKC[Formula: see text].

Linear polyborosiloxane for improving the flame-retardancy of cyanate ester resin

The increasing demands for electronic packing materials necessitate stringent criteria for the overall properties of cyanate ester (CE) resins. In this work, a novel linear polyborosiloxane with a distinctive organic-inorganic hybrid Si–O–B backbone, featuring functional epoxy and phenyl groups (denoted as LPSi-B), was synthesized via a solvent- and catalyst-free one-pot polycondensation. Subsequently, the synthesized LPSi-B was co-crosslinked within the bisphenol A dicyanate ester (BADCy) thermoset network. The presence of abundant active epoxy groups in LPSi-B facilitated its involvement in the cyanate curing reaction, demonstrating excellent compatibility within the resin matrix. The resulting LPSi-B/BADCy composite not only exhibits outstanding mechanical properties but also demonstrates notable flame-retardant and dielectric characteristics. Specifically, the hybrid nature of LPSi-B, combining the flexibility of Si–O–B chains with the rigidity of side-chain phenyl groups, fosters intermolecular non-covalent π-π interactions directly linked to boron atoms, thus mitigating network polarization. Furthermore, the synergistic flame-retardant effect arising from boron and silicon components was harnessed to achieve halogen-free, phosphorus-free, and environmentally friendly fire safety outcomes. This innovative design ensures exceptional compatibility and interface bonding between LPSi-B and the polymer matrix, thereby endowing cyanate ester resin with superior comprehensive performance suitable for advanced applications in wave-transparent and electronic packing materials.

Electropolymerization of an EDOT-Quinoxaline Monomer for Green Electrochromic Thin Films and Devices.

In this study, we present a 5,8-bis(3,4-ethylenedioxythiophene)quinoxaline monomer with two 4-(octyloxy)phenyl side chains (EDOTPQ) that can be electropolymerized on ITO glass in standard electrolytes containing lithium salts and propylene carbonate as solvent. The electrochemically deposited PEDOTPQ layers show very good adhesion and homogeneity on ITO. The green-colored polymer thin films exhibit promising electrochromic (EC) properties and are interesting for applications such as adaptive camouflage, as well as smart displays, labels, and sensors. Novel organic-inorganic (hybrid) EC cell configurations were realized with Prussian blue (PB) or titanium-vanadium oxide (TiVOx) as ion storage electrodes, showing a highly reversible and fast color change from green to light yellow.

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors.

The present work covers novel herbicidal lead structures that contain a 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine scaffold as structural key feature carrying a substituted phenyl side chain. These new compounds show good acyl-ACP thioesterase inhibition in line with strong herbicidal activity against commercially important weeds in broadacre crops, e.g., wheat and corn. The desired substituted 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines were prepared via an optimized BH3-mediated reduction involving tris(pentafluorophenyl)borane as a strong Lewis acid. Remarkably, greenhouse trials showed that some of the target compounds outlined herein display promising control of grass weed species in preemergence application, combined with a dose response window that enables partial selectivity in certain crops.

Effect of alkoxy substitution position of phenyl side chains on the photovoltaic performance of nonfused acceptors

Side chain configuration plays a significant role in intermolecular interaction and aggregation morphology of organic small molecules. In this work, by altering the position of the hexyloxy substitution on the phenyl side chains, three non-fused acceptors were designed and synthesized, e.g. o-2T2Se-F with 2,3-di(hexoxy)phenyl substituents, m-2T2Se-F with 2,4-di(hexoxy)phenyl substituents and p-2T2Se-F with 2,5-di(hexoxy)phenyl substituents. In comparison with its isomeric counterpart 2T2Se-F with 2,6-di(hexoxy)phenyl substituents, these three acceptors exhibit twisted backbones, which result in blue-shifted absorption and weak intermolecular interaction and molecular aggregation. When paired with donor PM6, all three blend films display weak crystallinity, leading to poor photovoltaic performance. The devices based on o-2T2Se-F, m-2T2Se-F and p-2T2Se-F obtained power conversion efficiencies (PCEs) of 4.43%, 1.77%, and 1.30%, respectively, which are significantly lower than that of 2T2Se-F-based devices (12.17%). The results reveal that manipulating the alkoxy-chain attaching point can significantly alter the molecular geometry, optoelectronic properties and molecular aggregation properties, thereby affecting the photovoltaic performance of OSCs.

High-efficiency organic solar cells enabled by nonfullerene acceptors with varying alkyloxy substitution positions of the phenyl outer side chains

Two isomeric molecules named m-BTP-OEH and p-BTP-OEH were developed by attaching a 2-ethylhexyloxyl substituent at the meta- or para-position of its phenyl side chains and a PCE promotion from 17.23% to 18.02% was achieved.

RETRACTED ARTICLE: Sulfonated polysulfone containing phenyl side chain as proton exchange membrane

RETRACTED ARTICLE: Sulfonated polysulfone containing phenyl side chain as proton exchange membrane

Effect of Hyperconjugation on Photovoltaic Performance in Pseduo‐2D Perylene Diimide Derivatives†

Comprehensive SummaryThe π‐π interaction is acknowledged as the predominant factor to determine the molecular packing in organic photovoltaic materials, while other non‐covalent intermolecular interactions especially the σ‐π hyperconjugation are often ignored. Herein, a perylene diimide (PDI) derivative named FIDT‐PDI is designed and synthesized to shed light into the effect of hyperconjugation on the molecular packing and further the photovoltaic performance. Dynamic NMR and 2D NOE NMR demonstrate the formation of intermolecular σ‐π hyperconjugation between the C—H bond of the PDI moiety in one molecule and the phenyl sidechain in another molecule of FIDT‐PDI. Benefiting from the σ‐π hyperconjugation, FIDT‐PDI with twisted backbone reversely exhibits more ordered packing and stronger crystallinity compared with another PDI derivative FIDTT‐PDI which has better planarity, consequently achieving superior PCE and higher carrier mobility. This contribution is the first paradigm to unravel the structure‐property relationship between σ‐π hyperconjugation of conjugated materials and corresponding photovoltaic performance.

Enhanced energy storage characteristics of the epoxy film with rigid phenyl-flexible etherified methylene chains

The introduction of highly polarized flexible segments into polymer molecular chains is an effective means to improve the dielectric constant and mechanical flexibility of polymers, which is important for improving the energy storage characteristics and applicability for the roll-to-roll process of metallic film capacitors. However, the introduction of flexible segments may adversely affect the heat resistance of polymer materials, which limits their application at high working temperatures. In this work, we have prepared a novel epoxy film with excellent comprehensive properties by introducing rigid phenyl and flexible etherified methylene side chains. For instance, the optimal epoxy film showed an energy storage density of 7.06 J cm–3 and 85% charge-discharge efficiency at room temperature and 420 kV mm–1. At 200 kV mm–1 and 110 °C, a working condition for the application of the electric vehicle, the prepared film still showed an energy storage density of 1.5 J cm–3 and charge-discharge efficiency of 86%, which is 3 times that of BOPP film. This work provides an idea for material designs of high-performance polymer film capacitors.

Designed Metal-Containing Peptoid Membranes as Enzyme Mimetics for Catalytic Organophosphate Degradation.

The detoxification of lethal organophosphate (OP) residues in the environment is crucial to prevent human exposure and protect modern society. Despite serving as excellent catalysts for OP degradation, natural enzymes require costly preparation and readily deactivate upon exposure to environmental conditions. Herein, we designed and prepared a series of phosphotriesterase mimics based on stable, self-assembled peptoid membranes to overcome these limitations of the enzymes and effectively catalyze the hydrolysis of dimethyl p-nitrophenyl phosphate (DMNP)─a nerve agent simulant. By covalently attaching metal-binding ligands to peptoid N-termini, we attained enzyme mimetics in the form of surface-functionalized crystalline nanomembranes. These nanomembranes display a precisely controlled arrangement of coordinated metal ions, which resemble the active sites found in phosphotriesterases to promote DMNP hydrolysis. Moreover, using these highly programmable peptoid nanomembranes allows for tuning the local chemical environment of the coordinated metal ion to achieve enhanced hydrolysis activity. Among the crystalline membranes that are active for DMNP degradation, those assembled from peptoids containing bis-quinoline ligands with an adjacent phenyl side chain showed the highest hydrolytic activity with a 219-fold rate acceleration over the background, demonstrating the important role of the hydrophobic environment in proximity to the active sites. Furthermore, these membranes exhibited remarkable stability and were able to retain their catalytic activity after heating to 60 °C and after multiple uses. This work provides insights into the principal features to construct a new class of biomimetic materials with high catalytic efficiency, cost-effectiveness, and reusability applied in nerve agent detoxification.

Benzotriazole-based asymmetric nonfullerene acceptors with A-D-A1-A2 type structure for organic solar cells

Although the wide-bandgap benzotriazole (BTA)-based A2-A1-D-A1-A2 type nonfullerene acceptors (NFAs) have realized super-high open-circuit voltage (VOC) of 1.3 V, the short-circuit current density (JSC) of these materials lag behind the narrow-bandgap A-D-A type analogs. Here, we design and synthesize two asymmetric A-D-A1-A2 type molecules, A301 and A302, by adopting 1,1-dicyanomethylene-3-indanone (IC), BTA and 2-(1,1-dicyanomethylene)rhodanine (RCN) as A, A1 and A2 units, respectively. Under the synergistic regulation of asymmetric end groups and side chain engineering, A302 with alkyl side chains on D unit exhibits red-shifted absorption, tighter molecular packing, and stronger crystallinity in comparison with A301 with phenyl side chain. Consequently, PM6:A302-based organic solar cells (OSCs) realize an enhanced efficiency of 11.09% with an improved JSC of 17.95 mA cm−2, compared to those of PM6:A301-based device (PCE = 8.18%, JSC = 14.57 mA cm−2). Notably, the JSC of 17.95 mA cm−2 is the highest value for BTA-based NFAs to date. This work demonstrates A-D-A1-A2 type NFAs have great potential to balance the JSC and VOC, and side chain on D unit also has a great impact on the properties of this kind of materials.

Antiferroptotic Activities of Oxindole GIF-0726-r Derivatives: Involvement of Ferrous Iron Coordination and Free-Radical Scavenging Capacities.

Ferroptosis and oxytosis are iron- and oxidative stress-dependent cell death pathways strongly implicated in neurodegenerative diseases, cancers, and metabolic disorders. Therefore, specific inhibitors may have broad clinical applications. We previously reported that 3-[4-(dimethylamino)benzyl]-2-oxindole (GIF-0726-r) and derivatives protected the mouse hippocampal cell line HT22 against oxytosis/ferroptosis by suppressing reactive oxygen species (ROS) accumulation. In this study, we evaluated the biological activities of GIF-0726-r derivatives with modifications at the oxindole skeleton and other positions. The addition of a methyl, nitro, or bromo group to C-5 of the oxindole skeleton enhanced antiferroptotic efficacy on HT22 cells during membrane cystine-glutamate antiporter inhibition and ensued intracellular glutathione depletion. In contrast, the substitution of the dimethylamino group on the side chain phenyl ring with a methyl, nitro, or amine group dramatically suppressed antiferroptotic activity regardless of other modifications. Compounds with antiferroptotic activity also directly scavenged ROS and decreased free ferrous ions in both HT22 cells and cell-free reactions while those compounds without antiferroptotic activity had little effect on either ROS or ferrous-ion concentration. Unlike oxindole compounds, which we have previously reported, the antiferroptotic compounds had little effect on the nuclear factor erythroid-2-related factor 2-antioxidant response element pathway. Oxindole GIF-0726-r derivatives with a 4-(dimethylamino)benzyl moiety at C-3 and some types of bulky group at C-5 (whether electron-donating or electron-withdrawing) can suppress ferroptosis, warranting safety and efficacy evaluations in animal models of disease.

Multitargeted 6-Substituted Thieno[2,3-d]pyrimidines as Folate Receptor-Selective Anticancer Agents that Inhibit Cytosolic and Mitochondrial One-Carbon Metabolism.

Multitargeted agents with tumor selectivity result in reduced drug resistance and dose-limiting toxicities. We report 6-substituted thieno[2,3-d]pyrimidine compounds (3-9) with pyridine (3, 4), fluorine-substituted pyridine (5), phenyl (6, 7), and thiophene side chains (8, 9), for comparison with unsubstituted phenyl (1, 2) and thiophene side chain (10, 11) containing thieno[2,3-d]pyrimidine compounds. Compounds 3-9 inhibited proliferation of Chinese hamster ovary cells (CHO) expressing folate receptors (FRs) α or β but not the reduced folate carrier (RFC); modest inhibition of CHO cells expressing the proton-coupled folate transporter (PCFT) by 4, 5, 6, and 9 was observed. Replacement of the side-chain 1',4'-phenyl ring with 2',5'-pyridyl, or 2',5'-pyridyl with a fluorine insertion ortho to l-glutamate resulted in increased potency toward FR-expressing CHO cells. Toward KB tumor cells, 4-9 were highly active (IC50's from 2.11 to 7.19 nM). By metabolite rescue in KB cells and in vitro enzyme assays, de novo purine biosynthesis was identified as a targeted pathway (at 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase (AICARFTase) and glycinamide ribonucleotide formyltransferase (GARFTase)). Compound 9 was 17- to 882-fold more potent than previously reported compounds 2, 10, and 11 against GARFTase. By targeted metabolomics and metabolite rescue, 1, 2, and 6 also inhibited mitochondrial serine hydroxymethyl transferase 2 (SHMT2); enzyme assays confirmed inhibition of SHMT2. X-ray crystallographic structures were obtained for 4, 5, 9, and 10 with human GARFTase. This series affords an exciting new structural platform for potent multitargeted antitumor agents with FR transport selectivity.

Rational Design and Lead Optimisation of Potent Antimalarial Quinazolinediones and Their Cytotoxicity against MCF-7.

Quinazolinedione is one of the most outstanding heterocycles in medicinal chemistry thanks to its wide ranges of biological activities including antimalarial, anticancer, and anti-inflammatory. TCMDC-125133 containing a quinazolinedione pharmacophore displays promising antimalarial activity and low toxicity, as described in the GlaxoSmithKline (GSK) report. Herein, the design and synthesis of novel quinazolinedione derivatives is described on the basis of our previous work on the synthesis of TCMDC-125133, where low-cost chemicals and greener alternatives were used when possible. The initial SAR study focused on the replacement of the valine linker moiety; according to the in silico prediction using SwissADME, concise four-step syntheses toward compounds 4-10 were developed. The in-house synthesized compounds 4-10 were assayed for antimalarial activity against P. falciparum 3D7, and the result revealed that only the compound 2 containing a valine linker was tolerated. Another round of lead optimization focused on the replacement of the m-anisidine moiety in compound 2. A library of 12 derivatives was prepared, and the antimalarial assay showed that potent antimalarial activity could be maintained by replacing the methoxy group in the meta position of the phenyl side chain with a fluorine or chlorine atom (21: IC50 = 36 ± 5 nM, 24: IC50 = 22 ± 5 nM). Further lead optimization is underway to enhance the antimalarial activity of this class of compound. The compounds included in the study possess little to no antiproliferative activity against MCF-7 cells.

Lanthanide and Ladder-Structured Polysilsesquioxane Composites for Transparent Color Conversion Layers

Ladder-type polysilsesquioxanes (LPSQs) containing phenyl as a high refractive index unit and cyclic epoxy as a curable unit were found to be excellent candidates for a transparent color conversion layer for displays due to being miscible with organic solvents and amenable to transparent film formation. Therefore, the LPSQs were combined with luminescent lanthanide metals, europium Eu(III), and terbium Tb(III), to fabricate transparent films with various emission colors, including red, orange, yellow, and green. The high luminescence and transmittance properties of the LPSQs-lanthanide composite films after thermal curing were attributed to chelating properties of hydroxyl and polyether side chains of LPSQs to lanthanide ions, as well as a light sensitizing effect of phenyl side chains of the LPSQs. Furthermore, Fourier-transform infrared (FT-IR) and X-ray photoelectron spectroscopy and nanoindentation tests indicated that the addition of the nanoparticles to the LPSQs moderately enhanced the epoxy conversion rate and substantially improved the wear resistance, including hardness, adhesion, and insusceptibility to atmospheric corrosion in a saline environment. Thus, the achieved LPGSG-lanthanide hybrid organic-inorganic material could effectively serve as a color conversion layer for displays.

Effect of Steric Hindrance at the Anthracene Core on the Photovoltaic Performance of Simple Nonfused Ring Electron Acceptors

Solving the contradiction between good solubility and dense packing is a challenge in designing high-performance nonfullerene acceptors. Herein, two simple nonfused ring electron acceptors (o-AT-2Cl and m-AT-2Cl) carrying ortho- or meta-substituted hexyloxy side chains can be facilely synthesized in only three steps. The two ortho-substituted phenyl side chains in o-AT-2Cl cannot freely rotate due to a big steric hindrance, which endows the acceptor with good solubility. Moreover, o-AT-2Cl displays a more ordered packing than m-AT-2Cl as revealed by the absorption measurement. When blended with polymer donor D18 for the fabrication of organic solar cells (OSCs), o-AT-2Cl-based devices exhibit a favorable morphology, more efficient exciton dissociation, and better charge transport. Consequently, the optimal OSCs based on D18:o-AT-2Cl exhibit a power conversion efficiency (PCE) of 12.8%, which is significantly higher than the moderate PCE (7.66%) for D18:m-AT-2Cl-based devices. Remarkably, o-AT-2Cl shows a higher figure-of-merit value compared with classic high-efficiency fused ring electron acceptors. As a result, our research succeeds in obtaining nonfused ring acceptors with cost-effective photovoltaic performance and provides a valuable experience for simultaneously improving solubility as well as ensuring ordered packing of acceptors through regulating the steric hindrance via changing the position of substituents.

Insight into the effect of side chains on thermal transport of organic semiconductors.

Understanding the correlation mechanism of side chains on thermal transport of organic semiconductors is crucial for functionalized organic electronics. In this study, phenyl and alkyl side chains, two representatives of side chain engineering, are chosen to modify dinaphtho-[2,3-b:2',3'-f]thieno[3,2-b]thiophene (DNTT) to synthesize Ph-DNTT and C10-DNTT. The thermal conductivities of the three organic semiconductors exhibit obvious anisotropy, and the corresponding relationships are along-chain > inter-chain > cross-chain. The phenyl side chains enhance the thermal conductivity in the along-chain direction and degrade it in the inter-chain direction, while the alkyl side chains hinder thermal transport. In the cross-chain direction, side chains have a slight effect on thermal transport. The structure orientation consistency between the phenyl side chains and the main chains in Ph-DNTT leads to phonon coupling in the along-chain direction, which improves phonon transport. In the inter-chain direction, the combined effect of the phonon group velocity and phonon participation ratio causes the thermal conductivity degeneracy of Ph-DNTT. For C10-DNTT, the vibrational mismatch between the alkyl side chains and the main chains results in the degradation of thermal transport in the along-chain and inter-chain directions. In the cross-chain direction, the nonbonding interaction dominates the energy transfer in the three organic semiconductors, which induces inferior phonon transport properties and weak effects of side chains.