Substituent Moiety Research Articles

Exploring the Antidiabetic Potential of Pyrimidine‐Derived Chalcones: Synthesis, Biological Evaluation, and Molecular Modeling

AbstractIn the current research work, we have prepared a series of pyrimidine moiety‐containing molecules due to their promising medicinal profile. First of all, we prepared two acetyl derivatives of pyrimidine (15, 16), and then they reacted with different aryl aldehydes to form various chalcones in a 63–84% yield. The synthesized compounds were characterized by different analytical techniques and screened for their antidiabetic activity. Almost all synthesized compounds (17–43) showed good to excellent antidiabetic activity. Among all the synthesized compounds, 17 and 30 showed remarkable antidiabetic activity with IC50 values of 5.118 µm and 5.187 µm respectively, as compared to the standard reference drug acrabose (IC50 = 37.38 µm). While compounds 18, 19, 21, 22, 23, 27, 31, 33, 38, 42, and 43 also showed excellent antidiabetic activity. Additionally, most biopotent drugs' molecular docking studies supported the distinct connections between substituent moieties and docking domains and agreed with the experimental findings. The molecular dynamics simulation study of the active compounds with the highest binding propensity to the enzyme revealed the robustness of the complexes from the docking study.

Design of Triphenylamine-based D-π-A Systems for Efficient Ternary WORM Memory Devices.

The impact of various substituent moieties on the molecular framework of a conjugated D-A system in resistive switching memory property has been scrutinized through an array of novel D-π-A molecules. The synthesized molecules with triphenylamine (TPA) as the electron donor and dicyanovinylindanone (IC) as the electron acceptor demonstrated substantial non-volatile WORM (Write-Once Read-Many) memory behaviour with appreciable ON/OFF current ratios up to 105 and a lowest recorded threshold voltage of -0.80 V. The well-balanced combination of these potent electron donating and accepting units culminated in exceptional intramolecular charge transfer interactions and minimal band gap values (1.82-2.31 eV) for the molecules, as demonstrated by photophysical and electrochemical investigations. These factors, coupled with the thin-film morphological studies, corroborated the superior performance of the fabricated devices. A longer retention time of 2000s and an endurance of 100 cycles mark the substantial stability of the memory devices. Moreover, conversion from binary to ternary WORM memory was achieved by the effective tuning of the electronic properties of the D-A systems by various substituent moieties. Molecular simulation studies revealed that the resistive switching phenomenon arises from a synergistic interplay of charge transfer and charge trapping processes within these D-A systems.

Quamtum Mechanical Study on Structural and Electronic Properties of Tert-Butyl Based Bridged Dithiophene Oxide Derivatives

Computational modeling is vital to designing and creating organic semiconductors used in solar cells, organic field-effect transistors, and other areas. This work studied the structural and electronic features of a group of substituted tert-butyl bridged dithiophene oxide derivatives using Density Functional Theory (DFT) calculations. Geometry improvements were carried out using the B3LYP hybrid functional and the 6-31G(d,p) basis set in Gaussian 09. Molecular shapes, bond lengths, bond angles, and dihedral angles were studied to find out how substitution patterns change the packing and conformation of molecules. Energy levels, distribution, and makeup of frontier molecular orbitals were found. This calculation also included finding other electronic qualities, such as electronic charges, dipole moments, and polarizabilities. Findings show that tert-butyl substitution makes the molecular backbone stiffer and limits its ability to twist compared to similar molecules that have not been replaced. The chemical geometry stays mostly the same when electron-withdrawing or electron-donating substituents are added to the tert- butyl groups. Nevertheless, the strength and location of substituents have a significant impact on frontier orbital energies. The HOMO-LUMO gap grew significantly when the nitro or cyano groups firmly pulled electrons away from derivatives. For successful charge transport, electron density plots show that the HOMO and LUMO are mainly located on the thiophene and substituent moieties, respectively. Molecular dipole moments are also strongly affected by the electronic features of substituents. This research shows how to change the optoelectronic properties of tert-butyl-based dithiophene oxide derivatives and how their structure-property relationships can be improved. The results help makes new organic semiconductors that work better in various electronic and optoelectronic uses.

Benzothiazole based sulfonamide scaffolds as active inhibitors of alpha-Amylase and alpha-glucosidase; synthesis, structure confirmation, In Silico molecular docking and ADME analysis

Benzothiazole based sulfonamide scaffolds as active inhibitors of alpha-Amylase and alpha-glucosidase; synthesis, structure confirmation, In Silico molecular docking and ADME analysis

The estrogen receptor modulatory activity and neuroprotective activity of novel prenylated flavonoids and their structure–activity relationship

AbstractPrenylated flavonoids are promising nutraceuticals with diverse bioactivities. However, publications on the mechanism of action and structure–activity relationship of prenylated flavonoids are limited. In the present work, six novel prenylated flavonoids (C8–C13) with diversity structure were prepared. Their estrogen receptor (ER) modulator activity and neuroprotective activity were investigated by cell assays. C8, C9, and C10 with 8‐C‐prenyl and 7‐OH showed agonistic activities toward ERα and ERβ, along with high ERβ selectivity. However, C11 and C12 were ERα‐selective agonists. The position and substituent moiety of prenylation, C‐ring configuration, and flavonoid skeleton were important for the ER modulating activities. Hydrogen bonds between 3′‐OH and Leu339 in ERβ, and 5′‐OH and Glu305 in ERβ might respond for the higher agonistic activity of C8 and C10, respectively. C8, C9, C11, and C12 showed more potency than 17β‐estradiol on neuroprotection in glutamate‐treated PC‐12 cells. C8 and C12 could reverse reactive oxygen species overproduction and reduction of Δψm induced by glutamate through increase of the expression of ERS1, SOD1, SOD2, CAT, and GPx4 and decrease of caspase‐3 expression, suggesting C8, and C9 might interact with ERα, promote antioxidant defense, mitigate oxidative stress, and improve mitochondrial function to exert the neuroprotection activities.

The Effect of Pendent Groups upon Flexibility in Coordination Networks with Square Lattice Topology.

Gas or vapor-induced phase transformations in flexible coordination networks (CNs) offer the potential to exceed the performance of their rigid counterparts for separation and storage applications. However, whereas ligand modification has been used to alter the properties of such stimulus-responsive materials, they remain understudied compared with their rigid counterparts. Here, we report that a family of Zn2+ CNs with square lattice (sql) topology, differing only through the substituents attached to a linker, exhibit variable flexibility. Structural and CO2 sorption studies on the sql networks, [Zn(5-Ria)(bphy)]n, ia = isophthalic acid, bphy = 1,2-bis(pyridin-4-yl)hydrazine, R = -CH3, -OCH3, -C(CH3)3, -N=N-Ph, and -N=N-Ph(CH3)2, 2-6, respectively, revealed that the substituent moieties influenced both structural and gas sorption properties. Whereas 2-3 exhibited rigidity, 4, 5, and 6 exhibited reversible transformation from small pore to large pore phases. Overall, the insight into the profound effect of pendent moieties of linkers upon phase transformations in this family of layered CNs should be transferable to other CN classes.

Rational Design of Ir(III) Phosphors to Strategically Manage Charge Recombination for High-Performance White Organic Light-Emitting Diodes.

Constructing high-quality white organic light-emitting diodes (WOLEDs) remains a big challenge because of high demands on the electroluminescence (EL) performance including high efficiency, excellent spectral stability, and low roll-off simultaneously. To achieve effective energy transfer and trap-assisted recombination in the emissive layer, herein, four Ir(III) phosphors, namely, mOMe-Ir-PI (1), pOMe-Ir-PI (2), mOMe-Ir-PB (3), and pOMe-Ir-PB (4), were strategically designed via simple regulation of the substituent moiety and π conjugation of the chelated ligands. Their photophysical and EL properties were systematically investigated. When these phosphors are employed as doped emitters, the monochromic green organic light-emitting diodes not only exhibit a superior performance with the characteristics of 50.2 cd A-1, 39.2 lm W-1, and 15.1%, but also maintain a negligible roll-off ratio of 0.2% at 1000 cd m-2, which are better than those of commercial green Ir(ppy)2acac and Ir(ppy)3 in the same device configuration. Inspired by these outstanding performances, we successfully fabricated the warm WOLED utilizing 2 as a green component, affording a peak efficiency of 42.0 cd A-1, 29.3 lm W-1, and 18.6% and retaining at 39.9 cd A-1, 23.7 lm W-1, and 17.4% even at 1000 cd m-2. The results herein demonstrate the superiority of the molecular design and propose a simple method toward the development of promising Ir(III) phosphors for high-efficiency WOLEDs.

Crystal Flexibility Design through Local and Global Motility Cooperation.

Incorporating local mobility into a flexible framework promises to create cooperative properties unattainable in a conventional soft porous crystal. In this study, we propose a design strategy that integrates substituent moieties and a flexible porous crystal framework via intra-framework π-π interactions. This integration not only facilitates framework structural transitions but also gives the porous coordination polymers (PCPs) different guest-free structures that depend on the activation conditions. The incorporated flexibility gives the material the ability to discriminate C6 alkane isomers based on different gate-opening behaviors. Thus, the PCP has potential applications in C6 isomer separation, a critical step in the petroleum refining process to produce gasoline with high octane rating. This strategy, based on ligand designability, offers a new approach to flexible PCP structural and functional design.

Crystal Flexibility Design through Local and Global Motility Cooperation

AbstractIncorporating local mobility into a flexible framework promises to create cooperative properties unattainable in a conventional soft porous crystal. In this study, we propose a design strategy that integrates substituent moieties and a flexible porous crystal framework via intra‐framework π–π interactions. This integration not only facilitates framework structural transitions but also gives the porous coordination polymers (PCPs) different guest‐free structures that depend on the activation conditions. The incorporated flexibility gives the material the ability to discriminate C6 alkane isomers based on different gate‐opening behaviors. Thus, the PCP has potential applications in C6 isomer separation, a critical step in the petroleum refining process to produce gasoline with high octane rating. This strategy, based on ligand designability, offers a new approach to flexible PCP structural and functional design.

Study of Electronic and Steric Effects of Different Substituents in Donor–Acceptor Molecules on Multilevel Organic Memory Data Storage Performance

AbstractTo study the influence of different types of substituent moieties onto the molecular backbones of conjugated donor–acceptor (D–A) molecules on the thin‐film morphology and performance of their memory devices, three new molecules X‐TBT were synthesized, which consist of the same backbone of two triphenylamine (T) groups and benzothiadiazole (BT) group, but have different substituents (X) with different electronic effects, that is, cyano group (CN), tert‐butyl group (tBu), and methoxy group (OMe). Nonvolatile ternary write‐once‐read‐many‐times (WORM) data storage behavior is achieved for the CN‐TBT and tBu‐TBT based devices as compared to the binary memory characteristic of TBT (X = H). In contrast, OMe‐TBT based device still maintains binary WORM behavior due to its unfavorable molecular packing motif and weak intermolecular charge transfer effect, but exhibits the lowest operating voltage (1.4 V) as a result of the lowest energy barrier between electrode and active layer. Notably, the tBu‐TBT based device displays the highest ION2/ION1/IOFF ratio of 107:103:1. Altering the substituents in D–A molecules can adjust the molecular packing, thin film morphology, and electron trap depth of the active layer, which then significantly influence the memory performance.

Water-soluble manganese porphyrins as good catalysts for cipro- and levofloxacin degradation: Solvent effect, degradation products and DFT insights

Synthetic manganese porphyrins (MnPs), in the presence of oxidants, were employed for the degradation of fluoroquinolone antibiotics. Ciprofloxacin (CIP) and levofloxacin (LEV) degradation by iodosylbenzene, iodobenzene diacetate, H2O2 and meta-chloroperbenzoic acid using water-soluble MnP catalysts yielded thirteen and nine products, respectively, seven of which have been proposed for the first time. The MnP catalysts have demonstrated the ability to degrade these antibiotics to a high degree (up to 100% degradation). The structures of the degradation products were proposed based on mass spectrometry analysis, and density functional theory calculations could confirm how the substituent moieties attached to the basic chemical structure of the fluoroquinolones influence the degradation reactions. CIP has been shown to be a more reactive substrate towards the porphyrinic catalysts tested because of its three-membered ring. However, the catalysts could almost completely degrade LEV, highlighting the ability of these porphyrins to act as catalysts to degrade environmental pollutants.

Copper-catalyzed one-pot relay synthesis of anthraquinone based pyrimidine derivative as a probe for antioxidant and antidiabetic activity

Abstract Synthetic compounds have modernized the globe due to its vast applicable fields. Anthraquinones, as well as pyrimidine derivatives, are used as essential pharmacophores in the field of medicine. Maintenance of a green disease-free environment by using these derivatives is being acknowledged in developed as well as developing countries of the world. Considering the use of active catalysts in the synthesis of anthraquinone based derivatives are the era of concern for researchers due to their distinctive properties. Owing to the remarkable activities of anthraquinone and pyrimidine derivative, we synthesize compounds having both functionalities with the utilization of novel synergically active copper catalysts. This study explores the application of synthesized compounds using fast, ecofriendly and cost-effective approaches.1H and 13C NMR, antioxidant, antidiabetic, molecular docking and QSAR studies were used for characterization and evaluation of newly synthesized anthraquinone based pyrimidine derivatives. The result of these techniques shows that our desired compounds were successfully synthesized and have potent applications. Among all synthesized compounds, G2 and G3 showed a remarkable antioxidant activity with IC50 of 15.09 and 21.88 μg/ml respectively. While the compound G2 and G4 showed a strong inhibitory antidiabetic activity with the IC50 value of 24.23 and 28.94 μg/ml respectively. Furthermore, molecular docking results for both of the proteins assist the experimental data and confirms the different interactions between binding domains and substituent moieties. SAR study also relates to the experimental facts by giving us positive results of synthesized compounds. According to the QSAR study, G4 and G2 emerged as the most stable and most reactive compound among other compounds respectively. While MEP shows moderate to good nucleophilic and electrophilic reactivity of all four compounds.

Influences of Structural Modification of Naphthalenediimides with Benzothiazole on Organic Field-Effect Transistor and Non-Fullerene Perovskite Solar Cell Characteristics.

Developing air-stable high-performance small organic molecule-based n-type and ambipolar organic field-effect transistors (OFETs) is very important and highly desirable. In this investigation, we designed and synthesized two naphthalenediimide (NDI) derivatives (NDI-BTH1 and NDI-BTH2) and found that introduction of 2-(benzo[d]thiazol-2-yl) acetonitrile groups at the NDI core position gave the lowest unoccupied molecular orbital (LUMO; -4.326 eV) and displayed strong electron affinities, suggesting that NDI-BTH1 might be a promising electron-transporting material (i.e., n-type semiconductor), whereas NDI-BTH2 bearing bis(benzo[d]thiazol-2-yl)methane at the NDI core with a LUMO of -4.243 eV was demonstrated to be an ambipolar material. OFETs based on NDI-BTH1 and NDI-BTH2 have been fabricated, and the electron mobilities of NDI-BTH1 and NDI-BTH2 are 14.00 × 10-5 and 8.64 × 10-4 cm2/V·s, respectively, and the hole mobility of NDI-BTH2 is 1.68 × 10-4 cm2/V·s. Moreover, a difference in NDI-core substituent moieties significantly alters the UV-vis absorption and cyclic voltammetry properties. Thus, we further successfully employed NDI-BTH1 and NDI-BTH2 as electron transport layer (ETL) materials in inverted perovskite solar cells (PSCs). The PSC performance exhibits that NDI-BTH2 as the ETL material gave higher power conversion efficiency as compared to NDI-BTH1, that is, NDI-BTH2 produces 15.4%, while NDI-BTH1 gives 13.7%. The PSC performance is comparable with the results obtained from OFETs. We presume that improvement in solar cell efficiency of NDI-BTH2-based PSCs is due to the well-matched LUMO of NDI-BTH2 toward the conduction band of the perovskite layer, which in turn increase electron extraction and transportation.

Synthesis and photophysical properties of S, N and Se-modified methyl salicylate derivatives

Abstract Three different S, N and Se-modified methyl salicylate derivatives, methyl 2-hydroxy-4-(pyridin-2-yl)benzoate (MHPB), methyl 2-hydroxy-4-(thiophen-2-yl)benzoate (MHTB) and methyl 2-hydroxy-4-(selenophen-2-yl)benzoate (MHSB) have been synthesized and their photophysical properties are examined in dichloromethane. The three derivatives produce absorption spectra with different shapes spanning over 260–370 nm region. The UV excitation of the derivatives produces characteristic emission features, associated with the Franck-Condon (FC) excited-state configuration at high-energy side and excited state intramolecular proton transfer configuration at low-energy side. For MHPB, two emission bands peaking at around 380 and 450 nm are observed with relatively strong intensities. However, for MHTB the intensity of the blue emission is significantly reduced and for MHSB the emission is significantly quenched. Quantum mechanical calculations on the structural geometry and the electronic transition are performed to reveal the effect of the substituent moieties on the photophysical properties.

Polypropylene synthesis in liquid monomer with titanium–magnesium catalyst: effect of different alkoxysilanes as external donors

The effect of a set of methoxy- and ethoxysilanes as external donors (ED) on propylene polymerization in liquid monomer with the supported titanium–magnesium catalyst (TMC) and on properties of the produced polypropylene (PP) are studied. Addition of the studied donors to the polymerization system significantly increases the PP isotacticity compared to polymerization over TMC without ED (up to 92–98% vs. 66%, respectively). It is found that activity and stereospecificity of the catalytic system, as well as the molecular weight of the produced PP, decline as the number and size of alkoxy groups increase and the size (branching) of alkyl substituents decreases. Bulky substituents in alkoxysilanes have a positive effect on activity and stereospecificity of TMC. However, the double bond in the substituent moiety reduces the catalyst activity. Nitrogen atom in the substituent (with the same alkoxy groups) increases isotacticity and crystallinity of PP, its flexural modulus and strength characteristics. Varying electron donors with different number and size of alkoxy groups and different substituents (aliphatic, aromatic, alicyclic, amino, and vinyl) at silicon atom allows one to control the catalyst activity and isotacticity, as well as the molecular and thermal characteristics and impact strength properties of PP.

Cybotactic nematic phase of achiral unsymmetrical bent-core liquid crystals – Quelling of polar ordering and the influence of terminal substituent moiety

Abstract Nematic phase of bent-core liquid crystals (LCs) exhibiting cybotactic clusters (NCyb) have gained significant importance owing to its promising ability to demonstrate macroscopic biaxiality and the ferronematic phase. In this context, three achiral unsymmetrical four-ring bent-core LC compounds, bearing a long alkyloxy chain and differing only in the terminal substituent moiety (methyl, chloro, nitro), are designed and synthesized followed by their optical, dielectric, electro-optic and structural investigations. The presence of NCyb in the methyl and chloro substituted compounds was confirmed via dielectric spectroscopy and X-ray diffraction observations. The absence of ferroelectric behaviour in any of these compounds, even in the cybotactic nematic phase and in presence of polar substituent moieties (chloro and nitro), is attributed to the increased alkyloxy chain length and antiparallel molecular arrangement. The density functional theory (DFT) optimized molecular structure along with the experimental observations further substantiates these findings. The study establishes that cybotactic clusters and polar end moiety, although being a prerequisite for ferroelectric-like nature, do not necessarily result in a ferronematic phase.

Farnesyl phenolic enantiomers as natural MTH1 inhibitors from Ganoderma sinense.

Cancer cells are more addictive to MTH1 than normal cells because of their dysfunctional redox regulations. MTH1 plays an important role to maintain tumor cell survival, while it is not indispensable for the growth of normal cells. Farnesyl phenols having a coumaroyl substitution are rather uncommon in nature. Eight farnesyl phenolic compounds with such substituent moiety (1–8), including six new ones, ganosinensols E–J (1–6) were isolated from the 95% EtOH extract of the fruiting bodies of Ganoderma sinense. Four pairs of enantiomers 1/2, 3/4, 5/6 and 7/8 were resolved by HPLC using a Daicel Chiralpak IE column. Their structures were elucidated from extensive spectroscopic analyses and comparison with literature data. The absolute configurations of C-1′ in 1–6 were assigned by ECD spectra. These compounds were predicted to have high binding affinity to MTH1 through virtual ligand screening. The enzyme inhibition experiments and cell-based assays confirmed their inhibitory effects on MTH1. Furthermore, siRNA knockdown experiments and the cellular thermal shift assay (CETSA) confirmed that the farnesyl phenolic enantiomers specifically bound with MTH1 in intact cells. Meanwhile, the low cytotoxicity of 1–8 on normal human cells further verified their good selectivity and specificity to MTH1. These active structures are expected to be potential anti-cancer lead compounds.

Ring‐Opening Polymerization of Lactide Catalyzed by Bimetallic Salen‐Type Titanium Complexes

Three kinds of bimetallic Schiff base titanium complexes with different substituent moieties on organic ligands were synthesized. Ring‐opening polymerizations (ROP) of lactides were carried out by using these titanium complexes as catalysts. The polymerization data and kinetic studies showed that complex 1a had the highest activity and complex 2a had the lowest activity for ROP of lactides. Moreover, all these three newly synthesized bimetallic titanium complexes showed higher polymerization activity and better molecular weight control than their monometallic counterparts reported in our previous work.

Rapid preparation of (3R,4S,5R) polyhydroxylated pyrrolidine-based libraries to discover a pharmacological chaperone for treatment of Fabry disease

The rapid discovery of a pharmacological chaperone toward human α-Gal A for the treatment of Fabry disease is described. Two polyhydroxylated pyrrolidines with the (3R,4S,5R) configuration pattern underwent rapid substituent diversity by conjugating the primary aminomethyl moiety of each with a variety of carboxylic acids to generate two libraries (2×60 members). Our bioevaluation results showed one member with the (2R,3R,4S,5R) configuration pattern and bearing a 5-cyclohexylpentanoyl group as a substituent moiety possessed sufficient chaperoning capability to rescue α-Gal A activity in the lymphocyte of the N215S Fabry patient-derived cell line and other α-Gal A mutants in COS7 cells.

Selectivity mapping of the binding sites of (E)-resveratrol imprinted polymers using structurally diverse polyphenolic compounds present in Pinot noir grape skins

This investigation describes a general procedure for the selectivity mapping of molecularly imprinted polymers, using (E)-resveratrol-imprinted polymers as the exemplar, and polyphenolic compounds present in Pinot noir grape skin extracts as the test compounds. The procedure is based on the analysis of samples generated before and after solid-phase extraction of (E)-resveratrol and other polyphenols contained within the Pinot noir grape skins using (E)-resveratrol-imprinted polymers. Capillary reversed-phase high-performance liquid chromatography (RP-HPLC) and electrospray ionisation tandem mass spectrometry (ESI MS/MS) was then employed for compound analysis and identification. Under optimised solid-phase extraction conditions, the (E)-resveratrol-imprinted polymer showed high binding affinity and selectivity towards (E)-resveratrol, whilst no resveratrol was bound by the corresponding non-imprinted polymer. In addition, quercetin-3-O-glucuronide and a dimer of catechin-methyl-5-furfuraldehyde, which share some structural features with (E)-resveratrol, were also bound by the (E)-resveratrol-imprinted polymer. Polyphenols that were non-specifically retained by both the imprinted and non-imprinted polymer were (+)-catechin, a B-type procyanidin and (-)-epicatechin. The compounds that did not bind to the (E)-resveratrol molecularly imprinted polymer had at least one of the following molecular characteristics in comparison to the (E)-resveratrol template: (i) different spatial arrangements of their phenolic hydroxyl groups, (ii) less than three or more than four phenolic hydroxyl groups, or (iii) contained a bulky substituent moiety. The results show that capillary RP-HPLC in conjunction with ESI MS/MS represent very useful techniques for mapping the selectivity of the binding sites of imprinted polymer. Moreover, this procedure permits performance monitoring of the characteristics of molecularly imprinted polymers intended for solid-phase extraction of bioactive and nutraceutical molecules from diverse agricultural waste sources.