Biphenyl Moiety Research Articles

Synthesis, anti-proliferative activity, gene expression, docking and DFT investigation of novel pyrazol-1-yl-thiazol-4(5H)-one derivatives

In this elucidation, the novel thaizolone derivatives 8a-n were synthesised via the reaction between thioamide derivatives 4a, b with chloroacetic acid and the appropriate aldehyde derivatives 7a-g in acetic acid which were confirmed through spectral analysis such as FT-IR, 1HNMR,13CNMR and mass spectrum. Furthermore, the optimization of these thiazolone were investigated utilized DFT/B3LYP/6-31(G) basis set and compared their energies and physical characterizations, which showed the most stable compounds from biphenyl and phenyl-piperidine fused thiazolone rings were 8f and 8m. The compounds 8f and 8m were exhibited as anti-proliferative compounds against MCF-7 breast cancer and PC-3 prostate cancer cells using neutral red uptake assay. Compound 8f showed more inhibitory influence on MCF-7 growth, while compound 8m revealed more cytotoxicity in PC-3 cells. The results were confirmed through a morphology study, where the expression levels of BCL2, Cyclin D1, FGF1 and HIF1α genes were examined by QRT-PCR. This study showed that compounds 8f and 8m exhibited significant pro-apoptotic effects, through the down regulation of BCl-2 and CCND1 genes. Also, the anti-angiogenic effect of compound 8f emerged due to the downregulation of FGF1 expression levels and the upregulation of HIF-1α. The stability and structural properties of the predicted conformers were studied using DFT theoretical calculations, which demonstrated that the stability of the anticipated conformers is affected by the configuration of the biphenyl and phenyl pipridine moieties in the synthesised thiazolone. Furthermore, the docking structures of these compounds 8f and 8m were investigated by (PDBID:4hdq), (PDBID:3ruk), (PDBID:5jsn) and (PDBID:5VZU) which confirmed the experimental results and showed the stability of 8f rather than 8m due to the presence of biphenyl and made more conjugation.

Liquid crystalline polyurethanes modified by Trisilanolisobutyl-POSS

A series of liquid crystalline polyurethanes based on 4,4′-bis(hydroxyhexoxy)biphenyl moieties and modified by Trisilanolisobutyl-POSS (TRIS-POSS) was synthesized via a polyaddition reaction. ATR-FTIR confirmed introduction of POSS moieties into the macrochain. Formation of liquid crystalline phases along with higher melting and crystallization temperatures due to the addition of the POSS moieties has been observed by Differential Scanning Calorimetry (DSC) and Polarized Optic Microscopy (POM). The influence of the POSS on the improvement of thermal stability and char residue after degradation is also discussed. Influence of the POSS particles on glass transition was found to be relevant for high mesogenic unit load. Morphological investigations by Scanning Electron Microscopy showed different distribution of the POSS nanoparticles for each examined matrix and absence of POSS originated agglomerates which was also confirmed by X-ray diffraction technique. Reinforcement effect of the POSS on mechanical properties was also investigated. Mechanically induced anisotropy was hypothesized to be one of the factor responsible for improved tensile strength at high strain.

Synthesis of a Mechanically Planar Chiral and Axially Chiral [2]Rotaxane.

In this study, we synthesized a [2]rotaxane that was both mechanically planar chiral and axially chiral, comprising a symmetrical bis-crown ether featuring a biphenyl moiety (as the macrocyclic component) and a symmetrical bis-ammonium salt (as the dumbbell-shaped component).

Donor-Acceptor Conjugated Heptazine Polymers with Highly Efficient Photocatalytic Degradations towards Tetracyclines.

Photocatalysis is an efficient and green technology in the environmental protection. Due to the high charge separation and transfer, donor-acceptor (D-A) conjugated polymers attract much attention for their photocatalytic degradations towards organic pollutants. Herein, the authors reported three novel D-A conjugated polymers, named as HPBP, HPTP, and HPF, with heptazine moieties as electron acceptors, while biphenyl, terphenyl, or fluorene moieties as electron donors, respectively, which indeed exhibit a highly efficient photocatalytic degradation towards tetracyclines upon the visible-light irradiation. Among them, the photocatalytic performance of HPF is especially noticeable with the degradation rate up to 87% within 30 min, almost 11 times in comparison to those of pristine g-C3 N4 , which is mainly attributed to its high crystallinity and conjugation. For their photocatalytic mechanism, the •O2 - radical anions are regarded as the active species.

3',5'-Di-chloro-N,N-diphenyl-[1,1'-biphen-yl]-4-amine.

The title tri-phenyl-amine derivative, C24H17Cl2N, featuring a 3,5-di-chloro-1,1'-biphenyl moiety has been synthesized and structurally characterized. The mol-ecular structure shows rotations of the phenyl rings in the range of 37-40° from the amine plane. In the crystal, the mol-ecules inter-act by van der Waals inter-actions.

Solid-State and Theoretical Investigations of Some Banister-Type Macrocycles with 2,2'-Aldoxime-1,1'-Biphenyl Units.

In the context of helical chirality, bridging of biphenyl units leads to banister-type compounds and the stability of the resulted atropisomers may increase dramatically if suitable changes are performed in the linker unit that coils around the biphenyl moiety. A rigorous density functional theory (DFT) study was conducted for macrocycles containing rigid oxime ether segments connected to the biphenyl backbone in order to determine how the rotation barriers are influenced by the presence of either a flexible oligoethyleneoxide or a more rigid m–xylylene component in the macrocycle. The calculated values for the racemization barrier were in good agreement with those obtained experimentally and confirm the benefit of introducing a more rigid unit in the macrocycle on the stability of atropisomers. Solid-state data were obtained and computed data were used to assess the contribution brought by supramolecular associations observed in the lattice to the stabilization of the crystal structure. Beside introducing rigidity in the linker, complexation of flexible macrocycles with alkali metal ions is also contributing to the stability of atropisomers, leading to values for the racemization barrier matching that of the rigid macrocycle. Using diethylammonium cation as guest for the macrocycle, a spectacular increase in the barrier to rotation was observed for the resulted pseudo[2]rotaxane.

Enzymatic transformation products of phloretin as potent antiadipogenic compounds.

Enzymatic structure modification of the representative chalcone phloretin (1) with polyphenol oxidase from Agaricus bisporus origin produced 2 new biphenyl-type phloreoxin (2) and phloreoxinone (3), and a previously undescribed (2R)-5,7,3',5'-tetrahydroxyflavanone (4). The structure of these new oxidized products 2-4 elucidated by interpreting the spectroscopic data (NMR and FABMS) containing the absolute stereochemistry is established by the analysis of the circular dichroism spectrum. Compared to the original phloretin, the new products (2) and (3) showed highly improved antiadipogenic potencies both toward pancreatic lipase and accumulation of 3T3-L1 cells. Also, phloreoxin (2) effectively inhibited the expression of C/EBPβ, PPARγ, and aP2 at the mRNA level in the 3T3 adipocytes. Thus, phloreoxin (2), containing a biphenyl moiety catalyzed by A. bisporus polyphenol oxidase, have the potential to influence the antiadipogenic capacity.

Polar Alkoxy Group and Pyridyl Effects on the Mesomorphic Behavior of New Non-Symmetrical Schiff Base Liquid Crystals

A series of non-symmetrical Schiff base liquid crystals were prepared and investigated. Schiff bases of p-alkyloxy aniline derivatives and 4-phenyl pyridine-4′-carbaldehyde were synthesized. The terminal alkoxy groups substituting aniline are of varied chain length, namely C6, C8, and C16. The structures of the compounds were confirmed via 1H NMR and 13C NMR spectroscopy. Different mesophases of the samples were thermally and optically characterized by differential thermal analysis (DSC) and polarized optical microscopy (POM). All samples revealed enantiotropic smectic B (SmB) and smectic A (SmA) mesophases. The results obtained were further correlated with the density functional theory (DFT) theoretical calculations. The results are compared to a series of compounds bearing biphenyl moiety in their mesogens. The thermal stabilities of the different mesophase reduced upon the increment of the alkoxy chain length. The temperature ranges of both the smectic mesophases of new compounds bearing the 4-phenyl pyridine moiety are generally expanded higher than the other series. In addition, the total mesophase range is greater in the new compounds when compared to their biphenyl analogues. The DFT results were investigated in terms of the molecular geometries and the frontier molecular orbitals as well as the charge distribution mapping to show and illustrate the difference in the mesomorphic properties.

Novel Poly(ionic liquid) Augmented Membranes for Unconventional Aqueous Phase Applications in Fractionation of Dyes and Sugar.

Poly(ionic) liquid (PIL) augmented membranes were fabricated through self-polymerization of 2-vinyl pyridine and 4-vinyl pyridine followed by dopamine triggered polymerization and bridging with inert polyamide support. The resulting membranes acquired a positive surface charge with a high degree of hydrophilicity. Fourier transformed Infra-red (FTIR) and Energy dispersive X-ray (EDX) spectroscopic investigation revealed the successful augmentation of PIL surface layer, whereas surface morphology was investigated through scanning electron microscopy (SEM) imaging. This manuscript demonstrates pi electron-induced separation of dyes with the trend in permeability: Coomassie Brilliant Blue G (CBBHG) > Remazol Brilliant Blue R (RBBR) > Eichrome Black T (EBT) > Congo Red (CR). CBBG exhibited extended conjugation over large aromatic domain. RBBR and EBT were associated withtheelectron-donating -NH2 group and electron-withdrawing -NO2 group, respectively, hence pi electron density on aromatic ring varied. The steric repulsion between two pairs of ortho hydrogens (Hs) in biphenyl moieties of CR resulted in deviation of planarity and hence aromaticity leading to the lowest permeability. The sugar fractionation followed the trend: Galactose > Mannose > Fructose > Glucose > Xylose. More hydroxyl (-OH) groups in sugars and their conformational alignment in the same direction, exhibited more lone pair of electrons leading to more interaction with PIL and hence better permeability. Pentose showed poorer permeation than hexose, whereas aldose showed better permeation than ketose.

Improving Druggability of Novel Diarylpyrimidine NNRTIs by a Fragment-Based Replacement Strategy: From Biphenyl-DAPYs to Heteroaromatic-Biphenyl-DAPYs.

A series of novel heteroaromatic-difluoro-biphenyl-diarylpyrimidines were designed as non-nucleoside anti-HIV inhibitors targeting reverse transcriptase by a fragment-based replacement strategy with the purpose of improving the druggability. Hopping five- or six-membered heterocycle groups on the biphenyl moiety as bioisosterism for intrinsically cyanophenyl gave 23 derivatives. All of these compounds possessed excellent HIV-1 inhibitory activity in the nanomolar range. Among them, 12g with a 4-pyridine group displayed excellent inhibitory activity toward WT and mutant HIV virus possessing significant selectivity. Moreover, this compound exhibited a decent improvement in druggability than etravirine and rilpivirine: (1) The hydrochloric acid salt of 12g exhibited significantly improved water solubility in different pH conditions. (2) 12g did not show apparent CYP enzymatic inhibitory activity or acute toxicity. (3) Excellent oral bioavailability was also revealed (F = 126%, rats) in 12g. Collectively, these novel heteroaromatic-biphenyl-DAPYs represent promising drug candidates for HIV clinical therapy.

On the identification and quantification of proton-initiated species in the synthesis of poly(2-alkyl-2-oxazoline)s by high resolution liquid chromatography

Hydrophilic poly(2-oxazoline)s represent a promising alternative to replace poly(ethylene glycol) in the biomedical field. For that purpose, reliable analytical protocols to confirm identity and quantity of impurities are required. In particular, side products deriving from chain transfer reactions occurring during the cationic ring-opening polymerization and incomplete end-capping processes may be present. The analytical approach must hence be capable of separating polymers according to minor changes regarding their end group. We demonstrate that liquid chromatography, relying on a monolithic C18-modified silica column and isocratic as well as gradient elution using water / acetonitrile mixtures and varying detectors, can accomplish such demanding high resolution separations. Poly(2-ethyl-2-oxazoline)s (PEtOx) with acetyl, hydroxyl, and phthalimide ω-end groups were investigated. Identification of side products was achieved through coupling with electrospray ionization mass spectrometry. UV / Vis detection was applied to quantify chain transfer products in PEtOx comprising biphenyl moieties. In addition, gradient elution enabled the separation of PEtOx into macromolecules according to their specific degrees of polymerization in molar mass ranges around 2,000 g mol-1.

Exploring New Scaffolds for the Dual Inhibition of HIV-1 RT Polymerase and Ribonuclease Associated Functions.

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. Pursuing on our investigation on potential anti HIV multi-target agents we have designed and synthesized a small library of biphenylhydrazo 4-arylthiazoles derivatives and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity. In particular, compound 2-{3-[(2-{4-[4-(hydroxynitroso)phenyl]-1,3-thiazol-2-yl} hydrazin-1-ylidene) methyl]-4-methoxyphenyl} benzamide bromide (EMAC2063) was the most potent towards RNaseH (IC50 = 4.5 mM)- and RDDP (IC50 = 8.0 mM) HIV RT-associated functions.

Soluble Polyarylates Based on Methyl-substituted Bisphenols Containing Pendent Biphenyl Moiety: Synthesis, Characterization, and Thermal Properties

Soluble Polyarylates Based on Methyl-substituted Bisphenols Containing Pendent Biphenyl Moiety: Synthesis, Characterization, and Thermal Properties

Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5-a]pyridine Scaffold: SAR of the Biphenyl Moiety.

The connection with acute myelogenous leukemia (AML) of dihydroorotate dehydrogenase (hDHODH), a key enzyme in pyrimidine biosynthesis, has attracted significant interest from pharma as a possible AML therapeutic target. We recently discovered compound 1, a potent hDHODH inhibitor (IC50 = 1.2 nM), able to induce myeloid differentiation in AML cell lines (THP1) in the low nM range (EC50 = 32.8 nM) superior to brequinar’s phase I/II clinical trial (EC50 = 265 nM). Herein, we investigate the 1 drug-like properties observing good metabolic stability and no toxic profile when administered at doses of 10 and 25 mg/kg every 3 days for 5 weeks (Balb/c mice). Moreover, in order to identify a backup compound, we investigate the SAR of this class of compounds. Inside the series, 17 is characterized by higher potency in inducing myeloid differentiation (EC50 = 17.3 nM), strong proapoptotic properties (EC50 = 20.2 nM), and low cytotoxicity toward non-AML cells (EC30(Jurkat) > 100 μM).

Multicomponent synthesis and anti-proliferative screening of biaryl triazole-containing cyclophanes

We report a practical two-step approach involving a Ugi 4-CR/ azide-alkyne cycloaddition for the synthesis of biaryl-containing cyclophanes. The series represents an extension of our previously reported macrocycles as an effort to enhance the anti-proliferative activity of this scaffold. In this variant, we incorporate a biphenyl moiety in the framework, thus enhancing the macrocycle size, lipophilicity, and structural diversity. Macrocycles were tested against different cell lines, being more cytotoxic against prostate (PC-3 and DU-145) and breast (MCF-7) tumor cells. Gratifyingly, the most active compound showed a significative enhancement of PC-3 growth inhibition with respect to our previous series, reaffirming the potential anti-proliferative activity of this kind of cyclophanes.

Arsenic‐Bridged Silafluorene and Germafluorene as a Novel Class of Mixed‐Heteroatom‐Bridged Heterofluorenes

AbstractArsenic‐bridged silafluorene and germafluorene were synthesized as a novel class of mixed‐heteroatom‐bridged heterofluorenes. Their structures, photophysical properties, and electronic natures were studied by experimental and computational means. The doubly‐bridged biphenyl moieties were distorted from the reported singly‐bridged ones. The intersystem crossing from the singlet excitation states to the triplet ones was enhanced by the arsenic‐bridging structures, implying that bridging through an arsenic atom is favorable for phosphorescence.

CO2 and CH4 adsorption on periodic mesoporous organosilica: A DFT study

Periodic mesoporous organosilicas (PMO) were proposed as potential adsorbents for CO2/CH4 adsorption-separation due to their strong interactions with CO2 and low affinity for CH4. Herewith, we present a comprehensive density functional theory (DFT) study about the binding properties of CO2 and CH4 with the pore walls of different PMO materials. The calculations considered the M06−2X DFT exchange-correlation functional, and cluster models of the walls of the PMO materials with organic bridges based on phenylene (Ph-), biphenylene (Bph-), pyridine (Py-) and bipyridine (Bpy-) fragments or on mixtures of Ph/Py- and Bph/Bpy- moieties. All materials showed stronger interactions with CO2 than with CH4, which suggests they are potentially selective for CO2 over CH4. From the calculated data it is demonstrated that the PMO materials with phenylene moieties establish more favorable contacts with CO2 than those found in their counterparts with bridges based on the homologous heteroaromatic nitrogen compounds, viz. pyridine. Independently of the size of the organic bridge, both phenylene- and biphenylene- PMO materials showed similar CO2 adsorption behavior. The presence of bipyridine-bridges improved the CO2 adsorption behavior only when mixed with biphenylene moieties. The adsorption behavior of CO2 gas can be directly related to the SiOH···OCO distance, i.e., the adsorption strength increases with the decrease of this distance. In the case of the CH4 adsorption, the least favorable adsorptions were determined for PMO materials with pyridine and phenylene/pyridine bridges.

Phase behaviors of classic liquid crystal dimers and trimers: Alternate induction of smectic and twist-bend nematic phases depending on spacer parity for liquid crystal trimers

A new heliconical mesophase without apparent molecular positional ordering, which was discovered in achiral bent molecules [i.e., the twist-bend nematic (NTB) phase], has become a hot topic of research in the field of liquid crystals (LCs). In this study, a series of classic LC trimer homologs, namely 4,4′-bis[ω-(4-cyanobiphenyl-4′-yloxy)alkoxy]biphenyls (CBOnOBOnOCB; n = 4–11), was synthesized, and their phase transitions and mesophase structures were evaluated in detail, to reinvestigate their elusive monotropic mesophases. Polarized optical microscopy (POM) observations revealed that below the nematic (N) phases, even-n homologs exhibited the fan-shaped and polygonal textures of the layered smectic (Sm) phase, while odd-n homologs displayed the blocky and striped textures associated with the recently discovered heliconical NTB phase. X-ray diffraction analyses of CBOnOBOnOCB (n = 10 and 11) revealed that their mesophases exhibited the cybotactic N phase property, and suggested that the monotropic mesophase observed for odd CBO11OBO11OCB was the pseudo-layered heliconical NTB phase rather than the layered Sm phase. Therefore, it was suggested that the Sm and NTB phases were alternately induced, depending on the spacer parity of classic LC trimer homologs CBOnOBOnOCB. This could be ascribed to the steric interactions associated with different molecular geometries, which are largely governed by the imposed spacer parity, and possess parallelly and obliquely located mesogenic biphenyl moieties for the even-n and odd-n homologs, respectively. In addition, the phase-transition behavior of a homologous series of ether-linked cyanobiphenyl-based LC dimers (CBOnOCB; n = 3–12) was investigated. POM observations shows that odd-n CBOnOCB homologs (n = 5, 7, 9, and 11) exhibited the monotropic N–NTB phase transition, which was only observed in the small supercooled N domains. Even-n CBOnOCB homologs exhibited only the N phase and did not exhibit Sm phases below the temperature of the N phase upon cooling. Hence, alternate induction of the Sm and NTB phases depending on n parity was observed only in the LC trimer homologs.

Mesomorphism of novel stilbene-based bent-core liquid crystals

ABSTRACT A series of asymmetric bent-core liquid crystals, bearing the stilbene moiety in the side wing, was synthesised and characterised. Structural modifications of the non-stilbene wing resulted in formation of various mesophases. Compounds 1 and 3 with an ester linking group between the phenyl rings in this wing have an enantiotropic non-polar smectic-type mesophase, while compound 2, incorporating the biphenyl moiety, has a ferroelectric SmCaPF phase. The molecules of 2 undergo photoisomerisation in solution under UV irradiation, while the mesophases are unstable and UV irradiation leads to irreversible changes. The mesophases of 1 and 3 do not show any electro-optical switching and polarisation current. Applying low frequency AC voltage on a planarly aligned film of compound 2, smectic domains grow, while the birefringence and an image flickering increase. The observed features of these compounds identify stilbene as an attractive moiety in the design of advanced materials based on bent-core molecules.

Helical Chirality Inversion of Poly(biphenylacetylene) with Hydroxyl Groups Induced by a Single Enantiomer and Memory of the Helices

The solvent- and temperature-driven high-/low-twist switch of the biphenyl moieties in a poly(biphenylacetylene) with hydroxyl groups [poly(BPhDHPA)] triggered the rapid helix inversion of the induced helices in poly(BPhDHPA) by a single enantiomer, and the induced helices under both high-twist and low-twist modes could be well memorized using achiral phenylmethanol. The addition of a small amount of polar solvent [e.g., dimethyl formamide (DMF), <10 vol %] to a toluene solution of l-menthol/poly(BPhDHPA) complex causes an immediate and complete inversion of the induced helices. Further analysis indicates that the biphenyl moieties in the complex take the high-twist structure in nonpolar solvents and low-twist structure in polar solvents. The helices induced under the high-twist mode in nonpolar solvents showed higher thermostability than helices induced under the low-twist mode in polar solvents. The chiral amplification following the “majority rule” under the low-twist mode is more efficient than that under the high-twist mode.