Biphenylcarboxylic Acid Research Articles

Synthesis and crosslinking of polyethers that have mesogenic cores and propargyl groups

AbstractWe modified poly(epichlorohydrin) (PECH) with biphenyl carboxylic and naphthalene carboxylic acid derivatives which contains propargyloxy moieties. The linear polymers were characterized by NMR and IR spectroscopy, elemental analysis, DSC and TGA. We obtained only one side chain liquid crystalline. A smectic A mesophase of this biphenyl derivative was identified by DSC, light polarized optical microscopy and X‐ray diffraction. Thermal crosslinking of the aryl propargyl ether group via sigmatropic rearrangement took place while the material was in the isotropic phase. Partially curing this reactive liquid crystalline polymer resulted in the formation of an anisotropic elastomer when the curing was radically initiated in the range of mesophase stability. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3883–3892, 2002

Surface-Enhanced Raman Scattering Study of 4-Biphenylcarboxylic Acid and a Liquid Crystalline Oligomer on Different Metal Surfaces

Surface-enhanced Raman spectra of 4-biphenylcarboxylic acid (BPCA) and ethyl 4‘-[4‘-oxy-4-biphenylcarbonyloxy]-4-biphenylcarboxylate with a poly(propylene oxide) coil of 12 (hereafter named P-12-4) adsorbed on two different metal substrates, Ag and Au colloid monolayers, were examined, to determine the relationship between adsorption strength and geometry. A significant downshift of νCOO- by 60 cm-1 and lack of a C−H aromatic stretching vibration band indicated that BPCA lies flat on the Au surface, while a smaller shift of 40 cm-1 to a lower wavenumber and weak appearance of the C−H aromatic stretching mode implied adsorption through mainly oxygen lone pair electrons of carboxylate with the benzene ring tilted on the Ag surface. These orientations were confirmed by the desorption behavior of a liquid crystalline (LC) oligomer, P-12-4, which contains the BPCA moiety, on the Au and Ag colloid monolayers with increasing temperature.

3D-Quantitative Structure Activity Relationships of Biphenyl Carboxylic Acid MMP-3 Inhibitors: Exploring Automated Docking as Alignment Method

3D-Quantitative Structure Activity Relationships of Biphenyl Carboxylic Acid MMP-3 Inhibitors: Exploring Automated Docking as Alignment Method

3D-Quantitative Structure Activity Relationships of Biphenyl Carboxylic Acid MMP-3 Inhibitors: Exploring Automated Docking as Alignment Method

A series of CoMFA models have been derived from docking-based and atom-based alignments. The statistics of these approaches has been compared to determine whether a docking approach can be employed as an automated alignment tool for the development of 3D-QSAR models. Using a well-characterized training set of 51 biphenyl carboxylic acid MMP-3 inhibitors, the docking-based alignment provided by a DOCK4/PMF-scoring protocol has yielded statistically significant, cross-validated CoMFA models comparable to those derived with a traditional atom-based alignment technique. Field fit minimization has been applied to refine the atom-based and docking-based alignments. The refinement appears to be beneficial for the docking-based approach. For the atom-based alignment, however, field-fit refinement has not resulted in improved CoMFA models. The statistically best CoMFA model has been created by the atom-based alignment that has been found, however, to be inconsistent with the stromelysin crystal structure. The docking alignment refined by field-fit alignment has resulted in a final alignment that is consistent with the crystal structure and only slightly statistically inferior to the atom-based aligned CoMFA model. The results show␣the ability of an automated docking/field-fit alignment technique to provide self-consistent CoMFA alignments.

Unexpected Biosynthetic Precursors of Amarogentin − A Retrobiosynthetic13C NMR Study

A root culture of Swertia chirata (Gentianaceae) produced the natural bitter compound amarogentin in 0.1% (dry weight) yield. The biosynthesis of amarogentin was studied by in vivo experiments, using [1-13C]glucose, [U-13C6]glucose, [1-13C]acetate, [2-13C]acetate, [7-13C]benzoic acid, [ring-13C6]cinnamic acid, or [7-13C]shikimic acid as precursors. Comparison between labeling patterns of amarogentin and amino acids showed that dimethylallyl pyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP), serving as building blocks of the sweroside moiety, are biosynthesized predominantly (> 95%) by the recently discovered deoxyxylulose phosphate pathway. The biphenylcarboxylic acid moiety is biosynthesized by a polyketide-type pathway, with three units of acetyl-CoA and one unit of 3-hydroxybenzoyl-CoA, this being formed from an early shikimate pathway intermediate and not via cinnamic or benzoic acid.

Effects of amino acids on the amidation of polyaromatic carboxylic acids by Bacillus cereus.

The soil bacterium Bacillus cereus Tim-r01 efficiently transformed polyaromatic carboxylic acids (PACA) such as 4-biphenylcarboxylic acid (4-BPCA), 4-biphenylacetic acid, and 4-phenoxybenzoic acid into their corresponding amides. The amidation activity was expressed at 37 degrees C (pH 7-8) in the presence of grown cells in nutrients under an aerobic atmosphere. Other strains of B. cereus, IFO 3001 and IAM 1229, also gave the amide from 4-BPCA. In phosphate-buffered saline (PBS), the addition of normal amino acids was essential, while sulfur-containing amino acids such as methionine and cysteine drastically inhibited the amidation. Tracer experiments using N-15-isoleucine and N-15-alanine showed that the nitrogen atom of the amide came from an amino group of amino acids but not from ammonia or alkylamines.

Surface-Enhanced Raman Scattering Study of 4-Biphenylcarboxylic Acid

The interfacial structures of biphenyl (BP), benzoic acid (BA), and 4-biphenylcarboxylic acid (BPCA) on a Au colloid monolayer surface were investigated using surface-enhanced Raman scattering (SERS). The absence of the C−H stretching vibrational mode in the SERS spectrum of BP indicated that the two benzene rings of BP were coplanar on the Au colloid surface, while their twisted structure was suggested in the bulk state. The downward frequency shift of the carboxylate stretching vibrational mode of BA implied the direct chemical adsorption of the carboxylate group onto the Au surface with a flat orientation. In BPCA, an absence of the C−H stretching vibrational mode and the red shift of the carboxylate stretching vibrational mode were observed. This fact strongly indicated that both the two benzene rings and the carboxylate group were adsorbed on the Au surface with flat orientation via their π-systems.

Amidation of polyaromatic carboxylic acids in aqueous medium

The amidation of polyaromatic carboxylic acids, such as 4-biphenylcarboxylic acid, 4-biphenylacetic acid, 4-carboxy-4′-hydroxybiphenyl, and N-phenylanthranilic acid, was satisfactorily carried out to give the corresponding amides using a wild-type bacterium, Bacillus cereus (w), in an aqueous medium.

Hydrogen-Bonding-Mediated Formation of Supramolecular Rod−Coil Copolymers Exhibiting Hexagonal Columnar and Bicontinuous Cubic Liquid Crystalline Assemblies

The preparation and characterization of the supramolecular rod−coil copolymers directed by molecular recognition of 4,4‘-bipyridine and 4-[poly(propyleneoxy)propyloxy]-4‘-bis(biphenyl carboxylic acid) with degrees of polymerization (DP) of poly(propylene oxide) coil of eight (P-8-HP), 10 (P-10-HP), 15 (P-15-HP), 17 (P-17-HP), 21 (P-21-HP), 27 (P-27-HP) and 34 (P-34-HP) are described. The introduction of poly(propylene oxide) (PPO) coils with different lengths into the rodlike polymeric system induces a rich variety of self-assembled microstructures. In the crystalline phase, the supramolecular rod−coil copolymers with DP of PPO 8−17 organize into a microphase-separated monolayer lamellar structure. In contrast, the supramolecular rod−coil copolymers with DP of PPO 21−34 exhibit a hexagonal columnar crystalline phase. A dramatic phase change after crystalline melting of the polymers is observed with the variation of the coil length. The supramolecular rod−coil copolymers P-8-HP and P-10-HP display a bicontinuous cubic mesophase with Ia3d symmetry, while the supramolecular rod−coil copolymers P-15-HP, P-17-HP, and P-21-HP with a medium length of PPO coil exhibit a hexagonal columnar mesophase. Further increasing the length of coil, as in the case of P-27-HP and P-34-HP, suppresses liquid crystallinity and induces only crystalline polymers.

Multikilogram-Scale Synthesis of a Biphenyl Carboxylic Acid Derivative Using a Pd/C-Mediated Suzuki Coupling Approach

Reaction of 4-bromo-3-methylaniline with 4-chlorobutyryl chloride/TEA and subsequent treatment of the resulting secondary amide intermediate with KOt-Bu gives 1-(4-bromo-3-methylphenyl)pyrrolidin-2-one in 65% yield. This procedure has been optimised (74−76% overall yield) and has been carried out on 41 molar scale. In a variation of this process, we have employed NaOH as the ring-closing base under phase-transfer conditions. NaOH is added to a mixture of 4-bromo-3-methylaniline, 4-chlorobutyryl chloride, and catalytic TBAC in THF/H2O. A further 2 equiv of aqueous NaOH is added, and the mixture is heated at 40−45 °C, providing access to cyclised product in an improved 86% yield. 1-(4-Bromo-3-methylphenyl)pyrrolidin-2-one is subsequently coupled with 4-carboxyphenylboronic acid under standard Suzuki coupling conditions [Pd(PPh3)4, Na2CO3, DME/H2O] to give 2‘-methyl-4‘-(2-oxo-1-pyrrolidinyl)biphenyl-4-carboxylic acid in 64% yield, contaminated with 40−80 ppm of residual Pd. In a modification of this process,...

Selective synthesis of aromatic dicarboxylic acid using cyclodextrin as catalyst

The selective synthesis of terephthalic acid from benzoic acid with carbon tetrachloride, copper powder and aqueous alkali was achieved by the use of β-cyclodextrin (β-CyD) as a catalyst at 60°C under nitrogen of atmospheric pressure, producing terephthalic acid in 74 mol% yield with 100% selectivity. The carboxylation of 4-biphenylcarboxylic acid with carbon tetrachloride, copper powder and aqueous alkali using β-CyD under similar conditions produced 4,4′-biphenyldicarboxylic acid in 71 mol% with 100% selectivity. 2,6-Naphthalenedicarboxylic acid was synthesized by the carboxylation using β-CyD under similar conditions in 67 mol% yield with 84% selectivity. When α-CyD or γ-CyD was used instead of β-CyD, the reaction hardly proceeded. The conformations of CyD–aromatic monocarboxylate inclusion complexes in aqueous alkaline solution were determined by the nuclear magnetic resonance spectroscopy using 1H homonuclear Overhauser enhancement on the rotating frame. The essential factor of the carboxylation was the inclusion complex formations of β-CyD with aromatic monocarboxylate and β-CyD with carbon tetrachloride in the reaction mixture. The high selectivity was ascribed to the conformation of the β-CyD–aromatic monocarboxylate inclusion complex. © 1997 John Wiley & Sons, Ltd.

Shg-Active Films Formed from Uniaxial and Biaxial Nematic Liquid Crystals with Polar Ordering

We found aromatic copolymers comprising 4′-hydroxy 4-biphenyl carboxylic acid and 6-hydroxy 2-naphthoic acid with high second-harmonic-generation (SHG) activity. The polarization dependence of SHG in the solid film formed from the nematic phase reveals uniaxial and biaxial polar orderings.

Localization and disposition of a non-peptide angiotensin II type 1 receptor antagonist, and its glucuronide metabolite, in rat

1. The disposition of radioactivity of a non-peptide angiotensin II type 1 receptor antagonist (E4177) has been studied in groups of male rats after a single oral 1 mg/kg dose of 14C-E4177 was administered by gavage. We have also used light-microscopic autoradiography to investigate the localization of radioactivity in the target tissues for this angiotensin II receptor antagonist. 2. The radioactivity was absorbed quickly, and the maximum blood levels (Cmax) were reached at 0·38 ± 0·14 h after dosing. The concentrations then declined bi-exponentially with a mean apparent half-life for the first phase (t½α) of 0·46 ± 0·07 h and a terminal half life (t½β) of 6·22 ± 1·08 h. By 24 h, the levels had decreased to 2·7 ± 1·5% Cmax. The blood beta max levels radioactivity at 48 h after administration were below the limit of quantification. 3. Radioactivity was distributed throughout the body at 15 min after administration. Tissues inwhich radioactivity was present at higher levels thaninplasma were the liver and kidney. Radioactivity was rapidly eliminated from the tissues and was not retained in any individual organ. 4. The major route of excretion was via the bile. Since > 90% of the administered radioactivity was recovered by 24 h after administration, the excretion was relatively rapid. The major metabolite in bile was a glucuronide of E4177 biphenylcarboxylic acid (E4177- Glu). 5. Light-microscopic autoradiographic observations revealed a strong localization of radioactivity throughout the surface cells of the adrenal glomerulosa, the blood vessels in kidney and the surface of the aortic smooth muscle cells, which are all rich in angiotensin II type 1 (AT1) receptors.

Preparation and crystal structure of dimolybdenum(ii) complexes with the 4-biphenylcarboxylate ligand and its bispyridine adduct

The crystalline compound [Mo 2(4-biphCO 2) 4] · THF ( I) and its bispyridine adduct [Mo 2(4-biphCO 2)4(py) 2] ( II), where 4-biphCO 2H is 4-biphenylcarboxylic acid, have been prepared and structurally characterized. Compound ( I) has a pattern of catenation due to bridging by oxygen atoms that is different from the usual one. The Mo-Mo bond distances are 2.0955(12)and 2.112(7)for complexes ( I) and ( II), respectively. The molecules in compound ( I) are arranged to form a typical extended polymeric chain with an average MoO intermolecular contact of 2.85 . Compound ( II) has two axial pyridine molecules weakly coordinated to dimolybdenum unit. The Mo-N distance is 2.653(4) . Compound ( I) smoothly loses THF (50–100°) and at ca 325° begins to decompose. No discotic liquid phase was observed.

Synthesis and Hydrogen Bonding Capabilities of Biphenyl-Based Amino Acids Designed To Nucleate beta-Sheet Structure.

The syntheses of 3'-(aminoethyl)-2-biphenylpropionic acid (1) and 2-amino-3'-biphenylcarboxylic acid (2) are described. These residues were designed to nucleate beta-sheet structure in aqueous solution when incorporated into small, amphiphilic peptides in place of the backbone of the i + 1 and i + 2 residues of the beta-turn. N-Benzyl-3'-(2-(benzylamido)ethyl)-2-biphenylpropamide (3) and N-benzyl-(2-benzylamido)-3'-biphenylamide (4) were synthesized and studied as model compounds to investigate the hydrogen-bonding capabilities of residues 1 and 2, respectively. The X-ray crystal structure of 3 indicates that a 13-membered intramolecular hydrogen-bonded ring is formed, while the remaining amide proton and carbonyl are involved in intermolecular hydrogen bonding. Infrared and variable-temperature NMR experiments indicate that, in solution (CH(2)Cl(2)), 3 exists as an equilibrium mixture of the 13- and the 15-membered intramolecularly hydrogen-bonded conformers with the 15-membered ring conformer being favored. Amide 4 was shown to exist in solution (CH(2)Cl(2)) as an equilibrium mixture of the 11-membered intramolecular hydrogen-bonded ring and a nonbonded conformation. No contribution from the 9-membered hydrogen-bonded ring conformation was observed. The X-ray crystal structure of 4 indicated the absence of intramolecular hydrogen bonding in the solid state.

Localization of a novel non-peptide angiotensin II type 1 receptor antagonist, E4177, in rat adrenal glomerulosa.

We investigated the distribution of a novel angiotensin II type 1 (AT1) receptor antagonist, E4177 (4'-[2-cyclopropyl-7-methyl-3H-imidazo[5,4-b]pyridine-3-yl]methyl-2- biphenylcarboxylic acid), in rat adrenal glomerulosa. In a binding assay of adrenal capsular tissue (mainly glomerulosa), E4177 exhibited a maximum displacement of approximately 80% of total 125I-labeled angiotensin II (125I-[Sal1, Ile8] Ang II) binding, and its IC50 value was 6.9 +/- 0.5 nM. This IC50 value indicated a slightly higher in vitro potency than that of losartan (21.0 +/- 0.6 nM). Also, in a receptor autoradiographic study, E4177 (10000 nM) displaced approximately 80% of radiolabeled 125I-[Sal1, Ile8] Ang II in rat adrenal glomerulosa and caused only slight displacement in rat adrenal medulla. Further, light and electron microscopic autoradiography of adrenal glomerulosa for 15 min after the intravenous administration of 1 mg/kg [14C]E4177, indicated the localization of 14C, possibly in the adrenal zona glomerulosa cell plasma membrane. It was strongly suggested that E4177 is a potent and selective antagonist of the AT1 receptor, and that it specifically binds to AT1 receptors in the adrenal zona glomerulosa.

A 2,3‘-Substituted Biphenyl-Based Amino Acid Facilitates the Formation of a Monomeric β-Hairpin-like Structure in Aqueous Solution at Elevated Temperature

An evaluation of [3‘-(2-aminoethyl)-2-biphenyl]propionic acid (1) and 2-amino-3‘-biphenylcarboxylic acid (2) as β-sheet nucleators was accomplished by incorporating these residues into water soluble peptides. Residue 1 was designed to replace the backbone of the i + 1 and i + 2 residues of a β-turn and reverse the polypeptide chain direction via a hydrogen-bonded hydrophobic cluster to initiate β-hairpin folding. An NMR structural evaluation of heptapeptides incorporating 1 revealed the presence of a hydrophobic cluster involving an aromatic ring of 1 and a side chain of one of the flanking hydrophobic α-amino acids, even though the peptides lack sufficient length to adopt a β-sheet structure. The flanking α-amino acid residues in these peptides exhibit significantly slower amide proton/deuterium exchange rates, indicating that they are intramolecularly hydrogen bonded in aqueous solution. In appropriate tridecapeptides, the hydrogen-bonded hydrophobic cluster nucleates the formation of a β-hairpin structure which subsequently self-associates. Unlinking the intramolecular folding and self-association equilibria was accomplished by strategically replacing two of the exterior amide protons in the tridecapeptide with methyl groups. These tertiary amide groups cannot act as hydrogen bond donors and sterically block the intermolecular β-sheet interactions between exterior β-strands, preventing self-assembly. The N-methylated tridecapeptide incorporating 1 has been characterized by analytical equilibrium ultracentrifugation, far-UV CD, FT-IR, and a variety of NMR experiments which support a β-hairpin-like structure. Interestingly, these peptides exhibit an increase in β-sheet structure with increasing temperature which may prove to be general for β-sheets stabilized by hydrophobic interactions. The incorporation of residue 2 into an identical α-amino acid sequence does not result in folding under the same conditions, implying that the hydrogen-bonded hydrophobic cluster promoted by 1 is required for β-hairpin folding.

Latent Fingerprint Visualization by Phosphorescence

In this report, the bases of a practical and simple method for effective visualizing of latent fingerprints by phosphorescence was investigated. After the cyanoacrylate treatment of latent fingerprint, phosphorescence reagents were used to enhance the visualization of the fingerprints. Only simple chemical treatments, physical, photographic methods and conventional light source were required. Sophisticated, electronic time imaging equipment or chopper system as used in previous reports were not required. Twenty one phosphorescence reagents were examined in this experiment, and three of them, 4-biphenylcarboxylic acid, p-aminobenzoic acid and p-aminoacetophenone were effective enough for the enhancement of latent fingerprints visualization and conventional use. The former two reagents were excited at 254 nm, but the last one was excited at 350nm. This latent fingerprints detection method utilizing phosphorescence was considered effective, especially, when the back ground printing has a strong fluorescence.

Competitive Inhibition of HIV-1 Protease by Biphenyl Carboxylic Acids

A novel series of nonpeptidic compounds that contain a biphenyl carboxylic acid group have been shown to inhibit HIV-1 protease. The active compounds, most of which are highly soluble, have IC50 values in the range of 3.4-74 μM. The structure-inhibitory activity relationship demonstrates the necessity of the biphenyl carboxylic acid group for inhibition, which is enhanced by the presence of a sulfone group and by halogenation of an adjacent phenyl group. A double reciprocal plot of inhibition data on two of the compounds clearly shows that the inhibition occurs in a competitive manner, with Ki values of 1.1 and 3.4 μM. Inhibition by several of the compounds was found to be reversible and fast-binding, while one of the biphenyl carboxylic acids inhibits in a reversible slow-binding manner. Time-dependent inhibition studies were conducted on this compound, and it was determined to have the kinetic values of kon = 0.18 μM−1min−1, koff = 9.7 × 10−2min−1, and Ki = 0.14 μM. Thus, the slow-binding inhibitor is the most potent in the series. Molecular modeling has provided information on a possible binding mode for two different biphenyl carboxylic acid inhibitors of HIV-1 protease.

Possible intermolecular interaction between quinolones and biphenylacetic acid inhibits gamma-aminobutyric acid receptor sites.

The combination of some new quinolone antibacterial agents with 4-biphenylacetic acid (BPAA), a metabolite of fenbufen, is known to specifically induce functional blockade of the gamma-aminobutyric acid (GABA) receptors. The mechanisms of these drug interactions were further examined. Scatchard analysis of [3H]muscimol binding to rat brain plasma membranes in the presence of enoxacin and BPAA revealed that a significant decrease in the number of muscimol binding sites was produced without affecting the affinity of binding to the receptors. In the presence of norfloxacin, BPAA inhibited muscimol binding the most potently of the six BPAA-related compounds tested. Fenbufen and 9,10-dihydro-gamma-oxo-2-phenanthrenebutyric acid also inhibited the binding, and 4-biphenylcarboxylic acid and methyl 4-biphenylacetate inhibited it slightly, but 3-benzoylpropionic acid exhibited no competitive inhibition. Accordingly, hybrid molecules of norfloxacin and BPAA were synthesized for stereochemical analysis of these drug interactions. A hybrid with a -CONH(CH2)3- chain between norfloxacin and BPAA (flexible structure) inhibited muscimol binding, and intracisternal injection of this hybrid caused clonic convulsions in mice more potently than the combination of norfloxacin and BPAA did. In contrast, a hybrid linked by -CONH- (stretched structure) showed almost no such inhibitory effect. 1H NMR analysis indicated the presence of intramolecular attraction at the quinoline ring of the hybrid exhibiting the antagonistic activity. These results suggest the possibility that quinolones and BPAA interact with the GABA receptor at nearby sites and that the binding affinity of quinolones to the GABA receptors is largely enhanced by the intermolecular interaction with BPAA.