6-phenylhexanoic Acid Research Articles

Secondary metabolites from fungus Nigrospora sp.

Six compounds were purified from the extracts of fungus Z18-17 (Nigrospora sp.) isolated from Scyphiphora hydrophyllacea, a tree from the intertidal zone of Shankou, Guangxi Province of China, which was reported to have cytotoxic activity. Systematic study on the chemical constituents of Nigrospora sp. resulted in the isolation of one new 6-phenylhexanoic acid derivative, one new derivative of uridine, and four known compounds. Their structures were characterized, respectively, as methyl 5-acetamido-6-(4-hydroxyphenyl)-4-oxohexanoate (1), uridine-5′α-hydroxypropanoate (2), 4-hydroxyphenethyl 2-hydroxypropanoate (3), methyl pyroglutamate (4), cyclo (Pro-Val) (5), and cyclo (Phe-Hyp) (6). The cytotoxic activities of the two new compounds against HL-60 cell line were tested and the IC50 values of the two new compounds were all over 100 μM.

Protective Effects of 4-Phenylbutyrate Derivatives on the Neuronal Cell Death and Endoplasmic Reticulum Stress

Endoplasmic reticulum (ER) stress responses play an important role in neurodegenerative diseases. Sodium 4-phenylbutyrate (4-PBA) is a terminal aromatic substituted fatty acid that has been used for the treatment of urea cycle disorders. 4-PBA possesses in vitro chemical chaperone activity and reduces the accumulation of Parkin-associated endothelin receptor-like receptor (Pael-R), which is involved in autosomal recessive juvenile parkinsonism (AR-JP). In this study, we show that terminal aromatic substituted fatty acids, including 3-phenylpropionate (3-PPA), 4-PBA, 5-phenylvaleric acid, and 6-phenylhexanoic acid, prevented the aggregation of lactalbumin and bovine serum albumin. Aggregation inhibition increased relative to the number of carbons in the fatty acids. Moreover, these compounds protected cells against ER stress-induced neuronal cell death. The cytoprotective effect correlated with the in vitro chemical chaperone activity. Similarly, cell viability decreased on treatment with tunicamycin, an ER stress inducer, and was dependent on the number of carbons in the fatty acids. Moreover, the expression of glucose-regulated proteins 94 and 78 (GRP94, 78) decreased according to the number of carbons in the fatty acids. Furthermore, we investigated the effects of these compounds on the accumulation of Pael-R in neuroblastoma cells. 3-PPA and 4-PBA significantly suppressed neuronal cell death caused by ER stress induced by the overexpression of Pael-R. Overexpressed Pael-R accumulated in the ER of cells. With 3-PPA and 4-PBA treatment, the localization of the overexpressed Pael-R shifted away from the ER to the cytoplasmic membrane. These results suggest that terminal aromatic substituted fatty acids are potential candidates for the treatment of neurodegenerative diseases.

ChemInform Abstract: Stereoselective Synthesis of N-Boc-O-Benzyl-(4S,5S)-5-amino-4-hydroxy- 6-phenylhexanoic Acid, the Hydroxyethylene Isosteric Moiety of Potent HIV-1 Protease Inhibitor.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Dependence of Hydrocarbon Sensitivity on the Distance of Linked Phenyl Group to CdSe Quantum Dots Surfaces

The hydrocarbon sensing properties of CdSe semiconductor quantum dots (QDs) tailored with benzoic, phenylacetic, 4-phenylbutanoic, or 6-phenylhexanoic acids as a surface enhancement agent have been studied to determine their dependence on the phenyl group distance from the QD surface. QDs of roughly the same size were used to attach each of the mentioned surface agents with similar surface coverages, as determined by nuclear magnetic resonance technique, followed by drop-coating and drying of the QD solutions onto porous anodic aluminum oxide substrates for sensing tests. Results indicated that normalized photoluminescence (PL) enhancement did not vary noticeably for QDs with longer chained phenyl groups compared to those with shorter length groups upon film exposure to xylenes vapors over the range of 15 to 9400 ppm in a balance of air. The quantum yield of CdSe QDs with the 6-phenylhexanoic acid surface ligand has a higher value, 29.4%, compared to those with benzoic acid, 4.5%. Moreover, the PL sensitivity toward xylenes exposure for QDs with 6-phenylhexanoic acid versus those with the surface-bound benzoic acid was about 8 times and 16 times greater at xylenes concentrations below 2500 ppm and above 4500 ppm, respectively. These results suggest that the QDs with longer length surface-enhancing ligands are more promising for this type of hydrocarbon sensing applications.

Effects of chromophore orientation and molecule conformation on surface-enhanced Raman scattering studied with alkanoic acids and colloidal silver nanoparticles

Experimental studies have been carried out to gain a better understanding of the effects of chromophore orientation and molecular conformation on surface-enhanced Raman scattering (SERS) based on metal nanostructures. A series of alkanoic acids that contain a phenyl ring separated by methylene groups from the carboxylic acid, including phenylacetic acid, 3-phenylpropionic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, and 6-phenylhexanoic acid, was investigated as model molecules with colloidal silver nanoparticles as SERS substrates. As the number of methylene groups increases, the molecules display an interesting zigzag intensity pattern of the phenyl ring bending mode around 1000 cm(-1) as well as a trend of appearance and disappearance of either the degenerate ring breathing mode or C[Double Bond]O vibrational mode near 1585 and 1630 cm(-1), respectively. Molecules containing an odd number of methylene units display a higher ring bending intensity and degenerate ring breathing mode and are suggested to have a trans conformation on the particle surface. Molecules with an even number of methylene units show a C[Double Bond]O vibrational mode and weaker ring bending in their SERS spectra and are suggested to have a gauche conformation on the silver nanoparticle surface. The different conformation is attributed to the varying interactions of the carboxylic group or the phenyl ring pi electrons with the silver surface. The SERS intensity was found to change little as the length between the phenyl ring and the carboxylic group was increased by adding CH(2) spacers. This is possibly because the effective distance between the phenyl ring and the silver surface does not change much with increasing number of CH(2) spacers as a result of changes in molecular conformation and variations in the phenyl ring orientation with CH(2) addition. The insight gained from this study is important for understanding SERS of complex molecules for which chromophore orientation and molecular conformation must be taken into careful consideration.

Naphthenic acids and surrogate naphthenic acids in methanogenic microcosms

Naphthenic acids (NAs) are a complex mixture of naturally occurring acyclic and cyclic aliphatic carboxylic acids in petroleum. In the Athabasca oil sands, NAs have been identified as the largest component of dissolved organic matter in the tailings waters from oils sands extraction processes. They are the major contributor to the acute toxicity of the fine tailings wastewaters at the oil sands extraction plants in northeastern Alberta, Canada. In this study, three sources of NAs were studied, including commercially available NAs, those extracted from oil sands process-affected waters, and individual naphthenic-like surrogate compounds. Analysis by gas chromatography–mass spectrometry demonstrated differences between the commercial and extracted NAs. The NAs derived from the process-affected waters showed a short-term inhibition of methanogenesis from H 2 or acetate, but with time the populations resumed methane production. It has been postulated that microbial metabolism of the carboxylated side chains of NAs would lead to methane production. The two NA mixtures failed to stimulate methanogenesis in microcosms that contained either oil sands fine tailings or domestic sewage sludge. However, in microcosms with sewage sludge, methanogenesis was stimulated by some surrogate NAs including 3-cyclohexylpropanoic acid at 400–800 mg/L, 5-cyclohexylpentanoic acid at 200 mg/L or 6-phenylhexanoic acid at 200 and 400 mg/L. When added at 200 mg/L to methanogenic microcosms containing fine tailings, 3-cyclohexylpropanoic and 4-cyclohexylbutanoic acids produced methane yields that suggested mineralization of the side chain and the ring.

Microbial synthesis of poly(beta-hydroxyalkanoates) bearing phenyl groups from pseudomonas putida: chemical structure and characterization.

New poly(beta-hydroxyalkanoates) having aromatics groups (so-called PHPhAs) from a microbial origin have been characterized. These polymers were produced and accumulated as reserve materials when a beta-oxidation mutant of Pseudomonas putida U, disrupted in the gene that encodes the 3-ketoacyl-CoA thiolase (fadA), was cultured in a chemically defined medium containing different aromatic fatty acids (6-phenylhexanoic acid, 7-phenylheptanoic acid, a mixture of them, or 8-phenyloctanoic acid) as carbon sources. The polymers were extracted from the bacteria, purified and characterized by using (13)C nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), and differential scanning calorimetry (DSC). Structural studies revealed that when 6-phenylhexanoic acid was added to the cultures, an homopolymer (poly-3-hydroxy-6-phenylhexanoate) was accumulated. The feeding with 8-phenyloctanoic acid and 7-phenylheptanoic acid leads to the formation of copolymers of the corresponding units with the n - 2 carbons formed after deacetylation, copoly(3-hydroxy-8-phenyloctanoate-3-hydroxy-6-phenylhexanoate) and copoly(3-hydroxy-7-phenylheptanoate-3-hydroxy-5-phenylvalerate), respectively. The mixture of 6-phenylhexanoic acid and 7-phenylheptanoic acid gave rise to the corresponding terpolymer, copoly(3-hydroxy-7-phenylheptanoate-3-hydroxy-6-phenylhexanoate-3-hydroxy-5-phenylvalerate). Studies on the chemical structure of these three polyesters revealed that they were true copolymers but not a mixture of homopolymers and that the different monomeric units were randomly incorporated in the macromolecular chains. Thermal behavior and molecular weight distribution were also discussed. These compounds had a dual attractive interest in function of (i) their broad use as biodegradable polymers and (ii) their possible biomedical applications.

1:1 and 1:2 Complexation Thermodynamics of γ-Cyclodextrin with N-Carbobenzyloxy Aromatic Amino Acids and ω-Phenylalkanoic Acids

The stability constants (K), standard free energies (ΔG°), enthalpies (ΔH°), and entropy changes (TΔS°) for the complexation of γ-cyclodextrin with N-carbobenzyloxy (CBZ)-d/l-phenylalanine, CBZ-d/l-tyrosine, CBZ-d/l-tryptophan, CBZ-d/l-histidine, CBZ-glycine, 3-phenylpropionic acid, 4-phenylbutyric acid, 5-phenylvaleric acid, and 6-phenylhexanoic acid have been determined in phosphate buffer solution (pH 6.9) at 298.15 K by titration microcalorimetry. The trends observed in the thermodynamic parameters for 1:1 and/or 2:1 host−guest complexation correlate with the systematic structural changes of the guest molecules. On the basis of the results obtained, we further discuss the possible thermodynamic implication for the entropic control of supramolecular systems.

Crystal structures and Mössbauer spectra of mixed-valence dinuclear iron(II,III) complexes: detrapped valence states †

Mixed-valence µ-phenolate bis(µ-carboxylate) diiron(II,III) complexes [FeIIFeIII(bpmp)(L)2][BF4]2 have been prepared, where Hbpmp represents 2,6-bis[bis(2-pyridylmethyl)aminomethyl]-4-methylphenol and HL is benzoic acid (Hba) 1, phenylacetic acid (Hpaa) 2, 3-phenylpropionic acid (Hppa) 3, 4-phenylbutyric acid (Hpba) 4, 5-phenylvaleric acid (Hpva) 5, 6-phenylhexanoic acid (Hpha) 6 or p-methoxybenzoic acid (Hmba) 7. The Mossbauer spectra were measured for the complexes and the crystal structures of 4 and 7 determined. Complexes 1, 2 and 4 show trapped Mossbauer spectra due to iron(II) and iron(III), 5–7 show detrapped Mossbauer spectra at 293 K and trapped ones at 78 K and 3 shows a similar temperature dependence to that of 1, but differs in some points. The quadrupole splittings and isomer shifts of 3 increase on rising temperature. The spectra are explained in terms of intramolecular electron exchange between two energetically inequivalent vibronic states FeA2+FeB3+ and FeA3+Fe B2+: the apparent valence states of the iron atoms are 2.2 and 2.8 on the Mossbauer timescale at 293 K. At both 293 and 130 K the cations of complex 7 sit on a center of symmetry, and the two irons in this cation are crystallographically equivalent. The mean Fe–O length is intermediate between FeII–O and FeIII–O values, which indicates that both iron atoms are in an averaged valence state at 293 and 130 K when considered in terms of a static description. However, Mossbauer spectra of the complex show that the valence states of the irons are localized to iron-(II) and -(III) at 130 K and are delocalized at 293K on the characteristic Mossbauer timescale. Complex 4 is composed of iron-(II) and -(III) moieties, in accordance with the observation that the valence states of the irons are localized on the Mossbauer timescale (10–7 s) at 293 K.

Comparison of rates of penetration through insect cuticle of amphiphylic analogs of insect pyrokinin neuropeptides

Rates of penetration through the cuticle of amphiphylic analogs, synthesized by addition of 6-phenylhexanoic acid or 9-fluoreneacetic acid or 1-pyrenebutyric acid to the amino terminus of the pentapeptide Phe-Thr-Pro-Arg-Leu-amide, were assessed by quantitative analysis using reversed phase liquid chromatography. The analogs effectively penetrated the cuticle of both the adult American cockroach and tobacco budworm moth. However, the amounts of analogs that penetrated the cuticle of the cockroach were significantly lower and the rates of penetration were slower than for moth cuticle. Penetration of the analogs through the cuticle was dependent upon the size of the lipidic attachment to the pentapeptide. The 6-phenylhexanoic acid analog penetrated most rapidly followed by the 9-fluoreneacetic acid analog and the 1-pyrenebutyric acid analog penetrated slowest. All of the analogs exhibited an initial rapid period of penetration lasting 2–3 h followed by the establishment of a steady slow release state which lasted between 9–24 h and was dependent upon both the size and surface area of the aromatic lipidic portion of the analog and species of insect to which the analog was applied. The results confirmed the hypothesis that the insect cuticle could be employed as a slow release device for delivery of analogs of insect neuropeptides.

Induction of pheromone production in a moth by topical application of a pseudopeptide mimic of a pheromonotropic neuropeptide.

An amphiphilic analog of Locusta myotropin II (Lom-MT-II), Glu-Gly-Asp-Phe-Thr-Pro-Arg-Leu-amide, was synthesized by addition of 6-phenylhexanoic acid (6-Pha) linked through alanine to the amino terminus. This pseudopeptide, [6-Pha-Ala0]Lom-MT-II, was found to have pheromonotropic activity equivalent to pheromone biosynthesis activating neuropeptide when injected into females of Heliothis virescens. Topical application of [6-Pha-Ala0]Lom-MT-II or Helicoverpa zea-pheromone biosynthesis activating neuropeptide (PBAN), dissolved in dimethyl sulfoxide, to the descaled abdomen of females induced production of pheromone, although more Hez-PBAN than [6-Pha-Ala0]Lom-MT-II was required to obtain significant production of pheromone. Application of [6-Pha-Ala0]Lom-MT-II, dissolved in water, to the abdomen induced production of pheromone, but neither Hez-PBAN nor Lom-MT-II dissolved in water stimulated production of significant amounts of pheromone. Dose- and time-response studies indicated that application of the amphiphilic mimetic in water induced pheromone production in as little as 15 min after application and that the effects were maintained for prolonged periods. These findings show that amphiphilic pseudopeptide mimics of insect neuropeptides will penetrate the insect cuticle when applied topically in water and induce an endogenous response.

Bacterial production of poly-3-hydroxyalkanoates containing arylalkyl substituent groups

6-Phenylhexanoic acid (6PHxA), 7-phenylheptanoic acid (7PHpA), 9-phenylnonanoic acid (9PNA), 11-phenylundecanoic acid (11PUA), 9- p-tolylnonanoic acid (9TNA) and 9- p-styrylnonanoic acid (9SNA) were prepared and evaluated as substrates for cell growth and polyester production by Pseudomonas oleovorans and Pseudomonas putida. P. putida was more effective than P. oleovorans for producing polyesters from these aromatic substrates. Poly-3-hydroxyalkanoates, PHAs, were obtained from 6PHxA, 7PHpA, 9PNA and 11PUA. The PHAs produced from all of these substrates contained mostly 3-hydroxy-5-phenylvalerate (H5PV) and 3-hydroxy-6-phenylhexanoate (H6PHx) units. Polymer yields ranging from 3 to 47% of cell dry weight were obtained with molecular weights ranging from 156 000 to 37 000 and polydispersities from 2.3 to 2.9. Cofeeding of most of these substrates with nonanoic acid produced mixtures of two different PHAs with different glass transitions, one in the region of −8 to 12°C for the PHA with arylalkyl substituent groups, and one in the region of −14 to −35°C for the PHA from nonanoic acid. The PHA from 9TNA also had a crystalline melting transition.

Acyl, pseudotetra‐, tri‐ and dipeptide active‐core analogs of insect neuropeptides

Pseudopeptides of the achetakinin insect neuropeptide family were synthesized by replacing the amino acid blocks Phe-, Phe-Tyr-, and Phe-Tyr-Pro- of the active-core pentapeptide Phe-Tyr-Pro-Trp-Gly-NH2 with hydrocinnamic acid, 6-phenylhexanoic acid, and both 9-phenylnonanoic and 6-phenylhexanoic acid, respectively. All four of these analogs retained myotropic activity, demonstrating that the active core could be reduced from a pentapeptide to a modified dipeptide. Most notable of these was the pseudotetrapeptide hydrocinnamyl-Tyr-Pro-Trp-Gly-NH2, which retained 70% of the potency and over 85% of the maximal activity of the parent pentapeptide. The N-terminal amino group, the phenol ring of the Tyr residue, the sulfate moiety and the Gly residue of the insect sulfakinin active core Tyr(SO3H)-Gly-His-Met-Arg-Phe-NH2 were all replaced by dodecanedioic acid. The resulting pseudotetrapeptide, dodecandioyl-His-Nle-Arg-Phe-NH2, elicited myostimulatory activity. Conversely, the related acyl pseudopentapeptide azelayl-Gly-His-Nle-Arg-Phe-NH2 proved myoinhibitory. A possible explanation for these disparate biological responses is discussed. These acyl pseudopeptides are important advances towards the eventual development of stable, potent mimetic agonists and antagonists of insect neuropeptides.