Synthesis and configuration determination of all enantiopure stereoisomers of the melatonin receptor ligand 4-phenyl-2-propionamidotetralin using an expedient optical resolution of 4-phenyl-2-tetralone

An efficient and practical approach for the synthesis of all four stereoisomers of the MT(2) melatonin receptor ligand 4-phenyl-2-propionamidotetralin (4-P-PDOT), each in enantiomerically pure form (ee > 99.9%), was developed. The strategy involved an optical resolution procedure of the key precursor (±)-4-phenyl-2-tetralone with the unusual resolving agent (S)-mandelamide, through the formation of four dihydronaphtalene-spiro-oxazolidin-4-one diastereomers. Interestingly, NMR experimental observations in combination with geometric calculations, provided unambiguous configuration assignments of all stereocenters of the key spiro stereoisomers. Cleavage of each single spiro diastereomer under acidic conditions gave enantiopure (R)- or (S)-4-phenyl-2-tetralone, which were then converted to each 4-P-PDOT single enantiomer by using stereoselective reactions.     

Enantioselective Alternating Olefin-Carbon Monoxide Copolymerization: A new concept for activity and stereoselectivity

Cationic Pd-complexes modified by dicyclohexyl{(R)-1-[(S)-2-(diphenylphosphino)ferrocenyl]ethyl}phosphine ( 1a ) give very active catalytic systems for the regioregular isotactic specific copolymerization of propene with CO. Other alk-1-enes also give stereoregular and regioregular copolymers, even if with lower productivity. The copolymers are isolated as poly(4-alkyl-tetrahydrofuran-2,2,5,5-tetrayl-2-oxy-2-methylenes) B in the solid state and give the isomeric poly(2-alkyl-1-oxopropane-1,3-diyls) A by dissolution in (CF₃)₂CHOH. Solid polymer A (R = Et) is formed back at least partially when the dissolved material is reprecipitated from MeOH. The use of the related (ferrocenyl)diphosphine ligands 1b ? e and 2 as the catalyst modifier shows that the presence of both elements of chirality and of large substituents on the P-atoms of the ligand is necessary to achieve good stereocontrol, and that the large difference in basicity between the two P-atoms is probably the reason for the good catalytic activity.     

Determination of terbuthylazine and desethylterbuthylazine in human urine and hair samples by eletrospray ionization-liquid chromatography/triple quadrupole mass spectrometry

Terbuthylazine (TBA) is a widely applied herbicide and an environmental contaminant. Following its use, humans, such as agricultural workers and rural residents, may be exposed. An isotope-dilution liquid chromatography coupled to electrospray-tandem mass spectrometry method for the determination of TBA, and its metabolite desethylterbuthylazine (DET) in human urine and hair was developed and validated. Under the optimised conditions, analytes were extracted from urine using a solid phase cartridge or from hair by sonication in methanol. Analytes were separated using a C18 reversed-phase chromatographic column and quantified, after positive ionization using a heated electrospray source, by a triple quadrupole mass detector in the selected reaction monitoring mode. Validation showed linear dynamic ranges up to 100 μg/L or 5.00 ng/mg hair, inter- and intra-run precisions <7%, and accuracies within 12% of spiked concentrations. Limits of quantification were 0.25 μg/L in urine and 0.01 ng/mg hair for both TBA and DET. Matrix effect evaluation showed that the isotope dilution approach allowed for the control of bias sources. TBA and DET were determined in specimens of agriculture workers exposed to TBA using the validated method. Hair samples contained TBA levels in the low nanogram per milligram range, and urine samples contained DET levels in the low microgram per liter range. Conversely, TBA levels in urine samples and DET levels in hair samples were always below the limit of quantification.     

Molecular dynamics reveal that isoDGR-containing cyclopeptides are true αvβ3 antagonists unable to promote integrin allostery and activation

Ain't got that swing(-out): The cyclopeptide isoDGR is emerging as a new αvβ3 integrin binding motif. Agreement between the results of computational and biochemical studies reveals that isoDGR-containing cyclopeptides are true αvβ3 integrin antagonists that block αvβ3 in its inactive conformation (see scheme). isoDGR-based ligands may give αvβ3 antagonists without paradoxical effects.     

Conformational and photophysical studies on porphyrin-containing donor-bridge-acceptor compounds. Charge separation in micellar nanoreactors

Photophysical studies with semi-rigid, 1, and flexible, 2, donor-bridge-acceptor (D-b-A2+) molecules with D a porphyrin and A2+ a methyl viologen moiety, were performed in neat polar solvents as well as included in surfactant (DTAB) aqueous and in reverse AOT/n-alkane micelles. The micelles acted as nanoreactors for the photoinduced electron transfer reaction upon laser excitation. In spite of the longer lifetime of the charge separated (CS) state in the semi-rigid tetrad 1(ca. 200 ns vs. ca. 100 ns for the flexible dyad 2), the CS formation quantum yield, for example in acetonitrile, was lower for the former (phi(CS) = 0.13) than for the latter (0.58). Comparison of the time-resolved fluorescence data in neat solvent and in the micelles yielded the phi(CS) values in the dilute micellar solutions. Application of laser-induced optoacoustic spectroscopy at various temperatures to 1 dissolved in a polar organic solvent (benzonitrile, BZN) included in aqueous DTAB nanoreactors afforded structural volume changes for the production in hundreds of ps of the CS state upon excitation of a polar molecule. The contraction during CS formation upon excitation of the collapsed conformer in BZN is attributed to the entering of solvent into the open molecular cavity. The opening upon formation of the CS state due to photoinduced electron transfer in the 1 collapsed conformation arises from the repulsion of the two positively charged ends in this state, as previously calculated. Inclusion of 1 in reverse AOT micelles in various n-alkanes also led to a contraction upon excitation, but the data had much more error due to the limited range of variability of the ratio of thermoelastic parameters. The data obtained with the more flexible "supermolecule" 2 showed the predicted large conformation flexibility of these molecules.     

Characterization of natural cellulosic fibers from Yucca aloifolia L. leaf as potential reinforcement of polymer composites

Cellulose - In this work lignocellulosic fibers were obtained from Yucca aloifolia L. leaves and their chemical, morphological, thermal and mechanical properties were studied. The fibers were...     

Polyphenolic QTOF-ESI MS Characterization and the Antioxidant and Cytotoxic Activities of Prunus domestica Commercial Cultivars from Costa Rica

There is an increased interest in plum research because of their metabolites’ potential bioactivities. In this study, the phenolic profiles of Prunus domestica commercial cultivars (Methley, Pisardii and Satsuma) in Costa Rica were determined by Ultra Performance Liquid Chromatography coupled with High Resolution Mass Spectrometry using a quadrupole-time-of-flight analyzer (UPLC-ESI-QTOF MS) on enriched phenolic extracts obtained through Pressurized Liquid Extraction (PLE) under acidic and neutral extraction conditions. In total, 41 different phenolic compounds were identified in the skin and flesh extracts, comprising 11 flavan-3-ols, 14 flavonoids and 16 hydroxycinnamic acids and derivatives. Neutral extractions for the skins and flesh from all of the cultivars yielded a larger number of compounds, and were particularly rich in the number of procyanidin trimers and tetramers when compared to the acid extractions. The total phenolic content (TPC) and antioxidant potential using the DPPH and ORAC methods exhibited better results for neutral extracts with Satsuma skins and Methley flesh, which showed the best values (685.0 and 801.6 mg GAE/g extract; IC₅₀ = 4.85 and 4.39 µg/mL; and 12.55 and 12.22 mmol TE/g extract, respectively). A Two-Way ANOVA for cytotoxicity towards AGS gastric adenocarcinoma and SW620 colon adenocarcinoma indicated a significant difference (p < 0.05) for PLE conditions, with better results for neutral extractions, with Satsuma skin delivering the best results (IC₅₀ = 60.7 and 46.7 µg/mL respectively) along with Methley flesh (IC₅₀ = 76.3 and 60.9 µg/mL, respectively). In addition, a significant positive correlation was found between TPC and ORAC (r = 0.929, p < 0.05), as well as a significant negative correlation (p < 0.05) between TPC and cytotoxicity towards AGS and SW620 cell lines (r = −0.776, and −0.751, respectively). A particularly high, significant, negative correlation (p < 0.05) was found between the number of procyanidins and cytotoxicity against the AGS (r = −0.868) and SW620 (r = −0.855) cell lines. Finally, the PCA clearly corroborated that neutral extracts are a more homogenous group exhibiting higher antioxidant and cytotoxic results regardless of the part or cultivar; therefore, our findings suggest that PLE extracts under neutral conditions would be of interest for further studies on their potential health benefits.     

Inorganic-Organic Hybrid Polymers from the Polymerisation of Methacrylate-Substituted Oxotantalum Clusters with Methylmethacrylate: A Thermomechanical and Spectroscopic Study

New inorganic-organic hybrid materials were prepared by free-radical polymerization of methyl methacrylate (MMA) with methacrylate-substituted oxotantalum cluster [Ta₄O₄(OEt)₈(OMc)₄] and their properties evaluated. The cluster was prepared by the reaction of the parent alkoxide with methacrylic acid. Samples of the hybrid materials were produced with Ta-cluster to methyl methacrylate in the ratios of 1:50 and 1:100 and were characterized by thermal and spectroscopic techniques. The glass transition temperatures of the hybrid materials are shifted to higher temperatures than pure PMMA as a result of cross-linking of the polymer by the oxotantalum clusters. The increase in T_g is also observed from the dynamic mechanical analysis (DMA). Evidence of crosslinking between the Ta-cluster and PMMA is obtained from infrared spectroscopic study. Surface studies performed by X-ray photoelectron spectroscopy (XPS) provide information about the atomic concentrations of the surface and indicate tantalum bonded to oxygen.