Palladium-catalyzed domino intramolecular N-arylation/intermolecular C-C bond formation for the synthesis of functionalized benzodiazepinediones

A divergent and regiocontrolled Pd-catalyzed domino sequence involving an intramolecular N-arylation and an intermolecular Heck reaction has been developed, providing rapid access to functionalized benzodiazepine-2,5-diones 3. The starting materials were synthesized by the Ugi four-component reaction. An unprecedented X-ray structure of bispalladacycle 6 was documented.     

A Study on the Phytotoxic Potential of the Seasoning Herb Marjoram (Origanum majorana L.) Leaves

In the search of new alternatives for weed control, spices appear as an option with great potential. They are rich in bioactive natural products and edible, which might minimize toxicity hazard. Marjoram (Origanum majorana L.) is an aromatic herb that has been widely employed as a seasoning herb in Mediterranean countries. Although marjoram boasts a plethora of therapeutic properties (painkiller, antibiotic, treatment for intestinal disorders, etc.), the potential for its extracts for weed control is still to be more thoroughly explored. In order to determine their phytotoxic potential, marjoram leaves were subjected to different bioguided extraction processes, using water, ethyl acetate, acetone or methanol. The most active extract (acetone) was sequentially fractionated to identify its most active compounds. This fractionation led to the isolation and identification of 25 compounds that were classified as monoterpenes, diterpenes or flavonoids. Among them, a new compound named majoradiol and several compounds are described in marjoram for the first time. The phytotoxicity of the major compounds to etiolated wheat coleoptiles was compared against that of the commercial herbicide (Logran^®), with similar or higher activity in some cases. These results confirm the extraordinary potential of the extracts from this edible plant to develop safer and more environmentally friendly herbicides.     

Micellar electrokinetic chromatographic method for the determination of letrozole, citalopram and their metabolites in human urine

A new micellar electrokinetic chromatographic method has been developed to analyse human urine samples containing a combination of a drug used for the treatment of breast cancer (letrozole), an antidepressant (citalopram) and their main metabolites. Best results were obtained by using 15 mM borate buffer (pH 9.2) containing 20 mM sodium dodecyl sulphate and 12% (v/v) 2-propanol as the background electrolyte. The separation was performed through a fused silica capillary at 40 degrees C with the application of 6s (3.45 kPa) of hydrodynamic injection and 30 kV of separation voltage. Detection wavelength was 240 nm. Under these conditions, the migration times for all the studied compounds were ranged between 3.0 and 8.0 min. Linearity ranges were determined as 0.4-5.0 microg/mL for all the compounds. Detection limits between 12.5 and 25 ng/mL were determined in urine samples. According to the validation study, the developed method has been proven to be accurate, precise, sensitive, specific, rugged and robust. This method has been used to determine letrozole, citalopram and their metabolites in human urine at clinical levels. Prior to determination, the samples are purified and enriched by means of an extraction-preconcentration step with a preconditioned C(18) cartridge and by eluting the compounds with methanol. The developed method was applied to the determination of these analytes in three urine samples from patients undergoing treatment with letrozole or citalopram.     

Micellar electrokinetic chromatographic screening of letrozole and its metabolite in human urine: validation and robustness/ruggedness evaluation

A simple, rapid, and sensitive method has been proposed and validated to directly quantify letrozole (LE) and its metabolite, bis-4-cyanophenylmethanol (ME) in urine samples (without any additional treatment) by micellar electrokinetic capillary chromatography (MEKC). In an effort to improve the selectivity and sensitivity of the method, the chemical and instrumental parameters were optimized. The best conditions were: 70 mM borate buffer (pH 9.2) and 40 mM SDS as BGE, 25 kV and 20 degrees C as working voltage and temperature, respectively, with hydrodynamic injection for 6 s. The reliability of the proposed method was also proved by means of a validation procedure based on precision, accuracy, linearity, LOD (15 microg/L for both of them) and LOQ studies. Moreover, an innovatory experimental and statistical design approach, upon a Plackett-Burman fractional factorial model, which involves the simultaneous evaluation of the global robustness and ruggedness effects, was applied. As it has been already stated, the proposed method has been successfully used to directly quantify both compounds in human urine samples, without any additional treatment, but the previously reached LOD and LOQ values can be improved by applying an SPE preconcentration procedure, also developed and optimized by the authors in this work. Real determinations of these analytes in clinical urines of a patient under LE treatment were performed, too.     

Predominant Information Quality Scheme for the Essential Amino Acids: An Information‐Theoretical Analysis

In this work we undertake a pioneer information‐theoretical analysis of 18 selected amino acids extracted from a natural protein, bacteriorhodopsin (1C3W). The conformational structures of each amino acid are analyzed by use of various quantum chemistry methodologies at high levels of theory: HF, M062X and CISD(Full). The Shannon entropy, Fisher information and disequilibrium are determined to grasp the spatial spreading features of delocalizability, order and uniformity of the optimized structures. These three entropic measures uniquely characterize all amino acids through a predominant information‐theoretic quality scheme (PIQS), which gathers all chemical families by means of three major spreading features: delocalization, narrowness and uniformity. This scheme recognizes four major chemical families: aliphatic (delocalized), aromatic (delocalized), electro‐attractive (narrowed) and tiny (uniform). All chemical families recognized by the existing energy‐based classifications are embraced by this entropic scheme. Finally, novel chemical patterns are shown in the information planes associated with the PIQS entropic measures.     

A Novel,One‐Pot Synthesis of Novel 3F, 5F,and 8F Aromatic Polymers

A series of novel, linear, soluble, high‐molecular‐weight, fluorinated aromatic polymers has been obtained for the first time using a superacid‐catalyzed polyhydroxyalkylation reaction of fluorinated carbonyl‐containing compounds: 1,1,1,‐trifluoroacetone ( 1 ), 2,2,2‐trifluoroacetophenone ( 2 ), 2,3,4,5,6,‐pentafluorobenzaldehyde ( 3 ), and octafluoroacetophenone ( 4 ) with aromatic hydrocarbons such as biphenyl ( a ), phenyl ether ( b ), terphenyl ( c ), and 4,4′‐diphenoxybenzophenone ( d ). These Friedel‐Crafts‐type aromatic electrophilic substitution reactions are performed at room temperature in trifluoromethane sulfonic acid or in its mixtures with dichloromethane. The polymers obtained are soluble in common organic solvents, and colorless transparent films could be cast from the solutions. ¹H and ¹³C NMR analyses of the polymers synthesized reveal their linear, highly regular structure. The polymers also possess high thermostability.

     

Electronic structure of cesium and thallium triple-decker anions

Cesocene [Cp₃Cs₂]− and thallocene [Cp₃Tl₂]− triple-deckers have been recently synthesized. The X-ray structure analysis in solid state phase shows that both compounds have a strong bent structure, Cp centroid–M–Cp´ centroid (M=Cs or Tl) angles are 115.6° and 134.2°, respectively. In this work we report the theoretical study of these new compounds using Gaussian 94 at B3LYP level, with a 6-31G* basis for all atoms, except Cs and Tl, for which a LANL2DZ basis set is considered. Our results show that in gas phase, thallocene presents a bent structure while cesocene does not. However, using a force field method, we prove that in solid state phase the cesocene becomes bent due to the interaction between neighbors, in agreement with experimental data.     

Aromaticity under star dust conditions

Astronomical observations have revealed diffuse interstellar bands ranging from blue in the visible spectrum to the near IR. It has been suggested that these bands exist, owing to the presence of polyaromatic hydrocarbons or fullerene in the vicinity of certain stars, and constitute residual material from stellar explosions. The intention here is to study the relative stability of these species, when exposed to extreme conditions. The aromaticity of polycarbon molecules is an important aspect of this explanation.     

Resonances and the Weinberg-Tomozawa 56-baryon-35-meson interaction

Vector meson degrees of freedom are incorporated into the Weinberg-Tomozawa (WT) meson-baryon chiral Lagrangian by using a scheme which relies on spin-flavor SU(6) symmetry. The corresponding Bethe-Salpeter approximation successfully reproduces previous SU(3)-flavor WT results for the lowest-lying s-wave negative-parity baryon resonances, and it also provides some information on the dynamics of the heavier ones. Moreover, it also predicts the existence of an isoscalar spin-parity ^- K^*N bound state (strangeness +1) with a mass around 1.7-1.8GeV, unstable through K^* decay. Neglecting d-wave KN decays, this state turns out to be quite narrow ( Γ≤15MeV) and it might provide clear signals in reactions like γp→ˉ⁰ pK ⁺ π ^- by looking at the three-body pK ⁺ π ^- invariant mass.     

Second-generation synthesis of protected phosphonothiodifluoromethylene analogues of nucleoside-3′-phosphates

A practical, eight-step synthesis of the key intermediate 14 in 19% overall yield from α-d-xylose is described. The preparation can be carried out on multi-gram scale and involves the use of the organomagnesium reagent 2d. The capability of derivative 14 to be transformed into the title compounds is examplified by the preparation of 15. Additionally, X-ray crystallography of intermediate 12 provided the first structural data on difluorophosphonothioates.