Synthesis and inverse virtual screening of new bi-cyclic structures towards cancer-relevant cellular targets

Structural Chemistry - We report here synthetic approaches to access new classes of small molecules based on three heterocyclic scaffolds, i.e. 3,7-dihydropyrimido[4,5-d]pyridazine-4,8-dione,...     

Competitive Gold‐Promoted Meyer–Schuster and oxy‐Cope Rearrangements of 3‐Acyloxy‐1,5‐enynes: Selective Catalysis for the Synthesis of (+)‐(S)‐γ‐Ionone and (−)‐(2S,6 R)‐cis‐γ‐Irone

We report a simple, highly stereoselective synthesis of (+)‐(S)‐γ‐ionone and (‐)‐(2S,6R)‐cis‐γ‐irone, two characteristic and precious odorants; the latter compound is a constituent of the essential oil obtained from iris rhizomes. Of general interest in this approach are the photoisomerization of an endo trisubstituted cyclohexene double bond to an exo vinyl group and the installation of the enone side chain through a [(NHC)Au^I]‐catalyzed Meyer–Schuster‐like rearrangement. This required a careful investigation of the mechanism of the gold‐catalyzed reaction and a judicious selection of reaction conditions. In fact, it was found that the Meyer–Schuster reaction may compete with the oxy‐Cope rearrangement. Gold‐based catalytic systems can promote either reaction selectively. In the present system, the mononuclear gold complex [Au(IPr)Cl], in combination with the silver salt AgSbF₆ in 100:1 butan‐2‐one/H₂O, proved to efficiently promote the Meyer–Schuster rearrangement of propargylic benzoates, whereas the digold catalyst [{Au(IPr)}₂(μ‐OH)][BF₄] in anhydrous dichloromethane selectively promoted the oxy‐Cope rearrangement of propargylic alcohols.     

Simultaneous determination of benzydamine hydrochloride and five impurities in an oral collutory as a pharmaceutical formulation by high-performance liquid chromatography

A reversed-phase high-performance liquid chromatographic method for the determination of benzydamine hydrochloride and its impurities 3-dimethylaminopropyl 2-benzylaminobenzoate, 3-dimethylaminopropyl-2-aminobenzoate,1-benzyl-1H-indazol-3-ol, 1-benzyl-2-(3-dimethylaminopropyl)-1,2-dihydro-3H-indazol-3-one, and 1-benzyl-3-(3-(3-dimethylaminopropyl)-3-methylamino)propoxy-(1)H-indazole in a collutory formulation is developed. The separation is carried out on a Gemini C(18) (250 × 4.6 mm, 5 μm) column using acetonitrile-methanol-ammonium carbonate buffer (10 mM; pH 10.5) (37.5:37.5:25, v/v/v) as mobile phase at a flow rate of 1.0 mL/min, column temperature 30°C, and UV detection at 218 nm. Famotidine is used as an internal standard. The total run-time is less than 15 min. The analytical curves present coefficients of correlation greater than 0.99, and detection limits are calculated for all analytes. Excellent accuracy and precision are obtained for benzydamine hydrochloride. Recoveries vary from 98.25 to 102.8%, and intra- and inter-day precisions, calculated as the percent relative standard deviation, are lower than 2.2%. Specificity and robustness for benzydamine hydrochloride are also determined. The method allows the quantitative determination of benzydamine hydrochloride and its impurities, and it is suitable for routine analysis in quality control laboratories.     

QUENCHING OF CHEMICALLY and ENZYMICALLY-GENERATED TRIPLET ACETONE BY TYROSINE and 3,5-DIHALOGENODERIVATIVES

Tyrosine and especially its 3,5-dihalogenoderivatives quench acetone triplets. When the excited acetone is generated free in solution, the Stern-Volmer plots for the quenching by these species, monitored via the sensitized emission of the 9,10-dibromoanthracene-2-sulfonate ion, are linear. When triplet acetone is generated enzymically by the peroxidase-catalyzed aerobic oxidation of isobutyral-dehyde, the Stern-Volmer plots for the quenching of the acetone phosphorescence curve upwards in the case of 3,5-dibromotyrosine and even more markedly with 3,5-diiodotyrosine. Quenching appears likely to occur by triplet-triplet energy transfer and especially in the case of the phenoxide form, also by electron transfer. The curvature denotes a static contribution to quenching favoured by the enzyme.     

Halogen Bonding Assembles Anion⋅⋅⋅Anion Architectures in Non-centrosymmetric Iodate and Bromate Crystals

Single crystal X-ray diffraction of iodate and bromate salts shows that the I and Br atoms in IO₃⁻ and BrO₃⁻ anions form short and linear O−I/Br ⋅⋅⋅ O contacts with the O atoms of nearby anions. Non-centrosymmetric systems are formed wherein anions are orderly aligned into supramolecular 1D and 2D networks. Theoretical evidences, namely the outcome of QTAIM and NCIplot studies, prove the attractive nature of these contacts and the ability of iodate and bromate anions to act as robust halogen bond (HaB) donors. The HaB is proposed as a general and effective assisting tool to control the architecture of acentric iodate salts.     

THE α-OXIDASE SYSTEM OF YOUNG PEA LEAVES (Pisum sativum) AS GENERATOR OF ELECTRONICALLY EXCITED STATES. EXCITATION IN THE DARK UNDER NATURAL CONDITIONS

Abstract. The aerobic oxidation of saturated long chain fatty acids to the lower aldehyde and CO₂ catalyzed by the α-oxidase system of young leaves from germinating Pisum sativum results in concomitant excitation of the chloroplasts or/and fractions present in the α-oxidase preparation. The excitation is attested to by both chlorophyll emission and Hill activity. This is the first case of photobiochemistry without light within a natural system.     

Studies on decarboxylation reactions. Part 5 . Micellar catalysis and mixed solvents effects on the decarboxylation of some N-alkyl- or N-aryl-substituted 5-amino-1,3,4-oxadiazole-2-carboxylic acids

The effect of micelles and mixed solvents on the decarboxylation of some N-alkyl- or N-aryl-substituted 5-amino-1,3,4-oxadiazole-2-carboxylic acids has been studied. The data support the unimolecular decarboxylation mechanism proposed by us. Moreover, they show that mixed solvents and micelles have different effects on reactivity of the amino acids under study.