Biodistribution study of free and microencapsulated 6‐methylcoumarin in Wistar rats by HPLC

A sensitive, specific and reproducible HPLC method has been developed and validated for the quantitative determination of 6‐methylcoumarin (6MC) in plasma and other tissues in Wistar rats. A C₁₈ column was used with UV detection at 321 nm and a gradient system consisting of methanol‐deionized water was used as mobile phase. The retention time for 6MC was 14.921 min and no interfering peaks were observed for any of the matrices. Linear relationships (r² > 0.997) were obtained between the peak height ratios and the corresponding biological sample concentrations over the range 0.4–12.8 µg/mL. Precision and accuracy were evaluated; the coefficient of variation and the relative error for all of the organs were <2 and 7%, respectively. The limit of quantitation was 0.20 µg/mL for the heart and 0.30 µg/mL for the other tissues evaluated. This HPLC method was successfully used in the determination of 6MC in the biodistribution study after administration of 200 mg/kg of both 6MC‐free and 6MC‐loaded polymeric microparticles. In this study, extensive 6MC was found, in both free and microencapsulated forms, in all the organs tested. The 6MC‐free showed a range of between 1.7 and 11.5 µg/g, while the microencapsulated 6MC showed concentrations of between 6.35 and 17.7 µg/g, suggesting that 6MC improved absorption rate. Copyright © 2014 John Wiley & Sons, Ltd.     

Metabolomics techniques applied in the investigation of phenolic acids from the agro-industrial by-product of Carapa guianensis Aubl

Processing of Carapa guianensis seeds to obtain oil on an industrial scale generates a significant amount of by-product, approximately 66% w/w, which is called cake and is a potential source of biomolecules, including simple phenolic structures. For this reason, studies were carried out on the chemical profiles of hydrolyzed extract from this agro-industrial by-product through High Performance Thin-Layer Chromatography (HPTLC) and Gas Chromatography coupled to Mass Spectrometry (GC–MS). These techniques were used to detect metabolic classes and/or groups, and to identify, for the first time, thirteen simple phenolic acids in this by-product. The sample antioxidant capacity was determined by methods of 2,2-diphenyl-1-picrylhydrazyl (DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS⁺) radicals direct sequestration. The hydrolyzed fraction showed a total of 63.47% in the relative abundance of the total of compounds, standing out: p-hydroxybenzoic acid (39.19%) and protocatechuic acid (3,4-dihydroxybenzoic acid) (5.62%), both from hydroxybenzoic acids and 3-(3,4-dihydroxyphenyl)lactic acid, (7.76%) hydroxycinnamic acids derivatives. In these results, the fraction rich in simple phenolic acids was obtained, attributing the prominent behavior of this matrix antioxidant activity, expressed by (IC₅₀: of 16.42 µg/mL and 6.52 µg/mL for DPPH and ABTS⁺ radicals, respectively). The research demonstrated an alternative to applicability that involves sustainability from agro-industrial. These techniques were used to detect metabolic classes and/or groups, and to identify, for the first time, thirteen simple phenolic acids in this by-product, generating a process capable of converting biomass into a bioproduct, consisting of bioactive compounds, in addition to adding value to the industrial chain.     

12β-Acetyloxyperforatin,a New Limonoid from Harrisonia Perforata

A new A, D-seco limonoid, named 12-acetyloxyperforatin (1), along with three known ones, were isolated from the leaves of Harrisonia perforata. Their structures were elucidated on the basis of spectroscopic analysis, including extensive NMR techniques and computational modelling. These compounds showed no inhibitory activity against the 11β-HSD1 enzyme.     

Buffering effects on the solution behavior and hydrolytic degradation of poly(β-amino ester)s

With a vast, synthetically accessible compositional space and highly tunable hydrolysis rates, poly(β-amino ester)s (PBAEs) are an attractive degradable polymer platform. Leveraging PBAEs in a wide range of applications hinges on the ability to program degradation, which, thus far, has been frustrated by multiple confounding phenomena contributing to the degradation of these charged polyesters. Basic conditions accelerate hydrolysis, yet reduce solubility, limiting water access to amines and esters. Further, the high buffering capacity of PBAEs can render buffers ineffective at controlling solution pH. To unify understanding of PBAE degradation and solution properties, this study examines PBAE hydrolysis as a function of pH and buffer concentration as well as polymer hydrophobicity. At low buffer concentrations, the PBAE amines and the acid produced during hydrolysis control solution pH. Meanwhile, at high buffer concentrations that afford relatively constant pH, hydrolysis rate increases with pH, despite the reduced PBAE solubility. Increasing the hydrophobic content of PBAEs eventually hinders the capacity of the polymer to accept protons from solution, limiting the pH increase and slowing hydrolysis. These studies showcase the role of buffering on the pH-dependent degradation and solution properties of PBAEs, providing guidance for programming degradation in applications ranging from drug delivery to thermosets.     

Transition‐Metal‐Free Trifluoromethylthiolation of N‐Heteroarenes

A general and efficient methodology for the direct transition metal free trifluoromethylthiolation of a broad range of biologically relevant N‐heteroarenes is reported employing abundant sodium chloride as the catalyst. This method is operationally simple, exhibits high functional group tolerance, and does not require protecting groups.     

New organoruthenium metallates containing ferrocenecarboxalidine thiosemicarbazones and their nucleic acid/albumin binding and in vitro cytotoxicity

A string of four new hetero binuclear Ru(III) complexes of ferrocenecarboxaldehyde-4(N)-substituted thiosemicarbazones were synthesized and characterized by various spectral (infrared, ultraviolet–visible, Electron Paramagnetic Resonance (EPR) and High Resolution Mass Spectrometry (HR-MS) techniques. The binding abilities of the ligands/complexes with nucleic acid (calf thymus DNA, CT-DNA) and bovine serum albumin (BSA) were analyzed by absorption and emission titration methods. The complexes exhibited better DNA binding affinity than their parent ligands. The interaction with CT-DNA was found to be intercalative and with BSA static quenching mechanism was observed. All the synthesized Ru(III) complexes were subjected to study their in vitro cytotoxicity against MCF-7 (human breast cancer) and HT-29 (human colon cancer) cell lines. Among the four complexes, complex 3 [RuCp (FF-etsc)PPh₃]Cl exhibited the highest cytotoxicity in MCF-7 cells and complex 4 [RuCp (FF-ptsc)PPh₃]Cl was the most active on HT-29 cells.     

Double Michael Additions of Lithium Enolate of 1,4-Dioxaspiro[4.5]dec-6-en-8-One to Acrylates

Double Michael additions of lithium enolaie of 1,4-dioxaspiro[4.5]dec-6-en-8-one to four acrylates afforded bicyclo[2.2.2]octan-2-ones with high regio- and stereoselectivities in moderate yields.     

Conjugate addition of pyrroles to α,β-unsaturated ketones using copper bromide as a catalyst

Copper bromide was used as a catalyst for the addition of pyrroles to enones. When both the reactants were used in equimolar amounts, mono and dialkylated products were obtained. However, the use of excess enone furnished only dialkylated products. Thus, copper bromide was shown to be an efficient catalyst for the dialkylation of pyrroles.     

[Na(18-C-6)]2[Cu(i-mnt)2]的合成与结构分析

研究了18-冠-6与Na2[Cu(i-mnt)2][i-mnt=异丁二腈烯二硫醇阴离子,S2CC(CN)2-2]的反应,得到的配合物[Na(18-C-6)]2[Cu(i-mnt)2](1)通过元素分析、红外光谱、X射线单晶衍射进行了结构分析.配合物为单斜晶系,空间群P2(1)/c.晶体学结构数据a=1.2819(11),b=1.1793(10),c=1.4928(13)nm,β=99.121(16)°,V=2.228(3)nm3,Z=2,Dcaled.=1.369g/cm3,F(000)=958,R1=0.0521,wR2=0.1003.1中的[Cu(i-mnt)2]基团通过配体i-mnt的氮原子与两个[Na(18-C-6)]基团中的钠原子成键,形成稳定的中性配合物.