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•The synthesis of a library of 13 chiral pyrrolidine derivatives.•Enzyme kinetics implied a mixed inhibition mode, corroborating our molecular docking studies.•Toxicological studies ...showed that they were non-toxic.•Molecular docking studies indicated the mechanism of competitive inhibition.
Thirteen pyrrolidine-based iminosugar derivatives have been synthesized and evaluated for inhibition of α-glucosidase from rat intestine. The compounds studied were the non-hydroxy, mono-hydroxy and dihydroxypyrrolidines. All the compounds were N-benzylated apart from one. Four of the compounds had a carbonyl group in the 2,5-position of the pyrrolidine ring. The most promising iminosugar was the trans-3,4-dihydroxypyrrolidine 5 giving an IC50 of 2.97±0.046 and a KI of 1.18mM. Kinetic studies showed that the inhibition was of the mixed type, but predominantly competitive for all the compounds tested. Toxicological assay results showed that the compounds have low toxicity. Docking studies showed that all the compounds occupy the same region as the DNJ inhibitor on the enzyme binding site with the most active compounds establishing similar interactions with key residues. Our studies suggest that a rotation of ∼90° of some compounds inside the binding pocket is responsible for the complete loss of inhibitory activity.
Despite the fact that activity was found only in the mM range, these compounds have served as simple molecular tools for probing the structural features of the enzyme, so that inhibition can be improved in further studies.
Introduction: Crimes involving firearms have been increasing and is a current transnational concern. To face such issues the development of analytical procedures is paramount to increase the efficacy ...of criminal investigation on homicides and other gun related crimes. The identification of an ammunition type or brand from a simple residue would represent a major contribution for gunshot residues analysis. Such a breakthrough will benefit homicides and war crimes investigation. The composition of gunpowder varies and each ammunition type contains a given formula and often specific components
1-3
suggesting that Fourier-transform infrared spectroscopy (FTIR) might be a useful technique for the rapid analysis of gunpowders
2
. Indeed, FTIR has an outstanding discriminatory ability when coupled with chemometrics analysis
3
. Here we present the optimization of the extraction organic solvent for analysis of ammunition contents by FTIR which is an essential step for the discriminatory study of ammunition brands.
Materials and methods: An ammunition of caliber .22RL was purchased at Soldiers®. The sample was dissolved in eight different solvents (Acetone, Acetonitrile, Dichloromethane (DCM), Ethanol, Isooctane, Methanol, Methyl Ethyl ketone and n-Hexane), subjected to ultrasound for 30 min and followed by centrifugation. The supernatant was collected and analyzed on a Perkin Elmer 65 FTIR spectrometer coupled to an ATR accessory. A spectral window of 4000-525 cm
−1
was used and 32 scans were accumulated at 1cm
−1
resolution.
Results:
Figure 1
shows the FTIR spectra of methanol and n-hexane for the sample used. From the spectra it is clear that methanol is a better extractor than n-hexane. Of the eight solvents used, methyl ethyl ketone, acetone and methanol had the better extraction efficiency of gunpowder (GP) while n-hexane and dichloromethane were not able to extract GP.
Discussion and conclusions: This study showed that the best solvents for extraction of GP are the more polar solvents containing carbonyl (C = O) and hydroxyl (OH) groups. The best extraction solvents were Methyl ethyl ketone and acetone followed by methanol.
Com o aumento do número de crimes envolvendo armas de fogo, surgiu na investigação criminal, a necessidade de ligar um suspeito à arma do crime. Para esse efeito, recorre-se a balística, onde os ...vestígios deixados pela arma (resíduos de disparo da arma), que são como uma impressão digital da arma, são analisadas através de técnicas forenses, e assim obter as informações relevantes para a investigação criminal. A detecção e a identificação dos resíduos, são factores chave para a análise forense. O objectivo deste trabalho de investigação é o estudo do poder de discriminação das pólvoras através da análise discriminatória. Para isso foram utilizadas 12 tipos diferentes de pólvora (várias marcas e modelos) e 9 compostos, que geralmente são encontradas nas pólvoras, que foram utilizados como padrão. Das várias técnicas de análise existentes, para este trabalho optou-se pela Espectroscopia no Infravermelho por Transformada de Fourier e pela Cromatografia Gasosa acoplada a espectrometria de massa, que são as técnicas mais utilizadas para a análise de pólvora. Para a análise discriminatória recorreu-se á Análise da Componente Principal. Além da análise química da pólvora, estas também foram sujeitas a uma análise física, onde foram analisadas as características macroscópicas de cada pólvora. A discriminação da pólvora é possível, tanto a nível das características macroscópicas como através da análise dos resíduos da pólvora. Das técnicas de análise utilizadas, verificou-se que a análise por Cromatografia Gasosa foi a melhor na obtenção de resultados e que esta técnica junto com a Espectroscopia no Infravermelho por Transformada de Fourier são técnicas que se complementam. Em relação ao poder discriminatório, a análise pela Cromatografia Gasosa foi a melhor na discriminação das pólvoras, onde as melhores marcas que se conseguem discriminar são a Federal Ammunition, a Eley (Match Pistol) e RWS (Semi-auto).
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