Betaine and Carnitine Derivatives as Herbicidal Ionic Liquids

This study focused on the synthesis and subsequent characterization of herbicidal ionic liquids based on betaine and carnitine, two derivatives of amino acids, which were used as cations. Four commonly used herbicides (2,4‐D, MCPA, MCPP and Dicamba) were used as anions in simple (single anion) and oligomeric (two anions) salts. The obtained salts were subjected to analyzes regarding physicochemical properties (density, viscosity, refractive index, thermal decomposition profiles and solubility) as well as evaluation of their herbicidal activity under greenhouse and field conditions, toxicity towards rats and biodegradability. The obtained results suggest that the synthesized herbicidal ionic liquids displayed low toxicity (classified as category 4 compounds) and showed similar or improved efficacy against weed compared to reference herbicides. The highest increase was observed during field trials for salts containing 2,4‐D as the anion, which also exhibited the highest biodegradability (>75 %).     

氯化3-氰-2-羟丙基三甲铵的拆分

研究了利用N-乙酰-L-谷氨酸为拆分试剂，成功的对氯化3-氰-2-羟丙基三甲胺进行光学拆分，一次拆分光学纯度为92％，产率为37％；二次拆分光学纯度达95％，产率为29．1％。     

L-卡尼丁分子压印聚合物作为手性分离色谱固定相的研究

以L－卡尼丁为模板分子，分别以α－甲基丙烯酸和丙烯酰胺为功能单体，乙二醇二甲基丙烯酸酯为 剂，采用分子压印技术合成了对L－卡尼丁具有高选择性的分子压印聚合物。将所得聚合物用作高效液相色谱固定相，研究了它们对外消旋卡尼丁盐酸盐的拆分能力，分析结果表明，α－甲基丙烯酸作为功能单体所得聚合物对外消旋卡尼丁盐酸盐具有良好的拆分作用，其分离因子α为1．89。     

Simple determination of betaine,l‐carnitine and choline in human urine using self‐packed column and column‐switching ion chromatography with nonsuppressed conductivity detection

A sequential online extraction, clean‐up and separation system for the determination of betaine, l ‐carnitine and choline in human urine using column‐switching ion chromatography with nonsuppressed conductivity detection was developed in this work. A self‐packed pretreatment column (50 × 4.6 mm, i.d.) was used for the extraction and clean‐up of betaine, l ‐carnitine and choline. The separation was achieved using self‐packed cationic exchange column (150 × 4.6 mm, i.d.), followed by nonsuppressed conductivity detection. Under optimized experimental conditions, the developed method presented good analytical performance, with excellent linearity in the range of 0.60–100 μg mL⁻¹ for betaine, 0.75–100 μg mL⁻¹ for l ‐carnitine and 0.50–100 μg mL⁻¹ for choline, with all correlation coefficients (R²) >0.99 in urine. The limits of detection were 0.15 μg mL⁻¹ for betaine, 0.20 μg mL⁻¹ for l ‐carnitine and 0.09 μg mL⁻¹ for choline. The intra‐ and inter‐day accuracy and precision for all quality controls were within ±10.32 and ±9.05%, respectively. Satisfactory recovery was observed between 92.8 and 102.0%. The validated method was successfully applied to the detection of urinary samples from 10 healthy people. The values detected in human urine using the proposed method showed good agreement with the measurement reported previously.     

Neuronal dysfunction with aging and its amelioration

The author focused on the functional decline of synapses in the brain with aging to understand the underlying mechanisms and to ameliorate the deficits. The first attempt was to unravel the neuronal functions of gangliosides so that gangliosides could be used for enhancing synaptic activity. The second attempt was to elicit the neuronal plasticity in aged animals through enriched environmental stimulation and nutritional intervention. Environmental stimuli were revealed neurochemically and morphologically to develop synapses leading to enhanced cognitive function. Dietary restriction as a nutritional intervention restored the altered metabolism of neuronal membranes with aging, providing a possible explanation for the longevity effect of dietary restriction. These results obtained with aging and dementia models of animals would benefit aged people.     

人体必需的营养物质——肉毒碱

肉毒碱被发现百余年来,科学界对其研究经久不衰,含有肉毒碱的药品、营养品倍受消费者青睐.介绍了L-(-)-肉毒碱的来源、生物学功能、合成与应用.     

Enantio- and chemo-selective HPLC separations by chiral-achiral tandem-columns approach: the combination of CHIROBIOTIC TAG and SCX columns for the analysis of propionyl carnitine and related impurities

We describe a new tandem-columns chiral-achiral HPLC arrangement by using a chiral column (CHIROBIOTIC TAG) connected in series with an achiral column (Spherisorb S5 SCX), based on a strong cationic exchange mechanism; this approach is very useful for the analysis of chiral molecules, containing cationic groups in their structures. We used this special combination to develop an easy and convenient procedure for the enantio- and chemo-selective dosage of propionyl L-carnitine (1) and relative impurities (2-6), which allowed for the simultaneous separation and quantitation within 30 min. Under the best chromatographic conditions (acetonitrile-10 mM sodium dihydrogen phosphate 65:35, v/v (pHa 6.80) as the mobile phase and UV detection at 205 nm], all the individual peaks were well separated. The applicability of the method, fully validated, was demonstrated by the analysis of a pharmaceutical batch of propionyl L-carnitine, where we found the following contents: 98.5% for 1 (drug substance); 0.15% for 3; 0.1% for 5 and 0.2% for 6. The enantiomeric excess (e.e.%) measured for the drug substance was 98.9%. Finally, a single mixed-bed column, packed with a binary mixture of the chiral and achiral phases, in a 1:1 ratio, gave similar chromatographic results as the tandem-columns approach, and thus, offered an easy alternative solution to the separation of the considered mixture.     

Effects of L-Carnitine and its Derivatives – Studies on Isolated Hearts

Summary. The metabolism in the heart prefers long-chain fatty acids to other substrates. L-Carnitine, a co-factor of coenzyme A, plays an essential role in the transport of long-chain fatty acids through the inner mitochondrial membrane. Without carnitine, metabolisation of long-chain fatty acids in the mitochondria is not possible. In addition, acyl groups from acyl-CoA compounds can be transferred to L-carnitine, thus influencing the enzymatic activities of important mitochondrial enzymes.The isolated heart model developed by Langendorff was used to investigate the effects of L-carnitine on the heart. During aerobic perfusion, the hemodynamic parameters of isolated hearts reacted in a very sensitive way to alterations in the external conditions (temperature, preload, composition of the perfusion solution). During postischemic perfusion, recovery of the hearts was also influenced by the composition of the perfusion. The hemodynamic parameters of the reperfused hearts increased markedly if there was a sufficiently high supply of long-chain fatty acids and/or glucose. The insufficient recovery of hearts perfused without glucose and at low fatty acid concentrations could be improved by adding L-carnitine. Determination of carnitine levels in heart tissue found that the heart loses about 30% of its carnitine content during ischemia, and that exogenous carnitine is taken up by the heart during reperfusion. There it effects the restoration of sufficient concentrations of creatine phosphate and ATP, a fact that was confirmed by ³¹P NMR spectroscopy. NMR spectroscopy also established that L-carnitine lessens the harmful effects of ischemia-induced metabolic acidosis.The favourable influence of L-carnitine on the heart in the reperfusion period could be due to a reduction in oxygen radicals (lowering of MDA concentrations during reperfusion, raising of GP_x and SOD activities).The findings of these experiments on isolated hearts as well as the favourable results of two placebo-controlled and double-blind clinical studies (investigating the effects of carnitine in cardiomyopathy patients and the effects of L-carnitine in hemodialysis patients) demonstrate that L-carnitine produces positive therapeutic effects, particularly in heart and circulatory diseases.     

Influenza virus pathogenicity regulated by host cellular proteases,cytokines and metabolites,and its therapeutic options

Influenza A virus (IAV) causes significant morbidity and mortality. The knowledge gained within the last decade on the pandemic IAV(H1N1)2009 improved our understanding not only of the viral pathogenicity but also the host cellular factors involved in the pathogenicity of multiorgan failure (MOF), such as cellular trypsin-type hemagglutinin (HA₀) processing proteases for viral multiplication, cytokine storm, metabolic disorders and energy crisis. The HA processing proteases in the airway and organs for all IAV known to date have been identified. Recently, a new concept on the pathogenicity of MOF, the “influenza virus–cytokine–trypsin” cycle, has been proposed involving up-regulation of trypsin through pro-inflammatory cytokines, and potentiation of viral multiplication in various organs. Furthermore, the relationship between causative factors has been summarized as the “influenza virus–cytokine–trypsin” cycle interconnected with the “metabolic disorders–cytokine” cycle. These cycles provide new treatment concepts for ATP crisis and MOF. This review discusses IAV pathogenicity on cellular proteases, cytokines, metabolites and therapeutic options.     

Metabolomics‐based parallel discovery of xenobiotics and induced endogenous metabolic dysregulation in clinical toxicology

Intoxication by xenobiotics triggers the perturbation of metabolic fingerprints in biofluids, including the accumulation of xenobiotic compounds and the dysregulation of endogenous metabolites. In this work, an untargeted metabolomics workflow was developed to simultaneously profile both xenobiotic and endogenous metabolites for the identification of the xenobiotic origin and an in‐depth understanding of the intoxication mechanism. This workflow was demonstrated in a real‐world clinical case. Plasma samples were collected from four intoxicated children and another three healthy children. Untargeted metabolomics analysis was performed using ultraperformance liquid chromatography (UPLC) coupled to a high‐resolution mass spectrometer (HRMS) with data‐independent MS^E acquisition. LC–MS^E data was processed using an untargeted metabolomics data interpretation workflow, in which the identities of xenobiotics and altered endogenous metabolic features were determined via database searching. Five xenobiotic chemicals and 19 endogenous metabolites were found to be dysregulated. Combined with the clinical evidence, penfluridol was confirmed as the xenobiotic toxin. Furthermore, a mechanistic hypothesis was developed to explain the dysregulation of the four endogenous acyl‐carnitines. This workflow can be readily applied to a wide range of clinical toxicology cases, offering a powerful and convenient means of simultaneous discovery of intoxication source and the understanding of intoxication mechanisms.