硝基芳烃对圆腹雅罗鱼毒性的DFT研究

对30种硝基芳烃化合物进行DFT-B3LYP/6-311G**水平全优化计算, 据所得量子化学参数分类建立了硝基苯类和硝基苯胺类化合物对圆腹雅罗鱼急性毒性(－lgEC₅₀)的定量构效关系(QSARs)模型. 结果表明, 硝基苯类化合物的毒性主要由硝基基团的电荷(Q_-NO2)和前线轨道能级差(ΔE)决定; 硝基苯胺类化合物的毒性则由分子最低未占轨道能级(E_LUMO)和ΔE决定. 苯环上取代基的类型、数目和取代位置直接影响到标题化合物的毒性大小, 强吸电子基如硝基会降低Q_-NO2和E_LUMO大小, 使化合物毒性增强, 且邻对位硝基取代的毒性高于间位取代; 相反, 给电子基团氨基的存在则会使化合物的毒性降低. 总之, 硝基是这两类化合物致毒的主要基团, 将硝基包覆或还原为氨基应为此类化合物解毒的重要途径. 最后以1,4-二硝基苯为例, 模拟了其活性亚硝基中间产物与蛋白质中还原性巯基间的反应, 并将其与硝基苯和1,3-硝基苯的反应活化能进行了比较, 讨论了不同取代基数目和位置对分子活性的影响, 结果与QSAR模型分析一致, 进一步验证了硝基芳烃化合物的致毒历程, 研究结果对品优高能炸药的分子设计也有助益.     

Functional toxicity and tolerance patterns of bioavailable Pd(II), Pt(II), and Rh(III) on suspended Saccharomyces cerevisiae cells assayed in tandem by a respirometric biosensor

Toxicological implications of exposure to bioavailable platinum group metals, here Pd, Pt, and Rh, are still to be clarified. This study obtained by a biosensor-based method preliminary information on potential effects on cellular metabolism as well as on possible tolerance mechanisms. Aerobic respiration was taken as the toxicological end point to perform tandem tests, namely functional toxicity test and tolerance test. Cells were suspended in the absence of essential constituents for growth. The dose–response curves obtained by exposure (2 h) to the metals (nanogram per gram range) suggested the same mechanisms of action, with Rh showing the greatest curve steepness and the lowest EC₅₀ value. Conservative (95% lower confidence interval) EC₁₀ values were 187, 85 and 51 ng g⁻¹ for Pt, Pd, and Rh respectively. Tolerance patterns were tested during the same runs. The full tolerance obtained after 12 h of exposure to each metal suggested mitochondrial inhibition of aerobic respiration as a target effect. The hazard rating of the metals in the tolerance test changed in the Rh EC₅₀ range, where Rh showed the lowest toxicity. The observed tolerance might suggest a protective mechanism such as metallothionein induction at concentrations around the EC₅₀ values. The performance of the bioassay was satisfactory, in terms of the limit of detection, repeatability, reproducibility, roboustness, sensibility, and stability; the method’s critical uncertainty sources were identified for improvements. Figure Respirometric curved     

Disordering in the crystal structures of thienylgermatranes

The crystal structure of a series of thienylgermatranes has been studied using X-ray diffraction. Disorder of the thiophene ring in a 2-thienylgermatrane has been established. In the same positions of the unit cell of the crystal there are found both molecules with an O(2)-Ge-C-S torsional angle of −166.8(4)° and molecules in which this angle is 14.0(4)°. The lengths of the transannular N→Ge bonds (2.183–2.283 Å) agrees in value with the values of crystalline germatrane structures with a Ge-C bond. The length of the transannular N→Ge bond (2.248 Å) in 4-(2-thienyl)phenylgermatrane (molecule A) is the largest amongst germatranes with a Ge-C_ar bond. Introduction of a second thiophene ring into the 2-thienylgermatrane molecule lowers the acute toxicity of the compound by about 27 times (LD₅₀ for the 2,2′-bithienylgermatrane = 447 mg/kg). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 299–306, February, 2007.     

A new method for the synthesis of silicon-and germanium-containing 2-acetylfurans and 2-acetylthiophenes

A new method was developed for the synthesis of silicon-and germanium-containing acetylfurans and acetylthiophene by metallation of 2-acetylfuran or 2-acetylthiophene with n-BuLi at low temperature after protection of the carbonyl group with lithium N-methylpiperazide and reaction of the lithium derivative with various trialkyl-, alkylphenyl-, and cycloalkylchlorosilanes or trialkylchloro(bromo)germanes. The cytotoxic activity of the new compounds was studied, and it was established that the silicon-and germanium-containing acetylfurans and acetylthiophenes are substances with low toxicity (LD₅₀ 312->2000 mg/kg) and have low cytotoxicity toward HT-1080 and MG-22A tumor cells. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 192–199, February, 2007.     

离子液体的毒性

离子液体因其特有的物化性质受到越来越多的关注,并被认为是环境友好的"绿色产品"。但是有关离子液体的潜在毒性一直被人们所忽视,直到最近才有少量报道。本文综述了离子液体毒性研究的相关情况：详细介绍了离子液体毒性研究的各种方法及优缺点;离子液体对各类生物的急性毒性和慢性毒性;离子液体的各部分组成,尤其是阳离子核种类、取代烷基碳链长度和阴离子种类对离子液体毒性的影响情况,以及SAR理论在离子液体毒性研究中的应用情况。在此基础上提出今后离子液体毒性研究的发展方向。     

Chemical composition and insecticidal activities of essential oils against diamondback moth,Plutella xylostella (L.) (Lepidoptera: Yponomeutidae)

Five Himalayan plants namely, Acorus calamus, Cedrus deodara, Aegle marmelos, Tagetes minuta and Murraya koenigii were used for the extraction of essential oils through hydrodistillation and the major volatile constituents as identified by GC and GC–MS techniques were β-asarone (91.1%), β-himachalene (45.8%), limonene (59.5%), Z-ocimene (37.9%) and α-pinene (54.2%), respectively. Essential oils were tested for their insecticidal properties against larvae of diamondback moth, Plutella xylostella (L.) (Lepidoptera: Yponomeutidae). Results showed that A. calamus was most toxic (LC_50?=?0.29 mg mL^?1) to P. xylostella followed by C. deodara (LC_50?=?1.08 mg mL^?1) and M. koenigii (LC_50?=?1.93 mg mL^?1) via residual toxicity bioassay. Per cent feeding deterrence index and growth inhibition was significantly higher in A. calamus (42.20 and 68.55, respectively) followed by C. deodara (35.41 and 52.47). In repellent activity studies, C. deodara showed high repellence (64.76%) followed by A. calamus (55.05%).     

The index of ideality of correlation: improvement of models for toxicity to algae

Toxicity to algae is important characteristic of substances from ecologic point of view. The CORAL software (http://www.insilico.eu/coral) gives possibility to build up model of toxicity to algae using data on the molecular architecture and experimental toxicity, without additional data on physicochemical and/or biochemical parameters. Considerable improvement of the model is observed in the case of using the index of ideality of correlation (IIC) in the role of additional criterion of predictive potential. The IIC is calculated with using of the correlation coefficient between experimental and calculated values of endpoint for the calibration set, with taking into account the positive and negative dispersions between experimental and calculated values. The best model calculated with use the IIC is characterized (the validation set) by n?=?50, r²?=?0.947, RMSE?=?0.401 whereas, model calculated without use the IIC is characterized by n?=?50, r²?=?0.805, and RMSE?=?0.539. The suggested models are built up in accordance to five OECD principles.

     

Synthesis of Nonionic Oligomeric Manganese（ Ⅱ ） Complexes and Investigation of Their Toxicity and T1 -Relaxation Enhancement

Six nonionic oligomeric manganese （ Ⅱ ） complexes with oligomeric phosphate-polyglycol-EDTA ester ligands were synthesized and characterized. The longitudinal relaxivities of these complexes were measured. One of these complexes, which showed the highest relaxivity, was chosen to be used in the acute toxicity test and the T1-weighted imaging experiment. It has been found that compared to Gd-DTPA, this nonionic oligomeric Mn（ Ⅱ ） complex exhibits no acute toxicity, generates highly enhanced MRI signals and increases the intention time in the rat liver tissue.     

In Vitro Antineoplastic and Antiviral Activity and In Vivo Toxicity of Geum urbanum L. Extracts

This study evaluated the in vitro antineoplastic and antiviral potential and in vivo toxicity of twelve extracts with different polarity obtained from the herbaceous perennial plant Geum urbanum L. (Rosaceae). In vitro cytotoxicity was determined by ISO 10993-5/2009 on bladder cancer, (T-24 and BC-3C), liver carcinoma (HEP-G2) and normal embryonic kidney (HEK-293) cell lines. The antineoplastic activity was elucidated through assays of cell clonogenicity, apoptosis induction, nuclear factor kappa B p65 (NFκB p65) activation and total glutathione levels. Neutral red uptake study was applied for antiviral activity. The most promising G. urbanum extract was analyzed by UHPLC–HRMS. The acute in vivo toxicity analysis was carried out following OEDC 423. The ethyl acetate extract of aerial parts (EtOAc-AP) exhibited the strongest antineoplastic activity on bladder cancer cell lines (IC₅₀ = 21.33–25.28 µg/mL) by inducing apoptosis and inhibiting NFκB p65 and cell clonogenicity. EtOAc and n-butanol extracts showed moderate antiviral activity against human adenovirus type 5 and human simplex virus type I. Seventy four secondary metabolites (gallic and ellagic acid derivatives, phenolic acids, flavonoids, etc.) were identified in EtOAc-AP by UHPLC–HRMS. This extract induced no signs of acute toxicity in liver and kidney specimens of H-albino mice in doses up to 210 mg/kg. In conclusion, our study contributes substantially to the detailed pharmacological characterization of G. urbanum, thus helping the development of health-promoting phytopreparations.