可离子化有机污染物对大型溞的毒性及QSAR研究

取代苯酚、苯胺和苯甲酸类化合物是在环境水体中具有较强生物毒性的芳香族可离子化有机化合物,它们在水体中对水生生物和水生生态系统都有较大危害。测定此类化合物在p H值为6、7.8和9的条件下对大型溞的24 h急性毒性,计算化合物在不同p H值条件下的中性态分子所占比例F0。研究毒性与F0的相关性,结果表明F0对取代苯酚和苯甲酸类化合物的毒性的影响较大而对取代苯胺毒性的影响很小。对于卤代苯甲酸类化合物,毒性与疏水性的相关性较好,但是羟基苯甲酸类化合物的毒性与疏水性参数的相关性很差,引入量子化学参数EHOMO和取代羟基个数NOH,可以改进苯甲酸类化合物的模型的质量。     

QSAR模型内部和外部验证方法综述

验证定量-结构活性相关(QSAR)模型,是保证模型对未知样本的生物活性具有可靠预测能力的重要前提.然而,目前部分QSAR论文没有对模型进行有效验证.因此,本文详细综述QSAR模型的内部验证方法和外部验证方法.内部验证方法包括留一法(leave-one-out,LOO)交叉验证,留多法(leave-many-out,LMO)或留N法(leave-N-out,LNO)交叉验证,y随机化验证和自举法.评价模型外部预测能力的统计量包括Q2F1、Q2F2、Q2F3、一致性相关系数(concordance correlation coefficient,CCC)、r珋2m和Golbraikh-Tropsha方法.此外,从文献中总结出可接受QSAR模型对应的统计量参考数值,从而为QSAR建模者提供指导与帮助.     

Exposure and Health Effects of Cadmium

The results of a study of photocatalytic degradation of phenol using aqueous oxygenated TiO₂ (anatase) suspensions in a batch Pyrex photoreactor are reported. The influence on the photodegradation rate of various parameters as pH, phenol and TiO₂ content, oxygen partial pressure, anions present in the dispersions was investigated. A complete oxidation of phenol was observed. Intermediate compounds, catechol and quinone, were detected. It was observed that the photodegradation also proceeded with sunlight radiation. A mechanistic and kinetic model, which accounts for the results obtained, is given. Likely reasons for inactivity of the rutile modification for this reaction are also given.     

Determination of minimum inhibitory concentration and half maximal inhibitory concentration of antibiotics and their degradation products to assess the eco-toxicological potential

Abstract

Numerous studies have been reported on today’s ubiquitous presence of antibiotics in surface waters causing the emergence of multidrug-resistant bacteria. Advanced water treatment procedures aim at the complete prevention and elimination of antibiotics from entering natural water bodies. In this study, photoinduced degradation processes using UVC-irradiation were applied toward selected fluoroquinolone, tetracycline, macrolide, and sulfonamide antibiotics. Photodegradation products were elucidated using high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS). Rate constants and quantum efficiencies were determined for the active substances and their photo-transformation products. As a measure of ecotoxicity, minimum inhibitory and half-maximal inhibitory concentrations were determined against the Gram-negative bacterium Pseudomonas fluorescens and the Gram-positive Bacillus subtilis in a standard assay format. These values were further recorded as a function of UV exposure time. The irradiation time-dependent increase of minimum inhibitory concentration (MIC) values agreed well with the kinetic models. After 10?min of irradiation, the compound solutions ceased to inhibit bacterial cell growth, indicating removal of the pharmaceutical activity. These findings were found in agreement with quantitative structure–activity relationship analysis. The combination of microbiological activity testing, molecular structure analysis, chemical kinetic investigation, and quantitative structure–activity relationship models proved to be able to predict irradiation times and evaluate potential ecotoxicological hazard of the irradiated drugs.     

用电性拓扑态预测苯砜基乙酸酯对发光菌的毒性效应

应用电性拓扑态(Electrotopological State, E-state)指数模拟分析了a-取代苯砜基乙酸酯类化合物对发光菌的毒性(15min-EC50, mmol/L),构建了一个4变量QSAR模型.模型的相关系数(R²a_dj)和标准偏差(SD)分别为0.944和0.062,模型具有较高的预测能力和可靠性.模型分析表明,砜基和酯基是该类化合物的活性中心;化合物的疏水能力以及化合物与受体分子间的偶极/极化作用和氢键效应对化合物毒性起着重要影响.     

用QSAR模型预测苯酚类化合物对发光菌的联合毒性

测定了苯酚与11种取代苯酚对发光菌的单一毒性和毒性单位比为1:4,1:1,4:1二元混合物的联合毒性.采用相加指数法对联合毒性进行了评价,结果表明,苯酚和取代苯酚的二元混合物对发光菌的联合作用以相加作用为主.在此基础上,根据12种苯酚类化合物的单一毒性建立了QSAR方程: -lgEC₅₀=6.158-0.279pKa,对混合物中取代苯酚的毒性进行了预测,预测值与实测值吻合较好.     

磺胺类化合物对大肠杆菌突变QSAR预测模型初探

抗生素被广泛应用于医疗、农业和畜牧业等领域,但是长期滥用会促进细菌的突变作用。本文以大肠杆菌(E.coli)为受试生物,测定了10种磺胺类抗生素(SAs)单一暴露时对E.coli的突变效应,采用物化参数Ebinding(抗生素与其靶蛋白的相互作用能力)与突变效应参数lgRC0-2(最高可观测突变促进效应浓度)或lgRCmax(突变促进率最大值对应的浓度),建立了突变效应的QSAR模型,并采用雷达图进行验证。结果表明,lgRC0-2与Ebinding模型和lgRCmax与Ebinding、DMG(偶极矩)模型的拟合系数R2分别是0.888、0.873,即lgRC0-2或lgRCmax与Ebinding相关性均较好,可能由于磺胺类化合物(SAs)会作用于叶酸合成通路,影响嘌呤、嘧啶碱基的合成,从而对E.coli的突变具有促进效应,且雷达图验证表明,上述2个模型均具有良好的内部预测能力。本研究有望为抗生素使用带来的生态风险评价以及药物设计提供相关指导。     

苯酚类化合物对日本长腿蛙蝌蚪的急性毒性与构效关系研究

利用半静态法测定了21种取代苯酚类化合物对日本长腿蛙蝌蚪的24h 急性致死毒性(24h-LC50),并进行了定量结构活性相关研究.研究表明:大部分酚类化合物的毒性表现为极性麻醉作用.影响毒性的因素有化合物的疏水性、电性及离解行为等.     

The kinetics of reductive dehalogenation of a set of halogenated aliphatic hydrocarbons in anaerobic sediment slurries

Disappearance rate constants are reported for the reductive transformation of 17 halogenated aliphatic hydrocarbons in anaerobic sediment-water samples. Statistical experimental design in combination with multivariate chemical characterization of their chemical properties was used to select the compounds. Degradation followed pseudo first-order kinetics through at least two half-lives for 15 of the 17 compounds. Of all the compounds investigated, 1,2,3-trichloropropane and dichloromethane were unique in that they were dehalogenated according to zero-order kinetics. Reductive dehalogenation was the sole transformation reaction taking place.