發(fā)布時間：2018-06-02 15:10

  本文選題：恩諾沙星 + 高錳酸鉀�。� 參考：《哈爾濱工業(yè)大學(xué)》2015年碩士論文

【摘要】：恩諾沙星屬于目前最常用的獸用藥,被廣泛應(yīng)用于水產(chǎn)養(yǎng)殖業(yè)、畜牧業(yè)和農(nóng)業(yè)。由于該類藥物的大量使用,導(dǎo)致殘留的恩諾沙星隨著生活污水、醫(yī)療廢水等進(jìn)入污水處理廠,而污水廠的二級處理工藝難以將其有效去除,殘留恩諾沙星污染物隨污水廠出水排放到地表水體。近年來,恩諾沙星頻繁在水體和污水處理廠二級出水中被檢出,濃度范圍在ng/L~μg/L之間。而且,其氧化產(chǎn)物環(huán)丙沙星,作為常用抗生素,同樣在水體和污水處理廠二級出水中被大量檢出。環(huán)境中的恩諾沙星最主要的潛在風(fēng)險是誘導(dǎo)抗藥菌株產(chǎn)生,抗藥菌株的產(chǎn)生對人類健康以及生態(tài)環(huán)境都有嚴(yán)重威脅。目前多采用化學(xué)方法氧化恩諾沙星,主要氧化劑有高錳酸鉀、二氧化錳、臭氧、二氧化氯等。這其中,高錳酸鉀以其對有機(jī)物的氧化具有選擇性且穩(wěn)定性強(qiáng)的優(yōu)點,被認(rèn)為是一種解決水體中微量有機(jī)物問題的有發(fā)展前景的氧化劑。故本研究選用高錳酸鉀為氧化劑對恩諾沙星進(jìn)行氧化。四極桿-飛行時間串聯(lián)質(zhì)譜儀(Q-TOF)可以準(zhǔn)確得到氧化產(chǎn)物信息,為水環(huán)境中研發(fā)有效的去除污染物技術(shù)提供了快速準(zhǔn)確的技術(shù)保障。本文研究了高錳酸鉀與恩諾沙星及主要產(chǎn)物環(huán)丙沙星的反應(yīng),采用Q-TOF對其氧化產(chǎn)物進(jìn)行識別,對恩諾沙星反應(yīng)途徑進(jìn)行了初步討論,為接下來的產(chǎn)物抑菌特性分析及其與產(chǎn)物結(jié)構(gòu)的相關(guān)性分析提供相應(yīng)信息支持。高錳酸鉀氧化恩諾沙星及環(huán)丙沙星反應(yīng)后溶液抑菌特性的變化情況采用定量生物實驗來評價。分別從恩諾沙星混合產(chǎn)物和單一產(chǎn)物的抑菌特性兩個角度進(jìn)行了實驗,實驗方法采用了平板實驗和光學(xué)密度實驗。作為恩諾沙星的主要氧化產(chǎn)物,環(huán)丙沙星與高錳酸鉀反應(yīng)的混合產(chǎn)物及其分離產(chǎn)物的抑菌特性同樣進(jìn)行了光學(xué)密度實驗。最后,對恩諾沙星氧化產(chǎn)物結(jié)構(gòu)與其抑菌特性的相關(guān)性進(jìn)行分析。高錳酸鉀氧化恩諾沙星的反應(yīng)生成四種主要產(chǎn)物,質(zhì)荷比分別為362.1517(E5),334.1566(E4),332.1410(E3/CIP),376.1671(E7)和五種次要產(chǎn)物,質(zhì)荷比分別為263.0828(E1),306.1252(E2),374.1515(E6),390.1472(E8)和392.1622(E9)。恩諾沙星其中一種主要氧化產(chǎn)物為環(huán)丙沙星(E3)。在本實驗得到的四種主要氧化產(chǎn)物中,一種氮氧化物為新的產(chǎn)物,在之前發(fā)表的相關(guān)文獻(xiàn)中未見報道。高錳酸鉀投加比例、反應(yīng)時間、p H值及緩沖溶液對恩諾沙星主要產(chǎn)物種類沒有影響,但對各種產(chǎn)物豐度值有明顯影響。高錳酸鉀氧化環(huán)丙沙星的反應(yīng)生成兩種主要產(chǎn)物,質(zhì)荷比分別為334.1240(C1)和306.1248(C2)。高錳酸鉀氧化恩諾沙星的反應(yīng)途徑主要有三條,即哌嗪環(huán)上的氮原子上脫烷基作用,碳原子上羥基化作用,以及胺基氧化作用。反應(yīng)主要發(fā)生哌嗪環(huán)上,而各產(chǎn)物喹諾酮環(huán)保持完整。而且,本研究建立了一種分離、濃縮抗生素氧化后混合產(chǎn)物,并對單一產(chǎn)物抑菌特性定量評價的實驗方法。抑菌特性評價分別采用平板實驗和光學(xué)密度實驗。平板實驗操作簡單,所需實驗設(shè)備較少,方法較成熟,并且可以觀察到細(xì)菌生長速率變化情況,適宜實驗室條件有限的情況下采用;光學(xué)密度實驗工作量較小,可定量測定溶液抑菌特性,實驗周期短,重復(fù)性好,適宜需要短時間得到實驗結(jié)果,且實驗室條件滿足的情況下采用�；旌袭a(chǎn)物抑菌特性實驗結(jié)果表明,反應(yīng)前后溶液抑菌特性基本沒有發(fā)生變化。分離后的單一產(chǎn)物抑菌特性實驗表明,恩諾沙星氧化產(chǎn)物的抑菌特性較母物質(zhì)略有降低,但都未完全消失,且各氧化產(chǎn)物log(EC50)值與分子量呈正相關(guān),隨分子量增大而絕對值增大,表明其抑菌特性增強(qiáng)。對于恩諾沙星,盡管經(jīng)高錳酸鉀氧化后,所有氧化產(chǎn)物喹諾酮母核均保持完整,但是對其哌嗪環(huán)取代基的氧化可以改變產(chǎn)物抑菌特性。
[Abstract]:Enrofloxacin is the most commonly used veterinary drug at present and is widely used in aquaculture, animal husbandry and agriculture. Due to the large use of this kind of drugs, the residual enrofloxacin is entered into the sewage treatment plant with domestic sewage and medical wastewater, while the two stage treatment process of the sewage plant is difficult to remove it effectively, and the residue of enrofloxacin is contaminated. In recent years, enrofloxacin has been detected in two levels of water and wastewater treatment plants in water and sewage treatment plants. The concentration range is between ng/L~ and g/L. And the oxidation product ciprofloxacin, as a common antibiotic, is also detected in water and sewage treatment plant two. The main potential risk of the star is to induce the production of antidrug strains. The production of anti drug strains has a serious threat to human health and the ecological environment. At present, the main oxidants are Potassium Permanganate, manganese dioxide, ozone, chlorine dioxide, and so on. In this way, Potassium Permanganate is selected for the oxidation of organic matter. The advantages of high selectivity and strong stability are considered to be a promising oxidizing agent to solve the problem of trace organic matter in water. Therefore, Potassium Permanganate is used as oxidant to oxidize enrofloxacin. The quadrupole flight time tandem mass spectrometer (Q-TOF) can accurately obtain the information of oxidation products, which can be developed for the water environment. The technology of removing pollutants provides rapid and accurate technical support. The reaction of Potassium Permanganate with enrofloxacin and ciprofloxacin, the main product, was studied by using Q-TOF to identify the oxidation products. The reaction pathway of enrofloxacin was preliminarily discussed, which was related to the analysis of the antibacterial properties of the next product and the correlation with the structure of the product. The variation of the antibacterial properties of Potassium Permanganate oxidizing enrofloxacin and ciprofloxacin was evaluated by quantitative biological experiments. The experiments were carried out from two angles of the antibacterial properties of the enrofloxacin mixture and the single product respectively. The experiment method adopted the flat plate experiment and the optical density. As the main oxidation product of enrofloxacin, the mixed products of ciprofloxacin and Potassium Permanganate and the bacteriostasis characteristics of the separation products also carried out the optical density test. Finally, the relationship between the structure of the enrofloxacin oxidation product and its antibacterial properties was analyzed. The reaction of the Potassium Permanganate oxidization enrofloxacin was four main types. The product is 362.1517 (E5), 334.1566 (E4), 332.1410 (E3/CIP), 376.1671 (E7) and five secondary products, the mass ratio is 263.0828 (E1), 306.1252 (E2), 374.1515 (E6), 390.1472 (E8) and 392.1622 (E9). The major oxidation product of enrofloxacin is ciprofloxacin (E3). In this experiment, it is found in the four major oxidation products. A new kind of nitrogen oxide is a new product, which has not been reported in previous literatures. The proportion of Potassium Permanganate, reaction time, P H value and buffer solution have no effect on the main products of enrofloxacin, but have obvious influence on the abundance of various products. The reaction of ciprofloxacin oxidation of Potassium Permanganate produces two main products, mass charge The ratio of 334.1240 (C1) and 306.1248 (C2) respectively. There are three main ways for the reaction of Potassium Permanganate oxidation enrofloxacin, that is, the dealkylation of nitrogen atoms on the piperazine ring, the hydroxylation of carbon atoms, and the amine oxidation. The reaction mainly occurs on the piperazine ring, and the products of quinolone are intact. Moreover, this study has established a kind of study. The experimental method for the quantitative evaluation of the bacteriostasis characteristics of a single product after the oxidation of the concentrated antibiotics. The evaluation of the bacteriostasis characteristics of the single product was carried out by the flat plate experiment and the optical density test. The flat experiment was simple, the required experimental equipment was less, the method was more mature, and the growth rate of the bacteria could be observed and the laboratory was suitable for the laboratory. Under the condition of limited conditions, the optical density experiment was small, and the bacteriostasis characteristics of the solution could be measured quantitatively. The experimental period was short and the reproducibility was good. It was suitable for a short time to get the experimental results, and the laboratory conditions were satisfied. The experimental results of the antibacterial properties of the mixed products showed that the bacteriostatic characteristics of the solution before and after the reaction basically had no hair. The bacteriostasis characteristics of the single product after separation showed that the antibacterial properties of the enrofloxacin oxidation product decreased slightly than the mother substance, but all did not completely disappear, and the log (EC50) value of the oxidation products was positively correlated with the molecular weight, and the absolute value increased with the increase of molecular weight. After oxidation, all nucleosides of the quinolone remained intact, but the oxidation of piperazine ring substituents could change the antibacterial properties of the products.
【學(xué)位授予單位】：哈爾濱工業(yè)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：X703

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本文編號：1969217