臺灣博碩士論文加值系統

本研究使用氧電極偵測假單胞菌（ATCC 23973）分解碳源苯甲酸鈉的耗氧初始速率。共完成四個系列芳香族化合物的測試，包括苯系列、甲苯系列、苯胺系列及酚系列。由偵測在不同濃度各芳香族化合物對耗氧初始速率的影響，得到各化合物的抑制常數Ki值。以此抑制常數Ki值作為比較芳香族化合物對於假單胞菌相對毒性的依據。藉著比較不同化合物相對毒性的大小，評估芳香族化合物其結構對於假單胞菌毒性大小的影響。結果發現，當苯環上取代基為氯或硝基時，所得Ki值較小，即相對毒性較大。而含氯取代基化合物，其相對毒性隨著氯取代基增加而毒性上升。試著將酚類化合物所得結果利用Hammett 方程式評估化合物構造與毒性的關係。即以log (1/Ki) 對取代基常數  值作圖，利用結構-活性定量關係，將化合物結構與其毒性之間的關係予以量化，並以方程式表示之。經由分析結果得知， =0.17 ~ 0.00及 =0.00 ~ 0.55時，分別可由方程式log (1/Ki) = -5.73 — 1.75 (1)及方程式log (1/Ki) = 3.22 + 2.63Es — 1.77 (3)描述其關係。當 > 0.55時，由於化合物本身之pKa值變的較小，在水中部份以離子狀態存在，而造成毒性的減低。

Acute toxicity of compounds in benzene, toluene, aniline and phenol series to Pseudomonas putida (ATCC 23973) was estimated by an initial oxygen uptake method. Inhibition studies of these compounds on the oxidation of benzoate by Pseudomonas putida were expressed as oxygen uptake rates. Double reciprocal plots for the inhibition by these compounds of oxygen uptake in Pseudomonas, a physical constant, Ki, was obtained.
Inasmuch as most compounds inhibit noncompetively, the relative toxicity of different compounds can be estimated by a new toxicity parameter RT (relative toxicity) which is defined as 100/Ki. In benzene and toluene series, compounds with nitro- and chloro-substituent were found more toxic than other substituted benzenes and toluenes. In phenol series, an analysis of compound toxicity in quantitative structure-activity relationship (QSAR) was also conducted. In correlation of log (1/Ki) with sustituent constant , the following two equations were obtained.
log(1/Ki) = -5.73  — 1.75  = -0.17 ~ 0.00
log(1/Ki) = 3.22  + 2.63Es —1.77  = 0.00 ~ 0.55
While s > 0.55, the toxicity of compounds can not be estimated from these equations due to the fact that these compounds have low pKa (less than 8) and become ionized in the reaction condition.

謝誌-----------------------------------------------------------i
中文摘要------------------------------------------------------------ii
英文摘要-----------------------------------------------------------iii
目錄----------------------------------------------------------iv
表目錄--------------------------------------------------------vi
圖目錄-------------------------------------------------------vii
第一章 緒 論-------------------------------------------------1
一、 生物方法應用於毒性評估------------------------------------1
二、 以生物測試化合物毒性的方法--------------------------------2
三、 假單胞菌的簡介--------------------------------------------8
四、 結構-活性定量關係簡介-------------------------------------8
五、 實驗目的-------------------------------------------------12
第二章 實 驗------------------------------------------------13
一、 藥品-----------------------------------------------------13
二、 儀器-----------------------------------------------------15
三、 實驗內容-------------------------------------------------17
（一） 細菌的培養及處理---------------------------------------17
（二） 氧電極的測試-------------------------------------------19
（三） 數據的處理---------------------------------------------21
第三章 結果與討論-------------------------------------------27
一、 化合物的Ki值：-------------------------------------------27
二、 化合物毒性與構造分析-------------------------------------28
三、 Hammett方程式與毒性的關係--------------------------------29
四、 相對毒性與化合物立體組態的關係---------------------------30
結論----------------------------------------------------------39
參考文獻------------------------------------------------------40

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