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博碩士論文 etd-0709109-104227 詳細資訊
Title page for etd-0709109-104227
論文名稱
Title
鈦與錫二酮基抗癌藥物異構化研究
Isomerization Study on Anticancer Titanium and Tin β-Diketonato Complexes
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
149
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2009-06-22
繳交日期
Date of Submission
2009-07-09
關鍵字
Keywords
抗癌、異構物、鈦與錫錯合物、布度鈦
Budotitane, anticancer, isomer, Ti and Sn compounds
統計
Statistics
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The thesis/dissertation has been browsed 5775 times, has been downloaded 1703 times.
中文摘要
  關於鈦與錫抗癌藥物的作用機制到目前為止仍不明確。通常這類六配位含兩個苯甲醯丙酮基配位的鈦與錫錯合物Ti(bzac)2 X2 and Sn(bzac)2 X2都具有五種異構物,而抗癌的活性和哪種異構物有關現今仍是個謎。其中一種被命名為布度鈦(budotitane)的二酮基鈦錯合物Ti(bzac)2(OEt)2在抗癌研究已進入臨床實驗。因此本文將利用變溫氫核核磁共振光譜和其固態結構的關係,探討其在溶液中異構化行為、轉換反應速率常數k及能階大小ΔG‡。
  此類鈦與錫錯合物的抗癌活性和苯甲醯丙酮基上的苯環有很大的關係,若把苯環用甲基取代便會失去抗癌活性。因此我們推測布度鈦對DNA的作用模式可能為一種插入劑。進一步將配位基從1-苯基-1,3-丁二酮改變成4,4,4-三氟-1-萘基-1,3-丁二酮,並藉由我們所得到此類錯合物的晶體構形,來觀察其在變溫NMR光譜中的轉變,文中也將針對此配位基的改變所造成之立體障礙因素進行探討。
Abstract
The mode of Ti and Sn action of anticancer compounds is still poorly understood. For each octahedral Ti(bzac)2 X2 and Sn(bzac)2 X2 (Hbzac = 1-benzoylacetone) complexes there are five possible isomers. It is not known which of these isomers is responsible for the anticancer activity. One of the Ti complex Ti(bzac)2(OEt)2 whose trade name is budotitane® is a anticancer drug on clinically trial base. Therefore we use VT-NMR (low temperature to high temperature) studies and their crystal structures (1a, 1b, and 2a) to examine their isomerization behavior, conversion rate constant k, and conversion barrier energy ΔG‡.
We suspect the antitumor activity of Ti and Sn compounds strongly depends on the unsubstituted phenyl rings of the β-diketonato ligands in the outer sphere of the molecule. If these phenyl rings are replaced by methyl groups, the activity totally disappears. Therefore we propose that the anticancer activity of budotitane may be determined by a DNA intercalating mechanism. We further changed the ligand from Hbzac to FHnpac (FHnpac = 4, 4, 4-trifluoro-1-(naphthalen-3-yl) butane-1, 3-dione) in order to monitor their isomers exchange via 1H NMR. The related crystal structures (1a-NF, 1b-NF, and 2a-NF) were obtained fortunately. The stereochemistry of Ti and Sn complexes as well as their controlling factors is discussed.
目次 Table of Contents
提要…………………………………………………………………………… i
目錄…………………………………………………………………………… iii
表目錄……………………………………………………………………… v
圖目錄……………………………………………………………………… vi
附錄目錄…………………………………………………………………… viii
壹、緒論…………………………………………………………………… 1
貳、實驗部分………………………………………………………………… 17
一、試藥及純化..………………………………………………… 17
二、儀器設備…………………………………………………… 20
三、合成反應…………………………………………………… 22
1. Ti(bzac)2Cl2 -(1a)的合成與鑑定……………………………… 22
2. Ti(bzac)2(OEt)2 -(1b)的合成與鑑定…………………………… 22
3. Ti(bzac)2(Oipr)2 –(1c)的合成與鑑定......................................... 23
4. Ti(Fnpac)2Cl2 -(1a-NF)的合成與鑑定........................................ 24
5. Ti(Fnpac)2(OEt)2 -(1b-NF)的合成與鑑定.................................. 25
6. Sn(bzac)2Cl2 -(2a)的合成與鑑定................................................ 25
7. Sn(Fbzac)2Cl2 -(2a-F)的合成與鑑定…………………………. 26
8. Sn(bzac)2(OEt)2 -(2b)的合成與鑑定......................................... 27
9. Sn(Fnpac)2Cl2 -(2a-NF)的合成與鑑定..................................... 28
10. 配位基1-naphthalenylacetone的合成與鑑定...................... 29
參、結果與討論………………………………………………………….… 31
一、 苯甲醯丙酮基鈦與錫錯合物結構與其在溶液中異構物
分佈的探討…………………………………………………..
31
二、 三氟萘甲醯丙酮基鈦與錫錯合物結構與其在溶液中
異構物分佈的探討…………………………………….…
48
三、 二酮基鈦與錫錯合物在溶液中異構化的反應機構
探討………………………………………………….………
61
四、 二酮基鈦與錫錯合物溶液中異構化參數探討…………… 66
肆、結論……………………………………………………………………… 70
伍、參考文獻………………………………………………………………… 73
陸、附錄……………………………………………………………………… 74
參考文獻 References
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