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題 名 | Relationship of Structure and Brain Uptake between Cu(II)-Dimethylpropylene Imine Phenol and Cu(II)-Dimethylpropylene Amine Phenol=銅(II)-二甲基丙烷亞胺酚與銅(II)-二甲基丙烷胺酚結構與腦分佈之相關性 |
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作 者 | 羅建苗; 姚學華; 黃文濤; 盧天惠; | 書刊名 | 核子醫學雜誌 |
卷 期 | 22:2 2009.06[民98.06] |
頁 次 | 頁85-92 |
分類號 | 414.93 |
關鍵詞 | X光晶體結構; 生物分佈; 銅(II)-二甲基丙烷亞胺酚; 銅(II)-二甲基丙烷胺酚; X-ray structure; Biodistribution; Cu(II)-dimethylpropylene imine phenol; Cu(II)-dimethylpropylene amine phenol; |
語 文 | 英文(English) |
中文摘要 | 目的:本研究爲探討銅-(II)亞胺酚錯合物與銅(II)-胺酚錯合物其結構與生物分佈的相關性。 方法:銅(II)-二甲基丙烷亞胺酚[Cu-DmPn (IP)2]與銅(II)-二甲基丙烷胺酚[Cu-DmPn (AP)2]分別在本研究室合成出並以X光繞射解出其晶體結構。以放射性銅-64(II)離子與上述配位子在常溫、pH9條件下起反應分別得銅-64-DmPn (IP)2與銅-64-DmPn (AP)2。以此二放射性銅標誌錯合物在正辛醇與生理食鹽水箏體積下萃取反應,測定兩相之放射活度,求出分配係數,藉以評估此二銅(II)錯合物之親脂性。以銅-64-DmPn (AP)2進行Wistar公鼠之生物分佈,至於銅-DmPn (IP)2之生物分佈則採自文獻之值。 結果:X光繞射分析晶體結構結果顯示:銅-DmPn (IP)2爲單核結構,銅-DmPn (AP)2則爲雙核結構。銅-DmPn (IP)2在正辛醇-水相的分配係數遠大於銅-DmPn (AP)2,顯示前者親脂性遠大於後者。大鼠實驗顯示銅-64標誌銅-DmPn (AP)2可快速自血液廓清進入腦組織;銅-64標誌銅-DmPn (AP)2則相對地緩慢自血液廓清,而且幾乎不進入腦組織。 結論:銅-DmPn (IP)2與銅-DmPn (AP)2兩者結構不同,其在動物腦組織吸收亦顯著不同。 目的:本研究爲探討銅-(II)亞胺酚錯合物與銅(II)-胺酚錯合物其結構與生物分佈的相關性。 方法:銅(II)-二甲基丙烷亞胺酚[Cu-DmPn (IP)2]與銅(II)-二甲基丙烷胺酚[Cu-DmPn (AP)2]分別在本研究室合成出並以X光繞射解出其晶體結構。以放射性銅-64(II)離子與上述配位子在常溫、pH9條件下起反應分別得銅-64-DmPn (IP)2與銅-64-DmPn (AP)2。以此二放射性銅標誌錯合物在正辛醇與生理食鹽水箏體積下萃取反應,測定兩相之放射活度,求出分配係數,藉以評估此二銅(II)錯合物之親脂性。以銅-64-DmPn (AP)2進行Wistar公鼠之生物分佈,至於銅-DmPn (IP)2之生物分佈則採自文獻之值。 結果:X光繞射分析晶體結構結果顯示:銅-DmPn (IP)2爲單核結構,銅-DmPn (AP)2則爲雙核結構。銅-DmPn (IP)2在正辛醇-水相的分配係數遠大於銅-DmPn (AP)2,顯示前者親脂性遠大於後者。大鼠實驗顯示銅-64標誌銅-DmPn (AP)2可快速自血液廓清進入腦組織;銅-64標誌銅-DmPn (AP)2則相對地緩慢自血液廓清,而且幾乎不進入腦組織。 結論:銅-DmPn (IP)2與銅-DmPn (AP)2兩者結構不同,其在動物腦組織吸收亦顯著不同。 |
英文摘要 | Objective: This study was to explore the relationship between the structure and the brain uptake for both of the complexes of Cu(II)-imine phenol and Cu(II)-aminephenol. Methods: The X-ray structures of Cu(II)-dimethylpropylene imine phenol [Cu-DmPn(IP)2] and Cu(II)-dimethylpropylene amine phenol [Cu-DmPn(AP)2] were determined in this laboratory. By reaction of 64Cu2+ with both of the ligands under pH 9, 64Cu-DmPn(IP)2 and 64Cu-DmPn(AP)2 were obtained, and were subject to extraction between n-octanol and saline and subsequently the radioactivities in both phases were measured for estimation of the lipophilicities of the two Cu(II) complexes. 64Cu-DmPn(AP)2 was also employed for biodistribution study using male Wistar rates. The similar animal biodistribution of Cu-DmPn(IP)2 was cited from literature. Results: From X-ray crystallography, Cu(II)-dimethylpropylene imine phenol [Cu-DmPn(IP)2] exhibits a mononuclear structure whereas Cu(II)-dimethylpropylene amine phenol [Cu-DmPn(AP)2] exhibits a dinuclear structure. The observed dimeric structure arises from a pair of Cu-ligand chelates expanding their coordination number to five by interaction with one of the phenolic O coordination to the other Cu center. The lipophilicity of Cu-DmPn(IP)2 was much higher than that of Cu-DmPn(AP)2. In the animal trials by rats tracing by radioactive copper, the mononuclear Cu-DmPn(IP)2 was rapidly cleared from the blood and was diffusible across the blood-brain barrier (BBB) into the brain whereas the dinuclear Cu-DmPn(AP)2 was slowly cleared from the circulation and almost not diffusible across the BBB. Conclusion: Cu-DmPn(AP)2 is a dinuclear structure which is much different from the mononuclear structure of Cu-DmPn(IP)2. Cu-DmPn(IP)2 is much higher lipophilic and shows a much higher brain uptake compared to Cu-DmPn(AP). |
本系統中英文摘要資訊取自各篇刊載內容。