大環雙核配位子MB-DO2A Dimer、Methyl DO2A dimer、DO2A Dimer之合成與質子化常數

Abstract

一直以來設計、並合成出一種具有潛力作為人造限制脢的鑭系金屬大環錯合物是我們實驗室很感興趣的研究主題，這類型的大環錯合物具有高的熱力學穩定性、好的動力學活性、且鑭系金屬有高配位數和高的電荷密度(好的路易士酸性)，可以有效的切割磷酸雙酯鍵受質，而且錯合的金屬陽離子會被大環配位子勁固在環穴中不易釋放到環境中。 實驗室先前的研究告訴我們，單核大環錯合物EuDO2A+和其他的鑭系金屬錯合物LnDO2A+相比，有較高的BNPP水解速率，特別是在高pH值的時候。在高pH時，LnDO2A+在其配位水解離後會生成沒水解活性的多聚體物種。另有研究指出，雙核配位子錯合物由於金屬離子彼此會產生協同作用，可以促進水解磷酸酯鍵的能力。所以我們以DO2A為基底，設計並合成了三種雙核配位子MB-DO2A Dimer(1,3-Bis[4,10-diacetic acid- 7 -Methoxybenzene- 1,4,7,10 –tetraaza cyclododecane]benzene),Methyl DO2A Dimer (1,3-Bis[4,10-diacetic acid- 7 -Methane- 1,4,7,10 –tetraaza cyclododecane]benzene)以及DO2A Dimer (1,3-Bis[4,10-diacetic acid- 1,4,7,10 –tetraaza cyclododecane]benzene)。期待有Methoxybenzene基團的雙核子能藉由立體阻礙讓錯合物在高pH時不產生沉澱物，並能藉由苯環的包覆性使其作用環境更接近天然限制脢。為了避免配位子輸水性過高也合成了甲基取代基的對照組。最後由於ODO2A dimer的研究發現，雙核子在水溶液中的行為可能會異於單核子，所以也設計合成了沒有取代基的DO2A Dimer。 研究結果指出，MB-DO2A Dimer由於親油性高的緣故，形成鈣和銪離子的錯合物之後會形成沉澱物。Methyl DO2A Dimer親油性較低，不會和鈣離子形成沉澱物，但錯合銪離子後隨pH升高會形成少量的沉澱物。而DO2A dimer在目前研究中錯合鈣、鋅、銪隨著pH上升皆不會形成沉澱物，是三種中最適合進一步作人造限制脢切割磷酸酯鍵的配位子。

We have been interested in the design, synthesis, and characterizations of trivalent lanthanide macrocyclic complexes for use as potential artificial nucleases due to their suitable properties such as high thermodynamic stability, low kinetic lability, high coordination number, and charge density (Lewis acidity). Our previous work showed that the monomeric complex, EuDO2A+, had higher BNPP hydrolysis rates as compared to other LnDO2A+ complexes, particularly at higher pH. However, at higher pH, the LnDO2A+ complexes tend to form oligomeric species and gradually lose their hydrolytic activities. To avoid the formation of the inactive oligomeric species, we have designed and synthesized a ligand capable of forming dinuclear lanthanide complexes based on DO2A, i.e. MB-DO2Adimer , Methyl DO2A Dimer and DO2A Dimer. In this articale, we report the details of the ligand synthesis and initicial characterizations of the ligand and its Metal-complexes. The result shows that the complexes solution of Ca2+/Eu3+-MB-DO2A Dimer becomes misty and precipitates form after pH 7.0. Methyl DO2A Dimer coordinated with Eu3+ also formed precipitates slightly, means both are not suitable for futher kinetic study. However, the complexes solution of Ca2+/ Eu3+-DO2A Dimer would not become misty, so we can expect the futher application of DO2A Dimer in the study of artificial nuclease.