Urease Active Site Modeling 脲酶活性中心的模擬

　

                                   
                                                               圖: 脲酶的活性中心


脲酶的重要性:


1.對生物體而言: 尿素(urea)是含氮化合物代謝分解後的主要產物，每人每年平均會產生10公斤的尿素。然而尿素自發性水解成氨(NH3)和二氧化碳(CO2)的反應相當緩慢，需要3.6年的半生期(half-life)，自然界若沒有一個有效的分解過程，尿素的累積將造成嚴重的問題。很幸運地生物體內存在的脲酶(Urease)可加速此水解反應 ，達到自發性水解反應的1014倍。

2.就農業而言: 土壤細菌中的脲酶卻會使得肥料中的尿素快速水解並產生大量的氨氣至大氣中，讓pH值上升，造成肥料的損耗及對動植物的傷害，甚至會引發更嚴重的環境及經濟問題。因此，在肥料中加入脲酶的抑制物(urease inhibitor)，可有效提高植物對肥料中氮的利用率。

3.就醫學而言: 造成消化性潰瘍主因之ㄧ的幽門螺旋桿菌，因 為具有脲酶，會在人體的胃黏膜表面不斷地將尿素分解為氨來中和胃酸，使自己得以生存在如此酸性的環境， 然而過多的幽門螺旋桿菌所分解產生的氨會造成人體的胃黏膜變薄甚至破洞而造成潰瘍。

因此，了解脲酶及其催化的反應機制為一門有趣而有意義的研究，也是本實驗室的研究主軸。

脲酶活性中心的模擬—三牙基配子


A series of nickel complexes supported with a tripodal ligand bis(1-methylbenzimidazolyl-2-
methyl)amine (L) or bis(1-methylbenzimidazolyl-2-methyl)-10-camphorsulfonamide (L') on a Ni(II) ion
were synthesized and fully characterized. The complexes, [LNiCl(μ-Cl)]2·4CH3OH (1),
[LNi(CH3CN)3](ClO4)2·2CH3CN (3), and [L2Ni2(μ-OAc)3]X (X = Cl− (5) or ClO4− (7)), coordinated
with the tridentate L ligand, all possess an octahedral structure at the nickel center; in contrast, the
geometry of the complexes, L'NiCl2 (2), [L'Ni(CH3CN)3](ClO4)2·2CH3CN (4), and L'Ni(OAc)2·0.5Et2O
(6), employing the L' ligand are either tetrahedral or octahedral. Due to the weak coordinating ability
of the sulfonamide group and the steric hindrance of the camphorsulfonyl group of L', the tripodal L'
becomes a bidentate ligand in the presence of chloride or acetate groups, which have a stronger electron
donating ability than acetonitrile, bound to the nickel center. It is noteworthy that the nuclearity of the
nickel complexes can be controlled by the coordination ability of the central nitrogen of the supporting
bis-methylbenzimidazolyl ligand.                        

                      
                                               圖: 此研究所使用的配子以及錯合物的合成步驟簡圖

　

脲酶活性中心的模擬—大環多牙基配子

Two dinickel mimics, [LNi2(DMF)4](ClO4)3 (1) and [L'Ni2(CH3CN)4](ClO4)3 (3), for the active site of urease supported by a disubstituted benzoate polydentate ligand were synthesized and fully characterized, subsequently addition of urea afforded two urea adducts, [LNi2(urea)4](ClO4)3 (4) and [L'Ni2(urea)4](ClO4)3 (5).


                            圖: 有機配子的合成步驟


                          圖: 錯合物的結構1~3 (Ortep圖)


                          圖: 錯合物的結構4、5 (Ortep圖)

　

鎳錯合物之催化反應

The nuclearity of two previously prepared nickel complexes, [LNiCl(μ-Cl)]2 · 2CH3OH (1) and L′NiCl2 (2) (L=
bis(1-methylbenzimidazoyl-2-methyl)amine and L′ = bis(1-methylbenzimidazoyl-2-methyl)-10-camphorsulfonamide), was found to be temperature-dependent. Mononuclear [LNi(CH3OH)2Cl]Cl · 2H2O (3) and dinuclear [L′NiCl(μ-Cl)]2 (4) were obtained as crystals at -20 °C. It is noteworthy that complex 2 can catalyze the conjugate addition of thiophenols to α, β-enones in high yields; in contrast, the same reaction catalyzed by NiCl2 · THF or complex 3 was far less effective.


                    圖: 分別以三牙基配子L、L'合成之錯合物3、4


                         圖: 以固、液態UV光譜證明錯合物1、3的互變


                     圖: 以固、液態UV光譜證明錯合物2、4的互變


                圖: 錯合物2對硫醇類與未飽和烯酮類進行共軛加成之結果