C2-對稱脯胺酸衍生之鎳錯合物於超氧化物歧化酶之活性模擬及其於硫醇共軛加成反應之應用

Abstract

近年來，已有研究分別從土壤鏈黴菌及海生藍藍綠綠藻中發現了了含鎳超氧化物歧化酶(NiSOD)，此酵素可藉由二價及三價鎳之間的氧化態轉換，催化超氧離離子的歧化反應而轉化為氧氣及過氧化氫。為模擬NiSOD活性中心的功能，本研究設計並合成一系列列含吡啶基及脯胺酸衍生物之五牙配位基。所合成的配位基，以H2BDPP為例，經去質子化後與[Ni(CH3CN)6](ClO4)2反應可得Ni(BDPP) (5)，此化合物5於室溫下與氧化劑[Cp2Fe]PF6反應可形成穩定之三價鎳錯合物[Ni(BDPP)](PF6) (6)。錯合物5和6先後以UV/vis光譜分析，X-ray單晶繞射解析及循環伏安法完成鑑定。重要發現錯合物6可將超氧化物氧化為氧氣，且其電子順磁光譜也與氧化態NiSOD的光譜相似。另外，以配位基H2BDPP與Ni(BF4)2及t-butylisocyanide直接反應後會生成[Ni(H2BDPP)(tBuNC)](BF4)2 (7)，而錯合物7與超氧化鉀反應會產生氧氣和過氧化氫，我們可藉由GC、過氧化物偵測試紙、添加過氧化物指示劑(LCV)以及NMR光譜等方法發現氧氣及過氧化氫分子的生成。又為了增進此系列列NiSOD擬態化合物的水溶性以及給電子性質，我們分別設計了將吡咯烷環4號位置取代為氫氧基或三甘油甲基醚基之錯合物10、11、14與具苯環對位取代基修飾為甲氧基或三甲基矽基之錯合物12及13。另一方面，本研究將H2BDPP進行修飾後可得配位基2,6-bis(((S)-2-(alkyloxycarbonyl)-1-pyrrolidinyl)methyl)pyridine) (BRPP)，其中R可以是甲基(Me)或 異丙基(iPr)。分別將兩配位基與含鎳鹽類反應後，可得[Ni(BMePP)(CH3CN)](ClO4)2 (15)與[Ni(BiPrPP)(CH3CN)](ClO4)(BPh4) (16)等兩種鎳錯合物。且錯合物15及16可應用於催化硫醇類化合物與α,β- 烯酮類化合物的硫醇共軛加成反應上。令人關注的是錯合物15具有優異的硫醇共軛加成的催化效果，可得到高產率的1,4-加成產物。

Nickel-containing superoxide dismutase (NiSOD), has been discovered recently from Streptomyces species and marine cyanobacteria. NiSOD can catalyze the dismutation of O2− into O2 and H2O2 through a cycle of Ni(II) and Ni(III) oxidation states. In order to mimic the fuction of the active site of the NiSOD, a series of pentadentate ligands equipped with pyridine and proline derivatives have been designed and prepared. The prepared ligand, for instance 2,6-bis(((S)-2-(diphenylhydroxymethyl)-1-pyrrolidinyl)methyl)pyridine (H2BDPP), was deprotonated and employed to react with [Ni(CH3CN)6](ClO4)2 to give fivecoordinate Ni(BDPP) (5). Complex 5 can be readily oxidized by [Cp2Fe]PF6 at room temperature to form a stable Ni(III) complex, [Ni(BDPP)](PF6) (6). Complexes 5 and 6 were characterized by UV/vis spectroscopy, X-ray crystallography and cyclic voltammetry. Importantly, complex 6 can oxidized O2− to form O2, and its EPR spectrum is similar to that of the oxidaized form of NiSOD. In addition, direct reaction of H2BDPP reacted with Ni(BF4)2 and t-butylisocyanide gave six-coordinate [Ni(H2BDPP)(tBuNC)](BF4)2 (7), which exhibited the function of NiSOD. The reaction of 7 with KO2 released O2 gas, detected by GC, and generated H2O2, confirmed by peroxide test paper, peroxide indicator (LCV) and NMR spectroscopy.To enhance the water solubility and the electron donating ability of the NiSOD mimics, we designed and synthesized complexes 10, 11 and 14 with a hydroxy or methoxytriglycol (OTEG) group on the 4-position of pyrrolidine, and complexes 12 and 13 with a methoxyl and trimethylsilyl group on the para-position of four phenyl rings, respectively. On the other hand, two complexes, [Ni(BMePP)(CH3CN)](ClO4)2(15) and [Ni(BiPrPP)(CH3CN)](ClO4)(BPh4) (16) were synthesized (where BRPP =2,6-bis(((S)-2-(alkyloxycarbonyl)-1-pyrrolidinyl)methyl)pyridine), Me = methyl, iPr= isopropyl), and they can be employed as a catalyst for thia-Michael addition of thiols to α,β-enones. Notably, complex 15 possesses an excellent catalytic ability for thia-Michael reaction and gives good yields for 1,4-adducts.