非血基質三價鐵超氧化物之鑑定與反應性探討

Abstract

在自然界中，氧氣對於生物體是必要的物質，而在生物系統中有一類重要的金屬蛋白酶稱為細胞色素 P450，可藉由活化氧氣的反應使烷類轉化為醇類。在其催化循環中，鐵中心起始態會活化氧氣形成鐵超氧中間體，再繼續進行後續的催化反應。因此，鐵超氧化物的鑑定與反應性研究，是目前在生物無機化學領域中相當重要的議題。本研究成功地以近期開發之三氮二氧五牙配位基 (H2(BDPFP)) 合成三價鐵超氧化物 (Fe(BDPFP)(O2.))。再將三價鐵超氧化物分別與不同的受質如：質子酸 (HOTf)、路易斯酸 (Sc(OTf)3)、氫原子供體 (TEMPOH) 反應，並透過紫外-可見光光譜、電子順磁共振光譜、循環伏安法鑑定其中間體。我們發現三價鐵超氧化物與 HOTf 反應會產生兩種不同的中間體，並求出其中間體的 pKa 值為 16.56，我們同樣也發現三價鐵超氧化物與 Sc(OTf)3 反應會產生類似於與 HOTf 反應的中間體，而與 TEMPOH 反應則會產生三價鐵氫過氧化物 (Fe(BDPFP)(OOH))，並測得其 E1/2 值為 0.261 V，根據 Bordwell 方程式，我們算出 Fe(BDPFP)(OOH) 之 O-H 鍵能 (BDFE) 為 89.11 kcal/mol，說明我們的三價鐵超氧化物具有很好的催化潛力。我們接著將三價鐵超氧化物與 TEMPOH、TEMPOD、4-R-phenols (X = OMe、Me、H、Cl、CF3、CN、NO2)、1,2-dihydronaphthalene 反應並求得所有反應的二級速率常數 (k2) 以利我們進行動力學的分析。從三價鐵超氧化物與 TEMPOH/TEMPOD 反應之動力學同位素效應 (KIE) 為 1.31，說明其反應速率決定步驟應為質子耦合電子轉移 (PCET) 機制，從三價鐵超氧化物與 4-R-phenols (R = OMe、Me、H) 反應的 Marcus plot 我們得知與 4-R-phenols (R = OMe、Me、H) 反應之速率決定步驟應為氫原子轉移 (HAT) 機制，而從三價鐵超氧化物與 4-R-phenols 反應的 Hammett plot 我們得知其反應會有兩種不同的路徑，我們也發現當三價鐵超氧化物與 4-R-phenols 反應生成 Fe(BDPFP)(OOH) 後，會進一步產生鐵金屬中心接上苯酚根的產物並脫去 H2O2 。最後，三價鐵超氧化物也可和 1,2-dihydronaphthalene 反應，證實三價鐵超氧化物具有活化 C-H 鍵的能力。以上鑑定與動力學研究的結果，使我們對於所開發的三價鐵超氧化物之反應性有更深入的了解，同時也幫助我們探索那些透過氧氣活化的金屬蛋白酶的催化機制。中文關鍵字：鐵超氧化物、鐵過氧氫化物、氧氫鍵活化、碳氫鍵活化。In nature, oxygen is an essential element for organisms. One of the most important metalloproteins in the biological system called Cytochrome P450 could activate dioxygen to convert alkanes into alcohols. In the P450 catalytic cycle, the Fe center of the initial state would activate dioxygen to form an Fe superoxide intermediate, further continues the catalytic cycle. Therefore, the characterization and reactivity study of iron superoxide complexes is currently a critical concern in the field of bioinorganic chemistry.An Fe(III)-superoxo complex, Fe(BDPFP)(O2.), was successfully synthesized by using a recently developed pentadentate ligand H2(BDPFP). Fe(BDPFP)(O2.) could react with a variety of substrates, such as protonic acid (HOTf), Lewis acid (Sc(OTf)3), and Hydrogen atom donor (TEMPOH). The resulting intermediates are detected by UV-vis, and EPR spectroscopy, and CV. We found that the reaction of Fe(BDPFP)(O2.) with HOTf generates two different intermediates. The pKa of the protonated Fe(III)-superoxide is found to be 16.56. Also, the intermediates generated from the reation with Sc(OTf)3 are similar to those with HOTf. Whereas, the reaction of Fe(BDPFP)(O2.) with TEMPOH produced an Fe(III)-hydroperoxide complex, Fe(BDPFP)(OOH), which has a E1/2 value of 0.261 V (vs. Fc/Fc+). According to the Bordwell equation, the O-H bond BDFE of Fe(BDPFP)(OOH) is calculated to be 89.11 kcal/mol. The relative high value reveals Fe(BDPFP)(O2.) a good catalyst. Furthermore, the kinetic study of Fe(BDPFP)(O2.) was explored by reacting with different substrates, such as TEMPOH, TEMPOD, 4-R-phenols (X = OMe, Me, H, Cl, CF3, CN, NO2), and 1,2-dihydronaphthalene. The k2 values of aforementioned reactions were obtained, and the KIE value obtained by reacting with TEMPOH/TEMPOD is 1.31 showing that the rate-determining step is a PCET reaction. The Marcus plot of the reactions with 4-R-phenols (R = OMe、Me、H) shows a HAT reaction is the rate-determining step. The Hammett plot of the reactions with 4-R-phenols reveals two different reaction pathways. The reactions of Fe(BDPFP)(O2.) with 4-R-phenols generateed Fe(BDPFP)(OOH), which further reacted with 4-R-phenols to form FeIII-phenolate complexes and H2O2. Importantly, Fe(BDPFP)(O2.) also reacts with 1,2-dihydronaphthalene to give Fe(BDPFP)(OOH) demonstrating that Fe(BDPFP)(O2.) is capable of activating C-H bond.The characterization and kinetic studies of the Fe-superoxo complex help us to understand the reaction capability of our model compounds and the possible mechanisms for metalloenzymes of oxygenases.Keyword：Fe-superoxo complex, Fe-hydroperoxide complex, O-H bond activation, C-H bond activation.