非血基質三價鐵超氧化物之光譜與動力學研究
Abstract
在自然界中，α-酮戊二酸羥化酶是一種主要的非血紅素含鐵酵素，透過氧氣活化可以催化多種反應，並產生三價鐵超氧中間體，具有將烷類轉化成醇類的能力，鐵超氧化物的反應性研究，是目前相當重要的研究領域。 本研究使用實驗室近期所開發的N3O2五牙基 H2BDPRP，合成二價鐵錯合物Fe(BDPBrP)，其可與氧氣反應生成三價鐵超氧化物Fe(BDPBrP)(O2•)，加入不同反應物，可利用紫外光/可見光光譜儀、電子順磁共振光譜儀以及循環伏安法進行反應的追蹤。Fe(BDPBrP)(O2•)與質子酸 HOTf反應，預期會生成四價鐵氫過氧化物[Fe(BDPBrP)(OOH)](OTf)，再加入DBU進行逆滴定可得到pKa值為16.48，再結合測得Fe(BDPBrP)(OOH)的氧化還原半電位E1/2為0.236 V，可推測出三價鐵氫過氧化物Fe(BDPBrP)(OOH)的O-H鍵能為88.42 kcal/mol。而Fe(BDPBrP)(O2•)與路易斯酸 Sc(OTf)3的反應，會生成相似於與質子酸反應時所產生的中間體。接著對三價鐵超氧化物進行動力學分析，分別加入TEMPOH和TEMPOD進行反應，利用得到之二級速率常數，可求得同位素效應 (KIE) 為1.22，表明反應之路徑為質子耦合電子轉移 (PCET) 的反應機制。也透過與對位分別為推電子或拉電子取代基的苯酚反應，從Hammett plot得知有兩種不同的反應路徑，以及Marcus plot推測與對位為推電子基的苯酚 (R = OMe, Me, H) 反應過程中氫原子轉移 (HAT) 反應為速率決定步驟，所得到的三價鐵氫過氧化物中間體與苯酚反應，生成三價鐵鍵結苯酚根錯合物和H2O2。最後用Fe(BDPBrP)(O2•)與1,2-Dihydronaphthalene反應觀察到Fe(BDPBrP)(O2•)具有活化碳氫鍵的能力。 上述研究可幫助我們更詳細地了解由氧合酶之含金屬酵素進行氧氣活化時的反應機制，及所製備之仿生化合物的反應性探討。中文關鍵字 : 鐵氫過氧化物之O-H鍵能、鐵超氧化物之動力學分析
In nature, α-ketoglutarate-dependent hydroxylases is a major non-heme Fe-containing enzyme that catalyzes various reactions, and is capable of activating dioxygen to produce a FeIII superoxo intermediate, which further convert alkanes into alcohols. Reactivity study of Fe-superoxo species is an important research field.In this study, a N3O2 pentadentate ligand, H2BDPBrP, developed recently was employed to synthesize FeⅡ starting material, Fe(BDPBrP). The FeIII superoxo complex, Fe(BDPBrP)(O2•), was generated by bubbling O2 into a THF solution of Fe(BDPBrP). Different substrates were added into the in-situ generated Fe(BDPBrP)(O2•) solution, and the reaction was monitored by UV/vis and EPR and CV. A FeIV hydroperoxo complex, [Fe(BDPBrP)(OOH)](OTf) was suspected to be generated from the reaction of Fe(BDPBrP)(O2•) with protonic acid (HOTf). Then, DBU titration was performed on the proposed FeIV hydroperoxo species to determine the pKa value at 16.48. The redox potential E1/2 of Fe(BDPBrP)(OOH) was also measured to be 0.236 V. With pKa and E1/2 values, the O-H bond dissociation free energies of Fe(BDPBrP)(OOH) was calculated to be 88.42 kcal/mol. It was also found that intermediates generated by the reaction of Fe(BDPBrP)(O2•) with Sc(OTf)3 were similar to those with protic acid. Furthermore, the kinetic analysis of Fe(BDPBrP)(O2•) was carried out. TEMPOH and TEMPOD were added to the solution of Fe(BDPBrP)(O2•), and both k2 values were obtained to further determine KIE to be 1.22, indicating that the reaction pathway is proton-coupled electron transfer. Reactions of Fe(BDPBrP)(O2•) with 4-R-phenols, which have an electron-donating or electron-withdrawing substituent at the para position, revealed two different reaction mechanisms by the Hammett plot. The hydrogen atom transfer recation is speculated to be the rate-determining step of the reaction with 4-R-phenols (R = OMe, Me, H) by the Marcus plot. The generated FeIII hydroperoxo intermediate will further react with the substrate to generate a Fe-phenolate complex and H2O2. Finally, Fe(BDPBrP)(O2•) also reacts with 1,2-Dihydronaphthalene, demonstrating the C-H bond activation ability of Fe(BDPBrP)(O2•).This study allows us to comprehensive the details of the mechanism proceeded in O2 activation by metalloenzymes of oxygenases, and the reactivity of our model compounds.Keywords: BDFE of FeⅢ(BDPBrP)(OOH)、Kinetic Analysis of FeⅢ(BDPBrP)(O2•)
In nature, α-ketoglutarate-dependent hydroxylases is a major non-heme Fe-containing enzyme that catalyzes various reactions, and is capable of activating dioxygen to produce a FeIII superoxo intermediate, which further convert alkanes into alcohols. Reactivity study of Fe-superoxo species is an important research field.In this study, a N3O2 pentadentate ligand, H2BDPBrP, developed recently was employed to synthesize FeⅡ starting material, Fe(BDPBrP). The FeIII superoxo complex, Fe(BDPBrP)(O2•), was generated by bubbling O2 into a THF solution of Fe(BDPBrP). Different substrates were added into the in-situ generated Fe(BDPBrP)(O2•) solution, and the reaction was monitored by UV/vis and EPR and CV. A FeIV hydroperoxo complex, [Fe(BDPBrP)(OOH)](OTf) was suspected to be generated from the reaction of Fe(BDPBrP)(O2•) with protonic acid (HOTf). Then, DBU titration was performed on the proposed FeIV hydroperoxo species to determine the pKa value at 16.48. The redox potential E1/2 of Fe(BDPBrP)(OOH) was also measured to be 0.236 V. With pKa and E1/2 values, the O-H bond dissociation free energies of Fe(BDPBrP)(OOH) was calculated to be 88.42 kcal/mol. It was also found that intermediates generated by the reaction of Fe(BDPBrP)(O2•) with Sc(OTf)3 were similar to those with protic acid. Furthermore, the kinetic analysis of Fe(BDPBrP)(O2•) was carried out. TEMPOH and TEMPOD were added to the solution of Fe(BDPBrP)(O2•), and both k2 values were obtained to further determine KIE to be 1.22, indicating that the reaction pathway is proton-coupled electron transfer. Reactions of Fe(BDPBrP)(O2•) with 4-R-phenols, which have an electron-donating or electron-withdrawing substituent at the para position, revealed two different reaction mechanisms by the Hammett plot. The hydrogen atom transfer recation is speculated to be the rate-determining step of the reaction with 4-R-phenols (R = OMe, Me, H) by the Marcus plot. The generated FeIII hydroperoxo intermediate will further react with the substrate to generate a Fe-phenolate complex and H2O2. Finally, Fe(BDPBrP)(O2•) also reacts with 1,2-Dihydronaphthalene, demonstrating the C-H bond activation ability of Fe(BDPBrP)(O2•).This study allows us to comprehensive the details of the mechanism proceeded in O2 activation by metalloenzymes of oxygenases, and the reactivity of our model compounds.Keywords: BDFE of FeⅢ(BDPBrP)(OOH)、Kinetic Analysis of FeⅢ(BDPBrP)(O2•)
Description
Keywords
鐵氫過氧化物之O-H鍵能, 鐵超氧化物之動力學分析, BDFE of FeⅢ(BDPBrP)(OOH), Kinetic Analysis of FeⅢ(BDPBrP)(O2•)