以三級丁基修飾三氮二氧配基之三價鐵超氧錯合物的鍵能、化學動力學及取代基效應比較
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2023
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在大氣當中，氧氣的成分為第二多，而對於生物體來說，氧氣也是能夠維持其生命最不可或缺的物質之一。例如以鐵為活性位點的細胞色素P450 1，透過氧氣活化產生活化物質，將脂肪烴類的物質氧化，形成醇類，以利人體合成酵素、代謝毒素等作用。抑或者是α-酮戊二酸羥化酶2，可以氧化含氮鹼基上因突變而甲基化的位置，最後以羰基的方式離去，達到修復的功能。然而，像是這樣的金屬酶，皆需要氧氣活化1,2才得以發揮其效用。而生物無機化學領域除了研究本就在生物體中的金屬酶之外，也致力於發展擬態的化合物，試圖達到與生物體中金屬酶相似的催化效用。 本研究透過實驗室近期開發的N3O2五牙配位基 (H2(BDPtBuP))，合成FeII(BDPtBuP，以氧氣活化生成(FeIII(BDPtBuP)(O2.))，並且加入不同的受質：質子酸 (HOTf)、氫原子供體 (TEMPOH)、4-X-Phenols (X = OMe、Me、H、Cl、CF3、CN、NO2)，透過UV-visible 光譜鑑定反應。其中三價鐵超氧化物與質子酸 (HOTf) 為平衡反應，求出其中間體的 pKa 值為10.787，比較進行氟取代與溴取代的中間體之pKa 值分別為10.042、10.686，可以發現在配基進行取代修飾對於pKa 值有些微差異。並且透過先前與TEMPOH反應得E1/2值分別為氟取代10：0.236 V 、溴取代9：0.261 V、三級丁基取代8：0.323 V。根據Bordwell 方程式，計算出FeIII(BDPRP)(OOH) ( = F、Br、tBu)之O-H鍵能分別為 氟取代：80.70 (kcal/mol)、溴取代：80.60 (kcal/mol)、三級丁基取代：82.70 (kcal/mol)，說明依據若在配基上之取代基有不同推拉電子效應，可能會使得FeIII(BDPRP)(OOH) (R = F、Br、tBu) 之O-H鍵能有所差異，而就目前實驗所得之結果，配基為推電子基則可能有更好的催化潛力。 而針對三價鐵超氧化物 (FeIII(BDPtBuP)(O2.)) 之反應性研究，我們將TEMPOH、TEMPOD、4-X-phenols (X = OMe、Me、H、Cl、CF3、CN、NO2)、4-methoxyphenol-D，與 (FeIII(BDPtBuP)(O2.)) 反應，所求得之二級速率常數 (k2) 作為後續動力學分析的重要數據，目的是為了理解三價鐵超氧化物與受質反應速率決定步驟之反應路徑。從三價鐵超氧化物與 TEMPOH/TEMPOD 反應之動力學同位素效應 (KIE) 為 1.58，比較文獻9,10 之結果，氟取代為 1.31、溴取代為1.22，表明反應速率決定步驟為質子耦合電子轉移 (PCET) 機制。而從三價鐵超氧化物與4-X-phenols 反應的 Hammett plot 我們得知其反應會以不同的路徑進行，也透過Marcus plot的結果表明，三價鐵超氧化物與4-X-phenols (X = OMe、Me、H) 反應之速率決定步驟應為氫原子轉移 (HAT) 機制。此外也發現以碘試劑進行H2O2 的測定，發現H2O2 的生成，也表明與過量之4-X-phenols 反應，最後會脫去H2O2 生成接上苯酚根之產物。 透過以上動力學研究，使我們對於所開發出的三價鐵超氧化物有更深入的理解，也有助於我們理解自然界中透過氧氣產生催化活性的金屬蛋白酶反應機制。
In the atmosphere, oxygen has the second most composition, and for organisms, oxygen is also one of the most indispensable substances to maintain their life. Many important functions of living organisms also need to be activated by oxygen before they can function. For example, cytochrome P450 1, which uses iron as the active site, is activated by oxygen to generate activity and oxidize aliphatic hydrocarbons to form alcohols to facilitate the human body to synthesize enzymes and metabolize toxins. Or α-ketoglutarate hydroxylase 2, which can oxidize the methylated position on the nitrogenous base due to mutation, and finally leave in the form of carbonyl to achieve the function of repair. However, metalloenzymes like these require oxygen activation1,2 to be effective. In the field of bioinorganic chemistry, in addition to the study of metalloenzymes in living organisms, it is also committed to the development of mimic compounds, trying to achieve a catalytic effect similar to that of metalloenzymes in living organisms.For the reactivity research of ferric superoxide (FeIII(BDPtBuP)(O2.)), we will use TEMPOH, TEMPOD, 4-X-phenols (X = OMe, Me, H, Cl, CF3, CN, NO2 ), 4-methoxyphenol-D, react with (FeIII(BDPtBuP)(O2.)), the obtained second-order rate constant (k2) is used as important data for subsequent kinetic analysis, the purpose is to understand the superoxidation of ferric iron The rate of reaction between substance and substrate determines the reaction path of the steps. The kinetic isotope effect (KIE) of the reaction between ferric superoxide and TEMPOH/TEMPOD is 1.58, compared with the results of literature 9 and 10, the fluorine substitution is 1.31, and the bromine substitution is 1.22, indicating that the reaction rate is determined by proton-coupled electrons transfer (PCET) mechanism. According to the Hammett plot of the reaction between ferric superoxide and 4-X-phenols, we know that the reaction will proceed in different ways, and the results of Marcus plot show that ferric superoxide and 4-X-phenolsThe rate-determining step of the 4-X-phenols (X = OMe, Me, H) reaction should be the hydrogen atom transfer (HAT) mechanism. In addition, it was also found that the iodine reagent was used to measure H2O2, and the formation of H2O2 was found, which also indicated that it reacted with excess 4-X-phenols, and finally H2O2 would be removed to form a product connected with phenoxide.Through the above kinetic studies, we have a deeper understanding of the developed ferric superoxide, and it also helps us understand the metalloproteinase reaction mechanism that produces catalytic activity through oxygen in nature.
In the atmosphere, oxygen has the second most composition, and for organisms, oxygen is also one of the most indispensable substances to maintain their life. Many important functions of living organisms also need to be activated by oxygen before they can function. For example, cytochrome P450 1, which uses iron as the active site, is activated by oxygen to generate activity and oxidize aliphatic hydrocarbons to form alcohols to facilitate the human body to synthesize enzymes and metabolize toxins. Or α-ketoglutarate hydroxylase 2, which can oxidize the methylated position on the nitrogenous base due to mutation, and finally leave in the form of carbonyl to achieve the function of repair. However, metalloenzymes like these require oxygen activation1,2 to be effective. In the field of bioinorganic chemistry, in addition to the study of metalloenzymes in living organisms, it is also committed to the development of mimic compounds, trying to achieve a catalytic effect similar to that of metalloenzymes in living organisms.For the reactivity research of ferric superoxide (FeIII(BDPtBuP)(O2.)), we will use TEMPOH, TEMPOD, 4-X-phenols (X = OMe, Me, H, Cl, CF3, CN, NO2 ), 4-methoxyphenol-D, react with (FeIII(BDPtBuP)(O2.)), the obtained second-order rate constant (k2) is used as important data for subsequent kinetic analysis, the purpose is to understand the superoxidation of ferric iron The rate of reaction between substance and substrate determines the reaction path of the steps. The kinetic isotope effect (KIE) of the reaction between ferric superoxide and TEMPOH/TEMPOD is 1.58, compared with the results of literature 9 and 10, the fluorine substitution is 1.31, and the bromine substitution is 1.22, indicating that the reaction rate is determined by proton-coupled electrons transfer (PCET) mechanism. According to the Hammett plot of the reaction between ferric superoxide and 4-X-phenols, we know that the reaction will proceed in different ways, and the results of Marcus plot show that ferric superoxide and 4-X-phenolsThe rate-determining step of the 4-X-phenols (X = OMe, Me, H) reaction should be the hydrogen atom transfer (HAT) mechanism. In addition, it was also found that the iodine reagent was used to measure H2O2, and the formation of H2O2 was found, which also indicated that it reacted with excess 4-X-phenols, and finally H2O2 would be removed to form a product connected with phenoxide.Through the above kinetic studies, we have a deeper understanding of the developed ferric superoxide, and it also helps us understand the metalloproteinase reaction mechanism that produces catalytic activity through oxygen in nature.
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Keywords
含鐵-氧合酶, 三價鐵過氧錯合物, 三價鐵過氧氫化物, iron-oxygenase, ferric peroxocomplex, ferric peroxyhydrogenase