Theoretical studies and industrial applications of oxidative activation of inert C-H bond by metalloporphyrin-based biomimetic catalysis

High costs and low catalytic efficiency of metalloporphyrins, which are an analogue of cytochrome P450 enzyme, are the bot-tlenecks in the industrialization of biomimetic hydrocarbon oxidation reactions. The basic principle and research technique of physical organic chemistry were applied to the process of biomimetic oxidation of hydrocarbon catalyzed by metalloporphyrins. This biomimetic technology could be adapted to bulk chemicals production by developing the new methods for efficient scale-up synthesis of metalloporphyrins, new pathways for molecular oxygen activation on an industrial scale and new approaches to elevate the catalytic efficiency of metalloporphyrins. This review mainly focuses on research carried out in our group.     

担载金属卟啉模拟细胞色素P-450的催化丙烯环氧化

制备了SiO2化学键合金属卟啉Mn（TPP）Cl，Mn（TDCPP）Cl的担载配合物催化剂，并与单氧给体次氯酸钠（NaClO）构造了细胞色素P－450单加氧酶模拟体系，并考察了该体系的反应性能及其影响因素．金属卟啉经化学修饰的SiO2担载之后，由于表面官能团与金属中心的轴向配位及刚性载体SiO2对金属卟啉在载体表面很好的位置分离作用，使得金属卟啉的抗氧化性及稳定性显著增加，表现出优良的催化丙烯环氧化反应性能．     

Synthesis and catalytic activities in cyclohexane hydroxylation of metalloporphyrins supported on styrene-methylacrylic acid copolymer microspheres

Through a new synthetic strategy, metalloporphyrins (M = Fe(III), Mn(III) or Co(II)) were covalently immobilized on styrene-methylacrylic acid copolymer microspheres. These copolymer-immobilized metalloporphyrins were found to be more efficient catalysts than the analogous non-supported metalloporphyrins for cyclohexane hydroxylation in metalloporphyrin–O₂–ascrobate mixtures. The catalytic activities of the immobilized catalysts follow the order Fe>Mn>Co.     

High-performance metal chelate affinity chromatography of cytochromes P-450 using Chelating Superose.

High-performance metal chelate affinity chromatography [immobilized metal ion affinity chromatography (IMAC)] using Chelating Superose (iminodiacetic acid adsorbent) was investigated for its suitability in purifying phenobarbital-induced rat liver microsomal cytochrome P-450 isozymes (P450) and optimized for preparative purposes. Starting with an 8-aminooctyl-Sepharose fraction of partially purified P450, it was found that only Ni(2+)- and Cu(2+)-charged columns could bind P450. No binding was ever observed when Zn2+, Co2+, Mn2+, Cd2+, Fe3+, Fe2+ or Tl3+ ions were employed. Of eight commonly used elution buffers, imidazole and tryptamine were found to cause some denaturation of P450. For desorption of proteins bound to Ni(2+)-charged columns, the following order of decreasing elution buffer strength was determined: cysteine approximately histidine greater than glycine greater than histamine greater than tryptophan greater than ammonium chloride. During protein desorption with some of these buffers, metal ions were found to bleed from the gel, resulting in P450 denaturation. This could be eliminated by prebleeding the charged columns prior to sample application and had an effect on product recovery and homogeneity. Ni2+ and glycine were chosen as a standard for further optimization involving sample adsorption conditions as influenced by equilibration buffer, detergent, load capacity and flow, gradient and temperature conditions. In this way, potassium phosphate (pH 7.75) and 0.4% Emulgen 911 were used to equilibrate a 1.6-ml column and purify 20-50 nmol of P450 (5-15 mg of protein) within 15 min. One gradient fraction consisted of a single sodium dodecyl sulphate-polyacrylamide gel electrophoresis band as judged by silver staining and represented about 25% of the total P450 applied to the column; total recoveries were usually more than 80%. Comparison with the molecular weights and spectral, catalytic and immunological properties of P450 forms isolated according to established procedures indicated that the form isolated here using Chelating Superose comprises mainly P450 2B1 (PB-B). A method is described for fully automated, programmable column regeneration and sample runs.     

Oxidation of caffeine with hydrogen peroxide catalyzed by metalloporphyrins

The biomimetic oxidation of caffeine with hydrogen peroxide using metalloporphyrins as catalysts, which are known to be good biomimetic models of cytochrome P450 enzymes, is investigated. The two manganese porphyrins tested, chloro[5,10,15,20-tetrakis(2,6-dichlorophenyl)porphyrinato]manganese(III), [Mn(TDCPP)Cl], and chloro [5,10,15,20-tetrakis(pentafluorophenyl)porphyrinato]manganese(III), [Mn(TPFPP)Cl], afford high conversions of caffeine for all substrate/catalyst molar ratios. Selectivity was found to be dependent on the catalyst employed, and a new spiro racemic compound is described and fully characterized in the solid state from X-ray diffraction studies.     

低温熔盐法制备球状多孔 La1-xSrxMn0.8Fe0.2O3（0≤x≤0.6）及其催化 CO氧化性能

汽车尾气中 CO, HC, NOx,硫化物及其颗粒粉尘严重危害人们身体健康和大气环境,是大气环境的主要污染源之一.目前,尾气净化是其减排的最主要方式.汽车尾气催化剂的发展经历了几代的研究,一直以来广泛采用 Pt, Pd和 Rh等贵金属,但因其资源匮乏,价格昂贵,容易被 S和 P中毒,因此人们逐渐将目光投向非贵金属催化剂的研发.钙钛矿复合氧化物因具有独特的物理化学性质以及灵活的“化学剪裁”特性而在材料研究等领域颇受青睐,有望成为贵金属催化剂的替代品.一般而言,催化剂的比表面积越大,表面活性位点越多,其催化活性越高,且会明显降低起燃温度.目前,一些制备工艺,如水热法、共沉淀法、微乳液法和硬模板法,虽可在一定程度上提高催化剂的比表面积,但却存在费时、耗能及制备工艺复杂等缺点.因此,如何简单有效地制备出大比表面积的钙钛矿型催化剂依然是一个难题.本文以合成的分级多孔δ-MnO2微球为模板,采用熔盐法制备出球状多孔 La1-xSrxMn0.8Fe0.2O3(0≤x≤0.6)钙钛矿氧化物,研究了球状多孔钙钛矿氧化物的形成过程和合适的制备温度,以及 B位 Fe3+掺杂量为20%时 A位 Sr2+掺杂量对钙钛矿催化剂结构和催化活性的影响.采用 X射线粉末衍射、扫描电子显微镜、透射电子显微镜、N2吸附-脱附、傅里叶红外光谱(FT-IR)和 X射线能谱(XPS)等方法对催化剂进行了表征.在固定床石英管反应器上评价了催化剂催化 CO氧化活性及稳定性,采用气相色谱联接氢火焰离子化检测器检测了产物和反应物的组成.结果表明,以分级多孔δ-MnO2微球为模板,采用熔盐法在450oC反应4 h制备出的球状多孔 La1-xSrxMn0.8Fe0.2O3(0≤x≤0.6)钙钛矿氧化物具有良好的结晶性、较大的比表面积(55.73 m2/g)和孔体积(0.37 cm3/g).其球状多孔结构的形成可分为两个阶段：原位形成钙钛矿相和纳片表面析出钙钛矿晶粒及钙钛矿晶粒的再生长.另外, FT-IR光谱表明, Fe3+和 Sr2+成功进入 A, B位.同时, CO转化曲线表明, B位 Fe3+的掺杂量为20%时, A位 Sr2+的掺杂量高于30%时可以明显改善催化剂催化 CO氧化活性： La1-xSrxMn0.8Fe0.2O3(0≤x≤0.3)的T50和T90分别在180和198oC左右;而 La0.55Sr0.45Mn0.8Fe0.2O3和 La0.4Sr0.6Mn0.8Fe0.2O3的T50均低于125oC; La0.55Sr0.45Mn0.8Fe0.2O3的T90为181oC,而 La0.4Sr0.6Mn0.8Fe0.2O3却仍低于125oC. XPS结果则证明,较高的催化活性得益于 La0.4Sr0.6Mn0.8Fe0.2O3表面存在较多的 Mn4+、氧空位及吸附氧.最后, La0.55Sr0.45Mn0.8Fe0.2O3和 La0.4Sr0.6Mn0.8Fe0.2O3的稳定性测试结果表明,采用熔盐法以δ-MnO2为模板在450oC焙烧4 h制备的多孔球状钙钛矿具有较好的催化稳定性.虽然催化剂制备工艺简单,周期短,但比表面积最大只有55.73 m2/g,为硬模板法的1/2,因此提高比表面积将是今后研究的方向.     

磁场对铁卟啉仿生催化性能的影响

在生命体中,细胞色素P－450单充氧酶辅基是具有铁Df琳结构的血红素．用金属叶琳作为细胞色素P－450单充氧酶的模型化合物探讨和研究人类生命现象一直是国内外化学仿生催化领域极为感兴趣的研究内容之一［’1．我们曾用p一氧代双铁叶琳作为细胞色素P－450单充氧酶的模型化合物,发现改变金属叶琳结构和金属原子电子自旋态将会引起金属叶琳磁性改变,而金属叶琳磁性改变会进一步导致金属叶琳仿生催化性能发生改变D”‘．我们认为,这一现象与人类和地球构成的生物圈可能有某些关联．为了考察地球磁场对人类生命现象的影响,我们进一步建立…     

Study of the catalytic behavior of montmorillonite/iron(III) and Mn(III) cationic porphyrins

Two samples of montmorillonite (one of Brazilian origin, BNC1 clay, and the other STX-1, supplied by the Clay Mineral Society Repository (University of Missouri, USA) were allowed to react with biomimetic metalloporphyrins of Fe(III) and Mn(III) in cationic form. The compounds were characterized by several techniques, showing that the metalloporphyrins molecules were adsorbed at the surface of the clay platelet crystals. The catalytic activities of the intercalated complexes for the oxidation of alkane were dependent upon the concentration of the porphyrin immobilized in the clay and factors such as the metal ion species in the porphyrins, choice of solvent, and concentration of the iodosylbenzene oxidant. Good selectivity to cyclohexanol instead of cyclohexanone was observed for the catalytic oxidation of cyclohexane by iodosylbenzene.     

Catalytic effects of peroxidase-like metalloporphyrins on the fluorescence reaction of homovanillic acid with hydrogen peroxide

Summary The catalytic effects of peroxidase-like metalloporphyrins (Me-P) on the fluorescence reaction of homovanillic acid with hydrogen peroxide have been studied. These metalloporphyrins are the complexes of Mn with tetrakis(carboxyphenyl)porphyrin (TPPC) and trikis(sulfophenyl)porphyrin(TPPS₃), Fe, Co, Ni, Cu, Zn, Ag and Sn with tetrakis(sulfophenyl)porphyrin(TPPS₄), and Rh, Pt and Pd with tetrakis(N-methylpyridiniumyl)porphyrin-(TMPyP) and hemin. The complexes of Mn, Fe, Co, Rh and Pt with porphyrins catalyzed the formation of the fluorescence product, while the complexes of Ni, Cu, Zn, Ag, Sn and Pd did not. Traces of hydrogen peroxide and glucose can be determined using the metalloporphyrins. The characteristics of peroxidase-like metalloporphyrins have been compared with those of horseradish peroxidase (HRP).     

双功能金属卟啉催化环氧化合物与 CO2 偶联反应合成环碳酸酯

 合成了新颖的双功能水溶性金属卟啉 催化剂 M(TTMAPP)I4(X) (M = Co, Fe, Mn 和 Cr; X = OAc, CF3COO, CCl3COO, OTs, Cl, Br 和 I), 研究了它们催化 CO2 与末端环氧化合物合成环碳酸酯的偶联反应. 分别考察了反应温度、不同金属的 Lewis 酸中心、抗衡离子和催化剂重复使用次数对反应性能的影响. 当以 Co(III)(TTMAPP)I4(OAc) 为催化剂, 底物与催化剂摩尔比为 1 000, 温度为 353 K, CO2 压力为 667 kPa 和无溶剂条件下, 反应 5 h 时丙烯环碳酸酯收率为 95.4%. 在 298 K, 底物与催化剂之比为 2 000 时, 加入 1 ml 甲醇, 反应 24 h 丙烯环碳酸酯收率为 19.4%. 催化剂可以用乙醚回收, 循环使用 5 次后催化剂活性没有明显降低.     

Oxygen activation by cytochrome p450: a thermodynamic analysis

Electrode potentials for every intermediate in the cytochrome P450 cycle were estimated and evaluated by means of an oxidation state diagram. By this approach, and within the uncertainties of the approximations, the superoxide complex of cytochrome P450 at pH 7 is oxidizing: E degrees ' (P450FeO(2)2+, H+/P450FeOOH2+) = +0.93 V, and the Gibbs energy for the reaction of the hydroperoxo complex of cytochrome P450 to form compound I and water, P450FeOOH2+ + H+ = P450FeO2+ por(*+) + H2O, is 0 kJ/mol. Although cytochrome P450FeOOH2+ and cytochrome P450FeO2+ por(*+) are approximately isoenergetic, they are likely to react at different rates with substrates and may yield different products. Homolysis of the hydroperoxo complex of cytochrome P450 to compound II and the hydroxyl radical, P450FeOOH2+ = P450FeO2+ + HO(*), is unfavorable (DeltaG degrees ' = +92 kJ/mol), as is the dissociation into HOO- and cytochrome P450Fe3+ (+73 kJ/mol). It is shown that the sum of the Gibbs energy of association for cytochrome P450Fe3+ with the hydroperoxo anion and the Gibbs energy for the one-electron reduction of cytochrome P450FeOOH2+, relative to NHE, is constant (-203 kJ/mol). While the estimated E degrees ' (P450FeO(2)2+, H+/P450FeOOH2+) = +0.93 V at pH 7 is larger than necessary to effect reduction of cytochrome P450FeO(2)2+, the magnitude of this electrode potential implies that the binding constant for cytochrome P450Fe3+ with hydrogen peroxide is ca. 3 x 106 M(-1) at pH 7. An association constant of this magnitude ensures that a fraction of cytochrome P450FeOOH2+ is available to form compound I or to react with substrates directly, while a larger one would imply that compound I is too weak an oxidant. In general, the energetics of the reduction of dioxygen to water determines the energetics of catalysis of hydroxylations by cytochrome P450. These results enable calibration of energy levels obtained for intermediates in the cytochrome P450 reaction cycle obtained by ab initio calculations and provide insights into the catalytic efficiency of cytochrome P450 and guidelines for the development of competent hydroxylation catalysts.     

苯环上氯取代位对四苯基金属卟啉催化烯烃环氧化性能的影响

以苯乙烯、环己烯和反式二苯乙烯为烯烃底物,以双氧水、叔丁基过氧化氢和异丙苯过氧化氢为氧化剂,以苯环上对位和邻位氯取代的四苯基金属卟啉为仿生催化剂,对烯烃的催化环氧化反应进行了对比研究.讨论了不同氯取代位的四苯基金属卟啉对烯烃环氧化性能的影响.实验结果表明,在没有助催化剂存在下,邻位氯代的四(2,6-二氯苯基)铁(锰)卟啉对烯烃的环氧化具有优异的催化性能,烯烃底物的转化率和环氧选择性都比对位氯代的四苯基铁(锰)卟啉高,且反应条件温和.其中FeⅢ(TDCPP)Cl的催化性能最好,环氧化选择性最高,催化氧化苯乙烯时,环氧苯乙烷的选择性达到了90.4%.相同金属离子不同配体的金属卟啉传递氧原子的能力为TDCPP>T(p-Cl)PP>TPP.氧化剂的结构对环氧化物的选择性有较大影响.过氧键连有吸电子基团的异丙苯过氧化氢对环氧化物的选择性最高.根据实验结果,对金属卟啉催化环氧化机理进行了分析.     

金属卟啉配合物对苯甲醛氧化的催化性能

不同金属四苯基卟啉(TPPM)催化氧化苯甲醛时,TPPMnOAc催化活性最高,TPPFeCl次之,TPPCo和TPPNi几乎无活性;TPPMnOAc苯环上吸电子取代基的存在有利于提高其催化活性和稳定性,苯环上邻位吸电子取代基能明显提高四苯基锰卟啉的稳定性,但由于空间位阻的原因,使其催化活性降低.在本模拟体系中,T(2,6 di Cl)PPMnOAc是一个较理想的催化剂.     

金属卟啉类超分子催化剂*

金属卟啉类超分子催化剂是超分子催化研究领域的重要内容之一,其关键环节是以金属卟啉为基础构建超分子微反应器,使反应活性中心处在一个特定的微环境中,从而实现高的催化效率和选择性。本文分别从超分子催化剂母体结构构筑（借助环糊精、模板等）和催化应用（模拟细胞色素P-450系列酶、光电催化等）的角度详细评述了近年来金属卟啉类超分子催化剂的设计、结构及催化作用的研究进展,并对该研究领域的前景进行了展望。     

金属卟啉催化条件下有机化合物与二氧化碳的电羧化反应Ⅰ. 金属卟啉对苄基氯电羧化催化活性的研究

本文研究了系列金属卟啉对苯基氯(phCH~2Cl)和CO~2电羧化反应的催化活性.用熔点,MS,IR,UV鉴别产物为苯乙酸卟脂,利用高效液相色谱(HPLC)定量分析了羧化产物,选出最佳电羧化电解电位为-1.6v(相对于饱和甘汞电极,vs.SCE,下同). 并对催化活性较高的钴卟啉系列配合物进行了深入研究. 探讨了金属卟啉具有催化活性的原因,认为能形成M(Ⅰ)中间体的金属卟啉配合物.具有较高的催化活性.     

Syntheses and Properties of Lanthanide Hydroxy-meso-tetra(p-chlorophenyl)porphyrin Complexes

Introduction The syntheses and characterization of porphyrins and metalloporphyrins have been studied extensively[1]. Hemoglobin, myoglobin or cytochrome P450, has been applied as a model compound[2]. Wong C. P. et al.[3] synthesized the first lanthanide porphyrin, acetylacetonate tetraphenylporphyrin europium, in 1974.     

乙酰糖基金属卟啉的合成及其对烷烃温和氧化的选择性催化作用

由吡咯和葡萄糖取代苯甲醛直接缩合制备了两种葡萄糖取代卟吩,四(邻位乙酰葡萄糖氧代苯基)卟吩和四(间位乙酰葡萄糖氧代苯基)卟吩,它们进一步金属化合成了四种葡萄糖金属卟啉,氯化四(邻位乙酰葡萄糖氧代苯基)卟吩合铁、氯化四(间位乙酰葡萄糖氧代苯基)卟吩合铁、氯化四(邻位四乙酰葡萄糖氧代苯基)卟吩合锰和氯化四(间位乙酰葡萄糖氧代苯基)卟吩合锰。它们的结构由紫外-可见光谱、元素分析和核磁共振证实。研究了这些葡萄糖取代金属卟啉对亚碘酰苯常温常压下氧化异戊烷反应的选择性催化作用。研究表明,糖基金属卟啉催化异戊烷端基碳氢键的氧化,对一级碳氢键表现出专一性催化作用。非糖基金属卟啉催化异戊烷二级和三级碳氢键的氧化。与非糖基金属卟啉比较,糖基金属卟啉对烷烃羟基化反应的催化行为更接近细胞色素P-450单充氧酶。     

金属卟啉及其与咪唑络合物的电喷雾质谱研究

利用电喷雾电离质谱（ESI－MS）研究了3种金属卟啉化合物（MTPP＝MnTPP,TeTPP和CoTPP）,探讨了在这些化合物中苯取代基与卟啉环间的键合能力以及金属卟啉与咪唑的配位情况。研究结果表明,金属卟啉的外围取代基苯基与卟啉环的键合能力按Mn、Fe和Co的次序变弱。金属卟啉与咪唑形成的络合物的离子丰度随配体浓度的增加而增强;在相同的配体浓度下,络合物的离子丰度按Mn、Fe和Co顺序依次增加,其中,CoTPP络合物的稳定性最强。     

Monooxygenase activity of metalloporphyrins and mechanism of activation of molecular oxygen

Reaction rate constants have been measured for the oxidation of cholesterol by atmospheric oxygen in the presence of tetra-meso-substituted metalloporphyrins [MP] (M = Ni, Cr, Mn, Fe, Co). The results have been interpreted by the use of data on the structure of metal complexes and reaction mechanisms. It has been established that the reaction proceeds at a high rate when the oxygen in the composition of the intermediate complex [MO₂P] is in the singlet spin state. The singlet state of O₂ is occupied in the case in wich the metal ion in the porphyrin complex is in a high-spin state. The spin state and related catalytic activity of the metalloporphyrin is regulated by meso-substituents in the porphine ring. The influence of meso-substituents is predicted theoretically within the framework of a generalized orienting effect, the presence of which is supported by an analysis of ¹³C NMR data for meso-substituted metalloporphyrins.Translated from Teoreticheskaya i Éksperimental'naya Khimiya, Vol. 23, No. 4, pp. 428–435, July–August 1987.     

Electrochemical metalloporphyrin-catalyzed reduction of chlorite

We measured the redox stoichiometry and rate constants for the electrochemical reduction of ClO(2)(-) at pH 7, catalyzed by a series of metalloporphyrins of Mn, Fe, and Co with different proximal and distal environments. A clean four-electron reduction was observed. The catalytic activity correlates well with that observed in reduction of H(2)O(2). The axial imidazole and/or a redox-active distal metal (Cu or Co) increases the turnover frequency in several compounds. The metalloporphyrins were inert to ClO(x)(-) (x = 3,4) and IO(3)(-) but catalyzed facile two-electron reduction of IO(4)(-); six-electron reduction of BrO(3)(-) was also observed.