Oscillatory dynamics protect enzymes and possibly cells against toxic substances

We have used the oscillating peroxidase-oxidase (PO) reaction as a model system to study how oscillatory dynamics may affect the influence of toxic reaction intermediates on enzyme stability. In the peroxidase-oxidase reaction reactive intermediates, such as hydrogen peroxide, superoxide, and hydroxyl radical are formed. Such intermediates inactivate many cellular macromolecules such as proteins and nucleic acids. These reaction intermediates also react with peroxidase itself to form an inactive enzyme. The fact that the PO reaction shows bistability between an oscillatory and a steady state gives us a unique possibility to compare such inactivation when the system is in one of these two states. We show that inactivation of peroxidase is slower when the system is in an oscillatory state, and using numerical simulations we provide evidence that oscillatory dynamics lower the average concentration of the reactive intermediates.     

单态卡宾与臭氧反应机理的量子化学研究

为了研究单态卡宾与臭氧反应机理,本文采用密度泛函理论Gaussian-3方法(G3B3)优化了反应物、中间体、过渡态和产物的几何构型。探讨了单态卡宾与臭氧反应可能途径,并通过频率分析对过渡态和中间体进行了验证,研究结果表明：单态卡宾与臭氧反应有两条反应通道,分别具有亲核反应和亲电反应特征,相对而言亲核反应通道较易发生,且为强放热反应。     

Detection and mechanistic relevance of transient ligand radicals formed during [Ru(bpy)2(OH2)]2O4+-catalyzed water oxidation

Mechanistic proposals to account for the reactivity of water-oxidizing ruthenium diimine complexes have often invoked participation of covalently hydrated or pseudobase intermediates formed by reaction of solvent with the polypyridyl ligands. Probing for these intermediates has proven difficult because the concentrations of detectable reactive species are very low under commonly used experimental conditions. However, we have recently found that these transients accumulate in photocatalytic oxidation systems at neutral pH. In this work, we show that the reaction rates of these transient species correlate with catalytic activity and, therefore, that they meet minimal kinetic criteria to be true reaction intermediates.     

Zinc triflate-promoted glycosidation: synthesis of lipid A disaccharide intermediates.

Zinc triflate was found to be superior to the heavy metal salts as a promoter in the Koenigs-Knorr type glycosidation reaction in the synthesis of lipid A disaccharide intermediates. It readily promoted the reaction of a complex glycosyl bromide with a reducing sugar moiety and gave the disaccharide with beta-selectivity in good yield. This method would be suitable for the bulk preparation of lipid A disaccharide intermediates.     

3,4,4-三甲基-1-乙酰基咪唑啉盐向邻苯二胺转移一 碳单元反应的理论研究

用PM3-MO半经验方法对叶酸辅酶模型化合物3,4,4-三甲基-1-乙酰基咪唑啉盐向邻苯二胺转移一碳单元的反应进行了理论研究。结果表明,咪唑环有两种开环方式,该反应可能通过两种途径实现,每一种途径都经历了六个反应步骤,包括两次质子转移步骤,其中第二次质子转移是限速步骤。优化计算了所有步骤的中间体和过渡态的结构,各个中间体和过渡态具有不同的构型,构象和能量。     

Decarbopalladation of pi-allylpalladium intermediates formed from palladium-catalyzed arylations of 3-allen-1-ols

[reaction: see text] Unusual palladium-catalyzed arylative fragmentations of acyclic 3-allen-1-ols were observed. Oxidative addition of Pd(0) to aryl halides would form the arylpalladium halides, which added to the central carbon of allenes via carbopalladation to form the pi-allylpalladium intermediates. The pi-allylpalladium intermediates would be reductively eliminated via carbon-carbon cleavage to give the arylated dienes and the alpha-hydroxyalkylpalladium intermediates, which were further reductively eliminated to the corresponding aldehydes.     

晶种数量对MOR分子筛上烷基转移反应的影响及反应机理研究

以丝光沸石(MOR)分子筛为催化剂,甲苯与三甲苯烷基转移反应为探针反应,系统考察了晶种数量变化对分子筛物化性能和催化性能的影响。研究表明,合成过程中晶种添加量的不同会显著影响催化剂的酸性、比表面积和孔体积,进而影响其催化剂活性和稳定性。当晶种添加量为8%时,MOR分子筛具有最多的B酸含量、最大的比表面积和孔体积,同时对应的催化剂活性和稳定性也最好。本研究还对甲苯和三甲苯烷基转移反应机理进行了深入研究,结果表明,发生在MOR分子筛上的烷基转移反应通过双分子中间体机理进行,并应用实验手段捕捉到了中间体的存在,证实了双分子中间体机理的合理性,同时推导出可能的反应机理路线图。     

固体氩中一氧化氮的低温氧化

本文研究了在低温固体Ar中NO和O~2的反应。采用Ar作基质, 将NO和O~2分层沉积或混合沉积在低温基板上, 通过逐渐升温来控制扩散速率, 在温度10K-35K范围内, 从样品付里叶变换红外光谱的变化, 首次观察了NO和O~2反应中间体的生成和转化, 由此给出了反应机理, 即NO在Ar基质中首先发生扩散和聚合, 生成cis-(NO)~2, 随后与氧反应生成asym-N~2O~3和iso-N~2O~4, 而asym-N~2O~3进一步氧化生成N~2O~4(D~2~h)。     

5,10-CH+-THF向邻苯二胺转移一碳单元反应的理论研究

叶酸辅酶在酶催化的一碳单元转移过程中具有重要的作用,已有大量的实验及实验模拟对其生物学功能进行了研究分析.本文用PM3半经验方法对5,10-CH⁺-THF向邻苯二胺转移一碳单元的反应进行了理论研究.结果表明,5,10-CH⁺-THF中的咪唑啉环有两种开环方式,从而使得该反应可以通过两种途径实现,每一种途径都经历了6个反应步骤,其中包括限制速度的两次质子转移步骤.优化计算了每个步骤所有可能的中间体和过渡态的结构和能量,并通过比较分析得到了各反应阶段的最优中间体和过渡态结构.     

ONIOM(DFT:MM) study of 2-hydroxyethylphosphonate dioxygenase: what determines the destinies of different substrates?

Why can enzymes provide different products from only slightly different substrates? While the reaction of 2-hydroxyethylphosphonate (2-HEP) catalyzed by 2-hydroxyethylphosphonate dioxygenase (HEPD) yields hydroxymethylphosphonate and formic acid, the HEPD-catalyzed reaction of 1-HEP gives acetylphosphate. ONIOM(DFT:MM) was used to uncover the distinct reaction mechanisms for the different substrates. Calculations show that, in both reactions, similar radical intermediates are generated by the same process. After the formation of common radical intermediates, proton-coupled electron transfer (PCET) operates in the 1-HEP reaction, whereas in the 2-HEP reaction, it cannot occur and an alternative pathway sets in. Thus, the PCET plays a critical role in defining the fates of the substrates.     

Are free radicals involved in IspH catalysis? An EPR and crystallographic investigation

The [4Fe-4S] protein IspH in the methylerythritol phosphate isoprenoid biosynthesis pathway is an important anti-infective drug target, but its mechanism of action is still the subject of debate. Here, by using electron paramagnetic resonance (EPR) spectroscopy and (2)H, (17)O, and (57)Fe isotopic labeling, we have characterized and assigned two key reaction intermediates in IspH catalysis. The results are consistent with the bioorganometallic mechanism proposed earlier, and the mechanism is proposed to have similarities to that of ferredoxin, thioredoxin reductase, in that one electron is transferred to the [4Fe-4S](2+) cluster, which then performs a formal two-electron reduction of its substrate, generating an oxidized high potential iron-sulfur protein (HiPIP)-like intermediate. The two paramagnetic reaction intermediates observed correspond to the two intermediates proposed in the bioorganometallic mechanism: the early π-complex in which the substrate's 3-CH(2)OH group has rotated away from the reduced iron-sulfur cluster, and the next, η(3)-allyl complex formed after dehydroxylation. No free radical intermediates are observed, and the two paramagnetic intermediates observed do not fit in a Birch reduction-like or ferraoxetane mechanism. Additionally, we show by using EPR spectroscopy and X-ray crystallography that two substrate analogues (4 and 5) follow the same reaction mechanism.     

A Molecular Analogue of the C−H Activation Intermediate of the Silica-Supported Ga(III) Single-Site Propane Dehydrogenation Catalyst: Structure and XANES Signature

Propane dehydrogenation is an important field of research due to an increasing world-wide demand of propene while classical production routes through naphtha cracking are in decline. In that context, silica-supported Ga(III) sites, synthesized from surface organometallic chemistry principles, show high selectivity and stability in the propane dehydrogenation reaction. This performance is in significant contrast to the reported fast deactivation and lower selectivity of most Ga₂O₃ and CrO₃ based materials. The Ga-catalyzed propane dehydrogenation reaction is proposed to proceed through the formation of Ga alkyl intermediates for which it would be desirable to have detailed structural and spectroscopic information. Here, we prepare a consistent series of Ga(III) molecular complexes with varying numbers of alkyl and siloxide ligands; they are characterized by single crystal X-Ray diffraction and X-Ray Absorption Near Edge Structure analysis, which is known to be highly sensitive to the Ga coordination environment. We report in particular the structure and the spectroscopic signatures of [Ga(ⁱPr)(OSi(O^tBu)₃)₂(HOSi(O^tBu)₃)], a molecular mimic of the key proposed reaction intermediates in the Ga-catalyzed PDH reaction.     

Notes on the synthesis of meso-substituted porphyrins from pyrryl carbinols and the mechanism of the rothemund reaction

Aryl pyrryl carbinols have been found to readily cyclize to meso-substituted tetraarylporphyrins in yields which are consistent with the intermediacy of the pyrryl carbinols in the Rothemund reaction. Acidic solutions of the pyrryl carbinols show absorption bands characteristic of pyrrolylmethenes. It is suggested that pyrrolylmethenes are likely intermediates in the Rothemund reaction.     

Destabilizing Predictive Copper-Catalyzed Click Reactions by Remote Interactions with a Zinc-Porphyrin Backbone

In order to obtain new supramolecular ligands that build up around a zinc-porphyrin scaffold, we envisioned to access sulfonyl triazole intermediates by well-known copper-catalyzed click reactions. Unexpectedly, these triazole intermediates do not form due to the presence of the zinc-porphyrin moiety at close proximity of the active copper species. Indeed, the copper catalyst undergoes a different chemo-selective reaction pathway reacting with traces of alcohols or water from the media that behave as effective nucleophiles leading to sulfonyl imidates or sulfonyl amides covalently connected to the zinc-porphyrin. We show that copper-catalyzed click reactions can follow different reaction mechanisms when the catalytic events occur at close proximity of a zinc-porphyrin unit which likely acts as a Lewis acid to stabilize otherwise inaccessible reaction intermediates.     

Phosphorus stereochemistry : Mechanistic implications of the observed stereochemistry of bond forming and breaking processes at phosphorus in some 5- and 6-membered cyclic phosphorus esters

The stereochemistry of endocyclic and exocyclic bond forming and breaking processes in 5- and 6-membered cyclic phosphorus esters is summarised and comparisons are made with analogous reactions in acyclic phosphorus esters. The factors that determine which bonds are broken and whether reactions occur with inversion or retention of configuration at phosphorus are complex and usually have more obvious effects for reactions in cyclic than in acyclic phosphorus esters ; in particular conformational effects may be important. The stereochemistry of migration of phosphorus ester groups across 1,3-diols is also described. It is suggested that nucleophilic substitutions at phosphorus are inherently stereospecific in the sense that trigonal bipyramidal reaction intermediates break down either directly or following a single Berry Pseudorotation or Turnstile rotation process. Multiple Turnstile rotations which would lead to racemisation, and which apparently do occur in stable phosphoranes, are insignificant for reactions involving trigonal bipyramidal intermediates.     

Base-mediated reaction of vinyl bromides with aryl azides: one-pot synthesis of 1,5-disubstituted 1,2,3-triazoles

A one-pot base-mediated reaction of azides and β- or α-vinyl bromides has been reported. The effects of bases and solvents have been investigated in the process. A variety of 1,5-disubstituted triazoles were prepared in low to good yields. Further studies reveal that the corresponding alkynes were produced as intermediates via elimination reaction. Under the same reaction conditions, the reactions of alkyl alkynes with phenyl azide would give 1,5-disubstituted 1,2,3-triazoles.     

Skeletal isomerization of butene in ferrierite: assessing the energetic and structural differences between carbenium and alkoxide based pathways

In this study, the results from a systematic analysis of two different mechanisms for the skeletal isomerization of cis-butene to isobutene in ferrierite (FER) are presented. One involves a conventional mechanism that proceeds via stable alkoxide intermediates and the other is one which proceeds via carbenium ions only. A 27T QM cluster model has been used in this study, which is described using the M06-2X DFT functional. It is found that the alkoxide intermediates formed over the course of the conventional pathway are considerably lower in energy than the carbenium ion formed over the course of the alternate pathway. However, the rate determining step in the latter pathway is predicted to be almost 10 kcal/mol lower in energy. The higher barrier for the latter process is due to the inherent stability of the alkoxide intermediates formed within FER. These results appear to suggest that while these intermediates are formed over the course of the reaction, the skeletal isomerization of linear butenes to form isobutene in FER may occur via a carbenium based mechanism. This proposal is consistent with experimental results that show alkoxide intermediates are experimentally observed species.     

O(3P)+O2H——OH+O2反应机理的密度泛函理论研究

用密度泛函理论方法研究了O(³P)与O₂H反应生成羟基和氧分子的反应机理.在PW91/6-31+G^*水平上用梯度解析技术全自由度优化上述反应物、产物和反应路径上的中间体及过渡态几何构型,并通过频率振动分析加以确认,计算IRC反应路径及中间体异构化过程,确定了此反应的可能反应通道.结果表明:该反应是多通道多步骤的强放热反应.首先形成顺式或反式O₃H富能中间体,此过程无能垒;然后跨过一个能垒分解成产物OH和O₂.通道IM1→TS1比IM2→TS2克服的能垒要大,反应放热372.822kJ.mol^-1.IM1TS3IM2可相互转化.     

Computational Analysis of the Oxygen Addition at the C4a Site of Reduced Flavin in the Bacterial Luciferase Bioluminescence Reaction

The energetic characteristics of selected reaction steps in the bacterial luciferase-catalyzed luminescence reaction were examined by computation using the MNDO-PM3 method. Specifically, a three-step model was proposed to account for the reaction between oxygen and reduced riboflavin 5'-phosphate (1,5H2-FMN) to generate first the 5-hydroFMN-4a-peroxide (5H-FMN-4aOO-) and then the 5-hydro-4a-hydroperoxyFMN (5H-FMN-4aOOH) intermediates. Lysine (Lys-H+) and aspartate (Asp-) were chosen as representative catalytic residues involved in the protonation and deprotonation processes. Results show that deprotonation at the N1 site of 1,5H2-FMN by a basic amino acid residue at the luciferase active site would efficiently accelerate the reaction rate of O2 addition to form 5H-FMN-4aOO-. The most favored site of oxygen attack is at the flavin C4a. With the aid of a catalytic acid group, the 5H-FMN-4aOO- so formed tends to undergo a spontaneous protonation reaction to yield the 5H-FMN-4aOOH.     

单重态二溴卡宾和甲醛环加成反应的量化研究

采用量子化学密度泛函理论,研究了单重态二溴卡宾和甲醛环加成反应的机理.在B3LYP/6-31G*基组水平上,优化得到了反应途径上反应物、过渡态、中间体和产物的几何构型;计算并考察了四种可能反应途径势能面上各驻点的构型参数、振动频率和能量;通过振动分析对过渡态和中间体构型进行了确认.计算结果表明,二溴卡宾和甲醛反应有四条反应通道,其中c反应通道(即0°-0°型)控制步骤的活化能仅为13.7 kJ·mol－1,反应容易进行.