反应类等键反应方法及类反应热动力学参数计算

本文提出了反应类等键反应方法,将通常用于热力学性质计算的等键反应方法推广用于类反应中反应势垒和反应焓变的计算. 对碳氢燃料低温燃烧反应机理中的一类重要反应类：?烷基自由基过氧化氢裂解生成烯烃和HO2自由基的反应势垒和反应焓变进行了计算. 通过对该类16个反应中的5个代表反应分别在不同计算水平HF、DFT、MP2、CCSD(T)的比较计算发现,采用等键反应方法可在较低从头算级别计算得到类反应较高精度的反应势垒,提高了计算的效率和精度. 本文采用反应类等键反应方法在B3LYP/6-311G(d,p)计算水平对该类16个反应进行了反应势垒和反应焓变的计算,并建立了反应势垒和反应能的线性自由能关系：delta V=71.02+0.41?delta E.     

烷基自由基β位裂解反应类反应势垒与速率常数的精确计算

提出反应类等键方法并用于高温燃烧机理中一类重要反应——烷基自由基β位裂解反应的反应势垒和速率常数的精确校正计算. 通过10种不同从头算水平对类反应中5个代表反应的反应势垒的计算发现, 用反应类等键反应方法和直接从头算方法获得的5 个代表反应的反应势垒最大绝对偏差的平均值分别为5.32 和16.16 kJ·mol^-1, 表明反应类等键反应方法计算的反应势垒对不同水平从头算方法的依赖性小, 可在较低从头算水平计算得到精确的反应势垒, 解决大分子体系反应势垒的精确计算问题. 此外应用反应类等键反应方法在BHandHLYP/cc-pVDZ 从头算水平计算了3 个代表反应的速率常数, 并与文献报道的实验值进行了比较, 其在500-2000 K温度区间内计算速率常数与实验速率常数中较大值与较小值的比值k_max/k_min的平均值为1.67, 最大值也仅有2.49. 表明应用反应类等键反应方法在较低从头算水平即可对同类反应的速率常数进行精确计算.最后在BHandHLYP/cc-pVDZ从头算水平用反应类等键反应方法计算了13个烷基自由基β位裂解反应的速率常数.     

Toward De Novo Catalyst Discovery: Fast Identification of New Catalyst Candidates for Alcohol-Mediated Morita–Baylis–Hillman Reactions**

Recently we have demonstrated how a genetic algorithm (GA) starting from random tertiary amines can be used to discover a new and efficient catalyst for the alcohol-mediated Morita–Baylis–Hillman (MBH) reaction. In particular, the discovered catalyst was shown experimentally to be eight times more active than DABCO, commonly used to catalyze the MBH reaction. This represents a breakthrough in using generative models for catalyst optimization. However, the GA procedure, and hence discovery, relied on two important pieces of information; 1) the knowledge that tertiary amines catalyze the reaction and 2) the mechanism and reaction profile for the catalyzed reaction, in particular the transition state structure of the rate-determining step. Thus, truly de novo catalyst discovery must include these steps. Here we present such a method for discovering catalyst candidates for a specific reaction while simultaneously proposing a mechanism for the catalyzed reaction. We show that tertiary amines and phosphines are potential catalysts for the MBH reaction by screening 11 molecular templates representing common functional groups. The method relies on an automated reaction discovery workflow using meta-dynamics calculations. Combining this method for catalyst candidate discovery with our GA-based catalyst optimization method results in an algorithm for truly de novo catalyst discovery.     

Rapid Optimization of Reaction Conditions Based on Comprehensive Reaction Analysis Using a Continuous Flow Microwave Reactor

Generally, the flow method has the advantage of a precise control over the reaction parameters and a facile modification of the reaction conditions, while a continuous flow microwave reactor allows for the quick optimization of reaction conditions owing to the rapid uniform heating. In this study, we developed a “9+4+1 method” to optimize reaction conditions based on comprehensive reaction analysis using a flow microwave reactor. The proposed method is expected to contribute to the synthesis of various fine and bulk chemicals by reducing cost and wastage, and by conserving time.     

烷烃与氢过氧自由基氢提取反应类反应能垒与速率常数的精确计算

氢过氧自由基从烷烃分子中提取氢的反应是碳氢燃料中低温燃烧化学中非常重要的一类反应。本文用等键反应方法计算了这一类反应的动力学参数。所有反应物、过渡态、产物的几何结构均在HF/6-31+G(d)水平下优化得到。以反应中的过渡态反应中心的几何结构守恒为判据,该反应类可用等键反应处理。本文选取了乙烷和氢过氧自由基的氢提取反应为参考反应,其它反应作为目标反应,用等键反应方法对目标反应在HF/6-31+G(d)水平的近似能垒和反应速率常数进行了校正。为了验证方法的可靠性,选取C5以下的烷烃分子体系,对等键反应方法校正结果和高精度CCSD(T)/CBS直接计算结果进行了比较,最大绝对误差为5.58k J?mol~(-1),因此,采用等键反应方法只需用低水平HF从头算方法就可以再现高精度CCSD(T)/CBS计算结果,从而解决了该反应类中大分子体系的能垒的精确计算。本文的研究为碳氢化合物中低温燃烧模拟中重要的烷烃与氢过氧自由基氢提取反应提供了准确的动力学参数。     

Multicoordinate driven method for approximating enzymatic reaction paths: automatic definition of the reaction coordinate using a subset of chemical coordinates

We present a generalization of the reaction coordinate driven method to find reaction paths and transition states for complicated chemical processes, especially enzymatic reactions. The method is based on the definition of a subset of chemical coordinates; it is simple, robust, and suitable to calculate one or more alternative pathways, intermediate minima, and transition-state geometries. Though the results are approximate and the computational cost is relatively high, the method works for large systems, where others often fail. It also works when a certain reaction path competes with others having a lower energy barrier. Accordingly, the procedure is appropriate to test hypothetical reaction mechanisms for complicated systems and provides good initial guesses for more accurate methods. We present tests on a number of simple reactions and on several complicated chemical transformations and compare the results with those obtained by other methods. Calculation of the reaction path for the enzymatic hydrolysis of the substrate by dUTPase for an active-site model with 85 atoms, including several loosely bound water molecules, indicates that the method is feasible for the study of enzyme mechanisms.     

Reaction path synthesis methodology for waste minimization

Being the core of whole process, a chemical process is a key step for reducing waste generation. Therefore, to organize a reasonable reaction path is very important for reducing waste emission. Because of the large amount of the feasible reaction path and other factors in a chemical reaction system, the opti-mizing for reaction path is difficult. Since the reaction path synthesis problem has presented, lots of re-searchers focused on it. At the beginning, only chem-ists took the research work,…     

An improved kinetic determination for creatinine using the Abbott ABA-100

An improved method for the kinetic determination of creatinine on the Abbott ABA-100 is described. By simplex optimization of the picrate and hydroxide reaction concentration a 35% increase in reaction rate, with respect to the Abbott methodology, was obtained. The new method correlated more closely with the Technician AutoAnalyzer Method (N-30) than did the latter method. The percentage CV for the improved method for high and low quality control sera was 2.4 and 3.6%, respectively. The presence of protein in the standards was found to cause a decrease in the reaction rate with respect to aqueous standards.     

A fast, simple colorimetric determination of total urinary estrogen

An improved method for the kinetic determination of creatinine on the Abbott ABA-100 is described. By simplex optimization of the picrate and hydroxide reaction concentration a 35% increase in reaction rate, with respect to the Abbott methodology, was obtained. The new method correlated more closely with the Technician AutoAnalyzer Method (N-30) than did the latter method. The percentage CV for the improved method for high and low quality control sera was 2.4 and 3.6%, respectively. The presence of protein in the standards was found to cause a decrease in the reaction rate with respect to aqueous standards.     

An initial-rate potentiometric method for the determination of uric acid using a fluoride ion-selective electrode

The principle of a general potentiometric method based on Emerson-Trinder reaction for the assay of various hydrogen peroxide generating systems is reported. Emerson-Trinder reaction, habitually employed as a spectrophotometric indicator reaction, is exploited in this method as a potentiometric indicator reaction. This method is based on the detection of F⁻ ions, liberated from the oxidation of a fluorophenol compound used as hydrogen-donor in Emerson-Trinder reaction, by a fluoride ion-selective electrode. The ability and usefulness of this method are illustrated by an initial-rate potentiometric determination of uric acid in aqueous and human serum samples, for which, initial-rate reaction progress curves, linear calibration curve, within-day precisions, upper and lower detection limits, and also its analytical recovery were reported.     

A new approach to response surface development for detailed gas‐phase and surface reaction kinetic model optimization

We propose a new method for constructing kinetic response surfaces used in the development and optimization of gas‐phase and surface reaction kinetic models. The method, termed as the sensitivity analysis based (SAB) method, is based on a multivariate Taylor expansion of model response with respect to model parameters, neglecting terms higher than the second order. The expansion coefficients are obtained by a first‐order local sensitivity analysis. Tests are made for gas‐phase combustion reaction models. The results show that the response surface obtained with the SAB method is as accurate as the factorial design method traditionally used in reaction model optimization. The SAB method, however, presents significant computational savings compared to factorial design. The effect of including the partial and full third order terms was also examined and discussed. The SAB method is applied to optimization of a relatively complex surface reaction mechanism where large uncertainty in rate parameters exists. The example chosen is laser‐induced fluorescence signal of OH desorption from a platinum foil in the water/oxygen reaction at low pressures. We introduce an iterative solution mapping and optimization approach for improved accuracy. © 2003 Wiley Periodicals, Inc. Int J Chem Kinet 36: 94–106, 2004     

The degradation and local tissue effects of collagen hydrogel and sponge implants in muscle

Collagen products will degrade and evoke certain local tissue reaction after being implanted. ISO 10993.6 is the international standard to evaluate local tissue reaction for biomaterials. However, even in the present version, it does not define the specific view fields for scoring local tissue reaction in the sections, which may influence the fair evaluation for the degradable polymer, such as collagen. In this study, 4 kinds of collagens and 2 kinds of bio-inert products were implanted into the rabbit muscle for 26 weeks, and two different scoring methods (uniform distribution scoring method and area locating scoring method) were applied to evaluate the local tissue reaction for each implant. The results showed that the tissue reaction on the interface was active, but the various scores in the implant and surrounding areas could help us to understand the differences of the degradation process. An area locating scoring method which selected the fields in the implant, interface and surroundings respectively showed a higher total score and offered more detailed information compared to the uniform distribution scoring method. Since the degradation and tissue reaction degree in the different areas are ever changing for the degradable implants, this area locating scoring method is sensitive, effective and applicable for the semi-quantitative evaluating system of ISO 10993.6.     

Quantification of anhydride groups in anhydride‐based epoxy hardeners by reaction headspace gas chromatography

We demonstrate a reaction headspace gas chromatographic method for quantifying anhydride groups in anhydride‐based epoxy hardeners. In this method, the conversion process of anhydride groups can be realized by two steps. In the first step, anhydride groups in anhydride‐based epoxy hardeners completely reacted with water to form carboxyl groups. In the second step, the carboxyl groups reacted with sodium bicarbonate solution in a closed sample vial. After the complete reaction between the carboxyl groups and sodium bicarbonate, the CO₂ formed from this reaction was then measured by headspace gas chromatography. The data showed that the reaction in the closed headspace vial can be completed in 15 min at 55°C, the relative standard deviation of the reaction headspace gas chromatography method in the precision test was less than 3.94%, the relative differences between the new method and a reference method were no more than 9.38%. The present reaction method is automated, efficient and can be a reliable tool for quantifying the anhydride groups in anhydride‐based epoxy hardeners and related research.     

The efficient synthesis of 14-alkyl or aryl 14H-dibenzo[a,j]xanthenes catalyzed by bismuth(Ⅲ)chloride under solvent-free conditions

An efficient method for the synthesis of 14-alkyl or aryl 14H-dibenzo[a,j]xanthene derivatives by the reaction of β-naphthol,and aldehydes in the presence of a catalytic amount of bismuth（Ⅲ） chloride（BiCl₃） under solvent-free conditions at 110℃is described.Aliphatic and aromatic aldehydes were used in the reaction and in all cases the desired products were synthesized successfully.This reaction was studied under different temperatures;the maximum yield was obtained in a short reaction period at 110℃.The method offers the advantages of high yields,short reaction times,simplicity and easy workup compared to the conventional method of syntheses.     

A recipe for the computation of the free energy barrier and the lowest free energy path of concerted reactions

The recently introduced hills method (Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 12562) is a powerful tool to compute the multidimensional free energy surface of intrinsically concerted reactions. We have extended this method by focusing our attention on localizing the lowest free energy path that connects the stable reactant and product states. This path represents the most probable reaction mechanism, similar to the zero temperature intrinsic reaction coordinate, but also includes finite temperature effects. The transformation of the multidimensional problem to a one-dimensional reaction coordinate allows for accurate convergence of the free energy profile along the lowest free energy path using standard free energy methods. Here we apply the hills method, our lowest free energy path search algorithm, and umbrella sampling to the prototype S(N)2 reaction. The hills method replaces the in many cases difficult problem of finding a good reaction coordinate with choosing relatively simple collective variables, such as the bond lengths of the broken and formed chemical bonds. The second part of the paper presents a guide to using the hills method, in which we test and fine-tune the method for optimal accuracy and efficiency using the umbrella sampling results as a reference.     

Diffusion and trapping in a suspension of spheres with simultaneous reaction in the continuous phase

Much progress has been made in modeling the reaction of Brownian particles with spherical traps. Previously, work has focused on the effective reaction rate of systems of particles that diffuse freely until they are trapped by spheres in the dispersion. A particularly effective and efficient method to describe the reacting system is based on first-passage time distributions, from which an effective reaction rate coefficient of the suspension can be determined. The analysis presented here addresses reaction and diffusion in systems in which particles can undergo reaction in the continuous phase as well as reaction at the sphere surface. The first-passage method is extended to allow reaction or decay of the diffusing species in the continuous phase. The diffusion path is divided into a series of first-passage regions and is considered the probability of the particle being consumed in each of these regions. This allows the determination of the total reaction rate of the suspension (continuous phase reaction plus trapping) and the relative consumption rate in each phase. The extended method is applied to a model system of concentric spheres with a known continuum solution. It is shown to be accurate for consumption of reactant in the continuous phase from approximately 0 to approximately 100%. The method then is applied to a suspension of spheres.     

Continuous configuration time-dependent self-consistent field method for polyatomic quantum dynamical problems

A new continuous configuration time-dependent self-consistent field method has been developed to study polyatomic dynamical problems by using the discrete variable representation for the reaction system, and applied to a reaction system coupled to a bath. The method is very efficient because the equations involved are as simple as those in the traditional single configuration approach, and can account for the correlations between the reaction system and bath modes rather well.     

偶合反应伏安酶联免疫分析测定人血清乙型肝炎E抗体的研究

本文提出用竞争性抑制偶合反应伏安酶联免疫分析法测定人血清乙型肝炎Ｅ抗体（ＨＢｅＡｂ）方法基于酶标ＨＢｅＡｂ辣根过氧化物酶（ＨＲＰ）催化Ｈ２Ｏ２氧化邻联甲苯胺（ＯＴ）的反应与邻联甲苯胺氧化产物在电极上的还原反应相偶合，测定标记在ＨＢｅＡｂ上ＨＲＰ量，以求得抑制免疫反应的乙型肝炎Ｅ抗体含量本法测定酶标ＨＢｅＡｂＨＲＰ及ＨＢｅＡｂ的灵敏度均高于经典的ＥＬＩＳＡ光度法方法用于病人血清样品分析，与ＥＬＩＳＡ光度法对照，其相关性很好     

Fluorometric assay protocol for protease-catalyzed transesterification reactions in organic solvents

A flourometric assay protocol for a subtilisin-catalyzed transesterification reaction in n-hexane has been developed. The method makes use of a Michael acceptor that forms a fluorescent adduct with thiophenol, one of the products generated in the transesterification reaction. The method may be employed for screening a biocatalyst useful for transesterification reactions in organic solvents and for optimizing the transesterification reaction conditions.     

Parallel iterative reaction path optimization in ab initio quantum mechanical/molecular mechanical modeling of enzyme reactions

The determination of reaction paths for enzyme systems remains a great challenge for current computational methods. In this paper we present an efficient method for the determination of minimum energy reaction paths with the ab initio quantum mechanical/molecular mechanical approach. Our method is based on an adaptation of the path optimization procedure by Ayala and Schlegel for small molecules in gas phase, the iterative quantum mechanical/molecular mechanical (QM/MM) optimization method developed earlier in our laboratory and the introduction of a new metric defining the distance between different structures in the configuration space. In this method we represent the reaction path by a discrete set of structures. For each structure we partition the atoms into a core set that usually includes the QM subsystem and an environment set that usually includes the MM subsystem. These two sets are optimized iteratively: the core set is optimized to approximate the reaction path while the environment set is optimized to the corresponding energy minimum. In the optimization of the core set of atoms for the reaction path, we introduce a new metric to define the distances between the points on the reaction path, which excludes the soft degrees of freedom from the environment set and includes extra weights on coordinates describing chemical changes. Because the reaction path is represented by discrete structures and the optimization for each can be performed individually with very limited coupling, our method can be executed in a natural and efficient parallelization, with each processor handling one of the structures. We demonstrate the applicability and efficiency of our method by testing it on two systems previously studied by our group, triosephosphate isomerase and 4-oxalocrotonate tautomerase. In both cases the minimum energy paths for both enzymes agree with the previously reported paths.