Ring-deactivated hydroxyalkylpyrrole-based inhibitors of alpha-chymotrypsin: synthesis and mechanism of action

13C NMR and mass spectrometry studies have been used to demonstrate that the inhibition of alpha-chymotrypsin by N-sulfonylhydroxymethylpyrrole inhibitors (10) is non-covalent. Hydroxyalkylpyrroles in which an electron-withdrawing group (acyl substituent) is introduced at the alternative C2 position have been synthesised and also shown to inactivate alpha-chymotrypsin. SAR studies on this class suggests that the incorporation of phenylalanine at C2 is favoured, however, there is little gain in introducing a hydrophobic substituent at C5.     

On the mechanism of electrochemical dispersion of platinum under the action of alternating current

The behavior of platinum electrodes in alkali solutions under the action of pulse alternating current was studied. A mechanism of electrochemical dispersion of platinum was proposed. An important step of the mechanism is the discharge and cathodic insertion of alkali metal cations into the crystalline lattice of platinum followed by the decomposition of intermetallic compound Pt _m Na upon the interaction with water. Dispersion is facilitated by the presence of an oxide film on the platinum surface formed in the anodic period of pulses, a periodical alternation of electrode polarity resulting in the electrochemical injection of vacancies from the metal bulk to the surface, and hydrogen and oxygen formation in the corresponding periods.     

核酸中碱基的氢键作用机理及电子特征理论研究

采用耦合簇量子化学方法 CCSD/aug-cc-pVDZ研究了嘧啶与嘌呤之间的相互作用,利用基函数叠加误差法(BSSE)消除相互作用能误差,并进行了几何结构优化;采用Gaussian 03程序包中的NBO程序分析了二阶稳定化能及自然键轨道.与此同时,应用约化密度函数(RDG)填色等值面图对体系进行了图形化分析,分析了氢键相互作用所在的空间位置和相对强度,以及氢键相互作用的性质,以进一步了解二者的相互作用.结果表明,嘧啶-嘌呤体系的相互作用属于闭合壳层静电相互作用.电子密度跃迁矩阵分析结果表明,激发区域主要集中在N原子和O原子处,涉及的空间广度很大,第一激发态主要涉及前线分子轨道,属于σ→π*或n→π*类型跃迁.     

On the mechanism of the lewis acid catalyzed cyclocondensation of aldehydes with siloxydienes

Competing cycloaddition versus aldolization-cyclization processes are demonstrated in the formation of 6-styryl-5,6-dihydro-y-pyronevia the BF₃ catalyzed reaction of cinnamaldehyde with trans-1-methoxy 3-trimethylsilyloxy-1,3-butadiene.     

Electron transfer mechanism for regulatory action by nitric oxide

Various mechanisms have been proposed for the regulatory action of nitric oxide. The most common mechanism involves stimulation of soluble guanylate cyclase (sGC) with consequent elevation of cyclic GMP levels. A more detailed chemical mode of action is given in this paper entailing electron transfer (ET) processes which ensue after binding of NO to iron-containing enzymes, and which may be responsible for some of the observed physiological effects. The focus is on immunological reactions and neurotransmission. Electrochemical data for model FeNO complexes are discussed which support the hypothesis. Comparisons are made with the mode of action by anti-infective drugs. The ET transformations suggested for NO in the nervous system are in marked contrast with the current concentration on ionic reactions. Based on the ET framework, analogies exist with a proposed mechanism for the plant hormone ethylene. Other supportive evidence from various categories is also presented. The general approach in this paper represents an elaboration of the one-electron redox processes put forth recently for NO action by Saran and Bors (Chem.-Biol. Interact., 90 (1994) 35).     

Kinetics and mechanism for the iodination of methylmalonic acid

The reaction\documentclass{article}\pagestyle{empty}\begin{document}$ CH\left({CH_3 } \right)\left({COOH} \right)_2 + I_2 \rightleftharpoons CI(CH_3)\left({COOH} \right)_2 + H^ + + I^ - $\end{document} was followed spectrophotometrically at 353 nm and 470 nm at 25°C under various conditions of pH and methylmalonic acid concentration. The equilibrium constant for the reaction is 0.11 ± 0.02. An iterative technique was used to integrate postulated rate equations. Agreement between experimental and calculated absorbance versus time curves was generally better than 0.005 A (approximately 5% of maximum) at both wavelengths for a mechanism where the rate-determining step is formation of an enolate (k = 1.63 Θ 10^?4 ± 0.03 Θ 10^?4 sec^?1). The enolate may be rapidly transformed to the enol or enol carboxylate anion depending on the pH. All three forms are rapidly iodinated. The mechanism of general base catalysis is supported by rate increases proportional to base concentration in buffer solutions. The bases, acetate ion, chloracetate ion, sulfate ion, dichloracetate ion, and water, follow a Brønsted relationship with β = 0.7.     

A general process for the haloamidation of olefins. Scope and mechanism

A methodology is described for the addition of a bromine atom and an amide nitrogen in a trans sense to an olefinic double bond. The process, which is illustrated by numerous examples, involves the use of an N-bromoamide and a Lewis acid as a source of Br+ which reacts with the olefin. The amide group is derived from a nitrile and a water molecule which serve as nucleophiles for the overall three-component reaction. The bromoamidation is general for a broad range of olefins and nitriles. This reaction pathway provides access not only to vicinal bromoamides but also to N-acyl aziridines and oxazolines. From these, many types of amines and amino alcohols can be prepared. Examples are provided which delineate diastereo- and regioselectivity preferences. An analogous chloroamidation reaction is also described.     

Substrate monolayers as electrochemical sensing elements for alpha-chymotrypsin

A disulfide, which carried two L-phenylalanyl p-nitroanilide (Phe-pNA) moieties at both ends, was prepared by the coupling of 11,11'-dithiodiundecanoic acid (DTUA) with Phe-pNA. The compound obtained (DTUA-Phe-pNA) formed a self-assembled monolayer (SAM) on a gold electrode and vacuum-evaporated gold thin film as proven by cyclic voltammetry, and reflection absorption spectroscopy, respectively. Incubation of alpha-chymotrypsin with the SAM-modified electrode induced both a decrease in anodic and cathodic peak currents (-DeltaIa and -DeltaIc) and an increase in potential difference (DeltaEp) in the cyclic voltammogram of potassium ferricyanide as a probe, which suggested the attack of the enzyme at the amide group between Phe and pNA groups of the SAM, resulting in the formation of an intermediate. The linear relationship between the initial rate of increase in the amount of enzyme bound to the SAM and in both DeltaIa (absolute value of the decrease in anodic peak current) and DeltaEp values was confirmed by the quartz crystal microbalance method. The binding rate of the enzyme to the Phe-pNA SAM was dependent on the surface density of the Phe-pNA group in the SAM. The alpha-chymotrypsin-induced increases in the DeltaIa and DeltaEp values were inhibited by the addition of N-acetyl-D-phenylalanine methyl ester (N-Ac-D-Phe-OMe). In contrast with alpha-chymotrypsin, trypsin did not show a significant increase in the DeltaIa and DeltaEp values upon incubation with Phe-pNA-carrying SAM. These results could be attributed to the specific attack of alpha-chymotrypsin to the amide group in the SAM. The inhibition constant for N-Ac-D-Phe-OMe in the SAM system was quite similar to that in the free substrate system, showing that the enzymatic reaction above the SAM proceeds in a similar way to that in the homogeneous solution system.     

On the simple Michaelis-Menten mechanism for chemical reactions

Several mathematical properties associated with the simple Michaelis-Menten mechanism for enzymatic reactions are proven. In particular it is shown that the usual interpretation of the slope of the experimental Michaelis-Menten rate law in terms of the reaction constants of the mechanism can be obtained, in the approximation in which the total concentration of the enzyme is small compared with the Michaelis-Menten constant, independently of the ratio between the total initial concentrations of the enzyme and substrate. Furthermore, the ratio of the total concentration of the enzyme to the Michaelis-Menten constant allows for the elimination of a fast variable in a singular perturbation method, yielding the Michaelis-Menten rate law as a first order approximation.     

Kinetics and mechanism for the sonophotocatalytic degradation of p-chlorobenzoic acid

The advanced oxidation processes of sonolysis (213 kHz), photocatalysis, and a hybrid combination of both (sonophotocatalysis) have been used in the degradation of a representative aromatic carboxylic acid, p-chlorobenzoic acid (PCBA), in ambient air saturated aqueous solutions. The formation of degradation products were monitored quantitatively and qualitatively using HPLC and MS/MS. A kinetic model was used to account for the degradation of the PCBA in the presence of intermediate degradation products and also their formation and subsequent degradation. Under certain experimental conditions a small (20% enhancement) synergistic effect in the degradation rate was evident in the combined process compared with the sum of the individual processes.     

Catalytic activity and mechanism for the action of pyridines in the phenolysis of epichlorohydrin

The reactivity of 3-chlorophenol with epichlorohydrin in the presence of substituted pyridines was studied. The reaction orders relative to the reagents and catalyst were determined. Correlations permitting evaluation of the effect of structure and concentration of the catalyst were obtained. The catalysis mechanism was found. Donetsk State University, 24 Universitetskaya ul., Donetsk 340055, Ukraine. Translated from Teoreticheskaya i éksperimental'naya Khimiya, Vol. 35, No. 2, pp. 89–91, March–April, 1999.