Non-enzymatic model glycation reactions--a comprehensive study of the reactivity of a modified arginine with aldehydic and diketonic dicarbonyl compounds by electrospray mass spectrometry

Non-enzymatic glycation (Maillard reaction) of long-lived proteins is a major contributor to the pathology of diabetes, and possibly aging and Alzheimer's disease. Among the amino residues in proteins arginine plays an important role, and its modification by sugar moieties generates the so-called advanced glycation end products (AGEs). Moreover, alpha-dicarbonyl compounds have been found as the main participants in those modifications.Four alpha-dicarbonyl compounds, aldehydic and ketonic, were reacted with the modified amino acid N(alpha)-acetyl-L-arginine (AcArg), in an attempt to establish structure/activity relationships for the reactivity of alpha-dicarbonyls with the amine compound. Electrospray ionization mass spectrometry (ESI-MS), combined with tandem mass spectrometry (MS/MS), was used to identify and characterize reagents, intermediates and reaction products. The fragmentation patterns of precursor ions showed similarities in all reaction systems studied, in which fragmentation of the amino acid residue prevails, especially for the dehydrated and/or multiple dehydrated precursor ions. For the non-hydrated ion species, fragmentation of the arginyl guanidino group was mainly observed. Specific information regarding the nature of the ions formed, in which the dicarbonyl electrophile character played an important role, was obtained. As an example, singly and doubly hydrated acetyl-argpyrimidine ions were detected for the methylglyoxal reaction only. For symmetrical dicarbonyls, glyoxal and diacetyl, the importance of steric contributions with respect to the energetic ones is discussed. Furthermore, the dehydrated acetyl-tetrahydropyrimidine ions for methylglyoxal and phenylglyoxal reactions revealed fragment ion compositions including the protonated molecules of acetyl-argpyrimidine, -hydroimidazolone and -5-methylimidazolone. An explanation for the acetyl-argpyrimidine formation from the acetyl-hydroimidazolone formation reaction is proposed. Aspects such as the amount of acetyl-hydroimidazolone formed, the response of the hydration equilibria of the dicarbonyl forms to the new unhydrated dicarbonyls introduced by the reversal of the acetyl-hydroimidazolone formation reaction and the stability of the dicarbonyl intermediate involved in the acetyl-argpyrimidine formation are proposed, as being responsible to control the formation of acetyl-argpyrimidine.     

A non‐enzymatic model based on an acyl transfer reaction for the formation of energy‐rich acetyl phosphate in organic solvents and in a biphasic system

The formation of acetyl phosphate (AcP), an energy‐rich phosphate compound, was studied through the reaction of 2,4‐dinitrophenyl acetate with H₂PO solubilized with Kryptofix® 222 or as a tetra‐n‐butylammonium ((n‐C₄H₉)₄N⁺) salt in organic media. The results indicated that the rate of the reaction in acetonitrile is strongly inhibited by the addition of water, suggesting that the water added to the medium preferentially solvates the H₂PO anion, inhibiting its action as a nucleophile and allowing it to act as a general base catalyst, which leads to the hydrolysis of the ester. The utilization of various organic solvents in the acetyl transfer process demonstrated that the specific interaction of the solvent with water accelerates the process, by desolvation of H₂PO, which can act as a nucleophile. Finally, a formation/transformation cycle of AcP was studied in a biphasic system (water/CH₂Cl₂) using Kryptofix® 222 and (n‐C₄H₉)₄N⁺BF as both the carrier and solubilizing agent for KH₂PO₄. Copyright © 2010 John Wiley & Sons, Ltd.     

Amino Acid Derivatives as Protein Side-Chain Model Compounds: The Partial Molar Volumes and Heat Capacities of Some N-Acetyl-N′-methyl Amino Acid Amides in Aqueous Solution

The partial molar heat capacities, C ^o _p,2, and partial molar volumes, V ^o ₂, at infinite dilution have been determined for the compounds N-acetyl-N-methylglycinamide, N-acetyl-N-methylalaninamide, N-acetyl-N-methylvalinamide, and N-acetyl-N-methylleucinamide in aqueous solution at the temperatures 15, 25, 40, and 55°C. The C ^o _p,2 and V ^o ₂ results have been used to calculate amino acid side-chain contributions to the thermodynamic properties. These side-chain contributions are compared with those derived in previous work using thermodynamic data for the corresponding acetylated primary amides and with results reported using peptide model compounds.     

醋酸催化氯化合成氯乙酸反应机理研究

本文通过对醋酸在乙酰氯为催化剂下进行氯化制备氯乙酸反应机理的研究。认为乙酰氯为催化剂的醋酸氯化反应属于连串反应,而且在此连串反应中,乙酰氯与氯气反应的活化能要比氯乙酰氯与氯气反应的活化能高。     

Determination of reactivity ratios and kinetics of free radical copolymerization of linalool with styrene

Copolymerization of acyclic monoterpenoid, namely linalool (LIN), with styrene (STY) initiated by benzoyl peroxide (BPO) p‐acetyl benzylidene triphenyl arsonium ylide (p‐ABTAY) in xylene separately at 80°C for 180 min under inert atmosphere of nitrogen was performed. The results give a nearly alternating copolymer as evidenced from reactivity ratios (r₁ = 0.016, r₂ = 0.057) w.r.t. BPO; (r₁ = 0.017, r₂ = 0.052) w.r.t. p‐ABTAY (i.e. r₁ = 0.0165 ± 0.0005 and r₂ = 0.0545 ± 0.0025 per initiator set) using Kelen–Tudos method. The FT‐IR spectrum shows a band at 3026 cm^?1 due to the aromatic ring of polystyrene and an alcoholic band of linalool at 3408 cm^?1. ¹H‐NMR spectrum shows peaks at δ 7.0–7.7 ppm of ? OH protons and peaks at δ 7.5–8.0 ppm due to phenyl protons of styrene. The system follows ideal kinetics i.e. Rp ∝ [LIN]^1.0[STY]^1.0[BPO]^0.5/[p‐ABTAY]^0.5. The overall energy of activation in the temperature range 75–85°C is 77.0 kJ mol^?1 and 90.0 kJ mol^?1, respectively. The values for Mark–Houwink constants for the functional copolymer has been evaluated as a = 0.40 and K = 1.60 × 10^?4 with the help of gel permeation chromatography (GPC). Alfrey–Price, Q and e parameters for linalool have been evaluated as Q₂ = 0.80; e₂ = 1.25 w.r.t. BPO and Q₂ = 0.90; e₂ = 1.54 w.r.t. p‐ABTAY. Thermal properties of copolymers were investigated by thermogravimetric analysis (TGA) techniques. Copyright © 2004 John Wiley & Sons, Ltd.     

基于Barton-Zard反应的2-乙氧羰基-3-三氟甲基-4-甲基吡咯及其卟啉衍生物的改进合成

由2-乙氧羰基-3-硝基-1,1,1-三氟丁烷(1b)与异氰基乙酸乙酯发生Barton-Zard反应制备2-乙氧羰基-3-三氟甲基-4-甲基吡咯(1)的过程中,分别用K2CO3和乙醇代替有机碱1,8-二氮杂二环[5.4.0]十一碳-7-烯(DBU)和四氢呋喃溶剂,这种改进的Barton-Zard方法具有操作简便、试剂价廉易得、溶剂毒性低和产率更高等优点。 另外,在3-硝基-1,1,1-三氟-2-丁醇(1a)通过乙酰化反应转变为中间体1b的过程中,用沸腾温度下的甲苯溶液与乙酰氯代替浓硫酸催化下的酸酐反应体系;合成化合物1b的最优化的反应条件被确定为：乙酰氯与反应物1a之间的摩尔比为1.2∶1,反应时间为3～3.5 h。 又根据改进的卟啉合成法,在低温下用过量氢化铝锂还原吡咯1,将还原所得的尚未干燥或储存的粗产物α-羟甲基-三氟甲基-4-甲基吡咯(1c),立即在未经处理的三氯甲烷溶剂中,以三氟化硼·乙醚(BF3·OEt2)为催化剂进行四聚化反应,然后用2,3-二氯-5,6-二氰基-1,4-苯醌(DDQ)氧化,合成出含三氟甲基取代的卟啉衍生物2。 研究发现,由化合物1c制备产物2时,用BF3·OEt2取代p-TsOH作为催化剂,在确定的反应条件下,能够将产物2的收率由14%提高至50%。     

Vibrational spectroscopy and DFT calculations of di‐amino acid peptides: α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu in the solid state

Experimental vibrational spectroscopic studies and density functional theory (DFT) calculations of the di‐amino acid peptide derivatives α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu have been undertaken. Raman and infrared spectra have been recorded for samples in the solid state. DFT simulations were conducted using the B3‐LYP correlation functional and the cc‐pVDZ basis set to determine energy minimized/geometry optimized structures (based on a single isolated molecule in the gaseous state). Normal coordinate calculations have provided vibrational assignments for fundamental modes, including their potential energy distributions. Significant differences are observed between α‐ and β‐N‐acetyl‐L‐Asp‐L‐Glu both in the computed structures and in the vibrational spectra. The combination of experimental and calculated spectra provide an insight into the structural and vibrational spectroscopic properties of di‐amino acid peptide derivatives. Copyright © 2009 John Wiley & Sons, Ltd.     

维生素 B_1 中间产物乙酰嘧啶的合成工艺

文中针对用Ｓ－Ｂ１工艺路线生产维生素Ｂ１工艺过程中的关键问题——乙酰嘧啶中间产物收率过低（６０％左右），研究了原料配比、水用量和乙酰嘧啶在水中的溶解度对总收率的影响，以及工艺操作条件对生成乙酰嘧啶的反应特性的影响。并用统计方法对实验数据进行了处理，研究了操作过程对总收率的影响。结果表明，相对于１ｍｏｌ缩醛，甲醇钠、盐酸乙脒的最佳使用量为２．７６ｍｏｌ和３．１ｍｏｌ。而且在５５～６５℃区间的升温时间应控制在最佳。这样，总收率依缩醛计可以提高５％～１０％。     

酶催化乙酰基转移反应的密度泛函研究（Ⅱ）

用密度泛函方法的B3LYP在6-31＋g（d，p）基组水平上，研究了底物对-氨基苯甲酸与芳基胺-N-乙酰基转移酶之间的乙酰化反应．该反应共有两种可能的反应机理：协同反应和分步反应．计算结果表明，协同反应机制在竞争中占优势，是势能面上的最低能量反应通道．