Proton affinities of saturated aliphatic methyl esters

The kinetic method was used to determine the proton affinities of methyl esters of several saturated fatty acids. Decompositions of the proton-bound dimers of the methyl esters, AHB⁺, were observed under different conditions with two instruments. The proton affinities (PAs) of the methyl esters increase continually with increasing carbon number in the acid. Equilibrium and initial rate experiments were performed with a Fourier transform ion cyclotron resonance mass spectrometer on the methyl ester of the C₂₂ saturated acid (methyl behenate). These experiments give values for PA (methyl behenate) that are perhaps slightly lower than those obtained with the kinetic method. The PAs of the methyl esters of the fatty acids could be correlated with the equation: PA (ester) = (40.0 ± 2.5)*log(n) + (784.7 ± 3.9) kJ/mol or PA (ester) = (864 ± 2) − (479 ± 41)/n, wheren = number of atoms in the molecule. Proton affinities of smaller sets of 1-alkylamines and 1-alkanols can be fit to similar equations.     

Iodo-controlled selective formation of pyrrolidino[60]fullerene and aziridino[60]fullerene from the reaction between C6) and amino acid esters

The reaction between glycine methyl ester and C60 can be effectively controlled by different iodo-reagents. Addition of DIB ((diacetoxyiodo)benzene) yields the 2,5-bismethoxycarbonyl pyrrolidino[60]fullerene under ultrasonic irradiation; whereas addition of DIB-iodine results in the N-methoxycarbonylmethyl aziridino[60]fullerene under ultrasonic irradiation. The reaction of sarcosine methyl ester with C60 is similar to that of glycine methyl ester under these two conditions. Addition of just iodine to a mixture of sarcosine methyl ester and C60 affords the tetra(amino)[60]fullerene epoxide C60(O)((Me)NCH2COOMe)4. Possible mechanisms are discussed.     

Kinetics of base hydrolysis of α-amino acid esters catalyzed by palladium(II) piperazine complex

The kinetics of base hydrolysis of glycine, histidine, and methionine methyl esters in the presence of [Pd(pip)(H₂O)₂]²⁺ complex, where pip is piperazine, is studied in aqueous solutions, at T = 25°C, and I = 0.1 mol dm⁻³. The rate of ester hydrolysis for glycine methyl ester is studied at different temperature and dioxane/water solutions of different compositions. The kinetic data are fit under the assumption that the hydrolysis proceeds in one step. The activation parameters for the base hydrolysis of the complexes are evaluated      

Ab initio studies of structural features not easily amenable to experiment. 18. Conformational analysis and molecular structure of glycine methyl ester

The structures of four conformations of the methyl ester of glycine were determined by standard single-determinant molecular orbital (MO ) calculations using Pulay's force method and the 4-21G basis set. The most stable conformation of this compound has a symmetry plane which contains all the heavy atoms; it is stabilized by hydrogen bonds between the NH₂ group and the carbonyl oxygen; it corresponds to the most stable, stretched form of free glycine. The structural parameters in the different conformations can vary significantly (bond distance by more than 0.02 Å and bond angles by up to 15°). The structural changes which are caused in glycine by esterification are discussed and some of them are interpreted in terms of hyperconjugative π-electron delocalization.     

Glycine enolates: the effect of formation of iminium ions to simple ketones on alpha-amino carbon acidity and a comparison with pyridoxal iminium ions

Equilibrium constants in D2O were determined by 1H NMR analyses for formation of imines/iminium ions from addition of glycine methyl ester to acetone and from addition of glycine to phenylglyoxylate. First-order rate constants, also determined by 1H NMR, are reported for deuterium exchange between solvent D2O and the alpha-amino carbon of glycine methyl ester and glycine in the presence of increasing concentrations of ketone and Br?nsted bases. These rate and equilibrium data were used to calculate second-order rate constants for deprotonation by DO- and by Br?nsted bases of the alpha-imino carbon of the ketone adducts. Formation of the iminium ion between acetone and glycine methyl ester and between phenylglyoxylate and glycine is estimated to cause 7 unit and 15 unit decreases, respectively, in the pKa's of 21 and 29 for deprotonation of the parent carbon acids. The effect of formation of iminium ions to phenylglyoxylate and to 5'-deoxypyridoxal (DPL) [Toth, K.; Richard, J. P. J. Am. Chem. Soc. 2007, 129, 3013-3021] on the carbon acidity of glycine is similar. However, DPL is a much better catalyst than phenylglyoxylate of deprotonation of glycine, because of the exceptionally large thermodynamic driving force for conversion of the amino acid and DPL to the reactive iminium ion.     

Thermal stability of Pd(1,4-bis(2-hydroxyethyl)piperazine)Cl2 and its role in the catalysis of base hydrolysis of α-amino acid esters

Pd(BHEP)Cl₂ was synthesized and characterized (BHEP = 1,4-bis(2-hydroxyethyl)piperazine). The complex decomposes in two steps, leaving a residue of palladium metal. Amino acid ester (L) reacts with [Pd(BHEP)(H₂O)₂]²⁺ (BHEP = 1,4-bis(2-hydroxyethyl)piperazine), giving mixed-ligand complexes, [Pd(BHEP)L]²⁺. The kinetics of hydrolysis of [Pd(BHEP)L]²⁺ have been studied by pH-stat technique, and rate constants were obtained. Rate acceleration observed for glycine methyl ester is high. The effect with methionine methyl ester is much less marked, as the mixed-ligand complexes with these ligands do not involve alkoxycarbonyl donors. Possible mechanisms for these reactions are considered.     

Gas-phase basicities of serine and dipeptides of serine and glycine

The gas-phase basicities of serine and dipeptides containing amino acid residues of serine and glycine were determined by proton transfer reactions in a Fourier transform ion cyclotron resonance mass spectrometer. The gas-phase basicity (GB) of L-serine was found to be 205.9 kcal/mol, with addition of a hydroxymethyl group (?CH₂OH) increasing the basicity by 4.5 kcal/mol relative to the simplest amino acid glycine (GB = 201.4 kcal/mol). This is attributed to a combination of intramolecular hydrogen bonding, induction, and symmetry effects. For the dipeptides, addition of a hydroxymethyl group does not result in a large increase in basicity relative to the basicity of glycylglycine (GB = 208.0 kcal/mol). The gas-phase basicities determined for glycyl-l-serine, l-serylglycine, and l-sery-l-serine are 209.3,210.6, and 210.9 kcal/mol, respectively. In comparison to glycylglycine, addition of the hydroxymethyl group at the N terminus has a greater impact on basicity than its placement at the C terminus. These data suggest that the protonation site for these dipeptides is the N-terminal amino nitrogen.     

Equilibria and kinetics for pH-dependent axial ligation of ethylester and methylester(aquo)cobaloximes with aromatic and aliphatic N-donor ligands and a molecular mechanistic study of the Co-C bond

Equilibrium constants are determined for the reaction of ethylester and methyl ester (aquo) cobaloximes with histamine, histidine, glycine and ethyl glycine ester as a function of pH at 25°C, using spectrophotometric technique. The functional dependence of pK _a on the substitution rate of H₂O varies with the pK _a of the incoming ligand, establishing the existence of nucleophilic participation of the ligand in the transition state. This data is interpreted with the help of kinetic data where dissociation kinetic reactions were also studied as a function of pH. Binding and kinetic data were correlated based on the basicity, steric hindrance of the entering ligand and HSAB principle. To compare the rate constants of the entering ligands pH-independent second-order rate constants were calculated. The effect of incoming ligand on Co-C bond is studied using molecular mechanics     

Synthesis of imidazole‐terminated hyperbranched polymers with POSS‐branching points and their pH responsive and coordination properties

An imidazole‐terminated hyperbranched polymer with octafunctional POSS branching units denoted as POSS‐HYPAM‐Im was prepared by the polymerization of excess amounts of tris(2‐aminoethyl)amine with the first‐generation methyl ester‐terminated POSS‐core poly(amidoamine)‐typed dendrimer, reacting with methyl acrylate, and ester‐amide exchange reaction with 3‐aminopropylimidazole. The imidazole‐terminated hyperbranched poly(amidoamine) denoted as HYPAM‐Im was also synthesized with 1‐(3‐aminopropyl)imidazole from a methyl ester‐terminated hyperbranched poly(amidoamine) by the ester‐amide exchange reaction. The transmittance of the POSS‐HYPAM‐Im solution drastically decreased when the solution pH was greater than 8.2. On the other hand, the transmittance of the HYPAM‐Im solution gradually decreased when the solution pH at 8.5 and was greater than 9. Spectrophotometric titrations of the hyperbranched polymer aqueous solutions with Cu²⁺ ions indicated the variation of the coordination modes of POSS‐HYPAM‐Im from the Cu²⁺–N₄ complex to the Cu²⁺–N₂O₂ complex and the existence of the only one complexation mode of Cu²⁺–N₄ between Cu²⁺ ion and HYPAM‐Im with increasing the concentrations. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2695–2701     

Synthesis of Some Novel Benzylidenehydantoins: Amino Acids Derivatives

5-Benzylidenehydantoin reacts with chlorosulfonic acid to give the corresponding p-sulfonyl chloride. Condensation of the latter with amino acids leads to sulfonylamino acid derivatives, which on coupling with glycine methyl ester hydrochloride in THF-Et₃N using the dicyclohexylcarbodiimide method furnish the desired dipeptide methyl esters. The spectral data of the compounds are briefly discussed.     

Experimental and theoretical studies of the basicity and proton affinity of SiF4 and the structure of SiF4H+

A combined experimental and theoretical approach has been employed to establish the basicity and proton affinity of SiF₄ and the structure of SiF₄H⁺. The kinetics and energetics for the transfer of a proton between SiF₄, N₂, and Xe have been explored experimentally in helium at 0.35±0.02 torr and 297±3 K with a selected-ion flow tube apparatus. The results of equilibrium constant measurements are reported that provide a basicity and proton affinity for SiF₄ at 297±3 K of 111.4±1.0 and 117.7±1.2 kcal mol^?1, respectively. These values are more than 2.5 kcal mol^?1 lower than currently recommended values. The basicity order was determined to be GB(Xe)>GB(SiF₄)>GB(N₂), while the proton-affinity order was shown to be PA(Xe)>PA(N₂)>PA (SiF₄). Ab initio molecular orbital computations at MP4SDTQ(fc)/6-311++G(3df,3pd) using geometries from B3LYP/6-31+G(d,p) indicate a value for PA(SiF₄)=118.7 kcal mol^?1 that is in good agreement with experiment. Also, the most stable structure of SiF₄H⁺ is shown to correspond to a core SiF ₃ ⁺ cation solvated by HF with a binding energy of 43. 9 kcal mol^?1. Support for this structure is found in separate SIFT collision induced dissociation (CID) measurements that indicate exclusive loss of HF.     

Initiation of polymerization of alkyl 2-cyanoacrylates in aqueous solutions of glycine and its derivatives

The polymerization of methyl 2-cyanoacrylate and heptyl 2-cyanoacrylate was carried out with the use of aqueous solutions of ¹⁴C-tagged glycine, methyl glycine, and acetyl glycine as initiators. When glycine and methyl glycine were used, radioactive polymers were formed. When acetyl glycine was used, the polymer formed was not radioactive. The data seem to indicate that free NH₂ groups appear to be necessary for the incorporation of the glycine initiator in the polymer. A possible mechanism for the polymerization is presented.     

Pd(II)-catalyzed vinylic polymerization of norbornene and copolymerization with norbornene and copolymerization with norbornene carboxylic acid esters

The vinylic polymerization of norbornene and its copolymerization with norbornene carboxylic acid methyl esters were investigated. Norbornene was polymerized by us using di-μ-chloro-bis-(6-methoxybicyclo[2.2.1]hept-2-ene-endo-5σ,2π)-palladium(II) as catalyst. The polymerization time can be decreased by a factor of 100000 by activation of the catalyst with methylaluminoxane (MAO). With this palladium catalyst activated by MAO, 140 t of norbornene can be polymerized per mol palladium per h. This catalyst system was much more active than [Pd(CH₃CN)₄](BF₄)₂ ( I ). The polymerization of norbornene by (6-methoxybicyclo[2.2.1]hept-2-ene-endo-5σ,2π)-palladium(II) tetrafluoroborate was also possible but it was not as fast as the polymerization by Pd catalysts activated with MAO. We were also able to obtain copolymers of norbornene and 5-norbornene-2-carboxylic acid methyl ester (exo/endo = 1/4 or 2/3) containing between 15 and 20 mol-% ester units. The copolymerization of norbornene and 2-methyl-5-norbornene-2-carboxylic acid methyl ester (exo/endo = 7/3) was faster than the copolymerization mentioned before. In contrast the homopolymerization of 2-methyl-5-norbornene-2-carboxylic acid methyl ester was 10 times slower than that of 5-norbornene-2-carboxylic acid methyl ester (exo/endo = 1/4).     

Copper(II) complexes of imino-bis(methyl phosphonic acid) with some bio-relevant ligands. Equilibrium studies and hydrolysis of glycine methyl ester through complex formation

Binary and ternary complexes of Cu(II) involving imino-bis(methyl phosphonic acid) (IdP) abbreviated as H₄A and some selected bio-ligands, amino acids, peptides and DNA constituents (L), were examined. Cu(II) forms CuA and CuAH complexes with IdP. Ternary complexes are formed in a stepwise mechanism whereby iminodiphosphonic acid binds to Cu(II), followed by coordination of amino acid, peptide or DNA. The concentration distribution of the various complex species has been evaluated. The kinetics of base hydrolysis of glycine methyl ester in the presence of Cu(II)-IdP was studied in aqueous solution at different temperatures, and in dioxane-water solutions of different compositions at 25°C. The activation parameters are evaluated and discussed.     

Gas-phase structure of protonated histidine and histidine methyl ester: combined experimental mass spectrometry and theoretical ab initio study

Gas-phase H/D exchange experiments with CD3OD and D2O and quantum chemical ab initio G3(MP2) calculations were carried out on protonated histidine and protonated histidine methyl ester in order to elucidate their bonding and structure. The H/D exchange experiments show that both ions have three equivalent fast hydrogens and one appreciably slower exchangeable hydrogen assigned to the protonated amino group participating in a strong intramolecular hydrogen bond (IHB) with the nearest N(sp2) nitrogen of the imidazole fragment and to the distal ring NH-group, respectively. It is taken for granted that the proton exchange in the IHB is much faster than the H/D exchange. Unlike in other protonated amino acids (glycine, proline, phenylalanine, tyrosine, and tryptophan) studied earlier, the exchange rate of the carboxyl group in protonated histidine is slower than that of the amino group. The most stable conformers and the enthalpies of neutral and protonated histidine and its methyl ester are calculated at the G3(MP2) level of theory. It is shown that strong intramolecular hydrogen bonding between the amino group and the imidazole ring nitrogen sites is responsible for the stability and specific properties of the protonated histidine. It is found that the proton fluctuates between the amino and imidazole groups in the protonated form across an almost vanishing barrier. Proton affinity (PA) of histidine calculated by the G3(MP2) method is 233.2 and 232.4 kcal mol(-1) for protonation at the imidazole ring and at the amino group nitrogens, respectively, which is about 3-5 kcal mol(-1) lower than the reported experimental value.     

白杨素甘氨酸类化合物的合成及抗癌活性

以白杨素为起始原料, 通过卤代和水解反应制得中间产物7-O-羧烷基化的白杨素衍生物(6~9); 然后以1-乙基-3-(3-二甲氨基丙基)碳二亚胺(EDCI)、 1-羟基苯并三氮唑(HOBt)和4-二甲氨基吡啶(DMAP)为催化体系, 4个中间产物分别与甘氨酸甲酯盐酸盐进行酰胺缩合反应, 制得白杨素甘氨酸甲酯类化合物12~15; 化合物12~15在pH=10~11和室温下水解得到相应的白杨素甘氨酸类化合物(16~19). 所有目标化合物的结构均经 ¹H NMR, ¹³C NMR, IR以及MS确认. 以顺铂为阳性对照药物, 采用噻唑蓝比色(MTT)法检测了目标化合物对人肝癌细胞HepG2和人胃癌细胞MGC-803的体外增殖抑制作用. 结果表明, 目标化合物14~16, 18和19的体外抗肿瘤活性明显强于白杨素, 且化合物18(IC₅₀=4.36 μmol/L)对MGC-803细胞的增殖抑制作用强于阳性药物顺铂(IC₅₀=4.40 μmol/L).     

Equilibrium investigation of complex formation reactions involving copper(II), nitrilo-tris(methyl phosphonic acid) and amino acids,peptides or DNA constitutents. The kinetics,mechanism and correlation of rates with complex stability for metal ion promoted hydrolysis of glycine methyl ester

The complex formation reactions of [Cu(NTP)(OH₂)]^4? (NTP?=?nitrilo-tris(methyl phosphonic acid)) with some selected bio-relevant ligands containing different functional groups, are investigated. Stoichiometry and stability constants for the complexes formed are reported. The results show that the ternary complexes are formed in a stepwise mechanism whereby NTP binds to copper(II), followed by coordination of amino acid, peptide or DNA. Copper(II) is found to form Cu(NTP)H _n species with n?=?0, 1, 2 or 3. The concentration distribution of the various complex species has been evaluated. The kinetics of base hydrolysis of glycine methyl ester in the presence of copper(II)-NTP complex is studied in aqueous solution at different temperatures. It is proposed that the catalysis of GlyOMe ester occurs by attack of OH^? ion on the uncoordinated carbonyl carbon atom of the ester group. Activation parameters for the base hydrolysis of the complex [Cu(NTP)NH₂CH₂CO₂Me]^4? are, ΔH^±?=?9.5?±?0.3?kJ?mol^?1 and ΔS^±?=??179.3?±?0.9?J?K^?1?mol^?1. These show that catalysis is due to a substantial lowering of ΔH^±.     

2-Benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxy-carbonylvinyl-1 as N-protecting groups in peptide synthesis. Their application in the synthesis of dehydropeptide derivatives containing N-terminal 3-heteroarylamino-2,3-dehydroalanine

Ethyl 2-benzoyl-3-dimethylaminopropenoate ( 6 ) and methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) were used as reagents for the protection of the amino group with 2-benzoyl-2-ethoxycarbonylvinyl-1 and 2-benzoylamino-2-methoxycarbonylvinyl groups in the peptide synthesis. Reactions of ethyl 2-benzoyl-3-dimethylaminopropenoate (6) with α-amino acids gave N-(2-benzoyl-2-ethoxycarbonylvinyl-1)-α-amino acids 13–19. These were coupled with various amino acid esters to form N-(2-benzoyl-2-ethoxycar-bonylvinyl-1)-protected dipeptide esters 20–31. The removal of 2-benzoyl-2-ethoxycarbonylvinyl-1 group, which was achieved by hydrazine monohydrochloride or hydroxylamine hydrochloride, afforded hydrochlo-rides of dipeptide esters 32–41 in high yields. Similarly, the substitution of the dimethylamino group in methyl 2-benzoylamino-3-dimethylaminopropenoate ( 46 ) by glycine gave N-(2-benzoylamino-2-methoxycar-bonylvinyl-1)glycine ( 47 ), which was coupled with glycine ethyl ester to give N-[N-(2-benzoylamino-2-methoxycarbonylvinyl-1)glycyl]glycine ethyl ester ( 48 ). Treatment of 48 with 2-arnino-4,6-dirnethylpyrimi-dine afforded N-[glycyl]glycine ethyl ester hydrochloride (34) in high yield. Amino acid esters and dipeptide esters were employed in the preparation of tri- 58-70, tetra- 71–82, and pentapeptide esters 83–85 containing N-terminal 3-heteroarylamino-2,3-dehydroalanine. 2-Chloro-4,6-dimethoxy-1,3,5-triazine was employed as a coupling reagent for the preparation of peptides 58–85.     

Quantification of methyl thiocyanate in the headspace of Pseudomonas aeruginosa cultures and in the breath of cystic fibrosis patients by selected ion flow tube mass spectrometry

Infection by Pseudomonas aeruginosa (PA) is a major cause of morbidity and mortality in patients with cystic fibrosis (CF). Breath analysis could potentially be a useful diagnostic of such infection, and analyses of volatile organic compounds (VOCs) emitted from PA cultures are an important part of the search for volatile breath markers of PA lung infection. Our pilot experiments using solid‐phase microextraction, SPME and gas chromatography/mass spectrometric (GC/MS) analyses of volatile compounds produced by PA strains indicated a clear presence of methyl thiocyanate. This provided a motivation to develop a method for real‐time online quantification of this compound by selected ion flow tube mass spectrometry, SIFT‐MS. The kinetics of reactions of H₃O⁺, NO⁺ and O₂^+? with methyl thiocyanate at 300 K were characterized and the characteristic product ions determined (proton transfer for H₃O⁺, rate constant 4.6 × 10^–9 cm³ s^–1; association for NO⁺, 1.7 × 10^–9 cm³ s^–1 and nondissociative charge transfer for O₂^+?_, 4.3 × 10^–9 cm³ s^–1). The kinetics library was extended by a new entry for methyl thiocyanate accounting for overlaps with isotopologues of hydrated hydronium ions. Solubility of methyl thiocyanate in water (Henry's law constant) was determined using standard reference solutions and the linearity and limits of detection of both SIFT‐MS and SPME‐GC/MS methods were characterized. Thirty‐six strains of PA with distinct genotype were cultivated under identical conditions and 28 of them (all also producing HCN) were found to release methyl thiocyanate in headspace concentrations greater than 6 parts per billion by volume (ppbv). SIFT‐MS was also used to analyze the breath of 28 children with CF and the concentrations of methyl thiocyanate were found to be in the range 2–21 ppbv (median 7 ppbv). Copyright © 2011 John Wiley & Sons, Ltd.     

Michael additions to acrylonitrile,methyl acrylate and methyl vinyl ketone to Nb-benzylidenetryptophan methyl ester

Michael addition to methyl acrylate and methyl vinyl ketone of N_b-benzylidene-L-tryptophan methyl ester 1 gave 2-(3-indolylmethyl)glutamic dimethyl ester 2a and α-(3-oxobutyl)tryptophan methyl ester 2b respectively. Addition to acrylonitrile of 1 yielded α,N_a-dicyanoethyltryptophan methyl ester 3 .