- The effect of disorder on the chemical reactivity of an organic solid, tetraglycine methyl ester: Change of the reaction mechanism
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Many drugs undergo chemical changes in the solid state, and understanding chemical reactivity of organic crystals is a critical factor in the drug development process. In this report, the impact of milling on the thermal chemical reactivity of an organic solid, tetraglycine methyl ester, was studied using DSC, isothermal calorimetry, chemical analysis (HPLC and insoluble residue determination), and powder X-ray diffraction. Significant changes in both X-ray diffraction patterns and DSC curves were detected after very brief milling (5 s). The changes were interpreted as the formation of a disordered phase. The disordered phase was tentatively identified as a crystal mesophase that combines properties of both crystalline (i.e., long-range order) and amorphous (i.e., glass transition) states. In the disordered material, the reaction mechanism changed from the methyl transfer reaction, which was observed in the intact crystal, to a polycondensation reaction when the reaction was performed at 165°C. Such changes in the reaction mechanism occurred in materials milled for > 30 s.
- Shalaev, Evgenyi,Shalaeva, Marina,Zografi, George
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- Single-phase and heterophase solid-state chemical kinetics of thermally induced methyl transfer in tetraglycine methyl ester
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To better understand the general interrelationships between chemical transformations and physical transformations in solid-state reactions, we have studied the kinetics of methyl transfer in polycrystalline samples of tetraglycine methyl ester (TGME) over the temperature range of 83 °C - 115 °C. Changes in the concentrations of the reactant and various intermediates (sarcosyltriglycine methyl ester METGME, and tetraglycine, TG) and products (sarcosyltriglycine, METG, and N,N-dimethyl glycyl triglycine, Me2TG) were measured over the entire time course of the reaction using HPLC. Corresponding measurements of physical transformations occurring during the course of the reaction were made using X-ray powder diffractometry and differential scanning calorimetry. Kinetic curves for the loss of TGME in the range of 83 °C - 115 °C have a sigmoidal shape and collapse into one curve when plotted in terms of reduced time, t/t0.5, as do plots of intermediate and product concentration plotted in the same manner. The first 25% of the reaction proceeds homogeneously through what is believed to be the formation of a crystalline solid solution of the intermediates and products in the reactant The acceleratory character of the kinetic curves in the single-phase portion of the reaction has been described by a kinetic scheme that contains a concentration-dependent rate constant. The appearance of a new crystalline phase beyond 35% of the reaction changes the reaction mechanism from a bulk reaction to an interface-controlled process that causes further acceleration of the methyl transfer. The apparent activation energies for both single-phase and heterophase stages of the reaction are about 100-130 kJ/mole.
- Shalaev,Byrn,Zografi
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- Mechanochemical Prebiotic Peptide Bond Formation**
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The presence of amino acids on the prebiotic Earth, either stemming from endogenous chemical routes or delivered by meteorites, is consensually accepted. Prebiotically plausible pathways to peptides from inactivated amino acids are still unclear as most oligomerization approaches rely on thermodynamically disfavored reactions in solution. Now, a combination of prebiotically plausible minerals and mechanochemical activation enables the oligomerization of glycine at ambient temperature in the absence of water. Raising the reaction temperature increases the degree of oligomerization concomitantly with the formation of a commonly unwanted cyclic glycine dimer (DKP). However, DKP is a productive intermediate in the mechanochemical oligomerization of glycine. The findings of this research show that mechanochemical peptide bond formation is a dynamic process that provides alternative routes towards oligopeptides and establishes new synthetic approaches for prebiotic chemistry.
- Cindro, Nikola,Grube?i?, Sa?a,Hernández, José G.,Me?trovi?, Ernest,Stolar, Tomislav,U?arevi?, Krunoslav
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supporting information
p. 12727 - 12731
(2021/05/07)
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- METHODS FOR CONJUGATING NUCLEIC ACIDS WITH SMALL MOLECULES
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A method for conjugating a nucleic acid with a molecule is provided. The method includes steps of (a) reacting the nucleic acid having a 5′-monophosphate with an activating agent in a first buffer to form a solution; (b) mixing an alcohol with the solution formed in the step (a) to obtain an intermediate; and (c) dissolving the intermediate in a second buffer containing an ethylenediaminetetraacetic acid (EDTA) and adding a nucleophile thereinto to react the intermediate with the nucleophile.
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- Spontaneous and promoted association of linear oligoglycines
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Linear oligoglycines of various lengths bearing a carboxyl or an amide group at their C-termini and also their poly(acrylamide) conjugates were synthesized. No self-assembly into supramolecular structures was observed for free oligoglycines H-(Gly)m-OH (m = 3-5). At the same time, oligoglycylamides H-(Gly)m-NH2 (m = 3-5) demonstrated ability for both self-assembly in aqueous solution and assembly promoted by an additional interaction with surface. In the case of polymer-bound oligoglycines (and their amides), no intramolecular clustering of peptide chains, as expected, was observed. This means that the presence of several oligoglycine chains bound to each other in one center is not a necessary prerequisite for polyglycine II-type association. Pleiades Publishing, Inc., 2006.
- Gorokhova,Chinarev,Tuzikov,Tsygankova,Bovin
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p. 420 - 428
(2008/02/10)
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- Convenient solid-phase synthesis of oligopeptides using pentacoordinated phosphoranes with amino acid residue as building blocks
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The reactive intermediates of pentacoordinated phosphoranes with amino acids (P(5)-AA) as building blocks, which were obtained by the reaction of O-phenylene phosphorochloridate with N,O-bis(trimethylsilyl)amino acids, were linked to a solid-phase support containing a hydroxymethyl polystyrene functional group. The first amino acid residue was coupled to the solid-phase support after washing the resin with organic solvent. Repeating the procedure led to oligopeptides linked on the resin. A series of free oligopeptides including tetra-Gly, di-Val, tri-Val, di-Leu, di-Phe, and Phe-Leu were obtained after cleavage from solid-phase support. The structure of these oligopeptides were determined by IR, 1H NMR, FAB-MS, and HPLC.
- Li, Zhaolong,Fu, Hua,Gong, Hegui,Zhao, Yufen
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p. 170 - 177
(2007/10/03)
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- Reaction of amino acids in a supercritical water-flow reactor simulating submarine hydrothermal systems
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A novel supercritical water flow-reactor was constructed in order to simulate submarine hydrothermal systems. The temperature of fluid inside the reaction tube could be monitored with thermocouples, which was proved to be different from the temperature outside the reaction tube. Oligomers of glycine up to tetraglycine were formed when a 100 mM glycine solution was heated at 200-350 °C for 2 minutes. None of glycine peptides were produced at 400 °C. It was suggested, however, that the formation of glycine condensates at higher temperature, including supercritical conditions of water. The stability of some amino acids under hydrothermal conditions was examined. ω-Amino acids and glutamic acid, which can form intramolecular condensates, showed higher stability than other α-amino acids at higher temperature, including supercritical conditions.
- Islam, Md. Nazrul,Kaneko, Takeo,Kobayashi, Kensei
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p. 1171 - 1178
(2007/10/03)
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- PEPTIDE FORMATION FROM AMINO ACID WITH PARTICULATE SEMICONDUCTOR PHOTOCATALYSTS
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Peptides of diglycine to pentaglycine are formed from glycine under irradiation in the presence of particulate semiconductor photocatalysts such as TiO2, CdS, CdSe, MoS2, In2O3, and GaP, with and without Pt deposition.Platinization of the semiconductors efficiently enhanced the yield of the peptides.
- Onoe, Jun,Kawai, Tomoji,Kawai, Shichio
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p. 1667 - 1670
(2007/10/02)
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