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• 13075-43-9 glycyl-glycyl-glycyl-glycine methyl ester 

Relevant academic research and scientific papers

The effect of disorder on the chemical reactivity of an organic solid, tetraglycine methyl ester: Change of the reaction mechanism

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.

Single-phase and heterophase solid-state chemical kinetics of thermally induced methyl transfer in tetraglycine methyl ester

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.