RESUMEN
The polymorphism of rac-5,6-diisobutyryloxy-2-methylamino-1,2,3,4-tetrahydro-naphthalene hydrochloride (CHF 1035) was investigated. Three different crystal forms (Form I, Form II, and Form III) were obtained by recrystallization procedures from common organic solvents. The polymorphs were characterized by Raman and carbon-13 nuclear magnetic resonance ((13)C NMR) spectroscopy, in solution and in solid state (cross polarization-magic angle spinning), powder X-ray diffractometry, and thermal methods (differential scanning calorimetry, hot stage microscopy, and thermogravimetry). Moreover, the diffraction patterns of Form I, collected at controlled temperatures, gave evidence of the presence of two reversible structural rearrangements at approximately 60 and approximately 75 degrees C. These structural variations were confirmed by the results obtained by differential scanning calorimetry and hot stage microscopy techniques. The analysis of the Raman spectra allowed the identification of peculiar absorption bands for each polymorph. Form III was the stable crystal form at room temperature as determined by the basis of slurry conversion method.
Asunto(s)
Ésteres , Naftalenos/química , Tetrahidronaftalenos , Rastreo Diferencial de Calorimetría , Cristalización , Espectroscopía de Resonancia Magnética , Espectrometría Raman , Difracción de Rayos XRESUMEN
This study investigates the polymorphism of piroxicam ester with pivalic acid. Two crystal modifications were prepared by recrystallization from toluene (form 1) and ethyl acetate (form 2). Data regarding preparation conditions, solid state properties, and physicochemical characterization of two polymorphs by means of FT/IR spectroscopy, X-ray diffractometry on powder, and thermal analysis are reported. Heat of fusion rule and thermodynamic formulas consistently indicate an enantiotropic stability relationship of forms 1 and 2 with a calculated transition point (32 degrees C) near the ambient temperature. The phase diagrams of each polymorph with piroxicam were also investigated in order to gain information about the thermal behavior of their solid mixtures. Liquidus curves calculated by the Schröder-Van Laar equation from fusion enthalpies and temperatures were found to agree satisfactorily with experimental results obtained by first heating runs with differential scanning calorimetry.
Asunto(s)
Antiinflamatorios no Esteroideos/química , Piroxicam/química , Antiinflamatorios no Esteroideos/síntesis química , Cromatografía Líquida de Alta Presión , Cristalografía por Rayos X , Ácidos Pentanoicos/química , Piroxicam/síntesis química , Espectroscopía Infrarroja por Transformada de Fourier , Estereoisomerismo , TermodinámicaRESUMEN
A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was synthesized by C6-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show and difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes ("cis effect"), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI.