a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

We report a semiquantitative method for determining trace amounts (less than 1%) of thermodynamically stable forms in polymorphic mixtures, focusing on sample preparation effects on solid phase transitions. Tegafur [5-fluoro-1-(oxolan-2-yl)-1,2,3,4-tetrahydropyrimidine-2,4-dione] was used as a model material in this study. The amounts of the thermodynamically stable β tegafur were increased to levels detectable by powder X-ray diffractometry by grinding the samples in a ball mill in the presence of water. The limit of detection for this method was as low as 0.0005% of β tegafur in α and β tegafur mixtures. The amount of β tegafur after sample preparation was found to be proportional to the initial weight fraction of β tegafur. The sum of Langmuir and Cauchy-Lorentz equations was used to describe the change in conversion degree due to the added water volume, where Langmuir equation described water sorption during the sample preparation and Cauchy-Lorentz equation described the grinding efficiency.

a. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

b. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

In the title compound, C21H26ClN2O 4S.Cl, also known as tianeptine hydrochloride, the seven-membered ring adopts a boat conformation. The dihedral angle between the mean planes of the benzene rings is 44.44(7)°. There is an intramolecular hydrogen bond formed via S= O⋯H-N. In the crystal, molecules are connected via pairs of N-H.·O, N-H⋯Cl and O-H⋯Cl hydrogen bonds, forming inversion dimers, which are consolidated by C-H⋯O interactions. The dimers are linked by C-H⋯O and C-H⋯Cl interactions, forming a two-dimensional network lying parallel to (011).

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

The objective of this work was to investigate the relative humidity (RH) and solvent vapor pressure effects on the phase transition dynamics between tegafur polymorphic forms that do not form hydrates and solvates. The commercially available α and β modifications of 5-fluoro-1- (tetrahydro-2-furyl)-uracil, known as the antitumor agent tegafur, were used as model materials for this study. While investigating the phase transitions of α and β tegafur under various partial pressures of methanol, n-propanol, n-butanol, and water vapor, it was determined that the phase transition rate increased in the presence of solvent vapors, even though no solvates were formed. By increasing the relative air humidity from 20% to 80%, the phase transition rate constant of α and β tegafur was increased about 60 times. After increasing the partial pressure of methanol, n-propanol, or n-butanol vapor, the phase transition rate constant did not change, but the extent of phase transformation was increased. In the homologous row of n-alcohols, the phase transition rate constant decreased with increasing carbon chain length. The dependence of phase transformation extent versus the RH corresponded to the polymolecular adsorption isotherm with a possible capillary condensation effect.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

b. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

The anti-depressant pharmaceutical tianeptine has been investigated to determine the dynamics of polymorph formation under various pH conditions. By varying the pH two crystalline polymorphs were isolated. The molecular and crystal structures have been determined to identify the two polymorphs. One polymorph is an amino carboxylic acid and the other polymorph is a zwitterion. In the solid state the tianeptine moieties are bonded through hydrogen bonds. The zwitterion was found to be less stable and transformed to the acid form. During this investigation an amorphous form was identified.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

b. Laboratory of Inorganic Chemistry, Department of Chemistry, University of Helsinki, Helsinki 00014, Finland

c. Latvia Institute of Organic Synthesis, Aizkraukles 21, Riga 1006, Latvia

Structural analysis of the supramolecular cocrystals formed by pyrogallol with acridine, 4,4′-bipyridine, and 1,10-phenanthroline shows that the studied cocrystals are assembled via the hydroxyl-pyridine heterosynthon. In the crystal and molecular structures of these cocrystals in order to form the maximum number of hydrogen bonds, taking into consideration steric effects, the pyrogallol moiety in the supramolecular arrangement has the following conformations: with acridine - syn1, 4,4′-bipyridine - anti, and 1,10-phenanthroline - syn2. Discrete supramolecular complexes are formed by acridine-pyrogallol and the 1,10-phenanthroline-pyrogallol polymorph I. The 1,10-phenanthroline-pyrogallol polymorph II and the 4,4′-bipyridine- pyrogallol trihydrate form extended hydrogen bonded chains.

a. Faculty of Chemistry, University of Latvia, Kr. Valdemara 48, Riga 1013, Latvia

A new methodology for the simulation of solid state phase transition kinetics has been developed by combining the influence of nucleation rate, nuclei growth rate and the power p characterizing the contact area between the growing particles. The equations used in this methodology were well known, and have been used previously for creating some of the most popular solid-state kinetic equations. The developed methodology made possible calculations of separate rate constants for two processes affecting the rate of phase transition-nucleation (described with K 1) and nuclei growth (described with K 2). Similar phase transitions were also approximated with the well-known single constant Avrami-Erofeev equation, but we successfully calculated both constants according to the new methodology, which allowed a separate evaluation of these two processes and explained the different induction periods. The effects of empirically adjusted constants on theoretically calculated kinetic curves were thus determined.