Solvates of Dasatinib: Diversity and Isostructurality
A series of dasatinib crystalline forms were obtained, and a hierarchical cluster analysis of their powder X-ray diffraction patterns was performed. The resulting dendrogram implies 3 structural groups. The crystal structures of several solvates representing 2 of these groups were determined. The crystal structure analysis confirms the isostructurality of solvates within structural group I and suggests a correlation between solvent molecule size and trends in crystal structures within this group. In addition, the formation relationships in 2-solvent media between different dasatinib solvate groups were determined. The formation preference of solvates was found to follow the ranking group I …
On the Formation of Droperidol Solvates: Characterization of Structure and Properties
A solvate screening and characterization of the obtained solvates was performed to rationalize and understand the solvate formation of active pharamaceutical ingredient droperidol. The solvate screening revealed that droperidol can form 11 different solvates. The analysis of the crystal structures and molecular properties revealed that droperidol solvate formation is mainly driven by the inability of droperidol molecules to pack efficiently. The obtained droperidol solvates were characterized by X-ray diffraction and thermal analysis. It was found that droperidol forms seven nonstoichiometric isostructural solvates, and the crystal structures were determined for five of these solvates. To b…
Solid Solutions in the Xanthone–Thioxanthone Binary System: How Well Are Similar Molecules Discriminated in the Solid State?
The binary system of xanthone–thioxanthone has been explored, showing that two solid solutions (formed based on xanthone and thioxanthone parent structures, respectively) exist for this system. One...
Comparison and Rationalization of Droperidol Isostructural Solvate Stability: An Experimental and Computational Study
In order to find a tool for comparison of solvate stability and to rationalize their relative stability, droperidol nonstoichiometric isostructural solvates were characterized experimentally and computationally. For the experimental evaluation of stability, three comparison tools were considered: thermal stability characterized by the desolvation rate, desolvation activation energy, and solvent sorption–desorption isotherms. It was found that the desolvation process was limited by diffusion, and the same activation energy values were obtained for all of the characterized solvates, while the solvent content in the sorption isotherm was determined by the steric factors. Therefore, the only cr…
Designing Solid Solutions of Enantiomers: Lack of Enantioselectivity of Chiral Naphthalimide Derivatives in the Solid State
The enantiomers of a previously reported naphthalimide derivative are shown in this study to form a solid solution; furthermore, on the basis of the knowledge of solid solution structural aspects other naphthalimide derivatives have been synthesized and shown to lack the enantioselectivity in the solid state. The structural origin of solid solution formation is the same as observed in most of the cases in the literaturequasi-centrosymmetric structures form at nonracemic compositions where the most abundant enantiomer adjusts its conformation to mimic the absent one. Such solid solutions belong to the type showing some enantioselectivity. An extended single crystal X-ray diffraction study o…
Structure and Stability of Racemic and Enantiopure Pimobendan Monohydrates: On the Phenomenon of Unusually High Stability
Study of structures and physicochemical properties of racemic (rac-H) and enantiopure (enant-H) hydrates of the active pharmaceutical ingredient pimobendan revealed that both hydrates have highly similar crystal structures and exhibit unusually high stability. Both structures contain identical two-dimensional layers and very similar conformations. The most significant difference is the stacking of these layers. The high stability of both hydrates appeared as extremely low solubility over a wide temperature range as well as an exceptionally high dehydration temperature and melting point. Study of the dehydration process showed that both hydrates have different activation energies of dehydrat…
Single Enantiomer’s Urge to Crystallize in Centrosymmetric Space Groups: Solid Solutions of Phenylpiracetam
A detailed thermochemical and structural study of the phenylpiracetam enantiomer system was performed by characterizing the solid solutions, rationalizing the structural driving force for their formation, as well as identifying a common structural origin responsible for the formation of solid solutions of enantiomers. Enantiomerically pure phenylpiracetam forms two enantiotropically related polymorphs (enant–A and enant–B). The transition point (70(7) °C) was determined based on isobaric heat capacity measurements. Structural studies revealed that enant–A and enant–B crystallize in space groups P1 (Z′ = 4) and P212121 (Z′ = 2), respectively. However, pseudoinversion centers were present res…
Formation and Transformations of Organic Salt Hydrates: Four Encenicline Hydrochloride Monohydrates and Respective Isostructural Desolvates
Encenicline hydrochloride (Enc-HCl) crystallizes in four different monohydrate phases, but at the same time crystallization in a nonsolvated phase is not observed, indicating that water plays a crucial role in guiding the crystallization process and ensuring structure stability. All monohydrate phases show exceptionally high stability, and the main structural motif stays intact even after dehydration, leading to isostructural (for I and II) or isomorphic (for III) desolvates. Three monohydrate phases with determined crystal structure information consists of Enc-HCl-water hexamers that are stacked into similar slabs, that are further packed identically in monohydrates I, II, and III. The fea…
Crystallization of chiral molecular compounds: what can be learned from the Cambridge Structural Database?
A detailed study on chiral compound structures found in the Cambridge Structural Database (CSD) is presented. Solvates, salts and co-crystals have intentionally been excluded, in order to focus on the most basic structures of single enantiomers, scalemates and racemates. Similarity between the latter and structures of achiral monomolecular compounds has been established and utilized to arrive at important conclusions about crystallization of chiral compounds. For example, the fundamental phenomenon of conglomerate formation and, in particular, their frequency of occurrence is addressed. In addition, rarely occurring kryptoracemates and scalemic compounds (anomalous racemates) are discussed.…
On the structural aspects of solid solutions of enantiomers: an intriguing case study of enantiomer recognition in the solid state
Structural aspects of solid solutions of enantiomers have been considered and the corresponding definitions of type 1 and type 2 solid solutions have been revised based on the available structures reported in the literature. Examples of both types are presented indicating that (e.g., type 1 solid solutions) there is a straightforward relationship between the particular structural aspects and the enantiomer miscibility limits in the solid state. Furthermore, enantiomer recognition in a type 2 solid solution formed by the enantiomers of a pharmaceutically active ingredient, pimobendan, has been studied in more detail. It was found that upon rapid crystallization from a solution a structure po…
Disorder in molecular crystals justified with the help of statistical mechanics: a case of two enantiomer solid solutions
An elegant statistical mechanics approach has been exploited in combination with accurate quantum chemical calculations to justify the disorder in two previously reported racemic solids. Generated canonical ensembles and performed lattice energy calculations show that the disorder in the studied systems of small organic enantiomer molecules can be modelled with great accuracy. Ensemble averages fully correspond to the disordered structure models repeatedly obtained in X-ray diffraction studies. The present work not only demonstrates that disorder and its extent in molecular crystals can be theoretically calculated, but also explains from a thermodynamic point of view the origins of the rare…
Polymorphism of R-Encenicline Hydrochloride: Access to the Highest Number of Structurally Characterized Polymorphs Using Desolvation of Various Solvates
In a study of the solid form landscape of R-encenicline hydrochloride (Enc-HCl), it was found that this compound is dodecamorphic and presents the first published example of polymorphism with a rec...
A Maze of Solid Solutions of Pimobendan Enantiomers: An Extraordinary Case of Polymorph and Solvate Diversity
Over 10 polymorphs and solvatomorphs of the chiral pharmaceutically active ingredient pimobendan were found to lack enantioselectivity in the solid state, accordingly, forming solid solutions of enantiomers, which is reported to be a rare phenomenon. Solid form screening was performed on different enantiomeric composition samples to analyze obtained phases with powder X-ray diffraction and thermogravimetric differential scanning calorimetry. For nonsolvated forms, a melt phase diagram has been constructed convincingly showing the existence of stable and metastable solid solutions near the pure enantiomer and around the racemic composition regions. A crystal structure study combined with sol…
CCDC 1584618: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 2030974: Experimental Crystal Structure Determination
Related Article: Kristaps Saršu̅ns, Agris Be̅rziņš, Toms Rekis|2020|Cryst.Growth Des.|20|7997|doi:10.1021/acs.cgd.0c01241
CCDC 1523462: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be̅rziņš, Lia̅na Orola Tamás Holczbauer, Andris Actinš, Andreas Seidel-Morgenstern, Heike Lorenz|2017|Cryst.Growth Des.|17|1411|doi:10.1021/acs.cgd.6b01867
CCDC 1895188: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1584619: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1569159: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1895194: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1916269: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2020|CSD Communication|||
CCDC 1420813: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1584616: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1895196: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1916266: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1050684: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be¯rzinš, Inese Sarcevica, Artis Kons, Ma¯rtinš Balodis, Lia¯na Orola, Heike Lorenz, Andris Actinš|2018|Cryst.Growth Des.|18|264|doi:10.1021/acs.cgd.7b01203
CCDC 1569164: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1916267: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1584621: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1895193: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1569163: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1453864: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be̅rziņš, Dia̅na Džabijeva, Ilva Nakurte, Lia̅na Orola, and Andris Actiņš|2017|Cryst.Growth Des.|17|1814|doi:10.1021/acs.cgd.6b01780
CCDC 1420812: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1420811: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1420810: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1895198: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1895189: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1584620: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1584617: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1895195: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1895199: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1571124: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be¯rzinš, Inese Sarcevica, Artis Kons, Ma¯rtinš Balodis, Lia¯na Orola, Heike Lorenz, Andris Actinš|2018|Cryst.Growth Des.|18|264|doi:10.1021/acs.cgd.7b01203
CCDC 1569161: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1569160: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1453863: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be̅rziņš, Dia̅na Džabijeva, Ilva Nakurte, Lia̅na Orola, and Andris Actiņš|2017|Cryst.Growth Des.|17|1814|doi:10.1021/acs.cgd.6b01780
CCDC 1569165: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 2030975: Experimental Crystal Structure Determination
Related Article: Kristaps Saršu̅ns, Agris Be̅rziņš, Toms Rekis|2020|Cryst.Growth Des.|20|7997|doi:10.1021/acs.cgd.0c01241
CCDC 1895190: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1420814: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1895192: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1420809: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1420807: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1916268: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1420808: Experimental Crystal Structure Determination
Related Article: Inese Sarceviča, IlzeGrante, Sergey Belyakov, Toms Rekis, Kārlis Bērziņš, Andris Actiņš, Liāna Orola|2016|J.Pharm.Sci.|105|1489|doi:10.1016/j.xphs.2016.01.024
CCDC 1895191: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1569157: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1584615: Experimental Crystal Structure Determination
Related Article: Raitis Bobrovs, Artis Kons, Agris Be¯rzinš, Toms Rekis, Andris Actinš|2018|Cryst.Growth Des.|18|2100|doi:10.1021/acs.cgd.7b01561
CCDC 1569158: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1895197: Experimental Crystal Structure Determination
Related Article: Artis Kons, Agris Bērziņš, Andris Actiņš, Toms Rekis, Sander Van Smaalen, Anatoly Mishnev|2019|Cryst.Growth Des.|19|4765|doi:10.1021/acs.cgd.9b00648
CCDC 1569162: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Simone d’Agostino, Dario Braga, Fabrizia Grepioni|2017|Cryst.Growth Des.|17|6477|doi:10.1021/acs.cgd.7b01146
CCDC 1523460: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be̅rziņš, Lia̅na Orola Tamás Holczbauer, Andris Actinš, Andreas Seidel-Morgenstern, Heike Lorenz|2017|Cryst.Growth Des.|17|1411|doi:10.1021/acs.cgd.6b01867
CCDC 1523461: Experimental Crystal Structure Determination
Related Article: Toms Rekis, Agris Be̅rziņš, Lia̅na Orola Tamás Holczbauer, Andris Actinš, Andreas Seidel-Morgenstern, Heike Lorenz|2017|Cryst.Growth Des.|17|1411|doi:10.1021/acs.cgd.6b01867