Rationalization of Lattice Thermal Expansion for Beta-Blocker Organic Crystals

Understanding the nature of the mechanical bond is critical to advancing the design of novel mechanically interlocked molecules. Given that numerous applications of new materials are related to solid-state properties, the behavior of the mechanical bond in the crystalline solid state is a key issue to be explored. Hence, this study sought to address how the freedom degree of the interlocked components can promote the formation of different crystalline phases. A series of rotaxanes substituted with different halogen atoms in the same position of the macrocycle were chosen as the model for study. Crystallization experiments were carried out in different solvents, obtaining 15 crystalline phases for the five studied compounds. The intercomponent interactions were evaluated in solution through variable-temperature 1 H NMR experiments and in the crystalline solid state through quantum mechanics calculations. All rotaxanes presented the same type of interaction in solution and the solid state, although the distribution of interaction energies was modified depending on the crystalline phase. Selecting the substituent at the macrocycle and using different crystallization solvents at different temperatures formed these different crystalline phases. At the supramolecular crystalline level, four similar comparisons were found correlating the different compounds, in which one was the anhydrous phase and the other three phases were solvates of chloroform, tetrahydrofuran, and toluene. The key to understanding the formation of the different crystalline forms is the presence of the mechanical bond, providing the flexibility and mobility of the entwined components for keeping the most favorable intermolecular interactions in each experimental condition assayed.

Section: Resultsmentioning

confidence: 99%

Mechanical Bonding as a Promoter of Crystalline Diversity in Halogenated [2]Rotaxanes

Orlando

Perez

Farias

et al. 2023

“…In the past, we have used X-ray diffraction (SCXRD, PXRD) thermoanalytical techniques (DSC, TGA, and HSM) and in-silico tools (e.g., modeling and data mining) to study the solid forms of APIs belonging to different classes (β-blockers, , NSAIDs) and in different forms (salts − and metal complexes) and to correlate their structural and physicochemical properties. , …”

Section: Introductionmentioning

confidence: 99%

“…In the past, we have used X-ray diffraction (SCXRD, PXRD) thermoanalytical techniques (DSC, TGA, and HSM) and insilico tools (e.g., modeling and data mining) to study the solid forms of APIs belonging to different classes (β-blockers, 11,12 NSAIDs) and in different forms (salts 13−15 and metal complexes) 16 and to correlate their structural and physicochemical properties. 17,18 With this in mind, and as part of our ongoing structural study of (S)-ketoprofen (S-Ket, hereafter), 19−21 its DSs with (R)-(+)-and (S)-(−)-1-phenylethylamine (α-methylbenzylamine; R-PEA and S-PEA, hereafter, Scheme 1) were prepared and investigated. 1-Phenylethylamine was chosen because (1) it is a commonly used resolving agent (it is cheap, and it has the chiral center close to the functional group involved in the recognition event); (2) with carboxylic acids, it forms robust charge-assisted hydrogen-bonded heterosynthons; 22 (3) the structures of both the homochiral and heterochiral DSs with (S)-ibuprofen (S-Ibu, hereafter) have already been described 23,24 as well as that of (S)-naproxen (S-Nap, hereafter) with R-PEA, 25 thus providing a first set of closely structurally related diastereomeric salts.…”

Section: ■ Introductionmentioning

confidence: 99%

Nonsteroidal Anti-Inflammatory Drugs–1-Phenylethylamine Diastereomeric Salts: A Systematic Solid-State Investigation

Rossi

Ceccarelli

Milazzo

et al. 2021

Self Cite

The solid-state investigation of the diastereomeric salts (S)-ibuprofen (S-Ibu), (S)-naproxen, (S-Nap), and (S)-ketoprofen (S-Ket) with (R)-(+)- and (S)-(−)-1-phenylethylamine, R-PEA, and S-PEA respectively, has been carried out by using a combination of experimental and in-silico tools. The focus was on their crystal packing and on the stability/transformation of their solid forms under different experimental conditions with the final aim of extracting useful information on the forces/features which could be exploited for the chiral separation of the corresponding racemic compounds. All the salts are 21-column crystals, each column consisting of API and 1-phenylethylamine ions assembled via the 1-phenylethylammonium-carboxylate supramolecular heterosynthon which originates a R 4 3 (10) pattern, the intercolumns contacts being definitely weaker. In spite of an overall similarity in the crystal packing forces and motifs of the anhydrous salts, the temperature stability range suggests that the homochiral species are the most stable. The fact that the homochiral salt of S-Ket (S-Ket_S-PEA) is stable toward the hydration, at variance with the heterochiral one (S-Ket_R-PEA), further confirms this hypothesis. On the other hand, preliminary sorption tests show that S-Ket and S-Ibu preferentially capture the homochiral PEA (S-Nap is not selective). This behavior has been correlated to the almost planar boundary surfaces which characterize and differentiate the 21 sheets in S-Ket_S-PEA and S-Ibu_S-PEA salts with respect to the corresponding heterochiral ones.

“…In particular, valuable information on the molecular and crystal structures of the corresponding crystalline solids have been extracted and correlated to their properties, e.g. , isotropic vs anisotropic thermal expansion, − chiral recognition, phase stability/transformation, solvation/desolvation processes, − and polymorphic behavior. − …”

Section: Introductionmentioning

confidence: 99%

Molecular-Level Investigation of Hydrate–Anhydrous Phase Transformations of the Dapsone Structurally Related Compound 3,3′-Diaminophenyl Sulfone

Paoli

Lippi

Milazzo

et al. 2022

Self Cite

The solid state of a novel hydrate form of 3,3′diaminophenyl sulfone (3APS_0.5H 2 Oo) as well as its temperatureinduced phase transitions is reported. On increasing the temperature, first a partial dehydration occurs, leading to the partially hydrated 3APS_0.1H 2 Oo, which then transforms into the monoclinic anhydrous form, 3APS_Am. Finally, by recrystallization of the melt 3APS_Am, a second anhydrous orthorhombic phase is obtained (3APS_Ao). This last phase transforms in 3APS_Am at a temperature between 360 and 400 K. XRD, DSC, TGA, HSM, and in silico data have been used to better understand the dehydration mechanism. With the same aim, hydration/ dehydration tests have been carried out. Finally, the dehydration behavior of 3APS_0.5H 2 O has been discussed in comparison with that of the dapsone hydrated phase 4APS_0.33H 2 Om.