Crystal engineering plays a crucial role in controlling the structure, morphology, and functional properties of crystalline materials across multiple disciplines, including pharmaceutical science. Among various particle engineering techniques, crystallo-co-agglomeration (CCA) has gained significant attention as an innovative method for tailoring the physicochemical and mechanical properties of crystalline drug substances. By combining crystallization and agglomeration in a single process, CCA enables the formation of spherical crystalline agglomerates with improved particle size distribution, flowability, and compressibility.

The technique typically employs a ternary solvent system consisting of a good solvent, an anti-solvent, and a bridging liquid that promotes crystal agglomeration during nucleation and growth. Through careful control of process parameters such as solvent composition, agitation intensity, temperature, and bridging liquid concentration, the morphology and internal structure of crystalline agglomerates can be precisely engineered. This approach enables the production of functional crystalline particles with enhanced downstream processing characteristics.

From a crystal engineering perspective, CCA offers unique opportunities to manipulate crystal habit, surface properties, and interparticle interactions. The method also allows the incorporation of excipients or secondary components to produce composite crystalline materials with tailored dissolution and mechanical behavior. Recent studies have further demonstrated the potential of integrating advanced analytical techniques and computational tools to understand and optimize agglomeration mechanisms. Consequently, CCA provides an effective strategy for designing advanced crystalline pharmaceutical materials while contributing to broader developments in crystal engineering and materials science.

Introduction: Xanthenes are important representatives of oxygen-containing tricyclic compounds. Several xanthene derivatives, including 9H-xanthene, xanthydrol, and xanthene-9-carboxylic acid, display diverse biological activities such as neuroprotective, antiparasitic, cytotoxic, and antibacterial effects. In this study, two xanthene-1,8(2H)-diones bearing 3-chloro-4-hydroxyphenyl (1) and 3,5-dibromo-4-hydroxyphenyl (2) groups in position 9 were synthesized via condensation of dimedone with the corresponding benzaldehydes. Their crystal structures were determined and analysed through the identification and quantification of simple dimeric motifs arising from distinct intermolecular interactions, thus extending our ongoing crystallographic studies on structurally related small molecules of pharmacological interest.

Methods: The structures were confirmed by spectroscopic methods. The single crystals suitable for X-ray diffraction were obtained by slow evaporation from ethanol. Data collection was performed on an Oxford Gemini S diffractometer. The computational calculations were conducted with Gaussian 09 and CrystalExplorer 21.5. These compounds were also examined with SwissADME and PreADMET in silico tools

Results: Both compounds share the same conformation, with a central shallow boat and twisted outer rings. Compound 1 forms chains along the a-axis via C–H···O interactions, which further assemble into zig-zag double chains through O–H···O hydrogen bonds and Cl···π interactions. In compound 2, alternating asymmetric units are connected by O–H···O, C–H···O, and Br···Br interactions and form chains, with additional C–H···O and C–H···π contacts extending the network. Both compounds display similar distributions of H···H, O···H and C···H contacts, although X···H and X···C interactions are more pronounced in 2. Based on the values of the molecular descriptors, these compounds meet all the necessary empirical criteria, which qualify them as interesting drug candidates.

Conclusions: These compounds demonstrate the potential of xanthene-1,8-diones as versatile building blocks for constructing interesting supramolecular structures of pharmaceutical relevance.

Introduction

Hydrodynamics plays a central role in antisolvent crystallization by governing mixing and supersaturation generation, which in turn controls crystal growth [1]. While previous studies report the distributions of flow and crystallization fields, the mechanistic role of shear rate in governing growth through transport phenomena remains insufficiently understood.

Methods

A coupled computational fluid dynamics–population balance model (CFD-PBM) is employed to investigate the influence of shear rate on crystal growth under steady-state laminar conditions [2]. A two-dimensional axisymmetric configuration is considered for nickel sulphate hexahydrate (NiSO₄.6H₂O) crystallization using ethanol as the antisolvent. Supersaturation is generated by the reduction in solubility caused by the addition of an antisolvent to the initially saturated aqueous salt solution at a constant temperature. The size-independent growth rate is applied to the crystal growth.

Results

Shear-induced mixing modifies the spatial distribution of supersaturation and thereby controls growth dynamics. Increasing shear rate enhances convective transport, producing sharper supersaturation gradients and leading to stronger spatial confinement of the growth zone near the mixing interface. In contrast, lower shear conditions result in broader supersaturation fields and more distributed growth regions. The magnitude of the crystal growth rate correlates directly with local supersaturation.

Conclusions

Shear does not intrinsically alter growth kinetics but acts indirectly through transport modulation. This study provides a mechanistic framework for understanding shear-mediated transport effects in growth-dominated antisolvent crystallization systems, connecting hydrodynamic shear to crystal growth and distribution.

References

[1] D.L. Marchisio, M. Soos, J. Sefcik, M. Morbidelli, A.A. Barresi, G. Baldi, Effect of fluid dynamics on particle size distribution in particulate processes, Chem. Eng. Technol. 29 (2006) 191–199. https://doi.org/10.1002/ceat.200500358.

[2] V. Jha, C. Duwig, S. Teimouri, K. Forsberg, Metal recovery from spent batteries through antisolvent crystallization in a T-mixer using a coupled CFD-PBE approach, in: Centre for Evaluation in Education and Science (CEON/CEES), 2025: pp. 407–412. https://doi.org/10.5937/imprc25407k.

Non-centrosymmetric superconductors are the subject of intensive study because the lack of an inversion center can lead to mixed spin-singlet and spin-triplet pairing states[1]. Here, we investigate the optical properties with the help of electronic transitions for non-centrosymmetric superconductors based on Th with the stoichiometry Th₇T₃ (T=Fe, Co, Ni) [3-5], which exhibit weak electron correlations. The full potential linear augmented plane wave (FP-LAPW) method was employed, as well as scalar and fully relativistic treatments. The Th₇T₃ ​ compounds crystallize in the hexagonal Th₇Fe₃-type structure (space group P6_3​mc) and undergo a superconducting transition at Tc≈2TK. The crystal unit cell contains three inequivalent thorium positions (Th1, Th2 at 6c, Th3 at 2b) and one transition metal position (6c). By replacing the Fe with Co or Co with Ni, one additional electron is added to the system. This substitution of one transition metal atom for another, along with the change in atomic masses and the role of the relativistic effect of the thorium atoms, leads to interesting properties in the electronic and optical structures of the Th₇T₃ compounds. We emphasize the role of the ASOC strength since anisotropic spin splitting, both in the band structure and optical properties, emerges when one takes into account the spin–orbit coupling in the calculations. By providing the frequency-independent dielectric function calculations at 2, 10, and 50 K temperatures, we assume that transitions between Th-6d and T-d valence electrons are mainly responsible for the superconducting properties.

[1]Bauer, E. & Sigrist, M. Non-Centrosymmetric Superconductors: Springer-Verlag Berlin Heidelberg 847 (2012).

[2-3] Sahakyan, M. & Tran, V. H. Journal of Physics: Cond Mat 28, 205701 (2016), Phil. Mag. 42, 957-966 (2017).

[4] Tran, V. H. & Sahakyan, M. Scientific Reports 7, 15769 (2017).

[5] R Idczak, M Sahakyan, VH Tran Journal of Physics: Condensed Matter 30 (47), 475802 (2018).

This study investigates the nanoindentation response of Ag coating deposited on Cu (111) substrate using molecular dynamics (MD) simulations, with a particular focus on the role of crystallographic orientation and loading conditions. Three different Ag bilayer orientations, namely Ag (100), Ag (110), and Ag (111), are systematically analyzed to evaluate how heterogeneous interfaces affect the deformation mechanisms and mechanical behavior at the nanoscale. The results demonstrate that the Ag (111)/Cu (111) configuration produces a higher indentation force compared to the Ag (100)/Cu (111) and Ag (110)/Cu (111) systems, indicating enhanced resistance to deformation. This behavior is attributed to the lower lattice mismatch and better atomic registry at the Ag (111)/Cu (111) interface, which promotes stronger interfacial bonding and improved load transfer. Furthermore, the influence of indentation velocity is examined for the Ag (111)/Cu (111) bilayer by varying the velocity from 120 m/s to 200 m/s. The simulation results reveal a clear trend of increasing force and hardness with higher indentation velocities, suggesting a strain-rate-dependent strengthening effect. At elevated velocities, limited time for atomic relaxation leads to increased resistance against plastic deformation. Dislocation extraction analysis (DXA) further supports these findings by revealing the nucleation and evolution of dislocations and defects, particularly near the interface region. The density and complexity of dislocation structures increase with both improved interface coherence and higher indentation velocities, providing deeper insight into the fundamental mechanisms governing the mechanical performance of Ag/Cu bilayer systems.

Introduction

The phage shock protein (Psp) system is essential for maintaining membrane integrity under stress conditions in bacteria. Determining its three-dimensional structure requires well-ordered crystals, typically obtained through controlled crystallization methods. In this manuscript we present a range of crystal morphologies, reflecting variations in nucleation and growth conditions.

Methods

Crystallization was performed using the sitting drop vapor diffusion technique. A drop containing purified phage shock protein mixed with precipitant solution was equilibrated against a reservoir with higher precipitant concentration. Vapor diffusion gradually increased protein supersaturation within the drop, promoting nucleation and subsequent crystal growth. Experimental parameters such as protein concentration, precipitant composition, pH, and temperature were systematically optimized.

Results

We have seen multiple crystal forms of same protein in different condition. Well-defined hexagonal crystals indicate highly ordered growth under near-equilibrium conditions. Rod-shaped crystals suggest anisotropic growth along a preferred axis, while dendritic and clustered structures are indicative of rapid nucleation at high supersaturation. Regions containing numerous microcrystals suggest excessive nucleation with limited crystal growth.

Discussion

Crystal formation can be interpreted using thermodynamic principles, where the Gibbs free energy change is given by:

Here, represents the bulk free energy change, is the interfacial surface tension, is the nucleus volume, and is the surface area. The presence of well-formed hexagonal crystals suggests minimized free energy and stable growth conditions, whereas dendritic and clustered morphologies indicate kinetically dominated regimes. These observations highlight the importance of controlling supersaturation to balance nucleation and growth, ultimately improving crystal quality for structural analysis.

TiNi alloy thin films have attracted significant attention in both research and industrial applications, owing to their remarkable functional properties. These include the shape memory effect and superelasticity, which originate from the reversible phase transformation between martensite and austenite. In addition, TiNi thin films exhibit excellent corrosion resistance, good biocompatibility, and superior damping capacity. Consequently, the investigation of the physical conditions enabling the achievement of these properties requires a thorough understanding of the production processes of these thin films. At present, experimental characterization techniques alone are not sufficient to fully elucidate the mechanisms governing thin film growth at the nanoscale. Implementing advanced simulation techniques, such as molecular dynamics (MD), offers an effective solution to this issue. In this study, we investigated the atomic-scale growth of TiNi films using MD method. The effects of the incident energy and substrate temperature are explored in details from the atomic scale. The films deposited with an incidence energy of 0.1 eV show a rough morphology due to their low surface mobility. However, as the energy increased from 1 to 15 eV, the morphology became smoother. This is explained by the high mobility of deposited atoms, which inhibits cluster formation on the surface. Increasing the substrate temperature from 300 to 600 K slightly reduces the film roughness. This is due to the enhanced agitation of the atoms, which also promotes the filling of surface voids. The results also show that at energies above 5 eV, at the film-substrate interface, some atoms from the film penetrate the upper layers of the substrate, while some atoms from the substrate are ejected into the film. The average atomic stress was calculated and found to be consistent with the experimental stress values.

Introduction: Noncovalent interactions act as a chemical glue that binds molecular entities and governs the formation of sophisticated functional materials. Beyond classical hydrogen bonding, halogen bonding, and related directional contacts involving elements across the periodic table, anti-electrostatic interactions have recently emerged as an unusual class of intermolecular interactions. These involve contacts between like-charged species that are expected to be repulsive based on simple electrostatic considerations, yet are frequently observed in crystalline solids.

Halogen oxyanions such as XO₃⁻ provide a particularly intriguing platform for examining such behavior. Numerous crystal structures display short X···O contacts between anions, often interpreted as halogen bonding. However, whether these contacts represent genuine attractive interactions or arise from environment-induced polarization remains unclear.

Results and discussion: In this work, we examined a series of anion–anion assemblies involving halogen oxyanions using density functional theory in both gas and solution phases. The optimized structures reveal that several systems stabilized in solution exhibit short X···O contacts that resemble halogen bonds. However, SAPT energy decomposition analysis shows that these interactions are characterized by large positive electrostatic contributions, and the total interaction energies are also positive when evaluated in the gas phase.

These findings indicate that the apparent stabilization of the dimers does not originate from intrinsic attractive halogen bonding. Instead, the structures are maintained by solvent screening and polarization effects that reduce Coulomb repulsion and allow weaker induction and dispersion contributions to shape the geometry. The persistence of these motifs in crystalline materials therefore arises from collective influences, including counterions, packing constraints, and polarization, rather than from intrinsic attractive forces between the isolated anions. These aspects are discussed in detail.

Non-covalent interactions, particularly halogen–halogen and halogen–hydrogen bonds, play a fundamental role in supramolecular chemistry and are key determinants in the design and stabilization of hierarchical molecular architectures. In this work, we investigate in detail the intermolecular interactions governing the formation and stabilization of a dimer composed of two bromine-substituted hexahelicene (Br-Hexahelicene) molecules, which are inherently chiral helical systems built from six fused aromatic rings.

Geometry optimizations were carried out using the semi-empirical MOPAC method, revealing the presence of two enantiomeric forms, denoted M and P. These enantiomers can self-assemble into energetically equivalent homo-chiral dimers (MM and PP), highlighting the role of molecular chirality in the organization of supramolecular systems. To better understand the origin of stability, an energy decomposition analysis was performed, showing that the dimers are stabilized by a combination of directional short-range interactions and dispersive forces.

In particular, characteristic contacts such as C–Br···Br–C (3.55 Å) and C–Br···H–C (2.97 Å) were identified, together with significant van der Waals contributions. The computed interaction energies (–4.50, –3.33, and –5.44 kcal/mol) clearly indicate that halogen–halogen and halogen–hydrogen bonding interactions constitute the dominant driving forces in the self-assembly process. Additionally, advanced topological and electronic analyses, including the Interaction Region Indicator (IRI), electrostatic potential mapping, and bond-path analysis using Multiwfn, provide a clear visualization and confirmation of the interaction regions, revealing the presence of triangular Br···Br···H binding motifs.

Overall, these results demonstrate the strong propensity of Br-Hexahelicene molecules to form well-organized supramolecular assemblies, emphasizing the crucial role of halogen bonding in the rational design of functional chiral materials with promising applications in nanoscience and surface-based molecular engineering.

The design of crystalline materials with tailored properties requires a profound understanding of molecular self-assembly principles. Quinazoline derivatives are essential pharmacophores [1]; however, the influence of specific substituents on their solid-state packing remains insufficiently explored. This study investigates the "chalcogen-switch" strategy, examining how substituting sulfur with oxygen and modifying the hydrocarbon radical volume serves as a directional mechanism for controlling supramolecular architecture. Three quinazoline derivatives—benzylthio-, methylthio- and ethoxy-substituted—were characterized via single-crystal X-ray diffraction. Structural refinement was performed using the Olex2 software package [2]. To visualize and quantify the competition between π∙∙∙π stacking of the quinazoline cores and directional chalcogen-mediated contacts, Hirshfeld surface analysis and 2D fingerprint plots were generated using CrystalExplorer [3] . The compounds crystallize in the monoclinic system (P21 and P21/c) with very good quality (R1: 2.09%–3.96%). Hirshfeld surface analysis (dnorm) revealed that while H∙∙∙H contacts dominate (45–55%), chalcogen-mediated interactions primarily dictate the crystal growth direction. Thio-derivatives exhibit diffuse yet numerous S∙∙∙H contacts, promoting flexible packing. In the ethoxy-derivative, the presence of the rigid, highly electronegative oxygen atom leads to shorter and more directional O∙∙∙H contacts, significantly altering the fingerprint plot landscape by shifting the "spikes" toward lower di/de regions. Our study demonstrates that subtle structural modulation, such as replacing sulfur with oxygen or increasing substituent bulk from methyl to benzyl, can fundamentally redirect the supramolecular landscape of quinazolines. These findings establish a predictive framework for using selective chalcogen substitution as a crystal engineering tool to design heterocyclic materials with controlled physicochemical properties.

1. Kalakwade, A. et all. Results in Chemistry, 2026, 19, 102932.
2. Dolomanov, O.V. et all. Journal of Applied Crystallography, 2009, 42, 339-341.
3. Spackman, M.A. and Jayatilaka D. . CrystEngComm, 2009, 11,19-32.