Crystal Growth & Design最新文献

Crystallization of proteins, specifically proteins of medical relevance, is performed for various reasons, such as to understand the protein structure and to design therapies. Obtaining kinetic constants in rate laws for nucleation and growth of advanced biotherapeutics such as capsids, an assembly of macromolecules, is challenging and essential to the design of crystallization processes. In this work, coupled population balance and species balance equations are developed to extract nucleation and growth kinetics for the crystallization of recombinant adeno-associated virus (rAAV) capsids. A comparison of model results with that of experimental data for capsid crystallization in a hanging-drop vapor diffusion system shows that the slow rate of vapor diffusion from the droplet controls the initial nucleation and growth processes, and the capsid nucleation occurs via heterogeneous nucleation in the microdroplet. Results also show that the capsids, which are of very high molecular weight (∼3.6 MDa), have a similar tendency to nucleate as small organic molecules such as glycine (∼75 Da), low-molecular-weight proteins, and small-molecule active pharmaceutical ingredients due to their ball-shaped outer structure/shape. Capsids also show a prolonged nucleation period as for proteins and other macromolecules but have a slow growth rate with a growth rate prefactor seven orders of magnitude smaller than that of lysozyme. The capsid crystal growth rate is weakly sensitive to supersaturation compared to lysozyme and is limited by the transport of capsids due to slow Brownian motion resulting from the very high molecular weight.

We developed a mathematical model based on population balance equation and compared the simulation results with the in-house experimental measurements for temporal evolution of crystal growth rate, crystal size distribution, total number density, total length, total radius, total surface area, and total volume.

Crystallization of proteins, specifically proteins of medical relevance, is performed for various reasons, such as to understand the protein structure and to design therapies. Obtaining kinetic constants in rate laws for nucleation and growth of advanced biotherapeutics such as capsids, an assembly of macromolecules, is challenging and essential to the design of crystallization processes. In this work, coupled population balance and species balance equations are developed to extract nucleation and growth kinetics for the crystallization of recombinant adeno-associated virus (rAAV) capsids. A comparison of model results with that of experimental data for capsid crystallization in a hanging-drop vapor diffusion system shows that the slow rate of vapor diffusion from the droplet controls the initial nucleation and growth processes, and the capsid nucleation occurs via heterogeneous nucleation in the microdroplet. Results also show that the capsids, which are of very high molecular weight (∼3.6 MDa), have a similar tendency to nucleate as small organic molecules such as glycine (∼75 Da), low-molecular-weight proteins, and small-molecule active pharmaceutical ingredients due to their ball-shaped outer structure/shape. Capsids also show a prolonged nucleation period as for proteins and other macromolecules but have a slow growth rate with a growth rate prefactor seven orders of magnitude smaller than that of lysozyme. The capsid crystal growth rate is weakly sensitive to supersaturation compared to lysozyme and is limited by the transport of capsids due to slow Brownian motion resulting from the very high molecular weight.

Structural studies of hydrates with simple tertiary amines are comparatively rare. We here present structures of the hydrated tertiary amines quinuclidine (quin) and tetramethylethylenediamine (tmeda), each with lower and higher water content, which were reproducibly crystallized by adjusting their stoichiometries. Our structures range from simple monohydrates to higher hydrates with extended hydrogen bond networks. Due to the excellent data quality and the absence of disorder, Hirshfeld atom refinements could be performed. This refinement with nonspherical scattering factors further increased the quality of the structure models and allowed fundamental insights into the character of hydrogen bonds and their networks. The dimensionality of the water substructures in our solids correlates with their composition: In our simplest monohydrate, individual water molecules bridge tmeda residues to a chain, the di- and trihydrates of quin feature layers of water, and a 3D network of water molecules is encountered for the tmeda heptahydrate, the compound with the highest ratio between H donor and N acceptor molecules presented.

Cocrystallization of piperine (PIPE), a natural alkaloid with several GRAS coformers, namely, 4HBA, 26DHBA, and PABA, resulted in the formation of new cocrystals. All of the synthesized cocrystals were further characterized using PXRD and single-crystal XRD analysis. Based on our investigation, it was observed that PIPE•PABA monohydrate cocrystal is the most stable form among all the synthesized cocrystals and does not undergo cocrystal dissociation and/or phase transformation under a humid environment. On the other hand, slurry stirring shows possible phase transformation of the PIPE•4HBA cocrystal and dissociation in the case of the PIPE•26DHBA cocrystal. The absence of a hydrogen bond donor group in PIPE might be the reason behind limited reports on PIPE cocrystals.

Three iron(III) spin crossover compounds, [Fe(salBzen-5-OMe)₂]A, where HsalBzen-5-OMe = 2-[(2-benzylaminoethylimino)methyl]-4-methoxyphenol and A = Cl^– 1, Br^– 2, I^– 3, have been synthesized and fully characterized. UV–vis spectroscopy reveals two LMCT bands corresponding to the LS and HS states in solution. X-ray crystallography indicates that the compounds crystallize in monoclinic P2₁/n or P2₁/c (1), (2) or tetragonal P4₃2₁2 (3) phases. At room temperature, complexes 1 and 2 display HS Fe^III centers, while complex 3 adopts an LS state. Notably, complexes 1 and 2 exhibit symmetry breaking, decoupling the phenomenon from spin crossover. A variety of intermolecular interactions, including C–H···π, C–H···O, N–H···O, C–H···anion, and N–H···anion, are responsible for linking the cations and forming a 3D supramolecular network. SQUID magnetometry studies show that compounds 1 and 2 remain high spin down to 10 K, while complex 3 undergoes a gradual spin crossover above 350 K. Crystallization of 2 at lower temperatures and humidity gives a tetragonal phase P4₃2₁2 (2’) that exhibits a spin crossover profile very similar to 3. Moreover, the crystal structure of 2’ reveals temperature-dependent modulation. These results highlight the significant role of counterions in modulating the magnetic properties of these compounds and demonstrate the independent control of symmetry breaking and spin crossover. This work offers valuable insights for designing advanced functional materials for molecular spintronics and materials science.

A series of solvent-free iron(III) complexes is explored, with larger anions leading to SCO behavior, while smaller anions result in symmetry breaking.

Calcium titanate thin films with high structural quality were grown heteroepitaxially on perovskite oxide substrates using the liquid-delivery spin metal-organic vapor phase epitaxy (MOVPE) technique. To determine the growth window, suitable metal-organic precursors were selected, and their evaporation conditions were established. Initially, the thermal decomposition behavior of the precursors was studied using thermogravimetric analysis, which showed that full pyrolysis at 460 °C is possible for both the Ca and Ti precursors. This enabled the growth of fully strained, stoichiometric CaTiO₃ films on SrTiO₃ and NdGaO₃ substrates, and potentially on other perovskite oxide substrates, within the diffusion-limited regime. The influence of vaporization temperatures, substrate temperature, oxygen-to-argon ratio, and Ca-to-Ti ratio on the structural properties of the CaTiO₃ thin films was investigated using high-resolution X-ray diffraction, atomic force microscopy, and transmission electron microscopy. Structural analysis was ultimately correlated with electrical properties measured via IV curves. Intrinsic resistive switching was observed for stoichiometric and slightly off-stoichiometric CaTiO₃ films grown on SrTiO₃ substrates with ≈2.2% tensile strain. Relative to our previous work on resistive switching in SrTiO₃ (Baki., Sci. Rep., 2021, 11 (1), 1-11), the underlying mechanism is discussed in the context of CaTiO₃. This highlights the potential of CaTiO₃ for technological applications such as resistive random-access memory (ReRAM) and neuromorphic computing.

This work presents the first in-depth crystallographic study of antivitamin-derived ionic liquids. Seven new amprolium salts incorporating hallmark ionic-liquid anions such as bis-(trifluoromethanesulfonyl)-imide (NTf₂ ^-), bis-(pentafluoroethanesulfonyl)-imide (BETI^-), tetrafluoroborate (BF₄ ^-), and hexafluorophosphate (PF₆ ^-) were synthesized and crystallized, and their structures and interactions were elucidated through crystallographic and computational analyses. The well-documented biological functions of amprolium can help simplify future applications of these compounds as well as open the pathway for the development of novel cations for ionic liquid development. Despite their dicationic nature and bearing multiple H-bonding donors and acceptors, these compounds exhibited unexpectedly low melting points and displayed challenging crystallization conditions. The analysis identified key structural features explaining this behavior: (i) two points of conformational disorder in the pyrimidine ring and propyl moiety; (ii) three distinct cation conformations affecting aromatic components; and (iii) novel high-energy conformations of anions, reported here for the first time. Hydrogen interactions dominated intermolecular forces (85% of total interactions), with H-bonding to oxygen and fluorine being most prevalent. These insights advance our understanding of how to engineer functional materials from natural sources for potential applications in sustainability and medicine. The combined experimental-computational approach validates these design principles, providing a foundation for more targeted development of similar compounds with tailored properties.

Calcium titanate thin films with high structural quality were grown heteroepitaxially on perovskite oxide substrates using the liquid-delivery spin metal−organic vapor phase epitaxy (MOVPE) technique. To determine the growth window, suitable metal−organic precursors were selected, and their evaporation conditions were established. Initially, the thermal decomposition behavior of the precursors was studied using thermogravimetric analysis, which showed that full pyrolysis at 460 °C is possible for both the Ca and Ti precursors. This enabled the growth of fully strained, stoichiometric CaTiO₃ films on SrTiO₃ and NdGaO₃ substrates, and potentially on other perovskite oxide substrates, within the diffusion-limited regime. The influence of vaporization temperatures, substrate temperature, oxygen-to-argon ratio, and Ca-to-Ti ratio on the structural properties of the CaTiO₃ thin films was investigated using high-resolution X-ray diffraction, atomic force microscopy, and transmission electron microscopy. Structural analysis was ultimately correlated with electrical properties measured via IV curves. Intrinsic resistive switching was observed for stoichiometric and slightly off-stoichiometric CaTiO₃ films grown on SrTiO₃ substrates with ≈2.2% tensile strain. Relative to our previous work on resistive switching in SrTiO₃ (Baki ., Sci. Rep., 2021, 11 (1), 1−11), the underlying mechanism is discussed in the context of CaTiO₃. This highlights the potential of CaTiO₃ for technological applications such as resistive random-access memory (ReRAM) and neuromorphic computing.

A potassium pyrocarbonate thermodynamically stable at atmospheric pressure has been revealed for the first time using first-principles calculations and modern crystal structure prediction technique. Our calculations indicate that at ambient pressure K₂C₂O₅ is stable in the C2 structure, which contains paired [CO₃] triangles forming [C₂O₅] pyrogroups. According to the calculation even at ambient pressure, it will not decompose into the mixture K₂CO₃ + CO₂ and thus can be obtained in the experiment. With increasing pressure to 4 GPa, a polymorphic transition to the K₂C₂O₅–P2₁ structure was observed, which is also characterized by the presence of [C₂O₅] pyrogroups. Thus, these predicted K₂C₂O₅ structures complement the recently discovered family of pyrocarbonates. K₂C₂O₅–P2₁ retains its stability up to a pressure of 37 GPa, where its decomposition into K₂CO₃ and CO₂ was observed. At a pressure of 87 GPa, K₂C₂O₅ is again formed as a result of the reaction K₂CO₃ + CO₂ and it is stable in the C2-hp structure. In the high-pressure modification C2-hp, the carbon atoms are in the sp³-hybridized state, and the paired triangles [CO₃] are replaced by polymerized [CO₄] tetrahedra in layers. This type of polymerization well established for the alkaline-earth carbonates, is observed for the first time for alkali metal carbonates. In addition, our calculations indicate the dynamic and thermal stability of the predicted structures in the corresponding pressure ranges.

Identifying and characterizing intermolecular forces in the condensed phase is crucial for understanding both micro- and macroscopic properties of solids; ranging from solid-state reactivity to thermal expansion. Insight into these interactions enables a holistic comprehension of bulk properties, and thus understanding them has direct implications for supramolecular design. However, even modest changes to intermolecular interactions can create unpredictable changes to solid-state structures and dynamics. For example, copper-(II) acetylacetonate (Cu-(C₅H₇O₂)₂) and copper-(II) hexafluoroacetylacetonate (Cu-(C₅HF₆O₂)₂) exhibit similar molecular conformations, yet differences between the methyl and trifluoromethyl groups produce distinct sets of intermolecular forces in the condensed phase. Ultimately, these differences produce unique molecular arrangements in the solid state, with corresponding differences in material properties between the two crystals. In this work, terahertz spectroscopy is used to measure low-frequency vibrational dynamics, which, by extension, provide detailed insight into the underlying intermolecular forces that exist in each system. The experimental data is coupled to theoretical quantum mechanical simulations to precisely quantify the interplay between various energetic effects, and these results highlight the delicate balance that is struck between electronic and dispersive interactions that underpin the structural and related differences between the two systems.