Crystallization Of Organic Molecules Research Articles

Routes of Theophylline Monohydrate Dehydration Process Proposed by Mid-Frequency Raman Difference Spectra

Two routes of the dehydration process of theophylline monohydrate have been proposed in this work from mid-frequency Raman difference spectra (MFRDS) results and experiments. MFRDS can establish short-range order correlations among various theophylline crystal forms. MFRDS results indicate that the short-range order of metastable Form III is most similar to that of monohydrate, which explains that Form III is the main dehydration products in the mild dehydration process. The phenomenon that unstable amorphous theophylline intermediate phase would appear during the dehydration process of theophylline monohydrate was confirmed indirectly by Powder X-ray Diffraction (PXRD) and optical microscope and reported in the previous reports, which could cause the nucleation of Form II, as MFRDS results indicate short-range order of amorphous solid dispersion of theophylline is most similar to that of Form II. MFRDS analysis shows the advantages in studying the phase transformation of small organic molecule crystals.

Shift Current in Molecular Crystals Possessing Charge-Transfer Characteristics

Further research on organic molecule crystals with spontaneous polarization as a possible candidate for the bulk photovoltaic effect is urgently needed to meet the requirements for optoelectric devices. We demonstrate the shift current in a type of molecular crystal that acts at high temperatures and contains organic molecules with electron donor-acceptor groups, such as paranitroaniline derivatives. We find an extremely strong multicomponent shift-current response along the parallel and perpendicular to polar molecules of the crystals using density-functional simulations, which is more than 10 times larger than the previously reported value for shift current over a broad spectral range from visible to ultraviolet spectrum. Even more intriguing, the remarkable dependency of the conduction- and valence-band dispersions on the lattice constant along polarization allows the shift current in these organic molecule structures to be tuned under stress and doping. Our findings not only suggest a class of organic compounds for realizing the highly controllable shift-current response, but also open up a channel for the search for solar materials.

X-ray Diffraction Topography (Imaging) of Crystals Grown from Solution: A Short Review

A short review of X-ray topographic studies of crystals grown from solution is presented. The dislocation configurations characteristic of such crystals are described, and Klapper’s explanation in terms of minimization of the elastic energy of a dislocation per unit growth length is highlighted. It is shown that the principles apply to crystals grown not only from low temperature solution but also by hydrothermal growth and growth from fluxed melts. Recent studies of growth of protein crystals have found that they have similar dislocation configurations and characteristics to those of ionic and small organic molecule crystals grown from solution.

Multistep Crystallization of Pharmaceutical Amorphous Nanoparticles via a Cognate Pathway of Oriented Attachment: Direct Evidence of Nonclassical Crystallization for Organic Molecules.

Crystallization of organic molecules is important in a wide range of scientific disciplines. However, in contrast to maturely studied crystallization of inorganic materials, the crystallization mechanisms of organic molecules involving nucleation and crystal growth are still poorly understood. Here, we used time-resolved cryogenic transmission electron microscopy to directly map the morphological evolution of amorphous cyclosporin A (CyA) nanoparticles during CyA crystallization. We successfully observed its initial nucleation and found that the amorphous CyA nanoparticles crystallized via a pathway cognate with oriented attachment, which is the nonclassical crystallization mechanism usually reported for inorganic compounds. Crystalline mesostructured intermediates (mesocrystals) were formed during crystallization. This study revealed clear and direct evidence of mesocrystal formation and oriented attachment in organic pharmaceuticals, providing new insights into the crystallization of organic molecules and theories of nonclassical crystallization.

Multifunctional Organic Single‐Crystalline Microwire Arrays toward Optical Applications

AbstractSingle‐crystalline micro‐/nanostructures based on organic stimulus‐responsive materials have attracted wide interests for their unique functional roles in various photonic applications including optical wave guiding, optical vapor sensing, and miniaturized lasing. Yet one imminent challenge is to pattern micro‐/nanostructured organic 1D arrays with controlled geometry, precise alignment, and pure crystallographic orientation owing to the uncontrollable dewetting dynamics in the solution processes. Herein, a smart assembly method is employed to regulate a confined crystallization of organic molecules. Sensitive, stable, and reproducible optical 1D‐array vapor sensors can detect the alkaline and acidic vapors based on the proton transfer process. As‐fabricated vapor sensors based on organic 1D arrays also selectively identify four similar amine vapors. Meanwhile, based on these 1D microstructure arrays, high‐performing Fabry–Pérot resonators with deep‐red laser emission, a low lasing threshold of 0.31 µJ, and high quality factor Q (≈2243) are realized. Owing to these multiple functions, organic microwire arrays not only provide intrinsic insight into optical vapor sensing but also offer guidance for the development of miniaturized lasers with specific functionalities, which show considerable potential in multifunctional photonic integrated circuits.

Optical and electrical modulation in ultraviolet photodetectors based on organic one‐dimensional photochromic arrays

AbstractOrganic photochromic materials have drawn considerable attention for their potential applications in large‐scale and low‐cost optoelectronics owing to unique tunable physicochemical properties. For organic photodetectors, photochromic materials have realized optical and electrical engineering of semiconductor layers, which incorporate not only tunable performance, but also functionalities to optoelectronic devices. However, the essential challenge is to assemble large‐area photochromic micro‐ and nanostructure arrays with controllable geometry and precise alignment, which restricts the integration of multifunctional optoelectronic devices. Herein, we fabricate organic photochromic one‐dimensional (1D) arrays via a feasible solution process through the confined crystallization of organic molecules. By modulating and controlling the photoisomerization behaviors, these 1D photochromic arrays possess broad spectral tunability, which ensure tunable photoresponse. Furthermore, we investigate the crystallographic transition and electronic performance variation of these 1D photochromic arrays. By adjusting the dwell time of ultraviolet (UV) irradiation, the UV photochromic photodetectors realize tunable and repeatable responsivity from 85.6 to 0.709 mA/W. Our work provides new possibilities for optical and electrical engineering of photochromic microwires towards the integration of multifunctional optoelectronic devices.

Control of self-assembly pathways toward conglomerate and racemic supramolecular polymers

Homo- and heterochiral aggregation during crystallization of organic molecules has significance both for fundamental questions related to the origin of life as well as for the separation of homochiral compounds from their racemates in industrial processes. Herein, we analyse these phenomena at the lowest level of hierarchy – that is the self-assembly of a racemic mixture of (R,R)- and (S,S)-PBI into 1D supramolecular polymers. By a combination of UV/vis and NMR spectroscopy as well as atomic force microscopy, we demonstrate that homochiral aggregation of the racemic mixture leads to the formation of two types of supramolecular conglomerates under kinetic control, while under thermodynamic control heterochiral aggregation is preferred, affording a racemic supramolecular polymer. FT-IR spectroscopy and quantum-chemical calculations reveal unique packing arrangements and hydrogen-bonding patterns within these supramolecular polymers. Time-, concentration- and temperature-dependent UV/vis experiments provide further insights into the kinetic and thermodynamic control of the conglomerate and racemic supramolecular polymer formation.

What We Need to Know about Solid-State Isothermal Crystallization of Organic Molecules from the Amorphous State below the Glass Transition Temperature.

In this Perspective, the authors have examined various principles associated with the isothermal crystallization of organic molecules from the amorphous state. The major objective was to better understand the underlying principles influencing long-term crystallization from the glassy state at temperatures sufficiently low enough to prevent crystallization over a period of about 2-3 years; this time frame was chosen based on the requirements for ensuring the physical stability of solid drug products. As such, after considering the general thermodynamic, dynamic (molecular mobility), and structural properties of both supercooled liquids and glasses, current understanding from the literature of overall crystallization, nucleation and growth from glasses, was reviewed. Typically, in attempting to establish the appropriate storage temperature, T, in the glassy state, relative to the glass transition temperature, Tg, i.e., Tg - T, most studies have tended to emphasize the rates of bulk diffusional molecular mobility of molecules at such temperatures and classical crystal nucleation and growth theory. However, a closer analysis of factors affecting crystallization from the glassy state revealed that greater consideration should be given to other contributing factors, including methods of producing the glass, heterogeneous nucleation due to processing conditions, secondary Johari-Goldstein relaxations, nondiffusional crystal growth in the glass (GC-growth), and surface crystallization.

TAAM: a reliable and user friendly tool for hydrogen-atom location using routine X-ray diffraction data.

Hydrogen is present in almost all of the molecules in living things. It is very reactive and forms bonds with most of the elements, terminating their valences and enhancing their chemistry. X-ray diffraction is the most common method for structure determination. It depends on scattering of X-rays from electron density, which means the single electron of hydrogen is difficult to detect. Generally, neutron diffraction data are used to determine the accurate position of hydrogen atoms. However, the requirement for good quality single crystals, costly maintenance and the limited number of neutron diffraction facilities means that these kind of results are rarely available. Here it is shown that the use of Transferable Aspherical Atom Model (TAAM) instead of Independent Atom Model (IAM) in routine structure refinement with X-ray data is another possible solution which largely improves the precision and accuracy of X-H bond lengths and makes them comparable to averaged neutron bond lengths. TAAM, built from a pseudoatom databank, was used to determine the X-H bond lengths on 75 data sets for organic molecule crystals. TAAM parametrizations available in the modified University of Buffalo Databank (UBDB) of pseudoatoms applied through the DiSCaMB software library were used. The averaged bond lengths determined by TAAM refinements with X-ray diffraction data of atomic resolution (dmin ≤ 0.83 Å) showed very good agreement with neutron data, mostly within one single sample standard deviation, much like Hirshfeld atom refinement (HAR). Atomic displacements for both hydrogen and non-hydrogen atoms obtained from the refinements systematically differed from IAM results. Overall TAAM gave better fits to experimental data of standard resolution compared to IAM. The research was accompanied with development of software aimed at providing user-friendly tools to use aspherical atom models in refinement of organic molecules at speeds comparable to routine refinements based on spherical atom model.

Preferred Formation of Minority Concomitant Polymorphs in 2D Self-Assembly under Lateral Nanoconfinement.

Control over polymorph formation in the crystallization of organic molecules remains a huge scientific challenge. Now, preferential formation is presented of one polymorph, formed by chiral molecules, in controlled two-dimensional (2D) nanoconfinement conditions at a liquid-solid interface. So-called nanocorrals to control concomitant polymorph formation were created in situ via a nanoshaving protocol at the interface between 1-phenyloctane and covalently modified highly-oriented pyrolytic graphite (HOPG). The preferentially formed polymorphs, which were less stable in the large-scale monolayers, could be selected simply by varying the orientation of the square nanocorrals with respect to the HOPG lattice.

Preferred Formation of Minority Concomitant Polymorphs in 2D Self‐Assembly under Lateral Nanoconfinement

AbstractControl over polymorph formation in the crystallization of organic molecules remains a huge scientific challenge. Now, preferential formation is presented of one polymorph, formed by chiral molecules, in controlled two‐dimensional (2D) nanoconfinement conditions at a liquid–solid interface. So‐called nanocorrals to control concomitant polymorph formation were created in situ via a nanoshaving protocol at the interface between 1‐phenyloctane and covalently modified highly‐oriented pyrolytic graphite (HOPG). The preferentially formed polymorphs, which were less stable in the large‐scale monolayers, could be selected simply by varying the orientation of the square nanocorrals with respect to the HOPG lattice.

Crystallization of Small Organic Molecules in a Polymer Matrix: Multistep Mechanism Enables Structural Control.

The widely employed crystallization of organic molecules in solution is not well understood and is difficult to control. Employing polymers as crystallization media may allow enhanced control via temperature-induced regulation of polymer dynamics. Crystallization of a small organic molecule (perylene diimide) is investigated in polymer matrices (polystyrene) that enable the mechanistic study and control over order evolution. The crystallization is induced by heating above the glass transition temperature of the polymer, and quenched by cooling, leading to stabilization of crystallization intermediates. The mechanistic studies include direct imaging by electron microscopy, revealing a complex self-assembly process starting from amorphous aggregates that densify and transform into an unstable crystalline phase of N ,N'-bis(2,6-dimethylphenyl)perylene-3,4,9,10-tetracarboxylic diimide (DMP-PDI), followed by a conversion into a more stable crystalline form. Stabilization of crystallization intermediates at room temperature provides diverse structures based on a single molecular component. These findings have implications for the rational design of organic crystalline materials.

Use of Aggregation-Induced Emission for Selective Detection of Phase Transformation during Evaporative Crystallization of Hexaphenylsilole.

Crystallization of organic molecules is quite complicated because the crystallization process is governed by weak intermolecular interactions. By exploiting aggregation-induced emission (AIE), we attempted to realize the selective detection of phase transformation during the evaporative crystallization of hexaphenylsilole (HPS), which shows different fluorescent colors in the amorphous and crystalline phases. No fluorescence emission was observed in the HPS solution immediately after dropping on the glass substrate due to the non-radiative deactivation induced by intramolecular rotational or vibrational motion, suggesting that HPS exists as a monomer in solution. As time elapsed after dropping, green emission first appeared, which changed to blue after solvent evaporation, because of phase transformation from the amorphous state to the crystalline state. This phenomenon supports not only the two-step nucleation model involving an intermediate such as a liquid-like cluster prior to nucleation but also the real-time detection of Ostwald's rule of stages during evaporative crystallization.

Frequency-dependent photothermal measurement of thermal diffusivity for opaque and non-opaque materials: Application to crystals of TIPS-pentacene

We propose the use of a frequency-dependent photothermal measurement as a complement to light-flash, i.e., time-dependent, measurements to determine the through-plane thermal diffusivity of small, thin samples, e.g., semiconducting polymers and small organic molecule crystals. The analysis is extended from its previous use with some opaque conducting polymers to materials with finite absorption coefficients, such as crystals of 6,13-bis(triisopropylsilylethynyl)pentacene. Taking into account the finite absorption coefficients of the latter gives a value of diffusivity, D ≈ 0.10 mm2/s, much smaller than previously estimated and more consistent with its expected value. We also briefly discuss the effects of coating samples for the measurement to improve their optical properties.

Crystallization of Organic Molecules: Nonclassical Mechanism Revealed by Direct Imaging.

Organic crystals are of primary importance in pharmaceuticals, functional materials, and biological systems; however, organic crystallization mechanisms are not well-understood. It has been recognized that “nonclassical” organic crystallization from solution involving transient amorphous precursors is ubiquitous. Understanding how these precursors evolve into crystals is a key challenge. Here, we uncover the crystallization mechanisms of two simple aromatic compounds (perylene diimides), employing direct structural imaging by cryogenic electron microscopy. We reveal the continuous evolution of density, morphology, and order during the crystallization of very different amorphous precursors (well-defined aggregates and diffuse dense liquid phase). Crystallization starts from initial densification of the precursors. Subsequent evolution of crystalline order is gradual, involving further densification concurrent with optimization of molecular ordering and morphology. These findings may have implications for the rational design of organic crystals.

The Effects of Ultrasound on Crystals: Sonocrystallization and Sonofragmentation

When ultrasound is applied to a solution for crystallization, it can affect the properties of the crystalline products significantly. Ultrasonic irradiation decreases the induction time and metastable zone and increases the nucleation rate. Due to these effects, it generally yields smaller crystals with a narrower size distribution when compared with conventional crystallizations. Also, ultrasonic irradiation can cause fragmentation of existing crystals which is caused by crystal collisions or sonofragmentation. The effect of various experimental parameters and empirical products of sonocrystallization have been reported, but the mechanisms of sonocrystallization and sonofragmentation have not been confirmed clearly. In this review, we build upon previous studies and highlight the effects of ultrasound on the crystallization of organic molecules. In addition, recent work on sonofragmentation of molecular and ionic crystals is discussed.

Crystallization-assisted nano-lens array fabrication for highly efficient and color stable organic light emitting diodes.

To date, all deposition equipment has been developed to produce planar films. Thus lens arrays with a lens diameter of <1 mm have been manufactured by combining deposition with other technologies, such as masks, surface treatment, molding etc. Furthermore, a nano-lens array (NLA) with a sufficiently small lens diameter (<1 μm) is necessary to avoid image quality degradation in high resolution displays. In this study, an organic NLA made using a conventional deposition technique - without combining with other techniques - is reported. Very interestingly, grazing-incidence small-angle X-ray scattering (GI-SAXS) experiments indicate that the NLA is formed by the crystallization of organic molecules and the resulting increase in surface tension. The lens diameter can be tuned for use with any kind of light by controlling the process parameters. As an example of their potential applications, we use NLAs as a light extraction film for organic light emitting diodes (OLEDs). The NLA is integrated by directly depositing it on the top electrode of a collection of OLEDs. This is a dry process, meaning that it is fully compatible with the current OLED production process. Devices with NLAs exhibited a light extraction efficiency 1.5 times higher than devices without, which corresponds well with simulation results. The simulations show that this high efficiency is due to the reduction of the guided modes by scattering at the NLA. The NLAs also reduce image blurring, indicating that they increase color stability.

Bifluorene Single Crystals with Extremely Low‐Threshold Amplified Spontaneous Emission

Organic single crystals offering numerous advantages due to their long‐range molecular order are considered a promising gain medium for realization of electrically‐pumped organic lasers provided their amplified spontaneous emission (ASE) threshold is sufficiently low. Unfortunately, ASE thresholds of such crystals are typically more than one order of magnitude higher (in the range of tens of kW cm−2) as compared to those of amorphous neat/doped films. Here, this issue is addressed by rationally designing bifluorene‐based compounds to express weak intermolecular coupling in the crystalline phase. The twisted molecular backbone as well as out‐of‐plane twisted dimethyl moieties attached at the fluorene end‐groups additionally benefit with enhanced electron–vibronic coupling resulting in a large Stokes shift (0.5 eV) and reduced reabsorption of emission. Endowed with such features the bifluorenes exhibit similarly high radiative decay rates (≈1.5 × 109 s−1) when doped in polystyrene matrix at low concentrations and in sublimation‐grown single crystals. The high radiative rates accompanied by excellent waveguiding properties, favorable orientation of transition dipole moments as well as non‐overlapping excited‐state absorption and gain regions enable achieving extremely low ASE thresholds (≈700 W cm−2) in the bifluorene single crystals. The achieved low threshold encourages employment of rationally designed molecules in organic crystals for lasing applications.

Control of organic polymorph formation: crystallization pathways in acoustically levitated droplets

Abstract Theoretical and experimental studies indicate that crystal nucleation can take more complex pathways than expected on the ground of the classical nucleation theory. Among these pathways are the formation of pre-nucleation clusters and amorphous precursor phases. A direct in situ observation of the different pathways of nucleation from solution is challenging since the paths can be influenced by heterogeneous nucleation sites, such as container walls. Here, we provide insights into the crystallization process using the in situ combination of an acoustic levitator, Raman spectroscopy, and X-ray scattering. The contactless sample holder enables the observation of homogeneous crystallization processes and the detection of intermediates and final crystalline forms. We provide evidence for the existence of multiple pathways of nucleation based on the investigation of the crystallization of organic molecules from different solvents. Starting from a diluted solution, a supersaturation is reached during the experiment due to the evaporation of the solvent. The highly supersaturated solution reveals different pathways of crystallization. Depending on the degree of supersaturation either the thermodynamically stable or the metastable crystal form is observed.

Novel Impinging Jet and Continuous Crystallizer Design for Rapid Reactive Crystallization of Pharmaceuticals

Reactive crystallization is an important operation in the pharmaceutical industry for the production of the active pharmaceutical ingredients (APIs), but has not been as widely studied as cooling or anti-solvent crystallization. Reactive crystallization has many unique features that make them different from cooling or anti-solvent crystallization, even leading to some concepts and methods not directly applicable to the former. Literature survey reveals that previous research on reactive crystallization has mainly been conducted for inorganic materials which are known to be simpler than crystallization of organic molecules. The focus of this research project was to carry out research on the process design and optimization of organic reactive crystallization. The objective was to research on novel crystallizer designs that suit and take advantages of the features of reactive crystallization, and on advanced modeling and optimization techniques with the aim of manufacturing high quality products. Process analytical technology was used as a supporting tool to achieve the above stated objectives. The results showed that by using novel impinging jet design, the product had uniform size distribution and superior crystallinity. In addition, continuous process design can achieve a greater amount of product handling and reduce the batch-to-batch variation.