Supersaturated Aqueous Solutions Research Articles

Kinetic and Thermodynamic Interplay of Polymer-Mediated Liquid-Liquid Phase Separation for Poorly Water-Soluble Drugs.

Understanding the interplay between kinetics and thermodynamics of polymer-mediated liquid-liquid phase separation is crucial for designing and implementing an amorphous solid dispersion formulation strategy for poorly water-soluble drugs. This work investigates the phase behaviors of a poorly water-soluble model drug, celecoxib (CXB), in a supersaturated aqueous solution with and without polymeric additives (PVP, PVPVA, HPMCAS, and HPMCP). Drug-polymer-water ternary phase diagrams were also constructed to estimate the thermodynamic behaviors of the mixtures at room temperature. The liquid-liquid phase separation onset point for CXB was detected using an inline UV/vis spectrometer equipped with a fiber optic probe. Varying CXB concentrations were achieved using an accurate syringe pump throughout this study. The appearance of the transient nanodroplets was verified by cryo-EM and total internal reflection fluoresence microscopic techniques. The impacts of various factors, such as polymer composition, drug stock solution pumping rates, and the types of drug-polymer interactions, are tested against the onset points of the CXB liquid-liquid phase separation (LLPS). It was found that the types of drug-polymer interactions, i.e., hydrogen bonding and hydrophobic interactions, are vital to the position and shapes of LLPS in the supersaturation drug solution. A relation between the behaviors of LLPS and its location in the CXB-polymer-water ternary phase diagram was drawn from the findings.

Impact of molecular symmetry on crystallization pathways in highly supersaturated KH2PO4 solutions

Solute structure and its evolution in supersaturated aqueous solutions are key clues to understand Ostwald’s step rule. Here, we measure the structural evolution of solute molecules in highly supersaturated solutions of KH2PO4 (KDP) and NH4H2PO4 (ADP) using a combination of electrostatic levitation and synchrotron X-ray scattering. The measurement reveals the existence of a solution-solution transition in KDP solution, caused by changing molecular symmetries and structural evolution of the solution with supersaturation. Moreover, we find that the molecular symmetry of H2PO4- impacts on phase selection. These findings manifest that molecular symmetry and its structural evolution can govern the crystallization pathways in aqueous solutions, explaining the microscopic origin of Ostwald’s step rule.

Water activity and surface tension of aqueous ammonium sulfate and D-glucose aerosol nanoparticles

Abstract. Water activity (aw) and interfacial energy or surface tension (σ) are key thermodynamic parameters to describe the hygroscopic growth of atmospheric aerosol particles and their ability to serve as cloud condensation nuclei (CCN), thus influencing the hydrological cycle and climate. Due to size effects and complex mixing states, however, these parameters are not well constrained for nanoparticles composed of organic and inorganic compounds in aqueous solution. In this study, we determined aw and σ by differential Köhler analysis (DKA) of hygroscopic growth measurement data for aerosol particles smaller than 100 nm composed of aqueous ammonium sulfate (AS), D-glucose (Gl), and their mixtures. High-precision measurements of hygroscopic growth were performed at relative humidities (denoted RH) ranging from 2.0 % to 99.6 % with a high-humidity tandem differential mobility analyzer (HHTDMA) in three complementary modes of operation: hydration, dehydration, and restructuring. The restructuring mode (hydration followed by dehydration) enabled the transformation of initially irregular particles into compact globules and the determination of mass equivalent diameters. The HHTDMA-derived growth factors complemented by DKA allows for determination of water activity and surface tension from dilute to highly supersaturated aqueous solutions that are not accessible with other methods. Thus, for mixed AS / Gl nanoparticles with mass ratios of 4:1 and 1:1, the upper limit of solute mass fraction (Xs) was 0.92 and 0.98, respectively. For pure AS and Gl, the DKA-derived aw is in good agreement with electrodynamic balance and bulk measurement data. For AS particles, our aw data also agree well with the Extended Aerosol Inorganics Model (E-AIM III) over the entire concentration range. In contrast, the UNIFAC model as a part of AIOMFAC (Zuend et al., 2011) was found to overestimate aw in aqueous Gl particles, which can be attributed to unaccounted intermolecular interactions. For mixed AS and Gl nanoparticles, we observed a non-monotonic concentration dependence of the surface tension that does not follow the predictions by modeling approaches constructed for mixed inorganic/organic systems. Thus, AS / Gl particles with a 1:1 mass ratio exhibited a strong decrease of σ with increasing solute mass fraction, a minimum value of 56.5 mN m−1 at Xs≈0.5, and a reverse trend of increasing σ at higher concentrations. We suggest that D-glucose molecules surrounded by ammonium sulfate ions tend to associate, forming non-polar aggregates, which lowers the surface tension at the air–droplet interface. We analyzed the uncertainty in the DKA-derived water activity and surface tension, related to the instrumental errors as well as to the morphology of the nanoparticles and their phase state. Our studies have shown that under optimal modes of operation of HHTDMA for moderate aqueous concentrations, the uncertainty in aw and σ does not exceed 0.2 %–0.4 % and 3 %–4 %, respectively, but it increases by an order of magnitude in the case of highly concentrated nanodroplet solutions.

Three-dimensional textures of Ryugu samples and their implications for the evolution of aqueous alteration in the Ryugu parent body

Samples collected from the surface/subsurface of C-type asteroid 162173 Ryugu by the Hayabusa2 mission were nondestructively analyzed in three dimensions (3D). Seventy-three small particles (approximately 10–180 µm in size) were observed using X-ray nanotomography, with an effective spatial resolution of approximately 200 nm. Detailed descriptions of these samples in terms of mineralogy, petrology, and variations among particles were reported. The 57 most common particles consisted of a phyllosilicate matrix containing mineral grains, mainly magnetite, pyrrhotite, dolomite and apatite. The remaining particles were mostly monomineralic particles (pyrrhotite, dolomite, breunnerite, apatite, and Mg-Na phosphate) with two unique particles (calcite in a Al2Si2O5(OH)4 matrix, and CaCO3, phyllosilicate, and tochilinite-chronstedtite inclusions in a carbonaceous material matrix). The results confirmed that the samples correspond to Ivuna-type carbonaceous chondrites (CI chondrites) or related materials. Many small inclusions of voids and carbonaceous materials were detected in pyrrhotite, dolomite, breunnerite, and apatite. However, no fluid inclusions were observed, except for those in pyrrhotite that have already been reported. Magnetite exhibited a wide variety of morphologies, from irregular shapes (spherulites, framboids, plaquettes, and whiskers) to euhedral shapes (equants, rods, and cubes), along with transitional shapes. In contrast, the other minerals exhibit predominantly euhedral shapes (pyrrhotite: pseudo-hexagonal plates, dolomite: flattened rhombohedrons, breunnerite: largely flattened rhombohedrons, and apatite: hexagonal prisms) or aggregates of faceted crystals, except for Mg-Na phosphate. The matrices were heterogeneous with variable phyllosilicate particle sizes, Mg/Fe ratios, density (1.7 ± 0.2 g/cm3), nanoporosities (36 ± 9 %), and abundances of nanograins of Fe(-Ni) sulfides. The macroporosity of the particles was estimated as 12 ± 4 %.The observed textural relationships among the minerals suggest a precipitation sequence of: magnetite (spherulite → plaquette/framboid → rod/equant) → pyrrhotite (pentlandite → pyrrhotite) → apatite → dolomite → breunnerite → coarse phyllosilicates. Fe-bearing olivine (or low-Ca pyroxene) might have precipitated later than dolomite, indicating a high Mg activity in the aqueous solution. This precipitation sequence corresponds to a transition from irregular crystal forms (as seen in some magnetite) to regular forms of euhedral crystals (observed in some magnetite and other minerals). Based on the precipitation sequence and mineral morphologies, together with previously reported observations, a model for aqueous alteration in the Ryugu parent body was proposed as follows: CO2-H2O ice, amorphous silicates (GEMS-like material), and some minerals (mostly metal, sulfides, and anhydrous silicates) accumulated to form the parent body of Ryugu. Amorphous silicates and Fe-Ni metal quickly dissolved into the melted ice to form a highly supersaturated aqueous solution. Poorly-crystalized phyllosilicate and spherulitic magnetite precipitated first, followed by plaquette/framboidal magnetites with decreasing degree of supersaturation due to precipitation. Pseudo-hexagonal pyrrhotite plates were formed by dissolution and reprecipitation under relatively low supersaturation. Subsequently, apatite, dolomite, and breunnerite precipitated in this order in response to decreasing supersaturation.

Implementation of the ISORROPIA-lite aerosol thermodynamics model into the EMAC chemistry climate model (based on MESSy v2.55): implications for aerosol composition and acidity

Abstract. This study explores the differences in performance and results by various versions of the ISORROPIA thermodynamic module implemented within the ECHAM/MESSy Atmospheric Chemistry (EMAC) model. Three different versions of the module were used, ISORROPIA II v1, ISORROPIA II v2.3, and ISORROPIA-lite. First, ISORROPIA II v2.3 replaced ISORROPIA II v1 in EMAC to improve pH predictions close to neutral conditions. The newly developed ISORROPIA-lite has been added to EMAC alongside ISORROPIA II v2.3. ISORROPIA-lite is more computationally efficient and assumes that atmospheric aerosols exist always as supersaturated aqueous (metastable) solutions, while ISORROPIA II includes the option to allow for the formation of solid salts at low RH conditions (stable state). The predictions of EMAC by employing all three aerosol thermodynamic models were compared to each other and evaluated against surface measurements from three regional observational networks in the polluted Northern Hemisphere (Interagency Monitoring of Protected Visual Environments (IMPROVE), European Monitoring and Evaluation Programme (EMEP), and Acid Deposition Monitoring Network of East Asia (EANET)). The differences between ISORROPIA II v2.3 and ISORROPIA-lite were minimal in all comparisons with the normalized mean absolute difference for the concentrations of all major aerosol components being less than 11 % even when different phase state assumptions were used. The most notable differences were lower aerosol concentrations predicted by ISORROPIA-lite in regions with relative humidity in the range of 20 % to 60 % compared to the predictions of ISORROPIA II v2.3 in stable mode. The comparison against observations yielded satisfactory agreement especially over the USA and Europe but higher deviations over East Asia, where the overprediction of EMAC for nitrate was as high as 4 µg m−3 (∼20 %). The mean annual aerosol pH predicted by ISORROPIA-lite was on average less than a unit lower than ISORROPIA II v2.3 in stable mode, mainly for coarse-mode aerosols over the Middle East. The use of ISORROPIA-lite accelerated EMAC by nearly 5 % compared to the use of ISORROPIA II v2.3 even if the aerosol thermodynamic calculations consume a relatively small fraction of the EMAC computational time. ISORROPIA-lite can therefore be a reliable and computationally efficient alternative to the previous thermodynamic module in EMAC.

Infrared Thermography Investigation of Crystallization in Acoustically Levitated Supersaturated Aqueous Solution

In this study, crystallization in highly supersaturated aqueous urea solutions was investigated using in situ infrared thermography facilitated by an acoustic levitation apparatus. A notable contribution of this thermographic approach is the identification of a transient heat release signature, particularly pronounced beyond the solubility limit, indicating the enhanced formation of bonds between urea molecules in the supersaturated states. Surprisingly, the temporal evolution of the heat release measurements on an acoustically levitated droplet strongly suggests a two-stage process for urea crystallization. A comprehensive statistical analysis based on classical nucleation theory is used to further investigate the exceptionally high degree of supersaturation and the emergence of prominent heat signatures observed toward the onset of crystallization.

Green biosynthesis of DHA-phospholipids in tailor-made supersaturated DHA aqueous solution and catalytic mechanism study

Docosahexaenoic acid-phospholipids (DHA-PLs) were prepared via lipase-mediated transesterification of DHA donor and phosphatidylcholine (PC) in a purely aqueous solution. Pre-existing carriers would play the role as “artificial interfaces” to adsorb water-insoluble PC and made them disperse in water. DHA donors were concentrated by a pH-responsive method and presented as supersaturated salt solutions. 153 triacylglycerol lipase structures were analyzed and screened in silico. Transesterification was carried out to further evaluate the six lipase candidates. Lipase B from Candida antarctica (CALB) was the best biocatalyst with 34.8% of DHA incorporation and 80.0% of PLs yields (involving 38.1% PC and 41.9% sn-1 lyso-PC). Toxic organic solvents were avoided. Six possible microunits of our aqueous system consisting of three PLs donors (PC, lyso-PC, sn-glycero-3-PC) and two DHA donors (DHA and DHA salts), were simulated by molecular dynamics (MD) to illustrate the enzymatic mechanism based on diffusional channels, competitive bindings, and enzymatic structures.

Crystallization and characterization of K2NixCo1-x(SO4)2·6H2O mixed crystals for ultraviolet light filters and sensors

Mixed Tutton salts K2NixCo1-x(SO4)2·6H2O (KNICOSH) single crystals with x = 0, 0.20, 0.50, 0.80 and 1 were grown at 309 K using the slow evaporation of supersaturated aqueous solutions. X-ray diffraction analysis revealed the monoclinic structure, space group P21/a (C_2 h^5) and Z = 2, for each crystal obtained in this work. Thermal investigation showed several peaks that indicated the dehydration process, the exothermic reactions and melting points of K2NixCo1-x(SO4)2·6H2O crystals. The temperatures of these peaks increased with increasing x value, and it means that the crystals rich with Ni have higher thermal stability than those rich with Co. The infrared spectra of KNICOSH crystals showed three types of modes (internal modes of the sulfate ion, internal modes of water and librational modes of water). The wavenumber of internal modes of water increased systematically with increasing Ni content which indicate that the water molecules in KNISH crystal have hydrogen-bonding stronger than that of KCOSH crystal. The wavenumber of other infrared spectra modes changed unsystematically with increasing Ni content. K2Ni0.50Co0.50(SO4)2.6H2O crystal has the most absorption for the light at the visible range while at the ultraviolet region the absorption is low (high transmittance). This behavior enhanced its efficiency for using in ultraviolet light filters and sensors.

Homogeneous nucleation of crystalline methane hydrate in molecular dynamics transition paths sampled under realistic conditions.

Methane hydrates are important from a scientific and industrial perspective, and form by nucleation and growth from a supersaturated aqueous solution of methane. Molecular simulation is able to shed light on the process of homogeneous nucleation of hydrates, using straightforward molecular dynamics or rare event enhanced sampling techniques with atomistic and coarse grained force fields. In our previous work [Arjun, T. A. Berendsen, and P. G. Bolhuis, Proc. Natl. Acad. Sci. U. S. A. 116, 19305 (2019)], we performed transition path sampling (TPS) simulations using all atom force fields under moderate driving forces at high pressure, which enabled unbiased atomistic insight into the formation of methane hydrates. The supersaturation in these simulations was influenced by the Laplace pressure induced by the spherical gas reservoir. Here, we investigate the effect of removing this influence. Focusing on the supercooled, supersaturated regime to keep the system size tractable, our TPS simulations indicate that nuclei form amorphous structures below roughly 260K and crystalline sI structures above 260K. For these temperatures, the average transition path lengths are significantly longer than in our previous study, pushing the boundaries of what can be achieved with TPS. The temperature to observe a critical nucleus of certain size was roughly 20K lower compared to a spherical reservoir due to the lower concentration of methane in the solution, yielding a reduced driving force. We analyze the TPS results using a model based on classical nucleation theory. The corresponding free energy barriers are estimated and found to be consistent with previous predictions, thus adding to the overall picture of the hydrate formation process.

Solution‐Processed Selective Area Homoepitaxial Growth of Suspended MAPbX3(X = Cl, Br) Perovskite Micro‐Arrays

AbstractSuspended nano/microstructures on semiconductor surfaces that can manage light are attractive for various on‐chip and efficiency‐enhanced optoelectronics. Hybrid halide perovskites have shown considerable potential for optoelectronic and photonic applications. However, the ionic and soft lattices of perovskites are sensitive to polar solvents, photons, and heat, limiting the post‐processing of suspended microstructures. Herein, a solution‐processed selective area homoepitaxial growth (SAEG) method is introduced to create well‐ordered, suspended microstructure arrays on the surface of MAPbX3(X = Br, Cl) single‐crystalline thin films. The suspended micro‐arrays exhibit single crystalline structures and 11.2 fold photoluminescence enhancement compared to the thin‐film substrates. The success of SAEG lies in the making use of perovskite supersaturated HX aqueous solutions that not only repair surface defects induced by lithography but also satisfy homoepitaxial growth kinetics. This study paves a pathway for the fabrication of cost‐effective perovskite surface‐suspended microstructures for efficiency‐enhanced and on‐chip optoelectronic devices.

The universal behavior of viscosity in supersaturated aqueous sugar solutions and the cryopreservation implications

The universal behavior of viscosity in supersaturated aqueous sugar solutions and the cryopreservation implications

Nucleation Rate Theory for Coordination Number: Elucidating Water-Mediated Formation of a Zigzag Na2SO4 Morphology.

Predicting and controlling nanostructure formation during nucleation can pave the way to synthesizing novel energy materials via crystallization. However, such control over nucleation and crystallization remains challenging due to an inadequate understanding of critical factors that govern evolving atomistic structures and dynamics. Herein, we utilize coordination number as a reaction coordinate and rate theory to investigate how sodium sulfate, commonly known as a phase-change energy material, nucleates in a supersaturated aqueous solution. In conjunction with ab initio and force field-based molecular dynamics simulation, the rate theoretical analysis reveals that sodium sulfate from an initially dissolved metastable state transits to a heterogeneous mixture of prenucleated clusters and finally to a large cylindrical zigzag morphology. Measurements of Raman spectra and their ab initio modeling confirm that this nucleated morphology contains a few waters for every sulfate. Rate processes such as solvent exchange and desolvation exhibit high sensitivity to the evolving prenucleation/nucleation structures, providing a means to distinguish between critical nucleation precursors. Desolvation and forming the first-shell interionic coordination structure via monomer-by-monomer addition around sulfates are found to explain the formation of large nuclei. Thus, a detailed understanding of the step-by-step structure formation across scales has been achieved. This can be leveraged to predict nucleation-related structures and dynamics and potentially control the synthesis of novel phase-change materials for energy applications.

Mechanical shock-induced nucleation in solution: Is cavitation necessary?

Mechanical shock-induced nucleation (MSIN) of crystals from aqueous supersaturated solutions of ammonium chloride is reported. A simple apparatus was constructed to expose solutions in glass vials to a single impact, while images were recorded using a fast camera. A strong correlation between cavitation in the liquid and nucleation of solid ammonium chloride was revealed. The measured fraction of solutions nucleated as a function of impact height was fitted using a Poisson model. The mean number of solution samples nucleated increased quadratically with impact height above a threshold height. Analysis of images showed that the accelerations achieved were sufficient to induce cavitation based on the cavitation number proposed by Pan et al. [Proc. Natl. Acad. Sci. USA 114 (2017) 8470]. The use of a hydrophobic coating on the internal glass surface was shown to significantly increase both the number of cavities observed and the probability of MSIN of solid crystals. The results presented suggest that MSIN of ammonium chloride salt is mediated by cavitation.

A Metastable Amorphous Intermediate Is Responsible for Laser-Induced Nucleation of Glycine.

Laser-induced crystal nucleation through optical tweezing, and in particular polymorph selection through laser polarization, promises unprecedented control over crystallization. However, in the absence of a nearby liquid-liquid critical point or miscibility gap, the origin of the required mesoscale clusters remains unclear. A number of recent studies of so-called nonclassical nucleation have suggested the presence of large amorphous clusters. Here, we show that supersaturated aqueous glycine solutions form metastable intermediate particles that are off the direct path to crystal nucleation. Laser-induced crystal nucleation only occurs when the laser "activates" one of these particles. In situ low-frequency Raman spectroscopy is used to demonstrate their amorphous or partially ordered character and transformation to various crystal polymorphs. The requirement for solution aging in many previously reported laser-induced crystal nucleation experiments strongly suggests that the presence of amorphous intermediates is a general requirement.

Условия зарождения и стабильности объемных нанопузырьков

The thermodynamic analysis of the nucleation of bulk nanobubbles (BNB) in a supersaturated aqueous solution is carried out. In the model of a charged BNB with double electric layer (DEL), the minimum work of nucleation and the radius of the critical the embryo are calculated. Simple analytical expressions are derived, when the BNB will not dissolve in water, i.e. it will be stable. For the first time, the authors successful to explain the mystery of the long life times of the BNB.

Organic contaminants and atmospheric nitrogen at the graphene-water interface: a simulation study.

Ordered nanoscale patterns have been observed by atomic force microscopy at graphene–water and graphite–water interfaces. The two dominant explanations for these patterns are that (i) they consist of self-assembled organic contaminants or (ii) they are dense layers formed from atmospheric gases (especially nitrogen). Here we apply molecular dynamics simulations to study the behavior of dinitrogen and possible organic contaminants at the graphene–water interface. Despite the high concentration of N2 in ambient air, we find that its expected occupancy at the graphene–water interface is quite low. Although dense (disordered) aggregates of dinitrogen have been observed in previous simulations, our results suggest that they are stable only in the presence of supersaturated aqueous N2 solutions and dissipate rapidly when they coexist with nitrogen gas near atmospheric pressure. On the other hand, although heavy alkanes are present at only trace concentrations (micrograms per cubic meter) in typical indoor air, we predict that such concentrations can be sufficient to form ordered monolayers that cover the graphene–water interface. For octadecane, grand canonical Monte Carlo suggests nucleation and growth of monolayers above an ambient concentration near 6 μg m−3, which is less than some literature values for indoor air. The thermodynamics of the formation of these alkane monolayers includes contributions from the hydration free-energy (unfavorable), the free-energy of adsorption to the graphene–water interface (highly favorable), and integration into the alkane monolayer phase (highly favorable). Furthermore, the peak-to-peak distances in AFM force profiles perpendicular to the interface (0.43–0.53 nm), agree with the distances calculated in simulations for overlayers of alkane-like molecules, but not for molecules such as N2, water, or aromatics. Taken together, these results suggest that ordered domains observed on graphene, graphite, and other hydrophobic materials in water are consistent with alkane-like molecules occupying the interface.

Hydration breaking and chemical ordering in a levitated NaCl solution droplet beyond the metastable zone width limit: evidence for the early stage of two-step nucleation.

For over two decades, NaCl nucleation from a supersaturated aqueous solution has been predicted to occur via a two-step nucleation (TSN) mechanism, i.e., two sequential events, the formation of locally dense liquid regions followed by structural ordering. However, the formation of dense liquid regions in the very early stage of TSN has never been experimentally observed. By using a state-of-the-art technique, a combination of electrostatic levitation (ESL) and in situ synchrotron X-ray and Raman scatterings, we find experimental evidence that indicates the formation of dense liquid regions in NaCl bulk solution at an unprecedentedly high level of supersaturation (S = 2.31). As supersaturation increases, evolution of ion clusters leads to chemical ordering, but no topological ordering, which is a precursor for forming the dense disordered regions of ion clusters at the early stage of TSN. Moreover, as the ion clusters proceed to evolve under highly supersaturated conditions, we observe the breakage of the water hydration structure indicating the stability limit of the dense liquid regions, and thus leading to nucleation. The evolution of solute clusters and breakage of hydration in highly supersaturated NaCl bulk solution will provide new insights into the detailed mechanism of TSN for many other aqueous solutions.

One‐Step Generation of Core–Gap–Shell Microcapsules for Stimuli‐Responsive Biomolecular Sensing

AbstractThe versatile design of stimuli‐responsive microparticles embedding valuable biomolecules has great potential in a variety of engineering fields, such as sensors, actuators, drug delivery, and catalysis. Here, results are reported on thermoresponsive core–gap–shell (TCGS) microcapsules made of poly(N‐isopropylacrylamide) (PNIPAm), which encapsulate hydrophilic payloads in a simple and stable manner. These are realized by a one‐step microfluidic approach using the phase separation of a supersaturated aqueous solution of NIPAm. Various designs of the microcapsules are achieved by individual control of the swelling or by incorporating pH‐responsive comonomers of the inner core and outer shell. The gap, i.e., the space between the inner core and outer shell, can be loaded with cargo‐like nanoparticles. The outer shell can serve as a stimuli‐responsive gateway for the transport of smaller molecules from the external solution. It is shown that the TCGS microcapsules are suitable as temperature controllable glucose sensors and hold promise in the design of controllable enzymatic reactions. The proposed platform provides an avenue for developing a new‐generation of microparticles for diverse and efficient engineering applications.

Stability of the Supersaturated State of Encapsulated Solutions

By the example of highly concentrated water-in-oil emulsions, in which droplets of a supersaturated aqueous ammonium nitrate solution are dispersed in industrial oil, it has been shown that a thermodynamically stable state is possible due to the limited volume of dispersed phase particles.

Crystals of Benzamide, the First Polymorphous Molecular Compound, Are Helicoidal.

The growth of spontaneously twisted crystals is a common but poorly understood phenomenon. An analysis of the formation of twisted crystals of a metastable benzamide polymorph (form II) crystallizing from highly supersaturated aqueous and ethanol solutions is given here. Benzamide, the first polymorphic molecular crystal reported (1832), would have been the first helicoidal crystal observed had the original authors undertaken an analysis by light microscopy. Polymorphism and twisting frequently concur as they are both associated with high thermodynamic driving forces for crystallization. Optical and electron microscopies as well as electron and powder X-ray diffraction reveal a complex lamellar structure of benzamide form II needle-like crystals. The internal stress produced by the overgrowth of lamellae is shown to be able to create a twist moment that is responsible for the observed non-classical morphologies.