Comprehending the Formation of Eutectics and Cocrystals in Terms of Design and Their Structural Interrelationships

The phenomenon of cocrystallization, which encompasses the art of making multicomponent organic solids such as cocrystals, solid solutions, eutectics, etc. for novel applications, has been less studied in terms of reliably and specifically obtaining a desired cocrystallization product and the issues that govern their formation. Further, the design, structural, and functional aspects of organic eutectics have been relatively unexplored as compared to solid solutions and cocrystals well-established by crystal engineering principles. Recently, eutectics were proposed to be designable materials on par with cocrystals, and herein we have devised a systematic approach, based on the same crystal engineering principles, to specifically and desirably make both eutectics and cocrystals for a given system. The propensity for strong homomolecular synthons over weak heteromolecular synthons and vice versa during supramolecular growth was successfully utilized to selectively obtain eutectics and cocrystals, respectively, in two model systems and in two drug systems. A molecular level understanding of the formation of eutectics and cocrystals and their structural interrelationships which is significant from both fundamental and application viewpoints is discussed. On the other hand, the obscurity in establishing a low melting combination as a eutectic or a cocrystal is resolved through phase diagrams.

Effect of inductive effect on the formation of cocrystals and eutectics

There is a growing need to understand the factors that control the formation of different yet related multicomponent adducts such as cocrystals, solid solutions and eutectics from both fundamental and application perspectives. Benzoic acid and its structural analogues, having gradation in inductive force strengths, are found to serve as excellent coformers to comprehend the formation of above adducts with the antiprotozoal drug ornidazole. The combination of the drug with para-amino and -hydroxybenzoic acids resulted in cocrystals in accordance with the induction strength complementarity between the participant hydrogen bond donor-acceptor groups. The lack of adequate inductive forces for combinations with benzoic acid and other coformers was exploited to make eutectics of the drug. The isomorphous/isostructural relationship between para-amino and -hydroxybenzoic acid-drug cocrystals was utilized to make solid solutions, i.e. solid solutions of cocrystals. All in all, we successfully steered and expanded the supramolecular solid-form space of ornidazole.

Interphase anisotropy effects on lamellar eutectics: A numerical study

In directional solidification of binary eutectics, it is often observed that two-phase lamellar growth patterns grow tilted with respect to the direction z of the imposed temperature gradient. This crystallographic effect depends on the orientation of the two crystal phases alpha and beta with respect to z. Recently, an approximate theory was formulated that predicts the lamellar tilt angle as a function of the anisotropy of the free energy of the solid(alpha)-solid(beta) interphase boundary. We use two different numerical methods-phase field (PF) and dynamic boundary integral (BI)-to simulate the growth of steady periodic patterns in two dimensions as a function of the angle theta(R) between z and a reference crystallographic axis for a fixed relative orientation of alpha and beta crystals, that is, for a given anisotropy function (Wulff plot) of the interphase boundary. For Wulff plots without unstable interphase-boundary orientations, the two simulation methods are in excellent agreement with each other and confirm the general validity of the previously proposed theory. In addition, a crystallographic ``locking'' of the lamellae onto a facet plane is well reproduced in the simulations. When unstable orientations are present in the Wulff plot, it is expected that two distinct values of the tilt angle can appear for the same crystal orientation over a finite theta(R) range. This bistable behavior, which has been observed experimentally, is well reproduced by BI simulations but not by the PF model. Possible reasons for this discrepancy are discussed.

Do carboximide-carboxylic acid combinations form co-crystals? The role of hydroxyl substitution on the formation of co-crystals and eutectics

Carboxylic acids, amides and imides are key organic systems which provide understanding of molecular recognition and binding phenomena important in biological and pharmaceutical settings. In this context, studies of their mutual interactions and compatibility through co-crystallization may pave the way for greater understanding and new applications of their combinations. Extensive co-crystallization studies are available for carboxylic acid/amide combinations, but only a few examples of carboxylic acid/imide co-crystals are currently observed in the literature. The non-formation of co-crystals for carboxylic acid/imide combinations has previously been rationalized, based on steric and computed stability factors. In the light of the growing awareness of eutectic mixtures as an alternative outcome in co-crystallization experiments, the nature of various benzoic acid/cyclic imide combinations is established in this paper. Since an additional functional group can provide sites for new intermolecular interactions and, potentially, promote supramolecular growth into a co-crystal, benzoic acids decorated with one or more hydroxyl groups have been systematically screened for co-crystallization with one unsaturated and two saturated cyclic imides. The facile formation of an abundant number of hydroxybenzoic acid/cyclic carboximide co-crystals is reported, including polymorphic and variable stoichiometry co-crystals. In the cases where co-crystals did not form, the combinations are shown invariably to result in eutectics. The presence or absence and geometric disposition of hydroxyl functionality on benzoic acid is thus found to drive the formation of co- crystals or eutectics for the studied carboxylic acid/imide combinations.

Multicomponent Adducts of Pyridoxine: An Evaluation of the Formation of Eutectics and Molecular Salts

Cocrystallization of pyridoxine (vitamin B6) with several biologically important molecules was undertaken with the intent of successfully designing various hydrogen bonded adducts such as salts, cocrystals, and eutectics. Pyridoxine formed eutectics with isoniazid (an antitubercular drug) and nicotinic acid (vitamin B3) and molecular salts with para-aminobenzoic acid (a bioactive) and saccharin (an artificial sweetener), respectively, in accordance to our design strategy. A salt cocrystal, a precisely conjugate acid-base cocrystal, was obtained for the pyridoxine-para-nitrobenzoic acid combination. The role of supramolecular affinity of hydrogen bonding functional groups and Delta pK(a) differences leading to the formation of above diverse adducts was discussed. This study underpins the need for full-fledged supramolecular compatibility studies of multivitamin/drug combinations toward the development of optimal and/or synergistic combination formulations.

Microstructure and mechanical properties of unidirectionally solidified Al-Si-Ni ternary eutectic

Al-10.98 pct Si-4.9 pct Ni ternary eutectic alloy was unidirectionally solidified at growth rates from 1.39μm/sec to 6.95μm/sec. Binary Al-Ni and Al-Si eutectics prepared from the same purity metals were also solidified under similar conditions to characterize the growth conditions under the conditions of present study. NiAl3 phase appeared as fibers in the binary Al-Ni eutectic and silicon appeared as irregular plates in the binary Al-Si eutectic. However, in the ternary Al-Si-Ni eutectic alloy both NiAl3 and silicon phases appeared as irregular plates dispersed in α-Al phase, without any regular repctitive arrangement. The size and spacing of NiAl3 and Si platelets in cone shaped colonies decreased with an increase in the growth rate of the ternary eutectic. Examination of specimen quenched during unidirectional solidification indicated that the ternary eutectic grows with a non-planar interface with both Si and NiAl3 phases protruding into the liquid. It is concluded that it will be difficult to grow regular ternary eutectic structures even if only one phase has a high entropy of melting. The tensile strength and modulus of unidirectionally solidified Al-Si-Ni eutectic was lower than the chill cast alloys of the same composition, and decreased with a decrease in growth rate. Tensile modulus and strength of ternary Al-Si-Ni eutectic alloys was greater than binary Al-Si eutectic alloy under similar growth conditions, both in the chill cast and in unidirectionally solidified conditions.

Phase diagram and dielectric studies of binary organic materials

The phase equilibrium studies of organic system, involving resorcinol (R) and p-dimethylaminobenzaldehyde (DMAB), reveal the formation of a 1:1 molecular complex with two eutectics. The heat of mixing, entropy of fusion, roughness parameter, interfacial energy, and the excess thermodynamic functions were calculated based on enthalpy of fusion data determined via differential scanning calorimetric (DSC) method. X-ray powder diffraction studies confirm that the eutectics are not simple mechanical mixture of the components under investigation. The spectroscopic investigations (IR and NMR) suggest the occurrence of hydrogen bonding between the components forming the molecular complex. The dielectric measurements, carried out on hot-pressed addition compound (molecular complex), show higher dielectric constant at 320 K than that of individual components. The microstructural investigations of eutectic and addition compound indicate dendritic and faceted morphological features. (C) 2000 Elsevier Science B.V. All rights reserved.

Effect of length scale on mechanical properties of Al-Cu eutectic alloy

This paper attempts a quantitative understanding of the effect of length scale on two phase eutectic structure. We first develop a model that considers both the elastic and plastic properties of the interface. Using Al-Al2Cu lamellar eutectic as model system, the parameters of the model were experimentally determined using indentation technique. The model is further validated using the results of bulk compression testing of the eutectics having different length scales. (C) 2012 American Institute of Physics. http://dx.doi.org/10.1063/1.4761944]

Structural and magnetic properties of ultra-small scale eutectic CoFeZr alloys

Aiming to develop high mechanical strength and toughness by tuning ultrafine lamellar spacing of magnetic eutectic alloys, we report the mechanical and magnetic properties of the binary eutectic alloys Co90.5Zr9.5 and Fe90.2Zr9.8, as well as the pseudo-binary eutectic alloys Co82.4Fe8Zr9.6, Co78Fe12.4Zr9.6 and Co49.2Fe49.2Zr9.6 developed by suction-casting. The lower lamellar spacing around 100 nm of the eutectics Co49.2Fe49.2Zr9.6 yields a high hardness of 713(+/- 20) VHN. Magnetic measurements reveal high magnetic moment of 1.92 mu B (at 5 K) and 1.82 mu B (at 300 K) per formula unit for this composition. The magnetization vs. applied field data at 5 K show a directional preference to some extent and therefore smaller non-collinear magnetization behavior compared to Co11Zr2 reported in the literature due to exchange frustration and transverse spin freezing owing to the presence of smaller Zr content. The decay of magnetization as a function of temperature along the easy axis of magnetization of all the eutectic compositions can be described fairly well by the spin wave excitation equation Delta M/M(0) = BT3/2 + CT5/2. (C) 2014 Elsevier B.V. All rights reserved.

Phase Diagram Study of Succinonitrile-Vanillin Organic Alloy System

Phase diagram studies of succinonitrile-vanillin system show the formation of 2:1 congruent melting type compound. Crystallization velocities of pure components, succinonitrile-vanillin complex, and two eutectics have been determined at different undercoolings. On the basis of heat of fusion measurements, excess thermodynamic functions have been calculated. Microstructural studies revealed that impurities modify the morphology. FTIR spectral studies and computer simulation have shown the existence of hydrogen bonding in the eutectics and the congruent melting compound. On the basis of experimental results, the mechanism of formation of eutectics and its solidification behavior are discussed.

Differential Cocrystallization Behavior of Isomeric Pyridine Carboxamides toward Antitubercular Drug Pyrazinoic Acid

Pyrazinoic acid, the active form of the antitubercular pro-drug Pyrazinamide, is an amphiprotic molecule containing carboxylic acid and pyridine groups and therefore can form both salts and cocrystals with relevant partner molecules. Cocrystallization of pyrazinoic acid with isomeric pyridine carboxamide series resulted in a dimorphic mixed-ionic complex with isonicotinamide and in eutectics with nicotinamide and picolinamide, respectively. It is observed that with alteration of the carboxamide position, steric and electrostatic compatibility issues between molecules of the combination emerge and affect intermolecular interactions and supramolecular growth, thus leading to either cocrystal or eutectic for different pyrazinoic acid-pyridine carboxamide combinations. Intermolecular interaction energy calculations have been performed to understand the role of underlying energetics on the formation of cocrystal/eutectic in different combinations. On the other hand, two molecular salts with piperazine and cytosine and a gallic acid cocrystal of the drug were obtained, and their X-ray crystal structures were also determined in this work.

Intermetallic eutectic alloys in the Ni-Al-Zr system with attractive high temperature properties

We describe a group of alloys with ultrahigh strength of about 2 GPa at 700 degrees C and exceptional oxidation resistance to 1100 degrees C. These alloys exploit intermetallic phases with stable oxide forming elements that combine to form fine nanometric scale structures through eutectic transformations in ternary systems. The alloys offer engineering tensile plasticity of about 4% at room temperature though both conventional dislocation mechanisms and twinning in the more complex intermetallic constituent, along with slip lengths that are restricted by the interphase boundaries in the eutectics.

On the issues of resolving a low melting combination as a definite eutectic or an elusive cocrystal: A critical evaluation

Cocrystals and eutectics are different yet related crystalline multi-component adducts with diverse applications in pharmaceutical and materials fields. Recently, they were shown to be alternate products of cocrystallization experiments. Whereas a cocrystal shows distinct diffraction, spectroscopic and thermal signatures as compared to parent components, the hallmark of a eutectic is its low melting nature. However, in certain cases, there can be a problem when one resorts to design a cocrystal and assess its formation vis-A -vis a eutectic. In the absence of a gold standard method to make a cocrystal, it is often difficult to judge how exhaustive should the cocrystallization trials be to ensure the accomplishment of a desired/putative cocrystal. Further, a cocrystal can manifest with intermolecular interactions and/or crystal structure similar to that of its parent compounds such that the conventional diffraction and spectroscopic techniques will be of little help to conclusively infer the formation of cocrystal in the lack of single crystals. Such situations combined with low melting behavior of a combination brings the complication of resolving the combination as a cocrystal or eutectic since now both the adducts share common features. Based on the curious case of Caffeine-Benzoic acid combination, this study aims to unfold the intricate issues related to the design, formation and characterization of cocrystals and eutectics for a way forward. The utility of heteronuclear seeding methodology in establishing a given combination as a cocrystal-forming one or a eutectic-forming one in four known systems is appraised.