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In this contribution the single crystal growth rates of four para substituted benzoic acids measured in toluene and isopropyl alcohol solutions are reported. Major objectives of the work have been to consider how such data might be correctly compared and how such comparisons may be related to underlying packing arrangements in the respective crystal structures. Morphological determinations formed an important part of the overall study. Consideration has been given to various practical issues arising from the varying solubility of the materials and growth rate dispersion among the measured crystal seeds. This provides suggestions as how best to measure growth rates for this purpose. The ultimate aims of such work have been to explore connections between growth and nucleation kinetics as well as to consider what such a data set might predict about the kinetics of other related molecules.

Increasing commercial application of state of the art crystal structure prediction to aid solid form discovery of new molecular entities allows the experimentalist to target the polymorphs with desired properties. Here we remind ourselves that in this field the gap between such prediction and experimentation can be vast, the latter depending strongly on kinetic processes not accounted for in the computations. Nowhere is this gap more evident than in examples of so-called “elusive” polymorphs, forms that have been found difficult to crystallize, sometimes taking years to appear or sometimes disappearing altogether. In attempting to probe the origins of such phenomena this work targets a well-known, relatively simple molecule, paracetamol (PCM), and explores the structural and kinetic origins of its elusive nature. It is noted that in general comparisons of the kinetic factors (nucleation and crystal growth) between polymorphs have rarely been reported and of course in cases where one or more forms is “elusive” this will, by definition, be essentially impossible. PCM however offers a unique opportunity and we show how the recent discovery of the impact of metacetamol (MCM) in stabilizing PCM form II can be used to advantage, enabling otherwise impossible comparative kinetic experiments to be made. Resulting from this study we now appreciate that MCM has a selective impact in blocking the growth of the thickness and width of PCM form I while it has no impact on form II. This is interpreted in terms of strong adsorption of MCM on the {011} faces (width and thickness) of form I in orientations that inhibit crystal growth (“wrong” orientations). Of more significance here is the use of the additive in allowing an otherwise impossible comparison of linear growth rates of forms I and II. This leads to the appreciation that only through calculation of growth volumes can we finally appreciate how the relative growth kinetics lead inevitably to the elusive nature of Form II.

In this contribution, the hydration kinetics of three anhydrous polymorphs (AH-A, AH-B, and AH-C) of fluconazole [2-(2,4-difluorophenyl)-1,3-bis (1H-1,2,4-triazol-1-yl)-propan-2-ol] were studied. The conversion kinetics from the anhydrous forms to the monohydrate (MH) was monitored at various relative humidities above the critical water activity. The studies revealed very different kinetic stabilities for the three anhydrous forms, with AH-A and AH-C converting much more easily to the MH than AH-B. Various energetic factors, which may be influencing the kinetics of hydration, were explored together with crystal structure and molecular conformation similarities between the anhydrous forms and the MH. The level of conformational and packing similarity between the anhydrous and MH structures was found to be consistent with the ease of hydration. We believe that surface similarity may be required for the nucleation of the hydrate, while the level of crystal packing similarity impacts the ease of growth. In terms of conformational variations, AH-B was found to require a significantly more dramatic conformational change to convert to the MH conformation than those in either AH-A or AH-C. Soft planes (low attachment energies) may allow for easier diffusion of solvent into the crystal structure to allow for solvation. The overall kinetic energy barrier of water diffusion into the lattice plus conformational change was found to correlate well with our observed hydration kinetics, indicating that both the crystal structure and the conformation play a role in the kinetic stability toward hydration of the various fluconazole polymorphs.

From a general formulation of batch crystallization in a polymorphic system, it is shown that the concept of an Ostwald ratio provides a fundamental parameter with which to understand and compute the variation in polymorph composition with time, temperature, and supersaturation. In particular, it defines the conditions under which a system will exhibit sequential development of polymorphs, as per the widely known Ostwald’s Rule of Stages and conversely when either only the stable polymorph will result or when forms appear simultaneously resulting in concomitant polymorphism. The Ostwald ratio is not a constant but varies with temperature, the initial supersaturation, crystal shape, and density. It is shown that its evaluation can lead to a kinetically based phase diagram enabling the construction of polymorph maps in compositional and temperature space. A review of relevant existing kinetic data reveals a lack of information concerning both the relative nucleation and growth rates of polymorphic phases. The specific case of gestodene is used as a means of demonstrating the significance and potential of this approach to the robust design of batch crystallization processes in polymorphic systems.

The experimental observation that certain crystal faces do not grow, despite being in contact with supersaturated solution, is a widely reported phenomenon. This concept of a growth “dead zone” has been known for many years, but its origin remains an unresolved problem in crystal growth. Sometimes it seems to be an inherent feature of the solution growth process, while at others it appears that an impurity is an essential element for its appearance. Here we review existing data and provide new experimental evidence to confirm the widespread existence of the dead zone across a range of molecular materials. Available crystal growth kinetics are confronted with mechanistic models. Examination of the packing arrangements of appropriate crystal faces suggests that this behavior is linked to molecular-scale surface roughness.

We report on the nucleation and growth kinetics of the α and β polymorphs of p-aminobenzoic acid (pABA) in the presence of two additives: 4-amino-3-nitrobenzoic acid (ANBA) and 4-amino-3-methoxybenzoic acid (AMBA). While the presence of additives slowed down the nucleation kinetics of both forms, they had a much larger impact on the growth kinetics of the α-form than the β-form. This allowed the nucleation and growth, for the first time, of the β-form (a form much harder to crystallize) in conditions which would normally afford the α-form. Given our previous findings that the nucleation and growth of α pABA is primarily controlled by aromatic stacking, our additive design strategy was based primarily on the idea that additives could be selected to attach strongly to pABA stacks while at the same time disrupting adjacent molecules. Such a strategy was successful in selective polymorph inhibition of α; this was possible because the growth of β-form is controlled by interactions other than aromatic stacks. More generally, our study also confirms that additives designed to modify the growth of macroscopic crystals also inhibit their nucleation.

The melting behaviors of three binary organic compounds, a racemate, a cocrystal, and a salt, are compared with their individual components and with each other. The three compounds are the racemic compound of mandelic acid, the benzophenone–diphenylamine cocrystal, and ephedrine pimelate. Similarities and differences are accounted for by changes in entropy, hydrogen bonding, molecular conformation, and charged state on melting. An unusual combination of thermodynamic, structural, and spectroscopic data gives insight into the nature and extent of association in these melts. The three binary compounds show surprisingly similar melting thermodynamics. The main differences are in the salt system, driven by ionization and access to a 2:1 salt. The implications for melt and solution eutectics are discussed.

Formation of inorganic barrier coatings on lead water pipes might be an attractive option for water companies wishing to reduce lead levels in drinking water. This paper concerns the treatment of such pipes with aqueous solutions containing oxidant together with sources of phosphate and chloride to generate coatings of the highly insoluble lead mineral chloropyromorphite, Pb₅(PO₄)₃Cl by simultaneous oxidation and precipitation. SEM, TEM, XRD and overnight leaching tests were used to characterise the structure and performance of the coatings. The impact of the choice of oxidant on the coating morphology and barrier properties is explored. Strategies for further refinement of the coatings via improved process control and morphological modification are discussed.

Crystal structure prediction was used to explore possible modes of assembly of 2-amino-4-nitrophenol (ANP) molecules in the solid state. The results from this simulation were employed for the rational selection of solvents for the isolation of solid phases by solution crystallisation. Implementation of this crystal engineering based approach is seen as a first step in utilising predicted structural data and in this example resulted in the isolation of three crystal forms, one non-solvated structure and two solvated forms. Though too complex to be predicted, each contained elements of the packing modes identified from the crystal modelling simulations. This work demonstrates the potential application and limitations of available crystal structure modelling techniques as part of a strategy for the discovery of new crystal forms of molecular materials.

Die Untersuchung einer dichten Probenserie in der mit Ammoniten datierten Abfolge des Speeton Clay (unteres Hauterivien) erlaubt eine Präzisierung der stratigraphischen Verteilung der Dinocysten und auf unterschiedlichen Palynofloren beruhende paläoökologische Interpretationen. Mehrere Dinocysten-Taxa besitzen besonders in Nordwesteuropa einen guten stratigraphischen Leitwert.

The variation in physical properties of crystals grown in the presence of additives or impurities have previously been attributed to lattice disorder developed during crystallization. Adipic acid crystallized in the presence of a variety of stereochemically related impurities typifies such behavior with disorder manifest in variations of dissolution rates and enthalpies of solution and fusion. In this case the most extreme habit, produced by the presence of added monoalkanoic acids, is a rounded dumbbell that was suggested previously to be a twinned crystal. In this contribution such crystals are fully characterized both through their external morphology and by means of single crystal X-ray diffraction. These techniques show that these particles are not twinned but rather are disordered single crystals comprising a small number of slightly misaligned domains. The interaction between additive and substrate is modeled and new additives selected that induce the formation of true mechanical twins in adipic acid. © 2000 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 89: 346–354, 2000

We present an automated method for measuring facet specific growth rates by combining a crystal growth flow cell with image processing. This paper details the design of the growth cell and its advantages over previous models. The method of image processing utilizes a Hough transform to identify crystal facets, ultimately leading to facet specific growth rate measurements. Finally, experimental results are presented for facet specific growth rates of α-glycine crystals and compared to previous data.

Understanding crystal growth kinetics is of great importance for the development and manufacturing of crystalline molecular materials. In this work, the impact of additives on the growth kinetics of benzamide form I (BZM-I) crystals has been studied. Using our newly developed crystal growth setup for the measurement of facet-specific crystal growth rates under flow, BZM-I growth rates were measured in the presence of various additives previously reported to induce morphological changes. The additives did not have a significant impact on the growth rates of BZM-I at low concentrations. By comparison to other systems, these additives could not be described as “effective” since BZM-I showed a high tolerance of the additives’ presence during growth, which may be a consequence of the type of growth mechanisms at play. Growth of pure BZM-I was found to be extremely defected, and perhaps those defects allow the accommodation of impurities. An alternative explanation is that at low additive concentrations, solid solutions are formed, which was indeed confirmed for a few of the additives. Additionally, the growth of BZM-I was found to be significantly affected by solution dynamics. Changes in some facet growth rates were observed with changes in the orientation of the BZM-I single crystals relative to the solution flow. Of the two sets of facets involved in the growth of the width and length of the crystal, the {10l̅} facets were found to be greatly affected by the solution flow while the {011} facets were not affected at all. Computational fluid dynamics simulations showed that solute concentration has higher gradients at the edges of the leading edge {10l̅} facets, which can explain the appearance of satellite crystals. {10l̅} facets were found to show significant structural rugosity at the molecular level, which may play a role in their mechanism of growth. The work highlights the complexities of measuring crystal growth data of even simple systems such as BZM-I, specifically addressing the effect of additives and fluid dynamics.

The simultaneous appearance of polymorphs of a substance has long been recognized but rarely noted or systematically studied. This phenomenon can be useful in the investigation of solid materials and in understanding the relative crystal energetics of polymorphic materials. This review covers the thermodynamic and kinetic factors that govern competitive and concomitant polymorphic crystallization. One of the many examples surveyed is a cyanine/oxonol complex, for which different relative molecular orientations in two of the many reported polymorphs are shown.

Das gleichzeitige Auftreten von polymorphen Modifikationen ist zwar ein schon lange bekanntes Phänomen, wird aber kaum wahrgenommen oder gar systematisch untersucht. Es kann aber hilfreich bei der Untersuchung von Feststoffen und zum Verständnis der relativen Kristallenergien von polymorphen Materialien sein. Der Beitrag behandelt die thermodynamischen und kinetischen Faktoren, die die konkurrierende und gleichzeitige Kristallisation von polymorphen Modifikationen bestimmen. Eines des betrachteten Beispiele ist ein Cyanin/Oxonol-Komplex, für den unterschiedliche relative Molekülorientierungen von zwei der vielen beschriebenen polymorphen Modifikationen gezeigt sind.

The successful selection, design and synthesis of additives for the control of nucleation and crystallisation of a red anthraquinone based dye is described. This procedure is based on the crystal structure and morphology of solution grown crystals and in this study the possibility of using the same approach to control crystallisation within an amorphous polymeric matrix is explored. The work has been motivated by the desire to prepare stable dye sheets for thermal transfer printing applications, yet the parallel with natural biomineralisation processes is clear.

The morphology of lepidocrocite crystals has been found to be significantly modified by the binding of certain hydroxybenzenes and aliphatic diols. The data have been combined in order to explore the geometric and stereochemical requirements of the binding process. Replacement of hydroxides by hydroxyl groups combined with appropriate iron-oxygen orbital overlap is found to be an essential requirement. Attempts to find molecules capable of binding to (010) were unsuccessful due either to the need for highly strained molecular conformations or due to the inherent passivity of the (010) surface. Copyright 1994, 1999 Academic Press

In December 1966, several new taxa from the Cenomanian of England were validly published and named as part of larger study on Mesozoic and Cainozoic dinoflagellate cysts (papers by Davey, Downie, Sarjeant and Williams in Bull. Brit. Mus. Nat. Hist., Supplement 3, 1966). A subsequent publication on dinoflagellate cyst assemblages from the Chalk of the Isle of Wight, England (Clarke and Verdier, 1967) included independent descriptions of these same taxa under different names: these latter names are junior synonyms and must be rejected, under Article 57 of the “International Code of Botanical Nomenclature”. These names are here listed.

Ionic bond or hydrogen bridge?Brønsted proton transfer to nitrogen acceptors in organic crystals causes strong N1s core‐level binding energy shifts. A study of 15 organic cocrystal and salt systems shows that standard X‐ray photoelectron spectroscopy (XPS) can be used as a complementary method to X‐ray crystallography for distinguishing proton transfer from H‐bonding in organic condensed matter (see picture).

The design and application of a novel plug flow crystalliser is described. Simultaneous collection of SAXS and WAXD during the nucleation and crystal growth of a small organic molecule from solution is reported. Preliminary data imply the separation of a non-diffracting phase prior to the appearance of crystalline solid.

We report the novel application of a stopped-flow device to the in situ study of solution crystallisation processes.

We report the development of a novel technique for the encapsulation of molecular and condensed organic and inorganic substrates within hollow calcium carbonate microspheres; the process utilises precipitation at the oil–water interface of a pseudovesicular water-in-oil-in-water emulsion liquid membrane (ELM) system in order to create an inorganic shell around the pre-dispersed media.

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