Nucleation of Organic Crystals—A Molecular Perspective

Davey, Roger J.; Schroeder, Sven L. M.; Horst, Joop H. ter

doi:10.1002/anie.201204824

Cited by 453 publications

(589 citation statements)

References 102 publications

(221 reference statements)

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“…The involvement of a nucleus in the cooperative formation of 1D assemblies holds an intriguing resemblance to classical nucleation phenomena well known in ice formation, precipitation of organic crystals [52] and colloidal crystallization. [53] However, notable differences can be recognized, for instance in the physical principles responsible for the involvement of a nucleus.…”

Section: Nucleation In One-dimensional Vs Three-dimensional Aggregationmentioning

confidence: 85%

See 1 more Smart Citation

Pathway Complexity in π-Conjugated Materials

2013

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Aim and outline of this thesisTo arrive at functional organic materials with optimal molecular organization, control over the aggregation process is a prerequisite. Often however, multiple pathways are involved that compete for the same molecular building block, a phenomenon known as pathway complexity. As a result, the material -made from small molecules or polymers -can get entrapped in a metastable pathway while a more stable, but slower formed morphology is aimed for. Vice versa, the equilibrium state can be obtained easily but another, less stable morphology is desired as it has more interesting properties. In both cases, the solution processing, starting from molecularly dissolved material, should be optimized to select the desired aggregation pathway. This introduction chapter aims to outline the importance of mechanistic insights derived from self assembly of one dimensional fibres in diluted solutions to unravel and control aggregation pathways involved in the processing of conjugated materials.Part of this work has been published as:

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Section: Nucleation In One-dimensional Vs Three-dimensional Aggregationmentioning

confidence: 85%

“…The same holds for the formation of organic crystals for supersaturated solutions. [52] In contrast to this, the formation of a 1D assembly in solution at the critical temperature of elongation is not associated with an infinite free energy barrier.…”

Section: Nucleation In One-dimensional Vs Three-dimensional Aggregationmentioning

confidence: 98%

Pathway Complexity in π-Conjugated Materials

2013

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“…This observation gives us insights into the nucleation of not only protein crystals but also other organic crystals. Scattering and spectroscopic techniques reveal the structure evolutions of organic materials in solutions and the existence of clusters (25). To understand the nucleation, our observations suggest the importance of the direct observation of nucleation events at the nanoscale to reveal the role of amorphous particles on crystal nucleation, whether they act as heterogeneous nucleation sites or precursors for nucleation.…”

Section: Significancementioning

confidence: 87%

Two types of amorphous protein particles facilitate crystal nucleation

Yamazaki

Kimura

Vekilov

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

150

157

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Nucleation, the primary step in crystallization, dictates the number of crystals, the distribution of their sizes, the polymorph selection, and other crucial properties of the crystal population. We used timeresolved liquid-cell transmission electron microscopy (TEM) to perform an in situ examination of the nucleation of lysozyme crystals. Our TEM images revealed that mesoscopic clusters, which are similar to those previously assumed to consist of a dense liquid and serve as nucleation precursors, are actually amorphous solid particles (ASPs) and act only as heterogeneous nucleation sites. Crystalline phases never form inside them. We demonstrate that a crystal appears within a noncrystalline particle assembling lysozyme on an ASP or a container wall, highlighting the role of heterogeneous nucleation. These findings represent a significant departure from the existing formulation of the two-step nucleation mechanism while reaffirming the role of noncrystalline particles. The insights gained may have significant implications in areas that rely on the production of protein crystals, such as structural biology, pharmacy, and biophysics, and for the fundamental understanding of crystallization mechanisms.nucleation | protein | lysozyme | transmission electron microscopy | in situ observation C rystallization can be divided into two processes: nucleation and crystal growth. The crystal growth process has been well examined for a long time, yet the nucleation process is not understood; for example, the nucleation rate of crystals provides a textbook example of order-of-magnitude discrepancies between theoretical predictions and experimental results. Recent proposals have attributed these discrepancies to a nonclassical nucleation pathway, along which a structured crystalline embryo forms within a highly concentrated disordered precursor (1). This mechanism was first proposed for protein crystals (2, 3). Direct observations have demonstrated its applicability to organic (4), inorganic (5, 6), and colloidal (7) crystals. In proteins, clusters of protein molecules have been suggested as precursors; these clusters have mesoscopic sizes from several tens to several hundreds of nanometers and are considered to behave like liquids. It has also been suggested that the precursor is thermodynamically stable with respect to the mother liquid phase but is metastable or unstable with respect to the crystalline phase. The latter nature of the precursor differs from the stable macroscopically dense liquid formed as a result of the liquid-liquid phase separation (8). Such protein-rich mesoscopic clusters have been observed for many proteins, primarily using optical techniques, and have been tentatively identified as precursors for crystal nucleation (9-12). Several important questions concerning this mechanism remain unanswered. First, are the observed mesoscopic clusters actually liquid-like or solid-amorphous? Second, do they play an active role in crystal nucleation? In addition, finally, do the clusters serve as classical heteroge...

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“…This observation, however, does not necessarily imply that the nucleation mechanism postulated by CNT as a molecule-bymolecule incremental growth of a crystal-like particle is actually a faithful description of the real process. In this paragraph, we delve into the molecular details provided by WT metadynamics to assess whether the nucleation process takes place according to a single-step mechanism or rather through a two-step process in which the crystal phase emerges within a liquid-like cluster, rich in solute molecules, a scenario that is currently debated in the literature (31).…”

Section: Free Energy Of Nucleation Of a Crystal-like Particle From Mementioning

confidence: 99%

Molecular-dynamics simulations of urea nucleation from aqueous solution

Salvalaglio

Perego

Giberti

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

152

221

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Despite its ubiquitous character and relevance in many branches of science and engineering, nucleation from solution remains elusive. In this framework, molecular simulations represent a powerful tool to provide insight into nucleation at the molecular scale. In this work, we combine theory and molecular simulations to describe urea nucleation from aqueous solution. Taking advantage of well-tempered metadynamics, we compute the freeenergy change associated to the phase transition. We find that such a free-energy profile is characterized by significant finite-size effects that can, however, be accounted for. The description of the nucleation process emerging from our analysis differs from classical nucleation theory. Nucleation of crystal-like clusters is in fact preceded by large concentration fluctuations, indicating a predominant two-step process, whereby embryonic crystal nuclei emerge from dense, disordered urea clusters. Furthermore, in the early stages of nucleation, two different polymorphs are seen to compete.T he nucleation of crystals from solution plays an important role in a variety of chemical and engineering processes. However, the very small scale that characterizes the early stages of nucleation makes its experimental study rather challenging. In this regard, molecular simulations play an important role and much work has been devoted to the study of homogeneous nucleation in simple model systems like Lennard-Jones particles or hard spheres (1-3). More recently, growing attention has been paid to the computer simulation of nucleation from solution of organic and inorganic materials (4-11).However, these simulations have to face an important challenge. Nucleation is a typical example of a rare event occurring on a timescale that is much longer than what atomistic simulations can typically afford. The problem is most easily understood if we focus on molecular dynamics (MD), which is the sampling method used here but it plagues other methods as well. In MD, the shortest timescale to be used for a correct integration of the equation of motion is dictated by the fastest atomic motions such as vibrations or rotations. Due to this constraint in the integration step, present MD simulations can reach timescales up to microseconds unless specific hardware, accessible only to few, is used. Even in this case the scale of the accessible times can be stretched only to the milliseconds range, a far cry from the much longer scale of nucleation phenomena.These timescale limitations affect molecular simulations in several other research fields, such as ligand protein binding, protein folding, or slow chemical reactions, to name just a few. To overcome this limit, many enhanced sampling methods have been proposed (12-21). Several of them are based on the application of a suitable external bias potential (12-14) that speeds up configurational sampling and permits free energies to be evaluated and transition rates to be computed (22)(23)(24). Here, we shall use well-tempered (WT) metadynamics to enhance the nucleation...

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Nucleation of Organic Crystals—A Molecular Perspective

Cited by 453 publications

References 102 publications

Pathway Complexity in π-Conjugated Materials

Pathway Complexity in π-Conjugated Materials

Two types of amorphous protein particles facilitate crystal nucleation

Molecular-dynamics simulations of urea nucleation from aqueous solution

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