Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.

@article{Du2015CanTS,
  title={Can the study of self-assembly in solution lead to a good model for the nucleation pathway? The case of tolfenamic acid.},
  author={Wei Du and Aurora J. Cruz‐Cabeza and Sander Woutersen and Roger J. Davey and Qiang Yin},
  journal={Chemical Science},
  year={2015},
  volume={6},
  pages={3515 - 3524}
}
To further our understanding of the role of solution chemistry in directing nucleation processes new experimental and computational data are presented on the solution and crystallisation chemistry of tolfenamic acid (TA), a benchmark polymorphic compound. 

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References

SHOWING 1-10 OF 33 REFERENCES
Linking solution chemistry to crystal nucleation: the case of tetrolic acid.
The application of FTIR spectroscopy to concentrated solutions of tetrolic acid shows, for the first time, a direct relationship between molecular self association in solution and H-bonded motifs in
Crystal engineering – nucleation, the key step
In the world of crystal engineering in which the focus of effort is on the assembly of molecular species by crystallisation, surprisingly little attention has been paid to the actual nucleation and
Revealing the roles of desolvation and molecular self-assembly in crystal nucleation from solution : benzoic and p -aminobenzoic acids
There has been much recent interest in the role of solution chemistry and in particular the importance of molecular self-assembly in the nucleation of crystalline phases. Techniques such as FTIR and
Nucleation of organic crystals--a molecular perspective.
TLDR
The extent to which CNT and nucleation rate measurements can yield molecular-scale information on this process is explored and current knowledge relating to molecular self-assembly in nucleating systems is summarized.
Two Major Pre-Nucleation Species that are Conformationally Distinct and in Equilibrium of Self-Association
To understand how solution chemistry governs polymorphic formation of organic crystals, solution NMR measurements of tolfenamic acid were conducted in ethanol. It was unveiled by chemical shift and
The nucleation of inosine: the impact of solution chemistry on the appearance of polymorphic and hydrated crystal forms.
TLDR
This contribution concerns the issue of crystal nucleation in the polymorphic and hydrate forming system inosine-water and it is evident that the initial nucleation of a metastable polymorph at temperatures above 10 degrees C is directed by dimeric self-association as revealed through proton NMR.
Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association
TLDR
As concentration increases, solute molecules rearrange their conformations to form stronger hydrogen-bonded dimers in solution, resulting in nucleation of the most stable form, contradicting Ostwald’s Rule of Stages.
Concerning the Relationship between Structural and Growth Synthons in Crystal Nucleation: Solution and Crystal Chemistry of Carboxylic Acids As Revealed through IR Spectroscopy
Little is known concerning the precise molecular pathway that links fluid-phase molecules to those in nascent crystal nuclei. In this paper the process of molecular self-assembly has been studied in
POLYMORPH FORMATION OF TOLFENAMIC ACID: AN INVESTIGATION OF PRE-NUCLEATION ASSOCIATION
OF DISSERTATION POLYMORPH FORMATION OF TOLFENAMIC ACID: AN INVESTIGATION OF PRE-NUCLEATION ASSOCIATION The majority of pharmaceutical products are formulated as solids in the crystalline state. With
Thermodynamic and structural study of tolfenamic acid polymorphs.
...
1
2
3
4
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