Crystal Polymorphism as a Probe for Molecular Self-Assembly during Nucleation from Solutions:  The Case of 2,6-Dihydroxybenzoic Acid

Davey, Roger J.; Blagden, Nicholas; Righini, S.; Alison, H.; Quayle, Michael J.; Fuller, Stuart

doi:10.1021/cg000009c

Cited by 149 publications

(161 citation statements)

References 21 publications

(39 reference statements)

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…This has been reported in the growth of 2,6-dihydroxybenzoic acid (35). It was found that carboxylic acid dimers were present predominately in toluene from which a dimer-based crystal form was produced, while polymeric aggregates appeared to dominate in chloroform, leading to a hydrogen-bonded catemer observed in the harvested crystal structure.…”

Section: Introductionsupporting

confidence: 57%

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association

Mattei

2011

Pharm Res

View full text Add to dashboard Cite

show abstract

Section: Introductionsupporting

confidence: 57%

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association

Mattei

2011

Pharm Res

View full text Add to dashboard Cite

show abstract

“…How the solute is dominantly present in solution could thus strongly influence the crystal nucleation process. It was for instance reported that 2,6-dihydroxybenzoic acid 11 associates into dimers in toluene and catemers in chloroform. Crystallization from these solvents leads to the dimer crystal structure form 1 in the case of toluene and to the catemer crystal structure form 2 in the case of chloroform.…”

mentioning

confidence: 99%

Isonicotinamide self-association: the link between solvent and polymorph nucleation

et al. 2012

View full text Add to dashboard Cite

We show that, in a controlled and reproducible way, specific solvents lead to specific polymorphic forms of isonicotinamide. We argue on the basis of Raman and FTIR spectroscopy that the hydrogen bonding in solution kinetically drives the nucleation towards a specific form. This generally may lead to good understanding and control of polymorphism and crystal nucleation.The ability to control and predict crystal nucleation is of paramount importance from the viewpoint of crystal engineering, materials synthesis and crystalline product quality. [1][2][3] In this communication we demonstrate the reproducible effect of solvents on the formation of isonicotinamide (INA) polymorphs. We establish that in solvents with strong hydrogen bond acceptors, the dominant configuration of the INA molecules with respect to each other is that of amide-pyridine heterosynthons (headto-tail chains) (Fig. 1). Similarly, solvents with strong hydrogen bond donors lead to dominancy of amide-amide homosynthons (head-to-head dimers). This self-association in solution controls the polymorph nucleation of INA by controlling the building unit attaching to the nucleus.Polymorphism can be defined as the ability of a single chemical compound to form more than one crystal structure. 4 Polymorphism of active pharmaceutical ingredients is the subject of intense interest in both science and industry. 4,5 On the one hand, this is because crystalline product quality aspects such as drug efficacy, bioavailability and safety are affected by the polymorphic form present. On the other hand, polymorphs have economic and intellectual property implications.Often through empirical research, effects of solvent, supersaturation and impurities are observed on polymorph formation. 6 Recently, next to the two known forms of INA, 7 a third form was reported which incidentally and irreproducibly formed during a co-crystal screen from a multicomponent solution. 8 More recently, the difficult to control evaporative crystallization process yielded two new forms of INA.9 Form IV was obtained only as a mixture together with form II and/or V. For form V yields were often poor, typically 10%, and in some cases it could not be obtained.The crystal nucleation of INA is a most interesting process because of the strongly differing packing of form II and the other forms (ESIw). Isonicotinamide form II has been reported to be the most stable form at room temperature. 8 In the structure of form II the amide groups form homosynthons (dimers), 8 which in turn are hydrogen bonded through the oxygen atom and the remaining hydrogen of the amide group. Interestingly, the pyridine group does not participate in hydrogen bonding in the crystal structure of form II, contrary to all other currently known forms of INA. These consist of differently packed head-to-tail chains connected through heterosynthons of the amide and the pyridine group.The classical view of crystal nucleation is that building units attach to and detach from clusters of molecules.10 This attaching building unit could be...

show abstract

“…To model the graphite surface, we employed a large cluster consisting of two graphitic layers, each containing 20 20 unit cells. For the muscovite mica surface, we employed a 8 4 unit cell cluster measuring approximately 34 40 2 and assigned ionic charges to all atoms (Al +3, Si +1, O surface À0.75, O interior À1, K +1, where the oxygen subscripts refer to their position in the mica slab) to be of consistent magnitude with other similar theoretical studies. [19] Although real muscovite mica corresponds to a blend of interlayer cations, only potassium surface cations were considered here for simplicity, with half of them removed from the external surface at random to ensure charge neutrality.…”

Section: Methodsmentioning

confidence: 89%

“…To control the formation of these self-assemblies it is therefore fundamental to study not only the molecule-molecule interactions but also the interactions of the molecule with the solvent and with the substrate. [2] Due to their structural and electronic characteristics, tetrathiafulvalenes (TTFs) have been the center of attention as a source of building blocks for the preparation of materials with interesting electrical properties. [3] TTFs have been used successfully for a large variety of purposes, such as preparing a multitude of conducting charge-transfer salts, [4] molecular wires, [5] donor-acceptor dyads, [6] ionic sensors, [7] molecular machines, [8] and organic field-effect transistors.…”

Section: Introductionmentioning

confidence: 99%

Influence of Intermolecular Interactions on the Formation of Tetra(carbomethoxy)‐tetrathiafulvalene Assemblies

et al. 2007

View full text Add to dashboard Cite

We study the assemblies that tetra(carbomethoxy)tetrathiafulvalene (TCM-TTF) forms in solution and when deposited on a surface depending on intermolecular interactions and on the interactions with the substrate and the solvent. Its organization on graphite and mica substrates was studied by atomic force microscopy, and different molecular assemblies were observed depending on the prevailing interactions. The promotion of molecule-molecule interactions gave rise to the formation of molecular fibers. The investigation of the influence of the solvent-molecule interactions on TCM-TTF molecular organizations was carried out by UV/Vis spectroscopy, and a new TCM-TTF polymorph was obtained by changing the nature of the solvent. Finally, an explanation for all these phenomena, supported by computational modeling, is put forward.

show abstract

Crystal Polymorphism as a Probe for Molecular Self-Assembly during Nucleation from Solutions: The Case of 2,6-Dihydroxybenzoic Acid

Abstract: Bradford Scholars -how to deposit your paper Overview Copyright check• Check if your publisher allows submission to a repository.• Use the Sherpa RoMEO database if you are not sure about your publisher's position or email openaccess@bradford.ac.uk.

Cited by 149 publications

References 21 publications

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association

Polymorph Formation and Nucleation Mechanism of Tolfenamic Acid in Solution: An Investigation of Pre-nucleation Solute Association

Isonicotinamide self-association: the link between solvent and polymorph nucleation

Influence of Intermolecular Interactions on the Formation of Tetra(carbomethoxy)‐tetrathiafulvalene Assemblies

Contact Info

Product

Resources

About