Abstract
The crystallisation behaviour of (RS)-diprophylline (DPL) in two different solvents is investigated to assess the incidence of solvated pre-associations on nucleation, crystal growth and chiral discrimination. In the solvated state, Raman spectroscopy shows that dimeric associations similar to those depicted in the crystalline solid solution (ssRII) predominate in isopropanol (IPA), which may account for the systematic spontaneous nucleation of this crystal form from this solvent. By contrast, spontaneous nucleation in DMF yields the stable racemic compound RI, consistently with the distinct features of the Raman spectrum collected in this solvent. A crystal growth study of ssRII in IPA reveals that the crystal habitus is impacted by the solution enantiomeric excess; this is explained by increased competition between homo- and heterochiral pre-associations. This is supported by a molecular modelling study on the enantiomeric selectivity of the DPL crystal lattices. The combination of assessment methods on solution chemistry, nucleation and chiral discrimination provides methodological tools from which the occurrence of solid solutions can be rationalised.
Original language | English |
---|---|
Pages (from-to) | 16103-16112 |
Number of pages | 10 |
Journal | Chemistry - A European Journal |
Volume | 22 |
Issue number | 45 |
Early online date | 26 Sept 2016 |
DOIs | |
Publication status | Published - 2 Nov 2016 |
Keywords
- aggregation
- chirality
- crystal growth
- enantiomeric solid solutions
- molecular modeling
- crystallisation
- (RS)-diprophylline
- chiral discrimination
Fingerprint
Dive into the research topics of 'Prenucleation self-assembly and chiral discrimination mechanisms during solution crystallisation of racemic diprophylline'. Together they form a unique fingerprint.Profiles
-
Joop Ter Horst
- Strathclyde Institute Of Pharmacy And Biomedical Sciences - Visiting Professor
Person: Visiting Professor