LAPSE:2019.1200
Published Article
LAPSE:2019.1200
Review and Modeling of Crystal Growth of Atropisomers from Solutions
Lotfi Derdour, Eric J. Chan, Dimitri Skliar
November 24, 2019
In this paper, theories on anisotropic crystal growth and crystallization of atropisomers are reviewed and a model for anisotropic crystal growth from solution containing slow inter-converting conformers is presented. The model applies to systems with growth-dominated crystallization from solutions and assumes that only one conformation participates in the solute integration step and is present in the crystal lattice. Other conformers, defined as the wrong conformers, must convert to the right conformer before they can assemble to the crystal lattice. The model presents a simple implicit method for evaluating the growth inhibition effect by the wrong conformers. The crystal growth model applies to anisotropic growth in two main directions, namely a slow-growing face and a fast-growing face and requires the knowledge of solute crystal face integration coefficients in both directions. A parameter estimation algorithm was derived to extract those coefficients from data about temporal concentration and crystal size during crystallization and was designed to have a short run time, while providing a high-resolution estimation. The model predicts a size-dependent growth rate and simulations indicated that for a given seed size and solvent system and for an isothermal anti-solvent addition crystallization, the seed loading and the supersaturation at seeding are the main factors impacting the final aspect ratio. The model predicts a decrease of the growth inhibition effect by the wrong conformer with increasing temperature, likely due to faster equilibration between conformers and/or a decrease of the population of the wrong conformer, if of low energy, at elevated temperatures. Finally, the model predicts that solute surface integration becomes the rate-limiting mechanism for high solute integration activation energies, resulting in no impact of the WC on the overall crystal growth process.
Keywords
conformer, growth inhibition, habit, Modelling, step propagation
Suggested Citation
Derdour L, Chan EJ, Skliar D. Review and Modeling of Crystal Growth of Atropisomers from Solutions. (2019). LAPSE:2019.1200
Author Affiliations
Derdour L: GlaxoSmithKline, Chemical Development, 1250 S. Collegeville Road, Collegeville, PA 19426, USA
Chan EJ: Department of Chemistry, New York University, New York, NY 10003, USA
Skliar D: Bristol-Myers Squibb Co. Chemical and Synthetic Development, 1 Squibb dr, New Brunswick, NJ 08901, USA
[Login] to see author email addresses.
Journal Name
Processes
Volume
7
Issue
9
Article Number
E611
Year
2019
Publication Date
2019-09-10
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr7090611, Publication Type: Review
Record Map
Published Article

LAPSE:2019.1200
This Record
External Link

doi:10.3390/pr7090611
Publisher Version
Download
Files
[Download 1v1.pdf] (2.9 MB)
Nov 24, 2019
Main Article
License
CC BY 4.0
Meta
Record Statistics
Record Views
459
Version History
[v1] (Original Submission)
Nov 24, 2019
 
Verified by curator on
Nov 24, 2019
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2019.1200
 
Original Submitter
Calvin Tsay
Links to Related Works
Directly Related to This Work
Publisher Version