Control of 11-Aza:4-X-SalA cocrystal polymorphs using heteroseeds that switch on/off halogen bonding

Keyao Li, Monalisa Roy, Madiha Nisar, Lawrence W.Y. Wong, Herman H.Y. Sung, Richard K. Haynes, Ian D. Williams

Research output: Contribution to journalArticlepeer-review

31 Downloads (Pure)

Abstract

A family of: 1:1 cocrystals 11-Aza:4-X-SalA have been prepared from the potent anti-malarial compound 11-azaartemisinin with 4-halosalicylic acids. When X = 4-Cl, 4-Br and 4-I, two conformational polymorphs can be isolated in each case. Monoclinic type-I was found previously for parent 11-Aza:SalA (1) and 11-Aza:4-Br-SalA (3a) which have polar 21 stacks of molecular pairs with no short halogen bond contacts between stacks. Orthorhombic type-II is found for 4-Cl (3b) and 4-I (4b) from solution growth. This has a translational stack of molecular pairs involving a conformational change of the acid-lactam hetero-synthon and supramolecular association of stacks via halogen bonds. Notably, phase pure polymorph type-I can be formed for 4-Cl (3a) and 4-I (4a) by hetero-seeding with 11-Aza:SalA, whist conversely phase pure type-II for 4-Br (2b) can be formed using homo-seeding from liquid assisted grinding (LAG) product. This work demonstrates both the viability of engineering polymorphic cocrystal forms using hetero-seeds and the involvement of halogen bonds in helping to discriminate quite different polymorphic types.

Original languageEnglish
Article number1368
Number of pages17
JournalCrystals
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 2022

Fingerprint

Dive into the research topics of 'Control of 11-Aza:4-X-SalA cocrystal polymorphs using heteroseeds that switch on/off halogen bonding'. Together they form a unique fingerprint.

Cite this