Work

Effect of Molecular Perturbation on Polymorphism: The Case of 8-Halotheophyllines (8-Cl-Tph and 8-Br-Tph)

Year: 2025

Type: article

Abstract: The common alkaloid theophylline (Tph) is known to exist in five polymorphic forms. The structures of its 8-halo analogues were previously unreported. Here we report three polymorphs for 8-chlorotheophylline (8-Cl-Tph) and an additional distinct one for 8-bromotheophylline (8-Tph). Whilst polymorphs for theophylline are dominated by NH---N inter-molecular hydrogen bonds, the halo compounds exclusively exhibit NH---O interactions. 8-Cl-Tph has two related structures with chains N(7)-H(7)---O(2), one is also the stable form for 8-Br-Tph. Polymorphs with a dimeric R22(10) ring structure using N(7)-H---O(6) H-bonds exist for all three compounds, though each with distinct 3D packing. DFT calculations indicate the alkaloid ring nitrogen N(9) is a weaker base in 8-halo compounds, disfavoring NH---N interactions in their polymorphic forms.

Source: Crystals

DOI: 10.3390/cryst15040340

Authors: Weijian Ye, Chao Zhang, Herman Ho-Yung Sung, Lawrence Wan-Yin Wong, Fu Kit Sheong, Ian Duncan Williams

Institutions: Hong Kong University of Science and Technology, The Hong Kong University of Science and Technology (Guangzhou)

Language: English

Topic: Crystallography and molecular interactions

Subfield: Physical and Theoretical Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $2,534

Funders: Innovation and Technology Commission, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou)