Structural and energy insights on solid-state complexes with trimethoprim: A combined theoretical and experimental investigation

Anaelle Tilborg, Andrea Carletta, Johan Wouters

Research output: Contribution to journalArticlepeer-review

2 Downloads (Pure)


We present here a new structure of a 1:1 salt of trimethoprim with hemifumarate, highlighted by single-crystal X-ray diffraction and computational conformational studies. This salt was formed during cocrystallization assays conducted to combine trimethoprim and other APIs whose combination exhibits interesting properties. Theoretical in vacuo investigations have been performed on the organic salt through a DFT two-dimensional conformational scan of torsion angles between the two aromatic moieties of trimethoprim. The evaluation of relative energies for hydrogen-bond interactions in the structure has also been performed. Comparison with conformational data from structures implying trimethoprim retrieved from the Cambridge Structural Database (CSD) shows good agreement with theoretical results, proving the validity of vacuum ab initio calculations in describing the energetic landscape of the molecule and thereby gain initial insight into the prediction process for possible new conformations and therefore potential new polymorphs.

Original languageEnglish
Pages (from-to)406-415
Number of pages10
JournalActa Crystallographica Section B: Structural Science, Crystal Engineering and Materials
Publication statusPublished - 1 Aug 2015


  • ab initio conformational study
  • density functional theory
  • organic salt
  • powder X-ray diffraction
  • single-crystal X-ray diffraction
  • trimethoprim

Cite this