Structure Solution of ACV-GLU Cocrystal by Combined XRD Refinement, 1D Solid State NMR and DFT Calculations

Abstract

The powder sample of ACV-GLU crystal complex was prepared by formic acid-assisted grinding. 13C and 15N chemical shifts were assigned by referring to the 1D NMR spectra of raw individual components. The crystal structure was first solved by Rietveld refinement. The calculated NMR parameters were compared with the experimental results to validate the proposed structure. ACV, an important antiviral drug, can be cocrystallized with GLU into a triclinic unit cell with a molar ratio of 1:1 where each unit cell consists of two ACV molecules and two GLU molecules. Six intermolecular hydrogen-bonding interactions exist in the cocrystal. An agreement between experimental and calculated NMR parameters would give a final confirmation of the correct model among the preliminary candidates. Such synergistic approach provides efficient and convincing method to obtain the crystal structure of powder cocrystal specimens.