Probing solids through THz spectroscopy: Differentiation of chiral and racemic forms of isostructural and non-isostructural cocrystals

Cocrystals of theophylline (tp) and racemic and chiral forms of both tartaric acid (tart) and malic acid (mal) were investigated using terahertz time-domain-spectroscopy (THz-TDS). Using X-ray powder diffraction (XRPD) the racemic and chiral malic acid cocrystal forms were found to be nearly isostructural and therefore almost indistinguishable using XRPD. Using THz-TDS clear differences were observed both at room temperature and at 109 K. This was rationalized using lattice energy calculations and attributed to a difference in the conformational strain of the acid groups between the two cocrystal forms.