Structural Determination of a Novel Polymorph of Sulfathiazole–Oxalic Acid Complex in Powder Form by Solid-State NMR Spectroscopy on the Basis of Crystallographic Structure of Another Polymorph

Two
polymorphic forms of a sulfathiazole (STZ):oxalic acid (OXA)
1:1 complex were successfully prepared by different cogrinding methods
and characterized by multiple analytical techniques. Rod-milled and
ball-milled ground mixtures had different powder X-ray diffraction
patterns, showing polymorph formation of the STZ-OXA complex (complex
A and complex B). The heat of fusion from differential scanning calorimetry
curves and terahertz time-domain spectra helped differentiating the
polymorphs. According to infrared spectra, 13C NMR chemical
shifts, and the relative intensities of 15N NMR peaks,
both polymorphs were salts where the proton of a −COOH group
in OXA was transferred to a −NH2 group in STZ. High-resolution 1H NMR and 1H–13C heteronuclear
correlation NMR spectra indicated that complex B in powder form had
a cocrystal type structure compared to complex A
having a clathrate-type structure. Complex B structure
suggested by solid-state NMR coincided well with the experimentally
determined one, which was formed from three layers of thiazole rings,
benzene rings, and OXAs, by using single-crystal X-ray diffraction
(SC-XRD) measurement. Advanced solid-state NMR spectroscopy measurements
was useful to elucidate the structure of a polymorph, for which SC-XRD
data are not available, by referring to the SC-XRD data of another
polymorph.