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

Abstract

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.

Structure and physicochemical characterization of a naproxen–picolinamide cocrystal

“…A combination of 1 H and 15 N SS-NMR is commonly used to determine proton positions over O-HÁ Á ÁO and O-HÁ Á ÁN hydrogen bonds due to the sensitivity of the chemical shift to the local environment. For example, two sulfathiazole-oxalic acid complexes have been shown to be salts by multinuclear SS-NMR (Koike et al, 2014) and recently a furosemide-isonicotinamide complex was confirmed to be a cocrystal by comparison of 15 N SS-NMR and DFT-calculated chemical shifts (Kerr et al, 2015). Another aspect of the study of proton position is the characterization of reversible proton migration over short strong hydrogen bonds, which is of fundamental interest but also potentially relevant to some types of functional materials (Ford et al, 2011;Frantsuzov et al, 2014).…”

Mechanistic insight into the dramatic improvement of probucol dissolution in neutral solutions by solid dispersion in Eudragit E PO with saccharin

“…SAC is an acidic compound, and the amidic proton has a p Ka of around 2, which makes it easy to deprotonate,[35,36] whereas the tertiary amino group in EPO is readily protonated because the p Ka of its conjugate base is 10 [37]. The interaction mode of a crystalline acid‐base complex is usually described by Δp Ka (p Ka of base – p Ka of acid); an ionic bond is favoured when Δp Ka > 3 [38–40]. The calculated Δp Ka between SAC and EPO is around 8, although applying this theory to amorphous solid dispersion systems may not be straightforward.…”

“…[37] The interaction mode of a crystalline acid-base complex is usually described by ΔpKa (pKa of base -pKa of acid); an ionic bond is favoured when ΔpKa > 3. [38][39][40] The calculated ΔpKa between SAC and EPO is around 8, although applying this theory to amorphous solid dispersion systems may not be straightforward. The amide group in SAC is potentially deprotonated, and the tertiary amino group of EPO is protonated leading to the formation of an ionic bond.…”

Enhancing electrode sensitivity for detection of antibiotic contamination in water using functionalized magnetic nanoparticles

“…This is in addition to the possible electrostatic interaction between poly-amines of NEO and the fatty acid [70,71]. In the same context, for detecting STNa (which was recruited as a representative of sulfonamide antibiotics), good detection capabilities were obtained on using OA-MNPs for detecting STNa in range 10 −2 -10 −13 M. This may be explained by the inherent ability of STNa to interact with carboxylic acids via its amine groups [72].…”