NMR internal standard signal shifts due to cyclodextrin inclusion complexes

Nuclear magnetic resonance (NMR)-based screening of materials is a powerful tool for quality control, authenticity testing, and purity testing of compounds. However, reliance on 3-(trimethylsilyl)-propane-1-sulfonate (DSS) and 3-(trimethylsilyl)propanoic acid (TMSP) for referencing the spectra of aqueous samples is not without hazard, particularly with automated analyses. The assumption that these reference signals always represent 0 ppm is ubiquitous in NMR spectroscopy and is routinely used for spectral alignment. However, it has been found that cyclodextrins readily generate inclusion complexes with DSS and TMSP with the effect of rendering this assumption incorrect. These inclusion complexes alter the electronic shielding of the trimethylsilane functional groups on DSS and TMSP yielding a small, but significant, shift to a higher frequency in the signal relied upon for spectral referencing. As a result, samples containing traces of these compounds may be incorrectly declared fraudulent, inconsistent with standards, or adulterated. In order to maintain the viability of this screening method, vigilance and/or improved referencing of spectra is needed.

Automated summary

Nuclear magnetic resonance (NMR)-based screening of materials is a powerful tool for quality control, authenticity testing, and purity testing of compounds. However, reliance on specific reference compounds for spectral alignment may be inaccurate due to the formation of inclusion complexes, requiring vigilance and improved referencing techniques for accurate results.