High-Accuracy Quantitative Nuclear Magnetic Resonance Using Improved Solvent Suppression Schemes.

Quantitative nuclear magnetic resonance (qNMR) has contributed to reliable and accurate measurements of organic compounds enabling quantitation even when no standards of the specific compounds are available. Such high-accuracy determinations are critical across the field of analytical chemistry, with the advances in qNMR being of utmost importance in the production of reference standards for a range of organic compounds. The ability to perform these accurate measurements in the presence of natural isotopic abundance solvents is important for increasing throughput and expanding the number of applications that benefit. In this work, we have assessed several pulse sequences for solvent suppression. The limitations of NMR acquisitions in the presence of large solvent signals and solvent suppression such as limited dynamic range, losses due to relaxation and proximity to the solvent peak where quantitation starts failing were studied in depth and discussed. We have shown that binomial-like sequences produce the most robust and reliable results in the majority of scenarios and propose alternative sequences using modern pulses that produce satisfactory results in situations where the most accurate sequences are not applicable. We present the development and use of binomial-like pulses in an inversion-recovery sequence that allows T1 measurement in experiments without deuterated solvent (no-D NMR) to enable the use of correct repetition times for high-accuracy measurements under these conditions. Although the binomial-like sequences present the limitation of having secondary suppression notches, there is enough flexibility to adjust the position of those notches. Finally, we present a full measurement uncertainty budget estimation including all uncertainty allowances that are relevant when solvent suppression is used.