Benchtop NMR Spectroscopy of Prebiotically-Relevant Peptide Reactions Enabled by Salt-Induced Chemical Shift Dispersion

Abstract

This Article describes a method that increases the chemical shift dispersion of signals in proton nuclear magnetic resonance ( 1 H NMR) spectra of peptides by the addition of salts to the sample. We demonstrate that the addition of potassium phosphate to aliquots of reactions of glycine peptides permits the measurement of their rate constants for hydrolysis by a 60 MHz benchtop instrument, which would otherwise be infeasible due to overlapping signals in the salt-free mixtures. The method is described in detail and validated by comparison to analysis on a 400 MHz spectrometer. The ability to use benchtop NMR spectroscopy to study reactions of simple peptides enables interested scientists at a broader array of institutionsnot just those institutions capable of affording high-field NMR instrumentsto participate in original research projects like those aimed at elucidating the chemistry that led to the origin of life on Earth.

Benchtop 19F nuclear magnetic resonance spectroscopy enabled kinetic studies and optimization of the synthesis of carmofur

“…In summary, through the application of benchtop 19 F NMR spectroscopy, we have determined the optimal conditions for synthesizing carmofur will be in temperatures from 40-50℃ in pyridine resulting in 72% NMR yield, conducted with rigorous sealing techniques to ensure the reaction is moisture-free. More importantly, we were able to identify NMP as a solvent that is easier, and safer to purify carmofur on-scale.…”

Low‐field benchtop NMR spectroscopy: status and prospects in natural product analysis†

“…Febrian et al . obtained increased resolution in 60 MHz spectra of oligopeptides by adding various salts 81 …”

Recent Applications of Benchtop Nuclear Magnetic Resonance Spectroscopy

“…The addition of lanthanide-based shift agents is also used to improve the resolution of overlapping signals. For example, the resolution of a 60 MHz benchtop NMR spectrum of a peptide was improved through the addition of salts as chemical shift agents [109]. In this study, improved resolution resulted in more accurate quantitative analysis, which allowed the researchers to better understand peptide reaction kinetics.…”

“…Solvent suppression based on gradient pulse sequence [97,107] Homo-decoupling method using different pure-shift methods [108] Addition of salts as chemical shift agents to peptide sample [109] Hyperpolarization methods (SABRE) [110][111][112][113][114] Figure 11 shows that spectral resolution can be increased using various pulse sequences and the homo-decoupling method, which is another technique commonly used in high-field NMR spectroscopy. Moreover, benchtop NMR spectrometers with gradient coils can be used to increase signal sensitivity through the programming of various pulse sequences [108].…”

“…In this study, improved resolution resulted in more accurate quantitative analysis, which allowed the researchers to better understand peptide reaction kinetics. benchtop NMR spectrum of a peptide was improved through the addition of salts as chemical shift agents [109]. In this study, improved resolution resulted in more accurate quantitative analysis, which allowed the researchers to better understand peptide reaction kinetics.…”