ViscY NMR experiments in phosphoric acid as a viscous solvent for individualization of small molecules within mixtures by spin diffusion

Abstract

The analysis of small molecules within complex mixtures is a particularly difficult task when dealing with the study of metabolite mixtures or chemical reaction media. This issue has fostered in...

Use of Diethanolamine as a Viscous Solvent for Mixture Analysis by Multidimensional Heteronuclear ViscY NMR Experiments

“…The use of viscous solvents provides an alternative approach to mixture analysis by NMR that relies on the tailoring of the molecular dynamics of the dissolved molecules. Indeed, the tumbling rate of small- and medium-sized molecules can be lowered in aqueous and organic viscous solvents − since the value of the overall correlation time τ c is governed by the medium viscosity according to the microviscosity theory of Gierer and Wirtz . As a result, for long τ c values (order of magnitude of ns), the analytes may undergo a negative nuclear Overhauser effect (NOE) regime, and their resonances can be clustered according to their ability to exchange magnetization through intramolecular spin diffusion.…”

“…The use of supercooled water in narrow capillaries was published in 2012 by the same team for the identification of small metabolites in biological samples . Our team described innovative outcomes in mixture analysis by NMR under spin diffusion conditions ( ViscY experiments) using glycerol and glycerol carbonate (in 2011), DMSO/glycerol (in 2016), DMSO/water (in 2017), sucrose solution, agarose gel (in 2019), sulfolane-based solvents (in 2020), and phosphoric acid solutions (in 2021) …”

“…The exploitation of 1 H NMR spectra may become intractable due to massive 1 H resonance overlapping when complex mixtures are analyzed. A traditional alternative solution consists in the spreading of the spectroscopic information along a second and sometimes a third dimension that encodes chemical shifts of nuclei other than 1 H. ,− , This method to mixture analysis is exemplified in the viscous binary DEA/DMSO- d 6 solvent using the 2D 1 H– 19 F and 1 H– 31 P HSQC-NOESY and 3D 1 H– 19 F– 1 H, 1 H– 31 P– 1 H HSQC-NOESY experiments, providing 1 H/ 19 F/ 31 P chemical shift lists for the mixture of four low-polarity fluorine- and phosphorus-containing compounds (see Figure ).…”

“…22 Our team described innovative outcomes in mixture analysis by NMR under spin diffusion conditions (ViscY experiments) 26 DMSO/glycerol (in 2016), 23 DMSO/water (in 2017), 24 sucrose solution, agarose gel (in 2019), 25 sulfolane-based solvents (in 2020), 26 and phosphoric acid solutions (in 2021). 27 So far, low-polarity molecules within mixtures have been only explored in a small number of viscous solvents. In this context, diethanolamine was considered in solvent blends by dilution with DMSO-d 6 .…”

“…The exploitation of 1 H NMR spectra may become intractable due to massive 1 H resonance overlapping when complex mixtures are analyzed. A traditional alternative solution consists in the spreading of the spectroscopic information along a second and sometimes a third dimension that encodes chemical shifts of nuclei other than 1 H. 20,[23][24][25][26][27][28]39 This method to mixture analysis is exemplified in the viscous binary DEA/DMSO-d 6 solvent using the 2D 1).…”