Solid-state ¹⁷O NMR as a sensitive probe of keto and gem-diol forms of α-keto acid derivatives

We have used solid-state ¹⁷O NMR experiments to measure the ¹⁷O quadrupole coupling (QC) and chemical shift (CS) tensors for two α-keto acids: sodium [2-¹⁷O]pyruvate and lithium [2,2′-¹⁷O₂]pyruvate. In the solid state, sodium [2-¹⁷O]pyruvate is in the keto form (–C(¹⁷O)–) whereas lithium [2,2′-¹⁷O₂]pyruvate takes the gem-diol form (–C(¹⁷OH)₂–). This study represents the first time that a full set of ¹⁷O NMR tensors are experimentally determined for α-keto acids in these two different tautomeric forms. We have found that the two forms exhibit drastically different ¹⁷O QC and CS tensors: for the keto form, δ_iso = 543 ± 1 ppm, C_Q = 10.8 ± 0.2 MHz, η_Q = 0.48 ± 0.05, δ₁₁ = 1020 ± 10, δ₂₂ = 640 ± 10, δ₃₃ = −40 ± 10 ppm, α = 80 ± 5°, β = 90 ± 2°, and γ = 83 ± 2°; for the gem-diol form, δ_iso = 62 ± 1 ppm, C_Q = 8.5 ± 0.5 MHz, η_Q = 1.0 ± 0.05, δ₁₁ = 140 ± 5, δ₂₂ = 45 ± 5, δ₃₃ = 0 ± 5 ppm, α = 55 ± 5°, β = 90 ± 5°, and γ = 80 ± 2°. The ¹⁷O chemical shift tensor observed for the gem-diol functional group also represents the first such measurement for any -ol functional group (e.g., alcohols, phenols, carbohydrates, etc.) Using these accurate experimental ¹⁷O NMR tensors, we were able to evaluate the accuracy of quantum chemical calculations. Our results showed that quantum chemical calculations using the crystal lattice approach are in much better agreement with the experimental solid-state ¹⁷O NMR data than those calculated using the molecular cluster approach. Quantum chemical calculations have also provided information about the sign of the ¹⁷O quadrupolar coupling constants and about the ¹⁷O NMR tensor orientations in the molecular frame of reference. Our findings suggest that solid-state ¹⁷O NMR may be useful in probing the tautomeric form of the α-keto functional group commonly found in intermediates of enzymatic reactions.