Low-level long-range1H-15N heteronuclear shift correlation at natural abundance using a combination of 2D and selective 1D NMR methods with submicro NMR probe technology

There has been burgeoning interest in the utilization of 15N as a structural probe. A growing body of reports have appeared using gradient long-range 1H–15N heteronuclear shift correlation experiments at natural abundance. The majority of studies have reported data acquired using conventional 5 mm NMR probe technology, which has mandated the use of sizable samples to maintain appropriate working concentrations to keep data acquisition times manageable. This paper reports the combined utilization of gradient 2D and selective 1D 1H–15N GHMBC NMR methods in conjunction with SMIDG (submicro inverse-detection gradient) NMR probe technology at 600 MHz which allows the acquisition of high quality, long-range natural abundance 1H–15N heteronuclear shift correlation data on samples as small as 1 µmol in 22 h and 0.5 µmol over a long weekend (84 h). In contrast, using 2D NMR methods alone, data on a 1 µmol sample of strychnine acquired over a weekend (65 h) are still of marginal quality.