Improvements, extensions, and practical aspects of rapid ASAP-HSQC and ALSOFAST-HSQC pulse sequences for studying small molecules at natural abundance

Previously we introduced two novel NMR experiments for small molecules, the so-called ASAP-HSQC and ALSOFAST-HSQC (Schulze-Sfinninghausen et al., 2014), which allow the detection of heteronuclear one-bond correlations in less than 30 s at natural abundance. We propose an improved symmetrized pulse scheme of the basic experiment to minimize artifact intensities and the combination with nonuniform sampling to enable the acquisition of conventional HSQC spectra in as short as a couple of seconds and extremely C-13-resolved spectra in less than ten minutes. Based on steady state investigations, a first estimate to relative achievable signal intensities with respect to conventional, ASAP-, and ALSOFAST-HSQC experiments is given. In addition, we describe several extensions to the basic pulse schemes, like a multiplicity-edited version, a revised symmetrized CLIP-ASAP-HSQC, an ASAP-IALSOFAST-HSQC sequence with broadband BIRD-based H-1,H-1 decoupling, and a symmetrized sequence optimized for water suppression. Finally, RF-power considerations with respect to the high duty cycle of the experiments are given. (C) 2017 Elsevier Inc. All rights reserved.