Polarization recovery during ASAP and SOFAST/ALSOFAST-type experiments

Abstract

Experiments with fast repetition schemes significantly enhance the capabilities of modern NMR spectroscopy. Two schemes for heteronuclear correlation experiments that have been presented are the ASAP and the ALSOFAST method. The first method is Acceleration by Sharing Adjacent Polarization (ASAP) for samples at natural abundance isotope level. It was originally derived in the ASAP-HMQC and recently received renewed attention in the ASAP-HSQC. Sharing the polarization of active protons with the surrounding reservoir can result in seemingly instant polarization recovery and therefore enormous gains in sensitivity, but can also lead to a slight reduction of polarization and spectral intensity, depending on sample and setup. A second type of setup has been introduced with the so-called Alternate SOFAST (ALSOFAST-) HMQC and ALSOFAST-HSQC for natural abundance ¹H,¹³C-correlation experiments and in the SOFAST-HMQC for ¹H,¹⁵N-correlations. In these cases, the reservoir spins are only maintained through the pulse sequence without Hartmann-Hahn-type mixing. A model for the estimation of the available polarization in the fast repetition schemes could be a valuable tool for experimentalists and pulse sequence developers. Starting from the well-known Ernst angle model, we derive in this article several mathematical models that describe the polarization over the course of ALSOFAST and ASAP type experiments. The models can be used to visualize the initial scans of an experiment and even more importantly, show the polarization and achievable signal intensity in the steady state of an experiment. In this way the two extreme applications of ASAP- and ALSOFAST-type acquisition schemes are covered: (i) acquisition using progressive excitation for experiments with few increments and shortest possible overall acquisition times and (ii) steady-state-type experiments with ultrahigh resolution and correspondingly large number of increments. The two resulting excitation strategies are applied to maximize SNR in different situations. To test the models, experimental data was obtained by special pulse sequences and examples are shown for different spin environments. The results show good agreement between theory and experiment.

Keywords: ALSOFAST; ASAP; ASAP-HSQC; Relaxation; Small molecules; Steady state; Variable flip angle.