Parallel NMR Supersequences: Ten Spectra in a Single Measurement

Abstract

The principles employed in parallel NMR and MRI are applied to NMR supersequences yielding as many as ten 2D NMR spectra in one measurement. We present a number of examples where two NOAH (NMR by Ordered Acquisition using 1H-detection) supersequences are recorded in parallel, thus dramatically increasing the information content obtained in a single NMR experiment. The two parallel supersequences entangled by time-sharing schemes (IPAP-seHSQC, HSQC-COSY, and HSQC-TOCSY) incorporate also modified (sequential and/or interleaved) conventional pulse schemes (modules), including HMBC, TOCSY, COSY, CLIP-COSY, NOESY, and ROESY. Such parallel supersequences can be tailored for specific applications, for instance, the analysis and characterization of molecular structure of complex organic molecules from a single measurement. In particular, the CASPER software was used to establish the structure of a tetrasaccharide, β-LNnTOMe, with a high degree of confidence from a single measurement involving a parallel NOAH-5 supersequence.

Primary Structure of Glycans by NMR Spectroscopy

“…The time-shared modules for the p -NOAH-10 included, e.g., HSQC-COSY/HSQC, HSQC-TOCSY/HSQC, and IP-HSQC/AP-HSQC, and interleaved modules such as HMBC and TOCSY with different sets of mixing times in the heteronuclear and homonuclear experiments, respectively, as well as COSY and ROESY experiments. A tailor-made p -NOAH-5 supersequence relying on 1 H and 13 C nuclei, BS C S J T/S, consisting of HMBC, multiplicity-edited HSQC-COSY, F 2 -coupled HSQC, TOCSY, and multiplicity-edited HSQC was developed, resulting in NMR spectral data optimal for use with the structural elucidation program CASPER and presented using a methyl glycoside of the milk oligosaccharide lacto- N -neotetraose . Moreover, using a room temperature inverse detection probe a p -NOAH-10 experiment was carried out on a cyclic peptide at a concentration of 50 mM in less than 10 min.…”

NMR spectroscopy of dissolved organic matter: a review

“…In NMR supersequences, different NMR experiments that all detect 1 H are combined into one pulse sequence that possesses only one recovery delay (Fig. 12) Claridge 2017, 2018;Kupče et al 2021). To avoid disturbance between the experiments, the sequence starts with the most insensitive module and phase cycling and refocusing gradients are applied.…”

Modular Pulse Program Generation for NMR Supersequences

“…Each module is given a unique abbreviation, usually one letter long (e.g., “B” for HMBC, “S” for HSQC, “M” for HMQC, “C” for COSY) and occasionally sub/superscripted (e.g., “S T ” for HSQC-TOCSY). The combinatorial nature of NOAH experiments means that there are a very large number of conceivable supersequences ranging from NOAH-2 to NOAH-5 (where the suffix indicates the number of modules); the use of parallel “ p -NOAH” supersequences 24 extends this maximum number even further.…”

“…However, such experiments require the incrementation of one or more indirect-dimension evolution periods, leading to long experiment times. The acceleration of n D NMR has therefore emerged as a highly popular area of research: developments in this area include (but are not limited to) ultrafast NMR, − nonuniform sampling (NUS), − multiple-FID experiments, ,− and the shortening or elision of recovery delays. − NOAH (NMR by Ordered Acquisition using 1 H detection) experiments, ,− which encompass the last two categories, consist of a series of multiple 2D experiments (“modules”), combined into one single “supersequence” that uses only one recovery delay for all modules. This provides up to 4× time savings compared to conventional acquisition, in which one recovery delay is used per module (Figure ).…”