NOAH: NMR Supersequences for Small Molecule Analysis and Structure Elucidation

Abstract

Nested NMR experiments combining up to five conventional NMR pulse sequences into one supersequence are introduced. The core 2D NMR techniques routinely employed in small molecule NMR spectroscopy, such as HSQC, HMQC, HMBC, COSY, NOESY, TOCSY, and similar, can be recorded in a single measurement. In this way the data collection time may be dramatically reduced and sample throughput increased for basic NMR applications, such as structure elucidation and verification in synthetic, medicinal, and natural product chemistry.

Practical aspects of the simultaneous collection of COSY and TOCSY spectra

“…Such signal saturation is particularly detrimental in the NOAH‐TO‐CO experiment, where COSY data are strongly attenuated. Similar behaviour has also been observed by Kupče and Claridge, where an ASAP‐COSY scheme has been proposed to recover the saturation partially.…”

“…Thus, a general design in NOAH experiments would involve first a low‐sensitive 1 H{ 15 N} experiment, then a 1 H{ 13 C} experiment, and finally the most sensitive homonuclear experiments. For instance, a NOAH‐2 experiment consisting of a ZZ‐HMBC scheme followed by an HSQC pulse train has demonstrated to be highly efficient by retaining 1 H{ 13 C} magnetization most of the time along the z‐axis at the same time that HMBC is executed …”

“…For instance, a NOAH-2 experiment consisting of a ZZ-HMBC scheme followed by an HSQC pulse train has demonstrated to be highly efficient by retaining 1 H{ 13 C} magnetization most of the time along the z-axis at the same time that HMBC is executed. [2] In a second MFA approach, several FID periods (referred to as FID1, FID2, … FIDn) are included in the same scan to detect different coherence transfer pathways (CTPs) that share the same incrementable t 1 period. The first MFA experiment was reported in 1984 under the Correction added on 18 March 2019, after first online publication: A prefix 'S' has been added to the pagination of this article, so the page range has changed from 85-94 to S85-S94.…”

Triplet NOAH supersequences optimised for small molecule structure characterisation

“…This period, the relaxation or recovery delay, is typically the longest element of any pulse sequence and represents time in which the NMR instrument is passive and, in effect, unemployed. In recent work, we have demonstrated the possibility of concatenating a series of 2D sequences such that only a single recovery delay is employed in a single “supersequence” that ultimately produces a nest of 2D experiments that may be employed for structure characterisation . This leads to significant time‐savings in data collection, optimising the use of valuable instrument time and reducing instrument redundancy.…”

“…In recent work, we have demonstrated the possibility of concatenating a series of 2D sequences such that only a single recovery delay is employed in a single "supersequence" that ultimately produces a nest of 2D experiments that may be employed for structure characterisation. [1,2] This leads to significant time-savings in data collection, optimising the use of valuable instrument time and reducing instrument redundancy. The approach relies on the appropriate ordering of individual techniques (modules) within each supersequence to control the sequential sampling of magnetisation pools, thus yielding the required data sets for characterisation in an approach that has been termed NMR by Ordered Acquisition using 1 H detection (NOAH).…”