Interleaved Dual NMR Acquisition of Equivalent Transfer Pathways in TOCSY and HSQC Experiments

Abstract

A dual NMR data acquisition strategy to handle and detect two active equivalent transfer pathways is presented and discussed. We illustrate the power of this time-efficient approach by collecting two different 2D spectra simultaneously in a single experiment: i) TOCSY or HSQC-TOCSY spectra with different mixing times, ii) F2-13 C-coupled and decoupled HSQC spectra, iii) conventional and pure-shift HSQC spectra, or iv) complementary HSQC and HSQC-TOCSY spectra.The overall experimental time of a 2D NMR experiment is defined fundamentally by the imposition of extended recycle delays for a proper T 1 relaxation, of an enough number of recorded t 1 increments to achieve an optimum resolution in the indirect F1 dimension and/or of a minimum number of scans per t 1 increment required to complete a phase cycle for efficient coherence transfer pathways (CTP) selection. This situation is commonly found in modern NMR applications on small molecules, where some milligrams of sample are often more than enough to run the most basic experiments in short experimental times. Possible solutions to economize spectrometer time could be the attempt to speed up data acquisition by some fast NMR method, including shortening the recycle delay, the collection of a moderate number of t 1 increments or the efforts to reduce the needs of long phase cycles by using pulsed field gradient (PFG) CTP selection. Another option relies on the acquisition of multiple NMR spectra using a single pulse sequence which can offer attractive benefits regarding simplicity, efficiency, automation and, in some cases, improved sensitivity per time unit. Some examples of this multiple data acquisition strategy include the collection of multiple FIDs within the same scan (MFA), [1][2][3] the recent concept of NOAH based on the interleaved acquisition of various experiments to avoid long recycle delays, [4,5] the simultaneous acquisition of equivalent 13 C and 15 N spectra by time-sharing NMR spectroscopy, [6] or the use of multiple receivers to detect different nuclei in a parallel or interleaved manner. [7] The simultaneous acquisition of multiple spectra is particularly useful when dealing on complementary NMR experiments having comparable sensitivity (requiring similar scans per t 1 increments, similar phase cycling), resolution (similar number of t 1 increments) and/or performance (similar parameters settings, the same acquisition mode…) requirements. The success of these timeefficient methods depends on which is the best multiple acquisition strategy (parallel, interleaved, afterglow, separate…) regarding sensitivity, performance and/or spectrometer time savings.On the other hand, NMR pulse sequences usually monitor a specific CTP by an appropriate phase cycle or PFG coherence selection procedure. However, some sequences have been designed to exploit several CTPs at the same time. A very representative example is the so-called Preservation of Equivalent Pathways (PEP) technique which has been used to add up two different co-existing magnetization components...

Triplet NOAH supersequences optimised for small molecule structure characterisation

“…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). The NOAH approach represents one category of techniques that employ multi‐FID acquisitions in a single concatenated experiment that are gaining recognition as time‐efficient data collection strategies . These are attractive as they can be executed using conventional spectrometer hardware without the need for multiple receivers, as used in parallel acquisition NMR spectroscopy, nor do they suffer the technical complexities associated with single‐scan ultrafast correlation methods …”

“…The NOAH approach represents one category of techniques that employ multi-FID acquisitions in a single concatenated experiment that are gaining recognition as time-efficient data collection strategies. [3][4][5][6] These are attractive as they can be executed using conventional spectrometer hardware without the need for multiple receivers, as used in parallel acquisition NMR spectroscopy, [7][8][9] nor do they suffer the technical complexities associated with single-scan ultrafast correlation methods. [10][11][12] Recently, we have demonstrated the NOAH BS-element as being the optimum ordering to sample HMBC (B) and HSQC (S) correlation data in a single experiment and exemplified its use in the BSC and BSCN combinations (where C signifies COSY and N NOESY).…”

Practical aspects of the simultaneous collection of COSY and TOCSY spectra

“…Collecting the COSY data during the NOESY mixing time does not change the duration of the NOESY experiment, and therefore, COCONOSY can be useful in situations requiring high sample throughput. Recently, it has been shown that MFA can also be efficient in the management of the two equivalent CTPs involved in sensitivity‐enhanced gradient‐selected TOCSY and HSQC experiments . The particularities of this dual acquisition approach have been exemplified by collecting two phase‐sensitive TOCSY spectra with different mixing times at the same time.…”

“…Recently, it has been shown that MFA can also be efficient in the management of the two equivalent CTPs involved in sensitivity-enhanced gradient-selected TOCSY and HSQC experiments. [8] The particularities of this dual acquisition approach have been exemplified by collecting two phasesensitive TOCSY spectra with different mixing times at the same time. Similarly, two HSQC data sets showing different features can be obtained using this time-efficient strategy.…”

New NOAH modules for structure elucidation at natural isotopic abundance

“…hundreds of NOAH-type combinations are possible [11], rather fewer NOAH supersequences, including BSC, BSCN, SBC, and SBCN, provide sufficient information in a single measurement to allow computer assisted structure elucidation (CASE) [12]. Here we introduce new NOAH modules based on the principles of isotope filtering [14], preservation of equivalent coherence pathways [15,16], time-sharing [17][18][19] and multiple receiver techniques [20,21]. These enable the design of new and efficient supersequences for fast structure elucidation of small organic molecules from a single measurement in conjunction with the CASE techniques.…”