Developing nonuniform sampling strategies to improve sensitivity and resolution in 1,1‐ADEQUATE experiments

Abstract

Nonuniform sampling (NUS) strategies are developed for acquiring highly resolved 1,1‐ADEQUATE spectra, in both conventional and homodecoupled (HD) variants with improved sensitivity. Specifically, the quantile‐directed and Poisson gap methods were critically compared for distributing the samples nonuniformly, and the quantile schedules were further optimized for weighting. Both maximum entropy and iterative soft thresholding spectral estimation algorithms were evaluated. All NUS approaches were robust when the degree of data reduction is moderate, on the order of a 50% reduction of sampling points. Further sampling reduction by NUS is facilitated by using weighted schedules designed by the quantile method, which also suppresses sampling noise well. Seed independence and the ability to specify the sample weighting in quantile scheduling are important in optimizing NUS for 1,1‐ADEQUATE data acquisition. Using NUS yields an improvement in sensitivity, while also making longer evolution times accessible that would be difficult or impractical to attain by uniform sampling. Theoretical predictions for the sensitivity enhancements in these experiments are in the range of 5–20%; NUS is shown to disambiguate weak signals, reveal some nJCC correlations obscured by noise, and improve signal strength relative to uniform sampling in the same experimental time. This work presents sample schedule development for applying NUS to challenging experiments. The schedules developed here are made available for general use and should facilitate the broader utilization of ADEQUATE experiments (including 1,1‐, 1,n‐, and HD‐ variants) for challenging structure elucidation problems.

Clustered sparsity and Poisson-gap sampling

“…Clearly, the benefits of using PG sampling are more pronounced for some spectra (such as 1 3 C HSQC) than for others that are less "clustered". As reported by other investigators, reconstructions of some other (nonclustered) spectra can be even worse when using PG (Bostock et al 2012;Mobli and Miljenović 2019;Roginkin et al 2020). We believe that the understanding of relation between spectral clustering and time-domain sampling allows a more rational use of PG sampling schemes.…”

NUScon: A community-driven platform for quantitative evaluation of nonuniform sampling in NMR

“…Along these lines, while it may be possible to measure fidelity of frequency, amplitude, and signal envelope (decay) of individual signals, this does not necessarily capture the fitness of a reconstruction to suit a given use. In particular, while NUS reconstruction methods can have excellent lineshape fidelity (Stern et al, 2002;Bostock and Nietlispach, 2017;Roginkin et al, 2020), it is seldom important in practice that a lineshape be conserved by a reconstruction, hence the common use of apodization that alters the lineshape, even if it conserves the integral (Naylor and Tahic, 2007). This is particularly true in multidimensional biomolecular data, where the indirect dimensions have little or no decay, so that the observed lineshape is primarily due to signal processing details rather than to any property of the underlying time-domain data.…”

Development of 19F‐detected 1,1‐ADEQUATE for the characterization of polyfluorinated and perfluorinated compounds

“…[11][12][13] Obviously, in the case of polyfluorinated or perfluorinated molecules, it is highly preferable to acquire those data with both 1 H and/or 19 F decoupling as appropriate to simplify resonance multiplet structures, thereby improving sensitivity and facilitating extraction of the carbon-carbon coupling constants. For molecules with protons in their structures, one has recourse to the much more sensitive J-modulated ADEQUATE experiment, [14][15][16][17][18] although that experiment is obviously inapplicable to perfluorinated molecules or for carbon-carbon couplings where both carbons in question are fluorinated, or where both carbons are quaternary. 13 C INADEQUATE Spectrum of a 53 mg sample of N,N-dimethylamino-2,5,6-trifluoro-phthalonitrile (1) dissolved in 700 μl d 6 -DMSO acquired with 19 F broadband BUSS (Broadband Uniform Sideband Suppression) decoupling.…”