Dual-optimized 1Jcc-edited 1,n-adequate: A novel NMR structure elucidation technique

Abstract

Establishing the carbon skeleton of a molecule is an integral aspect of structure elucidation. Recent advances in ADEQUATE experiments have highlighted their potential; 1,1-ADEQUATE, provides direct 13C-13C correlation via 1 J CC; and 1,n-ADEQUATE yields both long-range (typically 3 J CC) and direct 1 J CC correlation. Direct and long-range correlations are unfortunately indistinguishable in 1,n-ADEQUATE. A modified pulse sequence was developed in 2012 that inverted 1 J CC correlations in 1,n-ADEQUATE spectra. This change provided a significant improvement, allowing 1 J CC and n J CC correlations to be differentiated in the same spectrum. Careful matching of the amplitude transfer function with 1 J CC coupling constants was required with that version of the experiment to achieve near uniform inversion. Some 1 J CC correlations could still have positive intensity due to the oscillatory nature of the transfer function. Those shortcomings significantly limited application of the method. We now report a dual-optimized 1 J CC-edited 1,n-ADEQUATE experiment, that provides uniform inversion of 1 J CC correlations across the range of 29 – 82 Hz. Fine-tuning for a molecule's 1 J CC coupling constant values is not required. Beneficially, the dual-optimized version provides up to two-fold improvement in signal-to-noise for some long-range correlations. Using modern, cryogenically-cooled probes, the experiment can be successfully applied to samples as small as 1 mg. In addition to strychnine, examples of applications of the method to staurosporine and coniothyrione are also presented.