title: Broadband inversion of 1J(CC) responses in 1,n-ADEQUATE spectra.
abstract: Establishing the carbon skeleton of a molecule greatly facilitates the process of structure elucidation, both manual and computer-assisted. Recent advances in the family of ADEQUATE experiments demonstrated their potential in this regard. 1,1-ADEQUATE, which provides direct (13)C-(13)C correlation via (1)J(CC), and 1,n-ADEQUATE, which typically yields (3)J(CC) and (1)J(CC) correlations, are more sensitive and more widely applicable experiments than INADEQUATE and PANACEA. A recently reported modified pulse sequence that semi-selectively inverts (1)J(CC) correlations in 1,n-ADEQUATE spectra provided a significant improvement, allowing (1)J(CC) and (n)J(CC) correlations to be discerned in the same spectrum. However, the reported experiment requires a careful matching of the amplitude transfer function with (1)J(CC) coupling constants in order to achieve the inversion, and even then some (1)J(CC) correlations could still have positive intensity due to the oscillatory nature of the transfer function. Both shortcomings limit the practicality of the method. We now report a new, dual-optimized inverted (1)J(CC) 1,n-ADEQUATE experiment, which provides more uniform inversion of (1)J(CC) correlations across the range of 29-82 Hz. Unlike the original method, the dual optimization experiment does not require fine-tuning for the molecule's (1)J(CC) coupling constant values. Even more usefully, 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 of ~1 mg under favorable circumstances. The improvements afforded by dual optimization inverted (1)J(CC) 1,n-ADEQUATE experiment make it a useful and practical tool for NMR structure elucidation and should facilitate the implementation and utilization of the experiment.
authors.affiliation: Merck Research Laboratories, Discovery and Preclinical Sciences, Process and Analytical Chemistry, Structure Elucidation Group, Rahway, NJ 07065, USA. Electronic address: mikhail.reibarkh@merck.com.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Reibarkh
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Williamson
authors.forename: Gary E
authors.initials: GE
authors.lastname: Martin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bermel
keywords: 1,1-ADEQUATE; 1,n-ADEQUATE; Broadband inversion; Pulse sequence; Strychnine