title: HMBC-1,1-ADEQUATE via generalized indirect covariance: a high sensitivity alternative to n,1-ADEQUATE.
abstract: 1,1-ADEQUATE and the related long-range 1,n- and n,1-ADEQUATE variants were developed to provide an unequivocal means of establishing (2)J(CH) and the equivalent of (n)J(CH) correlations where n = 3,4. Whereas the 1,1- and 1,n-ADEQUATE experiments have two simultaneous evolution periods that refocus the chemical shift and afford net single quantum evolution for the carbon spins, the n,1-variant has a single evolution period that leaves the carbon spin to be observed at the double quantum frequency. The n,1-ADEQUATE experiment begins with an HMBC-type (n)J(CH) magnetization transfer, which leads to inherently lower sensitivity than the 1,1- and 1,n-ADEQUATE experiments that begin with a (1)J(CH) transfer. These attributes, in tandem, serve to render the n,1-ADEQUATE experiment less generally applicable and more difficult to interpret than the 1,n-ADEQUATE experiment, which can in principle afford the same structural information. Unsymmetrical and generalized indirect covariance processing methods can complement and enhance the structural information encoded in combinations of experiments e.g. HSQC-1,1- or -1,n-ADEQUATE. Another benefit is that covariance processing methods offer the possibility of mathematically combining a higher sensitivity 2D NMR spectrum with for example 1,1- or 1,n-ADEQUATE to improve access to the information content of lower sensitivity congeners. The covariance spectrum also provides a significant enhancement in the F(1) digital resolution. The combination of HMBC and 1,1-ADEQUATE spectra is shown here using strychnine as a model compound to derive structural information inherent to an n,1-ADEQUATE spectrum with higher sensitivity and in a more convenient to interpret single quantum presentation.
authors.affiliation: Discovery and Preclinical Sciences-Process & Analytical Chemistry, Merck Research Laboratories, Summit, NJ 07901, USA. gary.martin2@merck.com
authors.forename: Gary E
authors.initials: GE
authors.lastname: Martin
authors.forename: R Thomas
authors.initials: RT
authors.lastname: Williamson
authors.forename: Kirill A
authors.initials: KA
authors.lastname: Blinov
authors.forename: Clemens G
authors.initials: CG
authors.lastname: Anklin
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bermel
mesh_terms: D016477:Artifacts; D015394:Molecular Structure; D011789:Quantum Theory; D013331:Strychnine / Q000737:chemistry*
chemical_list: D013331:Strychnine