Inversion of ¹J_CC correlations in 1,n‐ADEQUATE spectra

Abstract

ADEQUATE experiments provide an alternative to the more commonly employed GHMBC experiment for the establishment of long-range heteronuclear connectivities. The 1,1-ADEQUATE experiment allows the unequivocal identification of both protonated and non-protonated carbon resonances adjacent to a protonated carbon. The 1,n-ADEQUATE experiment establishes correlations via an initial (1)J(CH) heteronuclear transfer followed by an (n)J(CC) out-and-back transfer, most typically, via three carbon-carbon bonds. Hence, the 1,n-ADEQUATE experiment allows the equivalent of (4)J(CH) heteronuclear correlations to be probed when they are not observed in a GHMBC spectrum. Aside from the lower sensitivity of the 1,n-ADEQUATE experiment relative to GHMBC experiments, the interpretation of the former is also complicated by the 'leakage' of (1)J(CC) correlations into the spectrum that must be identified. A method for the inversion of (1)J(CC) correlations to facilitate the interpretation of 1,n-ADEQUATE spectra is presented that allows a single experiment to be performed to access (1)J(CC) and (n)J(CC) correlation information.

Application of 1,n-ADEQUATE and Modified Variants to Structure Elucidation and Spectral Assignment Problems

“…If the 1 J CC component of magnetization happens to be in-phase at the end of the delay, 1 J CC correlations will also be observed in the eventual 1,n-ADEQUATE spectrum being recorded. 16 …”

“…As noted in section titled '1,n-ADEQUATE', it is possible and likely for both 1 J CC and n J CC correlations to be observed in a 1,n-ADEQUATE spectrum. 15,16,18 The predominant correlations in a 1,n-ADEQUATE spectrum will generally be due to 1 J CC and 3 J CC correlations, which are shown by solid black arrows in the schematic shown in Figure 2. Weaker correlations via 2 J CC and 4 J CC coupling pathways can be observed and are denoted by dashed arrows in Figure 2.…”

“…15 Recently, there have been two modified variants of the 1,n-ADEQUATE experiment described that have employed the asymmetric modification of the magnetization transfer delays in the pulse sequence to semi-selectively invert 1 J CC correlations, effectively 'editing' the spectrum on the basis of the coupling pathway in a fashion analogous to multiplicityediting of an HSQC spectrum. 16,18 The modified variants of the 1,n-ADEQUATE experiment are discussed in sections titled 'Inverted 1 J CC 1,n-ADEQUATE' and 'Development of Dual Optimization Inverted 1 J CC 1,n-ADEQUATE'.…”

“…Rather than seeking to eliminate 1 J CC correlations, it makes more sense to develop a method that facilitates their inversion, differentiating those correlations from n J CC correlations and rendering them identifiable. 16 Inverted 1 J CC 1,n-ADEQUATE Following the initial INEPT transfer in the pulse sequence shown in Figure 3, both n J CC and 1 J CC carbon-carbon couplings evolve according to sin(JπΔ). As all variants of ADE-QUATE are out-and-back experiments, the same transfer amplitudes apply for the delay before the reverse INEPT transfer.…”

“…By introducing asymmetry into the pulse sequence via the Δ5 and Δ3 delays, transfer amplitudes that are negative for 1 J CC but positive for n J CC can be obtained. 16 The Δ5 and Δ3 delays were made asymmetric in duration by optimizing them either for (4m + 5)/(2 1 J CC ) and (4m + 3)/(2 1 J CC ) or for (2m + 1)/(2 1 J CC ) and (2m − 1)/(2 1 J CC ), respectively. The value of m was calculated as the closest integer of 1 J/(2 n J CC ).…”