Connectivities in molecules by INADEQUATE: recent developments

Abstract

The INADEQUATE (Incredible Natural Abundance DoublE QUAntum Transfer Experiment) consists of a pulse sequence which eliminates the NMR signals from isolated spins (spin system A) displaying signals from coupled spins (spin system AX or higher spin systems). It is of great importance when applied to molecules with skeleton elements such as carbon, silicon or tungsten, all of which contain a small percentage of spin-1 2 isotopes embedded in magnetically inactive isotopes. Analysis of the AX type spectra gives one-bond and long-range coupling constants (see compound 6) and, most important, the connectivity pattern of the skeleton atoms in molecules of unknown structure such as the carbon compounds 1 or 2, the silicon compound 3 or the lithium compound 4b. Unfortunately, INADEQUATE is rather insensitive, in the case of carbon only one out of 10 4 molecules gives the desired response. Efforts to reduce this drawback are described; recently, a remarkable step forward has been made by concentrating the four lines of an AX spin system to just two signals (see Fig. 2).

1H-Detected IPAP DEPT-INADEQUATE and IPAP RINEPT-INADEQUATE for the measurement of long-range carbon–carbon coupling constants

“…The theoretical gains of the 1 H-detected version can be calculated [36] as 0.71 * (c H /c C ) 5/2 /3 = 7.6, where factors 0.71 and 3 account for the use of PFGs in the 1 H-detected experiments and the utilization of the heteronuclear NOE in the 13 C-detected experiment, respectively. As noted by others [37], such large sensitivity gains are rarely achieved. This is mainly because of a combination of 1 H-1 H couplings and short Fig.…”

“…1a) [40] and 180°BIBOP pulses [41] are indicated as wide rectangles with a sine wave. The 13 C adiabatic inversion pulses [37] are designated by an inclined arrow. The following delays were used:…”

13C‐detected IPAP‐INADEQUATE for simultaneous measurement of one‐bond and long‐range scalar or residual dipolar coupling constants

“…General reasons for such a good performance of the 13 C-detected INADEQUATE were discussed previously. 4,13,14 Specific to our experiment is the use of 1 H decoupling during long evolution intervals that prolongs the effective relaxation of carbon coherences and eliminates the leakage of magnetization for protonated carbon pairs. 13 The use of phase cycling, rather than pulsed field gradients for coherence selection, not only increases the S/N ratio by a factor of 1.41, but also eliminates diffusion related losses that could be severe for small molecules and long evolution intervals.…”

“…5,7,9 -12 Most of the more recent versions of INADEQUATE employ 1 H detection, 1 -3,3 -13 an approach which is only partially successful in increasing the sensitivity of this experiment, as discussed previously. 4,13,14 At the natural abundance of 13 C, INADEQUATE is indeed a rather insensitive experiment, as only one in 8734 molecules contains a 13 C, 13 C pair. Nevertheless, with the increasing availability of cryoprobes, INADEQUATE is about to realize its potential to become a mainstream NMR experiment.…”

J-modulated ADEQUATE (JM-ADEQUATE) experiment for accurate measurement of carbon–carbon coupling constants

“…Early experiments, such as the traditional INADE-QUATE [1][2][3][4][5][6][7][8][9][10][11] schemes use the evolution of carboncarbon double quantum coherence followed by carbon detection, and the undesired background carbon magnetization of 12 C-13 C isotopomers is suppressed by appropriate phase cycling. The inherent low sensitivity of these experiments, however, prevents their routine use, especially when only limited sample amount is available.…”