13C detection

Fig. 10.13. 2D J-resolved NMR spectrum of santonin (4). The data were acquired using the pulse sequence shown in Fig. 10.12. Chemical shifts are sorted along the F2 axis with heteronuclear coupling constant information displayed orthogonally in F . Coupling constants are scaled as J/2, since they evolve only during the second half of the evolution period, t /2. 13C signals are amplitude modulated during the evolution period as opposed to being phase modulated as in other 13C-detected heteronuclear shift correlation experiments.

Fig. 10.25. 13C CPMAS and 19F MAS SSNMR spectra of the drug formulation (top) and the physical mixture of API with excipients (bottom). Shown above each peak are the relaxation times calculated from the 13C detected...

Figure 7.2.3 (b) depicts a probe which is also suitable for 13C detection, due to the inclusion of a second coil. The main advantage of this probe compared to all of the others is the lock capillary, which is located in the centre of the titanium-sapphire flow cell. This can be used for the deuterated solvent, i.e. for locking and shimming the magnet. For the best shimming, however, the... 

In 1989, the first applications of multidimensional NMR were applied to humic substances (Buddrus et al., 1989).This study involved the application of 13C detected J-resolved (J-Res) spectroscopy. The study was successful in that it showed multidimensional NMR was applicable to the study of humic substances. However, in 1989 the lack of various modern experiments and the corresponding hardware (mainly probes fitted with pulse field gradients) made applying NMR to humic materials very challenging. In 1997, Simpson et al. demonstrated that the more sensitive inverse-detected NMR experiments were applicable to NOM (Simpson et al., 1997). In this manuscript COSY,TOCSY and HMQC were applied (Simpson et al.,... 

M. Pietrzak et al., 13C detected scalar nitrogen-nitrogen couplings across the intramolecular symmetric NHN hydrogen bond of proton sponge. J. Am. Chem. Soc. 123,4338 1339 (2001)... 

Another ID experiment that can be and has been utilized for 29Si line assignment in even more difficult situations [with /(29Si—13C) 1-2 Hz] is selective heteronuclear INADEQUATE253,254. ID heteronuclear INADEQUATE with 13C detection is a simple two-step pulse sequence in which the pulses are applied simultaneously to both nuclei ... 

Since the line-broadening effects of the magnetic susceptibility variations are directly proportional to the NMR frequency, lower frequency nuclei (like 13C) may produce narrower linewidths. In fact, this technique has been mostly used for this nucleus [37-43]. In some cases, the poor sensitivity associated with 13C detection was compensated by incorporating 13C labels near the reaction site of interest. This approach was called fast 13C NMR [44 48] and allowed to obtain data in a few minutes for each sample. 

HETCOR has been largely replaced by the far more sensitive inverse experiments, HSQC and HMQC. Because HETCOR is a 13C-detected experiment, it is called direct ... 

HMBC Heteronuclear multiple bond correlation, inverse CH correlation via long-range CH coupling, same format and information as described for (13C detected) CH COLOC but much more sensitive (therefore less time-consuming) because of Z/ detection... 

One of the main advantages of 13C-detected INADEQUATE is that, unlike 1H-detected INADEQUATE, it provides information about connectivity of quaternary carbons. However, quaternary carbons are handicapped by slow spin-lattice relaxation. In order to improve their sensitivity, the addition of relaxation agents has been proposed.9 It should be noted, however, that this procedure should be carried out with caution, as it may degrade signal strength by quenching the nuclear Overhauser effect.10 One study showed that a moderate... 

Chirp pulses have also been used in a double-J-modulated INEPT-INADE-QUATE.29 Universal rotators constructed by combining two point-to-point rotations30 have been recently used in 1H- and 13C-detected IPAP-INADEQUATE experiments.31,32... 

In practice, however, such considerable sensitivity gain is rarely realised by XH detection mainly due the complicated nature of H multiplets. 3C detection is performed under low-power 2H decoupling allowing acquisition times of 400 ms, while the acquisition times of 1H-detected experiments under high-power 13C decoupling is limited to 100 ms. 13C detection yields AP doublets with natural linewidths of few hertz, while H detection leads to the detection of broad, unresolved proton multiplets with much wider lines. 

Most of the carbon-carbon coupling constants published recently have been measured using 2D 13C-detected INADEQUATE spectra.39-44 ID INADEQUATE experiments were used less frequently43 45 due to potential overlap problems. The measured coupling constants are usually used to resolve stereochemical problems and also compared with theoretical values. 

Frequency separation between the two lines of AP doublets in 13C-detected INADEQUATE spectra corresponds to 1/cc coupling constants, which are simply read out from the spectra. However, accurate determination of njcc coupling constants is more problematic due to possible partial cancellation of closely spaced AP doublets. The peak-to-peak distance in such doublets does not correspond to actual value of the coupling constant. A solution to this problem was proposed recently in the form of IPAP-INADEQUATE experiment (Figure 9) 32... 

Figure 9 13C-detected I PAP INADEQUATE (A) non-refocused (AP) and (B) refocused (IP) INADEQUATE T = 0.S/nJcc, the 90° rectangular pulses are shown as filled rectangles 90° BEBOP and 180° BIBOP pulses are indicated as narrow and wide rectangles, respectively the adiabatic inversion pulse is designated by an inclined arrow. Phase cycling is given in Table 1. From Ref. 32, reproduced by permission of John Wiley and Sons. 

However, the analysis of NOESY spectra yielded several interactions that were not compatible with the proposed structure. A 13C-detected INADEQUATE spectrum (Figure 2) was therefore acquired, which showed several crucial connectivities between the carbons of the aliphatic chains, namely C5a, C6, C7, C7a, C7b and C15, C14a, C14, C13, revealing the existence of a cyclobutane ring in compound 2, 7,7a,13,14-tetrahydro-6H-cyclobuta[fo]pyrimido[l,2-fl 3,4-fl ]diindole. 

Several structures have been corrected and elucidated with the aid of 13C-detected INADEQUATE. For example, the aH and 13C assignment of frans-3,4, 5-trihydroxystilbene was corrected.53 The structure of a dimeric mero-terpenoid, tridentorubin, was also investigated by 13C-detected INADEQUATE,54 while the structure of A-74528, an inhibitor for 20,50-phosphodiesterase isolated from Streptomyces sp., was elucidated on the basis of several crucial carbon-carbon connectivities that could not be determined from the analysis of its HMBC spectrum.55 Additional examples of the use of 13C-detected INADEQUATE to aid structure determination of small molecules can be found in the literature.25 56-61... 

Ce Cg2 anion, [Ce C82A] 76 Crucial to this investigation was the full assignment of all carbon signals provided by the 2D 13C-detected INADEQUATE (Figure 21). 

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