Geminal-filtered correlation spectroscopy

Abstract

Two-dimensional correlation spectroscopy has proved extremely successful for assigning NMR spectra on the basis of homonuclear spin-spin coupling. However, when the molecules under investigation become large and complex, difficulties may arise because of crowding of the cross peaks and ambiguities in the assignments. One answer is to edit the COSY spectra in some appropriate manner, for example, by doubleor multiple-quantum filtration ( 1,2), spin topology filtration (3,4), or selective excitation (5, 6). We suggest here another editing technique designed to display only the geminal protons of methylene groups. Not only does this greatly simplify the COSY spectrum, but also it acts as a powerful method of assignment. The new technique is based on existing X-relayed coherence-transfer methods ( 7-ll ), modified so that the H --* 13C + H transfer is restricted to one-bond couplings. This condition is easily satisfied by suitably shortening the appropriate time intervals so that only the large one-bond C-H couplings generate sufficient divergence of the magnetization vectors. The magnitudes of the proton-proton couplings are irrelevant in this application and we may safely ignore the low concentration of molecules with two adjacent 13C nuclei. Inevitably the method suffers from a sensitivity lower than that of the conventional COSY spectrum since it relies on the naturally abundant 13C nuclei as intermediates. There are two basically different implementations of this experiment-through heteronuclear multiple-quantum coherence and by “X-relayed” heteronuclear polarization transfer ( 10, I2 ). The first method (“gem-COSY-MQ”) employs a principle that can be traced back to the early heteronuclear multiple-quantum experiments of Miiller ( 12). The spin dynamics may be described in the product operator formalism (13) with reference to the pulse sequence set out in Fig. 1. All evolution of proton and carbon chemical shifts is refocused except for the proton evolution during t, and we may for simplicity ignore such terms in the product operator treatment. Since the A and A’ delays are short (typically 3.6 ms) , we may also neglect the effects of evolution of proton-proton couplings during these periods. Consider the methylene fragment II-S-12, where S is 13C, and the I spins are nonequivalent geminal protons with chemical shifts 6, and 15~ and spin-spin coupling J12. We are interested in coherence transfer 1, + I2 and I2 + I,, but because of the symmetry of the problem it is sufficient to concentrate on the former. The initial excitation pulse 90,“(I) creates crl = -I,,, which evolves during the first delay A to give