Long-range correlation of proton and heteronuclear chemical shifts, in particular carbon, has proven invaluable in the investigation of mo lecular structure ( I7). The advent of indirect detection of heteronuclei via protons has made long-range correlation routine even on low concentration samples. The most useful indirect technique for long-range correlation proposed thus far is the heteronuclear mu ltiple-bond correlation (HMBC) experiment ( 7). We have used this technique with excellent results despite the fact that we use the proton-decoupl ing coil of our standard Varian 5 m m broadband switchable probe for observation. Typically, we achieve a nominal fivefold increase in signal-to-noise ratio (S/N) per unit measur ing time compared to the 13C detected experiment. We have recently encountered difficult assignment problems via work with analogs of the DNA-binding drug distamycin A (8-l 1) . These problems are due to low sensitivity and poor proton resolution. Distamycin A, for instance, shows a significant degree of aromatic proton overlap in its ‘H spectrum (Table 1) . Also, complete assignment of the 13C and ‘H spectra requires correlation of carbonyl resonances with aromatic ring protons via 4 JCH which is quite small, requiring the highest sensitivity possible. The sensitivity of HMBC has been addressed by Bax and Marion ( 12). They proposed a m ixed mode data-processing procedure for the HMBC experiment, which utilizes a hypercomplex Fourier transform (13) of the data, resulting in absorptive mode in F, followed by a magn itude calculation in F2. This technique results in a \Iz increase in S/N. The reason for applying a F2 magn itude calculation to the HMBC data in both the conventional method and Bax and Marion’s experiment is the presence of phase modu lation of the F2 data by proton chemical shift and homonuclear coupling during the delay, 7, in F ig. la. Since distamycin A and its congeners show only modest (e.g., 2 Hz) scalar coupling in the over lapped aromatic ‘H region, it seemed that the m inimal amount of phase modu lation due to these couplings m ight
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