HECADE - HMQC-BASED AND HSQC-BASED 2D NMR EXPERIMENTS FOR ACCURATE AND SENSITIVE DETERMINATION OF HETERONUCLEAR COUPLING-CONSTANTS FROM TOCSY-TYPE CROSS PEAKS

Two-dimensional pulse sequences for the determination of heteronuclear long-range coupling constants are presented. The sequences are based on the HMQC/HMBC or HSQC technique with subsequent optional homonuclea r I-spin transfer. However, they yield tilted cross-peak patterns disp laying antiphase heteronuclear coupling constants in the projections o f both dimensions, which allow accurate determination of the couplings even in cases where the linewidth is of comparable magnitude. Two cha racteristic pulse-sequence elements were implemented to shape the F-1 domain: the first element allows an arbitrary scaling of the heteronuc lear coupling splittings relative to S-spin chemical-shift differences , whereas the second element achieves homonuclear broadband decoupling among the I spins in the HMQC/HMBC experiments and thus allows purely absorptive representations of such spectra. In comparison with establ ished (omega(1)) X-half-filtered TOCSY spectra, the signal dispersion in F-1 is significantly improved and largely under experimental contro l. Furthermore, heteronuclear couplings of (I-1, S) pairs where S is e ither quaternary or carries one or more I spins that do not belong to the same I-coupling network as I-1 can also be measured, The implement ation of pulsed field gradients results in good suppression of spectra l artifacts. (C) 1997 Academic Press.