Two-dimensional Hadamard spectroscopy.

Direct frequency-domain excitation of NMR with an array of different radiofrequencies has been used to speed up two-dimensional NMR experiments by a large factor. Multiplex excitation in the F(1) frequency dimension is restricted to the signal-bearing regions and is encoded according to a Hadamard matrix of dimension N by N, where N is a relatively small number. The detected signals are decoded by reference to the same Hadamard matrix. Alternatively a phase-encoding scheme can be employed. Two-dimensional correlation experiments (COSY and TOCSY) and cross-relaxation measurements (NOESY) implemented on proton systems can be completed in less than a minute in cases where the intrinsic sensitivity is sufficiently high that prolonged multiscan averaging is not required. The results are presented in the form of a high-resolution contour diagram similar to the familiar two-dimensional spectra obtained by Fourier transform methods. Experiments on strychnine demonstrate more than two orders of magnitude improvement in speed compared with the traditional methods.