Quantitative analysis of total correlation spectra: Application to small biomolecules

The peak intensities of total correlation spectra are intimately related to J-coupling constants, which in turn are related to local geometry. Knowledge of J values is therefore useful in determining molecular structure. In the past, the complexity of the time development of total correlation cross-peaks has hindered their use in extracting structural information. This paper reviews the relevant quantum-mechanical equations. The series expansion of the density matrix for the most general spin-1/2 system undergoing isotropic mixing offers a convenient approximation that can be exploited to evaluate the extent of net transfer as a function of J values. A method for evaluating J-coupling constants from total correlation spectra of small biomolecules is presented as an application and as an illustration of the theory. Peak amplitude quantitation of short-mixing-time spectra provides tentative estimates of scalar couplings (accurate up to the third order of the series expansion as a function of mixing time). These estimates can be further refined by fitting the experimental data with theoretical transfers obtained by a full density matrix calculation. An experimental illustration of the method is given for a nucleic acid and a coenzyme system, although the conclusions should hold for every similar spin system.