31P-{1H} nuclear Overhauser effects of phosphorus-containing metabolites in chemical exchange between free and macromolecular bound states

Abstract The formalism for the steady-state 31 P-{ 1 H} nuclear Overhauser effect was extended to include the effects of nuclear-spin magnetization transfer between two sites, F ⇔ B, representing free and macromolecular bound ligand states, respectively, such as might be encountered in vivo . Theoretical interpretations of the NOE based on models excluding the effects of phosphorusmetabolite exchange between free and macromolecular bound ligand states are potentially inadequate for tissue systems and may not properly represent the experimentally measured NOE. Analytical expressions were derived describing the behavior of the steady-state transferred heteronuclear NOE assuming broadband proton saturation. Computer simulations are presented for different free and bound phosphorus-metabolite population distributions, ligand exchange rates, bound metabolite rotational correlation times, and varying order parameters under the extreme narrowing condition for bound ligand internal motion. The simulations reveal the pronounced effect of the phosphorus-metabolite transferred NOE that occurs with rapid to very slow bound metabolite motion. A substantial reduction of the NOE enhancement results from relatively small concentrations of macromolecular bound metabolites. Thus, the often expected gain in signal enhancement may not be realized. Application of the heteronuclear transferred NOE formalism derived in this study was made to the experimental 31 P-{ 1 H} NOE values obtained for 2,3-bisphosphoglycerate binding to hemoglobin in erythrocytes and to the major phosphorus metabolites present in ocular lens tissue homogenates. Reasonable agreement between theoretically predicted and experimental values was obtained.