Inframolecular protonation process of myo-inositol 1,4,5-tris(phosphate) and related compounds: Dynamics of the intramolecular interactions and evidence of C-H center dot center dot center dot O hydrogen bending

The intramolecular protonation process of myo-inositol 1.3,5-tris(phosphate ) (1, Ins(1,4,5)P-3) and the closely related analogues myo-inositol 1,4,6-t ris(phosphate) (2, Ins(1,4,6)P-3), and 3-deoxy-myo-inositol 1,4,5-tris(phos phate) (3) and the latter's epimer, 3-deoxy-muco-inositol 1,3,5-tris(phosph ate) (4). were explored by performing P-31 and H-1 NMR titration experiment s. The microprotonation scheme for compounds 1, 2, and 4 were quantitativel y derived. The influence of the configuration of the functional groups and of the presence of the hydroxyls on the P-31 and H-1 chemical shifts and ph osphate basicity was discussed. Thus, the basicity increase of the phosphat es and the shielding of the related phosphorus nuclei observed upon deletio n of a vicinal hydroxyl is mainly attributed to solvation changes around th e phosphate groups. A concerted wrongway shift of some protons and phosphor us nuclei provides information on the conformational dynamics of the phosph ates upon protonation. These wrongway shifts may be the result of electrost atic interactions between a ring proton and a doubly negatively charged pho sphate group in a trans diequatorial configuration. According to G. R. Desi raju, such an interaction may be considered as a C-H ... O hydrogen bond. T he necessary condition to observe this bond is a constraint of the phosphat e group such that it closely approaches the ring proton. This may occur as shown by molecular modeling studies when two phosphates strongly repel each other either directly or via the relaying effect of an intervening equator ial hydroxyl.