Aqueous Shift Reagents for High-Resolution Cation NMR Spectroscopy. 4.† DybPPPpob

The chelate Dy(PPP)₂⁷⁻ (where PPP⁵⁻ is tripolyphosphate) is a very effective shift reagent for the ²³Na NMR signal. However, it is also quite toxic to living animals. In addition to the effects of the equilibrium competitions of the biological metal cations Mg²⁺ and Ca²⁺ with Na⁺ for Dy(PPP)₂⁷⁻, this toxicity is most likely due to the potentially irreversible effects of ligand dissociation in vivo. In order to avoid this latter problem, two PPP moieties have been covalently linked so as to take advantage of the chelate effect. Thus, this paper reports the synthesis of the new shift reagent DybPPPpob⁵⁻ (where bPPPpob⁸⁻ is o-bis((3-(tripolyphosphato)propyl)oxy)benzene). In vitro ²³Na and ³¹P NMR experiments show that (1) DybPPPpob⁵⁻ is an upfield shift reagent (like Dy(PPP)₂⁷⁻), which shifts the ²³Na signal more than a third as well as Dy(PPP)₂⁷⁻, (2) the ²³Na shift has a pH profile similar to that of Dy(PPP)₂⁷⁻, (3) competition by Ca²⁺ and Mg²⁺ with Na⁺ for DybPPPpob⁵⁻ is not as severe as it is for Dy(PPP)₂⁷⁻ and (4) DybPPPpob⁵⁻ hydrolysis is catalyzed by alkaline phosphatase but neither as rapidly nor as extensively as that of Dy(PPP)₂⁷⁻. This latter result presumably implies that an uncoordinated PPP moiety of an incompletely dissociated DybPPPpob⁵⁻ chelate can still act as a substrate for the enzyme. The hydrolysis is slow enough that, with proper care, DybPPPpob⁵⁻ may be useful as an in vivo shift reagent.