Aqueous shift reagents for high-resolution cation NMR. V. Thermodynamics of interaction of DyTTHA^3- with Na⁺, K⁺, Mg ²⁺, and Ca ²⁺

Triethylenetetraminehexaacetate complexes of Dy(II) or Tm(III) (DyTTHA^3- and TmTTHA^3-, introduced as NMR shift reagents for alkali metal cations, Chu et al., J. Magn. Reson. 56, 33 (1984) bind to the four major biological inorganic cations: Na⁺, K⁺, Mg²⁺, and Ca²⁺. New ²³Na and ³⁹K NMR shift displacement data, obtained over wide and different ranges of concentration, were combined with the previous results (including some ²⁵Mg data) for computer analysis. With a proper treatment of the relevant activity coefficients using Pitzer's formulas, it is established that only mono complexes of the shift reagent and a cation need be considered. The cations bind competitively, with nearly identical limiting shifts of 159 and 155 ppm for Na⁺ and K⁺; the shift for ²⁵Mg is 3 5 as large. The thermodynamic formation constants for M-LnTTHA are 11 and 18 M^-1 with Na⁺ and K⁺ (enthalpy of binding, -54 kJ), and 130 and 3100 M^-1 with Mg²⁺ and Ca²⁺ at 3°C. The results suggest that all the cations bind at the same site, with Mg²⁺ probably forming a solvent-separated complex. The formation constants expected at 37°C indicate that, at useful shift reagent concentrations, and at physiological cation concentrations, DyTTHA^3- can be used not only to distinguish among cation pools but also for quantitative studies of cation relationships. In particular, ²³Na signals might be used to report free extracellular Ca²⁺ concentrations in vivo.