CHARACTERIZATION OF LANTHANIDE(III) DOTP COMPLEXES - THERMODYNAMICS, PROTONATION, AND COORDINATION TO ALKALI-METAL IONS

Several solution properties of complexes formed between the trivalent lanthanide ions (Ln(III)) and the macrocyclic ligand DOTP8-, including stability constants, protonation equilibria, and interactions of the LnDOTP(5-) complexes with alkali metal ions, have been examined by spe ctrophotometry, potentiometry, osmometry, and H-1, P-31, and Na-23 NMR spectroscopy. Spectrophotometric competition experiments between DOTP and arsenate III for complexation with the Ln(III) ions at pH 4 indic ate that the thermodynamic stability constants (log K-ML) Of LnDOTP(5- ) range from 27.6 to 29.6 from La-III to Lu-III. The value for LaDOTP5 - obtained by colorimetry (27.6) was supported by a competition experi ment between DOTP and EDTA monitored by H-1 NMR (27.1) and by a potent iometric competition titration between DTPA and DOTP (27.4). Potentiom etric titrations of several LnDOTP(5-) complexes indicated that four p rotonation steps occur between pH 10 and 2; the protonation constants determined by potentiometry were consistent with P-31 Shift titrations of the LnDOTP(5-) complexes. Dissection of the P-31 Shifts of the hea vy LnDOTP(5-) complexes (To --> Tm) into contact and pseudocontact con tributions showed that the latter dominated at all pH values. The smal ler P-31 shifts observed at lower pH for TmDOTP5- were partially due t o relaxation of the chelate structure which occurred upon protonation. The P-31 shifts Of Other LnDOTP(5-) complexes (Ln = Pr, Nd, Eu) showe d a different pH-dependent behavior, with a change in chemical shift d irection occurring after two protonation steps. This behavior was trac ed to a pH-dependent alteration of the contact shift at the phosphorus nuclei as these complexes were protonated. Na-23 NMR studies of the i nteractions' of TmDOTP5- with alkali and ammonium cations showed that Et(4)N(+) and Me(4)N(+) did not compete effectively with Na+ for-the b inding sites on TmDOTP5-, while K+ and NH4+ competed more effectively and Cs+ and Li+ less effectively. A Na-23 shift of more than 400 ppm w as observed at low Na+/TmDOTP5- ratios and high pH, indicating that Na + was bound near the 4-fold symmetry axis of TmDOTP5- under these cond itions. Osmolality measurements of chelate samples containing various amounts of Na+ indicated that at high Na+/TmDOTP5- ratios at least thr ee Na+ ions were bound to TmDOTP5-. These ions showed a significantly smaller Na-23-bound shift, indicating they must bind to the chelate at sites further away from the 4-fold symmetry axis. Fully bound Na-23 s hifts and relaxation rate enhancements and binding constants for all N axHyTmDOTP species were obtained by fitting the observed Na-23 shift a nd relaxation data and the osmometric data, using a spreadsheet approa ch. This model successfully explained the Na-23 shift and osmolality o bserved for the commercial reagent Na4HTmDOTP . 3NaOAc (at 80 mM at pH 7.4).