Synthesis and NMR studies of new DOTP-like lanthanide(III) complexes containing a hydrophobic substituent on one phosphonate side arm.

Abstract

Three derivatives of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylene phosphonic acid) (DOTP) containing a hydrophobic substituent on one side chain were prepared and their lanthanide complexes examined by NMR. The new ligands include 1-(1-octyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (C(8)-DOTP), 1-(1-undecyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (C(11)-DOTP), and 1-(1-4-nitro-phenyl-methyl-phosphonic acid)-4,7,10-tris(methylene phosphonic acid)-1,4,7,10-tetraazacyclododecane (NO(2)-Ph-DOTP). (1)H NMR spectra of the ytterbium(III) complexes were assigned by using a combination of COSY spectroscopy and a fitting procedure that matches experimental NMR hyperfine shifts with those estimated from a MMX-derived structure. The analysis showed that a single isomer is present in solution and that the bulky hydrophobic substituent occupies the less sterically demanding H(6) equatorial position in the YbL(5)(-) complexes. Although the YbL(5)(-) complexes have lower symmetry due to the added substituent, the average (1)H hyperfine shifts are 5-10% larger in these complexes compared to YbDOTP(5)(-). This was magnified further in the hyperfine (23)Na NMR shifts of ion-paired sodium ions where the extracellular Na(+) signal in perfused rat hearts displayed a 28% larger hyperfine shift in the presence of Tm(C(11)-DOTP)(5)(-) than with an equivalent amount of TmDOTP(5)(-).