binding affinity that does not track with lanthanide ionic radius,
with the greatest difference between terbium and europium. This
phenomenon, known as the “gadolinium break,” has been
reported in various studies of stability constants across the
lanthanide series, such as those with acetate and anthranilate
( 108 ) as well as in investigations of hydration enthalpy and
enzyme inhibition properties (109,110).
The interesting aspect of the gadolinium break observed in our
dipicolinate binding experiments is that it appears to beinduced
by binding of the ancillary ligand. The dipicolinate affinity for
the Ln^3 þ aquo ions exhibits little variation, but analogous [Ln
(DO2A)]þ complexes show an obvious divide between those to
the left of gadolinium (Sm, Eu) and those to the right (Tb, Dy).
Another study concerning lanthanide–macrocycle binary
complexes also noted a similar trend, in this case using chiral
heptadentate 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetate
(DO3A) derivatives. The authors noted an increase in the bind-
ing affinity of the terbium complex for certain oxyanions (acetate,
bicarbonate, and phosphate) in comparison to the analogous
europium complex by about the same margin as observed for
dipicolinate (Table III). As with our system, lifetime
measurements of these complexes indicated no differences in
hydration state that might explain the discrepancy, such as a
decrease from nine coordinated waters about the larger Eu^3 þ
ion to eight around Tb^3 þ. The authors instead attribute the affin-
ity trend to a divergence of pKafor the two complexes. If the pKa
of the europium complex were lower than that of the terbium
complex, the presence of a population of hydroxylated
TABLE II
ENHANCEDRECEPTOREFFECT INVARIOUSLANTHANIDE/ANALYTESYSTEMS.Ligand Analyte DlogK References
DO2A^2 – Dipicolinate 0.8–1.8 ( 92 )
EDTA^2 – Picolinate 0.2–1.5a (103,104)
L 1 Lactate 0.8–1.5b (105,106)
L 2 Acetate 0.1–1.4c (106,107)
L 1 ¼(SSS)-1,4,7-tris[1-(1-phenyl)ethylcarbamoylmethyl]-1,4,7,10-tetraazacyclododecane,
L 2 ¼(SSS)-1,4,7-tris[1-(1-phenyl)ethylcarbamoylmethyl]-10-methyl-1,4,7,10-
tetraazacyclododecane.
Change in the analyte binding affinity (DlogK¼logK^0 a–logKa) due to the ligand in
comparison to the lanthanide alone.
alogKa: 0.1 M KNO 3 , 25C; logK (^0) a: 0.5 M NaClO 4 , 25C.
blogKa: 0.1 M NaClO 4 , 20C; logK (^0) a: 0.1 M collidine/HCl, 21.8C, pH 7.4.
clogKa: 0.1 M NaClO 4 , 20C; logK (^0) a: 0.1 M collidine/HCl, 21.8C, pH 7.4.
18 MORGAN L. CABLEet al.