Synthesis of lanthanide(III) complexes appended with a diphenylphosphinamide and their interaction with human serum albumin

Two DOTA-based proligands bearing a pendant diphenylphosphinamide 4a and 4b were synthesised. Their Eu(III) complexes exhibit sensitised emission when excited at 270 nm via the diphenylphosphinamide chromophore. Hydration states of q = 1.5 were determined from excited state lifetime measurements (Eu.4a k(H2O) - 2.14 ms(-1); k(D2O) = 0.64 ms(-1); Eu.4b k(H2O) = 2.67 ms(-1); k(D2O) = 1.18 ms(-1)). In the presence of human serum albumin (HSA) (0.1 mM Eu.4a/b, 0.67 mM HSA, pH 7.4) q = 0.4 for Eu.4a (kH(2)O = 1.34 ms(-1); k(D2O) = 0.75 ms(-1)) and q = 0.6 for Eu.4b (k(H2O) = 1.83 ms(-1); k(D2)O = 1.05 ms(-1)). Relaxivites (pH 7.4, 298 K, 20 MHz) of the Gd(III) complexes in the absence and presence of HSA (0.1 mM Gd.4a/b, 0.67 mM HSA) were: Gd.4a (r(1) = 7.6 mM(-1) s(-1) and r(1) = 11.7 mM(-1) s(-1)) and Gd.4b. (r(1) = 7.3 mM(-1)s(-1) and r(1) = 16.0 mM(-1)s(-1)). These relatively modest increases in r(1) are consistent with the change in inner-sphere hydration on binding to HSA shown by luminescence measurements on Eu.4a/b. Binding constants for HSA determined by the quenching of luminescence (Eu) and enhancement of relaxivity (Gd) were Eu.4a (27,000 M-1 +/- 12%), Eu.4b (32,000 M-1 +/- 14%), Gd.4a (21,000 M-1 +/- 15%) and Gd.4b (26,000 M-1 +/- 15%).