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 = 2.14ms ^-1k _D2O = 0.64ms ^-1; Eu.4b K _H2O = 2. 67 ^-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 ( K _H2O = 1. 34 ms ^-1,k _D2O = 0. 75 ms ^-1) and q = 0.6 for Eu.4b ( K _H2O = 1. 83 ms ^-1,k _D2O = 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 ^-1s ^-1 and r ₁ = 11.7 mM ^-1s ^-1) and Gd.4b. (r ₁ = 7.3 mM ^-1s ^-1 and r ₁ = 16.0 mM ^-1s ^-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%).