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_{{{text{H}}_{ 2} {text{O}}}} = 2. 1 4 ,{text{ms}}^{ - 1} ,;k_{{{text{D}}_{ 2} {text{O}}}} = 0. 6 4 ,{text{ms}}^{ - 1} $ ; Eu.4b $ k_{{{text{H}}_{ 2} {text{O}}}} = 2. 6 7, {text{ms}}^{ - 1} ,;k_{{{text{D}}_{ 2} {text{O}}}} = 1. 1 8 ,{text{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_{{{text{H}}_{ 2} {text{O}}}} = 1. 3 4, {text{ms}}^{ - 1} ,;k_{{{text{D}}_{ 2} {text{O}}}} = 0. 7 5, {text{ms}}^{ - 1} $ ) and q = 0.6 for Eu.4b ( $ k_{{{text{H}}_{ 2} {text{O}}}} = 1. 8 3, {text{ms}}^{ - 1} ,;k_{{{text{D}}_{ 2} {text{O}}}} = 1.0 5 ,{text{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%).