Complexities of the Interaction of Ni II , Pd II and Pt II Pyrrole‐Imine Chelates with Human Serum Albumin**

Abstract

Human serum albumin (HSA) efficiently transports drugs in vivo: most are organic. Here, HSA binding affinity and site specificity are shown to depend on the identity of the d 8 metal ion in Ni II , Pd II and Pt II chelates of the bis(pyrrole‐imine) ligand H 2 PrPyrr. Fluorescence quenching data for native and probe‐bound HSA showed sites close to Trp‐214 (subdomain IIA) are targeted. The Stern‐Volmer constants, K SV , ranged from 10 4 M −1 to 10 5 M −1 while the affinity constants, K a , ranged from ∼3.5×10 3 M −1 to ∼1×10 6 M −1 at 37 °C, following the order Pd(PrPyrr) > Pt(PrPyrr) > Ni(PrPyrr) > H 2 PrPyrr. Ligand uptake is enthalpically driven, hinging mainly on London dispersion forces. Induced CD spectra for the protein‐bound ligands could be simulated by hybrid QM:MM TD‐DFT methods, proving that the metal chelates neither decompose nor demetallate after uptake by HSA. Transport and delivery of the metal chelates by HSA in vivo could therefore be feasible.