Work

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

Year: 2023

Type: article

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.

Source: ChemistryEurope

DOI: 10.1002/ceur.202300012

Authors: Sheldon Sookai, Orde Q. Munro

Institutions: University of the Witwatersrand, University of Leeds

Language: English

Topic: Protein Interaction Studies and Fluorescence Analysis

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: diamond

Funders: National Research Foundation, University of the Witwatersrand, Johannesburg, Center for High Performance Computing