Solution Speciation and Human Serum Protein Binding of Indium(III) Complexes of 8-hydroxyquinoline, Deferiprone and Maltol

Overview

Journal J Biol Inorg Chem

Publisher Springer

Specialty Biochemistry

Date 2022 Mar 4

PMID 35243522

Authors

Orsolya Domotor

Bernhard K Keppler

Eva A Enyedy

Affiliations

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Abstract

Solution speciation and serum protein binding of selected In(III) complexes bearing O,O and O,N donor sets were studied to provide comparative data for In(III) and analogous Ga(III) complexes. Aqueous stability of the In(III) complexes of maltol, deferiprone, 8-hydroxyquinoline (HQ) and 8-hydroxyquinoline-5-sulfonate (HQS) was characterized by a combined pH-potentiometric and UV-visible spectrophotometric approach. Formation of mono, bis and tris-ligand complexes was observed. The tris-ligand complexes of HQ (InQ) and deferiprone (InD) are present in solution in ca. 90% at 10 µM concentration at pH = 7.4, while the tris-maltolato complex (InM) displays insufficient stability under these conditions. Binding towards human serum albumin (HSA) and (apo)transferrin ((apo)Tf) of InQ, InD and InM complexes and Ga(III) analogue of InQ (GaQ) together with InCl was investigated by a panel of methods: steady-state and time-resolved spectrofluorometry, UV-visible spectrophotometry and membrane ultrafiltration. Moderate binding of InQ to HSA was found (log K' = 5.0-5.1). InD binds to HSA to a much lower extent in comparison to InQ. ApoTf is able to displace HQ, deferiprone and maltol effectively from their In(III) complexes. Protein binding of non-dissociated InQ was also observed at high complex-to-apoTf ratios. Studies conducted with the InQ/GaQ - HSA - Tf ternary systems revealed the more pronounced Tf binding of In(III) via ligand release, while the original GaQ scaffold is preferably retained upon protein interactions and significant albumin binding occurs. Significant dissociation of InQ was detected in human blood serum as well.

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