Is Less More? Influence of the Coordination Geometry of Copper(II) Picolinate Chelate Complexes on Metabolic Stability

Overview

Journal Inorg Chem

Specialty Chemistry

Date 2020 Oct 28

PMID 33112609

Citations 4

Authors

Brett A Vaughn

Alexander M Brown

Shin Hye Ahn

Jerome R Robinson

Eszter Boros

Affiliations

Soon will be listed here.

Abstract

A growing number of copper(II) complexes have been identified as suitable candidates for biomedical applications. Here, we show that the biocompatibility and stability of copper(II) complexes can be tuned by directed ligand design and complex geometry. We demonstrate that azamacrocycle-based chelators that envelope copper(II) in a five-coordinate, distorted trigonal-bipyramidal structure are more chemically inert to redox-mediated structural changes than their six-coordinate, Jahn-Teller-distorted counterparts, as evidenced by electrochemical, crystallographic, electron paramagnetic resonance, and density functional theory studies. We further validated our hypothesis of enhanced inertness in vitro and in vivo by employing Cu-64 radiolabeling of bifunctional analogues appended to a prostate-specific membrane antigen targeting dipeptide. The corresponding Cu-64 complexes were tested for stability in vitro and in vivo, with the five-coordinate system demonstrating the greatest metabolic stability among the studied picolinate complex series.

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