Abstract
SummaryThe design and synthesis of metal chelators with extraordinary metal affinities is a basic and challenging scientific problem of both fundamental and practical importance. Here, we demonstrate a “conformational stability effect” that can significantly enhance the metal affinity of ligands after conjugation to polymer chains with the ability to spontaneously adopt a specific conformation as an optimal “soft” scaffold to ensure maximum thermodynamic stability of the metal complexes. Using iron chelators as models, we show that simple conjugation of small molecule catechol ligands to a polyallylamine chain resulted in more than 8–9 orders of magnitude enhancement of the iron-binding affinity, which is comparable to that of enterobactin, the strongest iron chelator ever known. This study demonstrates that flexible polymer chelators may realize the highest possible metal affinities of the conjugated ligands owing to their ability to achieve an optimal conformation, which could advance the identification of strong metal chelators.
Highlights
Metal chelators are widely used and indispensable in a variety of fields in both the laboratory and industry
This study proved that soft polymer chelators with dynamic structures and simple preparation methods could spontaneously achieve the highest possible level of metal affinity of the ligands, even comparable to that of ENT, the strongest iron chelator ever known, providing a facile and efficient way of screening strong polymer metal chelators
Three iron chelators including a small molecule chelator N-methyl-2,3-dihydroxybenzamide (MDHBA), a polymer chelator prepared by conjugating 2, 3-dihydroxybenzoic acid (DHBA) to poly(allylamine hydrochloride) (PAH) (PAH-DHBA), and ENT were employed as models to investigate how the macromolecular characteristics affect the affinity of the ligands on the polymer chains (Figures 1C–1E)
Summary
Metal chelators are widely used and indispensable in a variety of fields in both the laboratory and industry. Owing to the rigid characteristics of these scaffolds, the metal-ligand coordination may induce distortions of the bond angles and generate strain in the formed complexes, which can greatly impair the thermodynamic stability (Cram and Cram, 1978; Rodgers and Armentrout, 2003; Buist et al, 2010; Alvarez, 2015). An optimal scaffold should ensure that the preorganized ligands coordinate the target metal with a best fit coordination geometry that produces minimum strain in the formed complexes, attaining maximum thermodynamic stability. Designing and screening that optimal scaffold is very challenging, as even a tiny change of the scaffold structure can produce substantial reduction of the metal affinity (Schwarzenbach, 1952; Cotton and Harris, 1955). Unique approaches are needed to facilitate the discovery of highaffinity metal chelators
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