Hydroxypyridinone-Based Metal Chelators towards Ecotoxicity: Remediation and Biological Mechanisms

Abstract

Hydroxypyridinones (HPs) are recognized as excellent chemical tools for engineering a diversity of metal chelating agents, with high affinity for hard metal ions, exhibiting a broad range of activities and applications, namely in medical, biological and environmental contexts. They are easily made and functionalizable towards the tuning of their pharmacokinetic properties or the improving of their metal complex thermodynamic stabilities. In this review, an analysis of the recently published works on hydroxypyridinone-based ligands, that have been mostly addressed for environmental applications, namely for remediation of hard metal ion ecotoxicity in living beings and other biological matrices is carried out. In particular, herein the most recent developments in the design of new chelating systems, from bidentate mono-HP to polydentate multi-HP derivatives, with a structural diversity of soluble or solid-supported backbones are outlined. Along with the ligand design, an analysis of the relationship between their structures and activities is presented and discussed, namely associated with the metal affinity and the thermodynamic stability of the corresponding metal complexes.

Hydroxypyridinone based chelators: a molecular tool for fluorescence sensing and sensitization

“…The design and preparation of compound 16 was done in isomerically pure form. A panel of probes was prepared where the Phe-residue in the tetrapeptide sequence central part (18,(21)(22), at the nitrogen-terminus (19) or the carbon-terminal lysine (20) was replaced by the dual fluorescent probe. A structural analog of 20 was represented by compound 23, where a protected Fechelating moiety (17) was incorporated into the structure.…”

“…The latest review on hydroxypyridinone was reported in 2022. 22 Most reviews focused on the therapeutical applications of HOPOs and other aspects. A review completely dedicated to the sensing properties has not been compiled despite the availability of several papers on the sensing aspect.…”

Inhibiting HCMV pUL89-C Endonuclease with Metal-Binding Compounds

“…Hydroxypyridinones have extensive applications in drug discovery for their unique ability to coordinate metal ions. − A carboxylic acid-modified 3-hydroxy-4-pyridone metal-binding pharmacophore (MBP) is present in FDA-approved antiviral drugs: dolutegravir ( 11 ), an HIV-1 INST inhibitor bearing a 5-carboxylate, and baloxavir ( 12 ), an influenza virus polymerase acidic (PA) endonuclease inhibitor containing a 2-carboxylate (Figure A). In addition, an extensive series of potent influenza virus PA endonuclease inhibitors exemplified by 13 features the HPCA metal chelating triad with a 5-carboxylic acid (Figure A) .…”

Synthesis of 5-Aroyl-2-aryl-3-hydroxypyridin-4(1H)-ones

“…3-Hydroxy-4-pyridones (3, are well-known bidentate chelation agents for many metals [1][2][3]. The first marketed drug possessing a 3,4-HPO scaffold, deferiprone (Ferriprox), is an iron chelating agent for treating thalassemia approved in 1999 (Figure 1).…”

“…The first marketed drug possessing a 3,4-HPO scaffold, deferiprone (Ferriprox), is an iron chelating agent for treating thalassemia approved in 1999 (Figure 1). Since the pyridine ring offers great possibilities for functionalization, a number of new 3,4-HPO-based polydentate chelators [2,4] and also 3,4-HPO-grafted fabrics for filtering uranium from wastewater [5] were developed afterward. Moreover, there are some natural examples of 3,4-HPOs, such as rubrifacine [6] and mimosine (leucenol), an amitotic agent first isolated from Mimosa pudica [7].…”