Design and characterisation of novel hexadentate 3-hydroxypyridin-4-one ligands

Hexadentate 3-hydroxypyridin-4-ones with high iron(III) affinity: Design, synthesis and inhibition on methicillin resistant Staphylococcus aureus and Pseudomonas strains

“…The bidentate ligand-containing conjugates form a range of complexes, including the 1:1, 2:1 and 3:1 ligand:iron species; however at the low concentrations utilised, the 1:1 complex is likely to be the dominant species [24] and this is the species transported by the monocatecholate carriers, Cir and Fiu. These bidentate complexes will bear a net positive charge, in contrast to the iron(III)-hexadentate hydroxypyridinones described in this work, where the iron(III) is completely complexed by the hydroxypyridinone rings and the resulting complex has a net charge of zero [17,25].…”

“…All the hexadentate chelators were fully characterized by 1 H NMR, 13 C NMR, mass spectrometry and highresolution mass spectrometry. In comparison with our previously reported hexadentate HPOs [17,18,25], structures of the hexadentate HPOs synthesized in this article could be changed by introducing different substituents on the side chain and position-1 on pyridinone ring. Thus, a large number of hexadentate HPO analogues possessing different partition coefficients can be prepared, which is useful in the establishment of a structureeactivity relationship.…”

New Tris(hydroxypyridinones) as Iron and Aluminium Sequestering Agents: Synthesis, Complexation and In Vivo Studies

“…Specifically, some polydentate 3,4-HP-based chelators have been developed, that is, tetradentate ligands, to be used alone or in combinedligand therapeutic protocols, [12,13] and hexadentate ligands, to fulfil the metal coordination by the formation of 1:1 M 3 + -L (metal-ligand) complexes with improved thermodynamic and kinetic stability. [14,15] Herein, we report results on the development and study of two new hydroxypyridinone-based tripodal hexadentate chelators with three 3,4-HP units appended to amino-triscarboxylic anchoring skeletons, namely, nitrilotriacetic acid (NTA) and nitrilotripropionic acid (NTP) (Scheme 1a). Besides the design and the synthetic strategy of the new compounds, this paper is focused on the study of the physicochemical properties of ligands and complexes in solution, especially those related to the lipo-hydrophilic character and complexation ability towards ironA C H T U N G T R E N N U N G (III) and aluminiumA C H T U N G T R E N N U N G (III), as well as some modelling studies on the iron complex structures.…”

MALDI mass spectrometric determination of dendritic iron chelation stoichiometries and conditional affinity constants

“…We have recently demonstrated that hexadentate hydroxypyridinone chelators possess strong iron(III) affinities, 10 MALDI mass spectrometry was adopted in our pervious study and the observed species correspond to the complexation profile in solution. 8 Upon binding an iron(III) ion, three protons are released from each hexadentate chelator and the mass of the protonated dendrimer can be calculated as…”

“…The relationship of the total iron and free iron [Fe] can be generated. The theoretical and experimental data are overlapped to minimize the least square differences of the experimental data and the theoretically distribution curves derived from Equations (1)-(3) by using Eqn (10), where V exp is the normalized mass data value of the corresponding species, V theo is the theoretical percentage value of the same species obtained from the molar fraction plot.…”