Synthesis of New Peptide‐Based Ligands with 1,2‐HOPO Pendant Chelators and Thermodynamic Evaluation of Their Iron(III) Complexes**

Abstract

Hydroxypyridones (HOPOs) are an important class of chelating compounds. They bind strongly to hard metal ions such as Fe(III). Here we present the solid-phase synthesis of peptides containing 1,2-HOPO moieties linked through a carboxylic acid placed at position 4 of the ring. A total of four ligands were studied, two bidentate and two hexadentate. The latter were synthesized by both stepwise and convergent strategies. The ligands and their complexes were characterized from the physico-chemical perspective. The pKa values for all ligands showed their total deprotonation at pH lower than the physiological pH. The formation constant of the Fe(III) complex (log β) ranged from 23.66, corresponding to ligand A, to 27.63, corresponding to ligand C. The pFe 3 + at pH = 7.4 revealed that ligands B and C had a strong iron affinity (26.91 and 28.58, respectively), thereby making them suitable for further study in therapeutic applications.

Synthesis of temporin L hydroxamate-based peptides and evaluation of their coordination properties with iron(iii )

“…Each peptide placed in the cuvette was titrated with various volumes of a fresh solution of FeCl 3 solution in MeOH to achieve Fe 3+ and peptide ratios between 0 and 0.8. 43 Each UV-vis spectrum was recorded in a wavelength ranging from 280 to 700 nm. During the titration, upon the addition of ferric iron to peptides, the solutions changed from colorless to red/pink.…”