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Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies

View Article: PubMed Central - PubMed

ABSTRACT

A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

No MeSH data available.


Related in: MedlinePlus

Spectrophotometric titration curves for uranyl with L1H6, conditions: [UO22+] = [L1H6] = 2 × 10−5 M; μ = 0.10 M KCl; T = 298.2 K; pH range = 2.1–10.2; 5.0 vol % methanol aqueous solution.
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f5: Spectrophotometric titration curves for uranyl with L1H6, conditions: [UO22+] = [L1H6] = 2 × 10−5 M; μ = 0.10 M KCl; T = 298.2 K; pH range = 2.1–10.2; 5.0 vol % methanol aqueous solution.

Mentions: The uranyl affinities of ligands L1–3H6 were determined by performing spectrophotometric titrations using a 1:1 metal to ligand ratio to avoid the decomposition of free ligand at high pH values. Maintaining this ratio may also ensure the formation of mononuclear complexes. The poor solubility of the uranyl complexes requires 2 × 10−5 M analyte and 5 vol % starting methanol for solvating the neutral uranyl complexes during titration. The uranyl titration spectra with L1–3H6 ligands generally exhibit similar absorption spectra within 250–400 nm, with a maximum absorption within 280–350 nm range and subtle shoulder at long wavelengths (Fig. 5 and Figures S5 and S6). These features resemble those of the free ligands and are attributed to π → π* transitions. The uranyl complexes routinely form [UO2(L1–3H4)] have been generated at pH 4.5, uranyl titration with all ligands displayed increased intensity from pH 4.5 to pH 7.5 for L1H6, pH 8.1 for L2H6, and pH 8.4 for L3H6. These finding indicated the deprotonation of more acidic two protons of the ligands and complexation of the uranyl ion [UO2(L1–3H2)]2−. Subsequently, the intensity rapidly decreased until around pH 9.0 and slowly increased until around pH 10.0 with red shift of the absorption peaks. This result revealed the complete deprotonation of the ligands and binding to the uranyl ion [UO2(L1–3)]4−. The acid titrations (pH 4.6 to 2.0) were also carried out for each ligand. The intensity decreased until around pH 3.0 and slowly increased until around pH 2.0 with blue shift of the absorption peaks, which indicated that the protonation of the ligands and binding to the uranyl ion [UO2(L1–3H5)]+.


Novel enterobactin analogues as potential therapeutic chelating agents: Synthesis, thermodynamic and antioxidant studies
Spectrophotometric titration curves for uranyl with L1H6, conditions: [UO22+] = [L1H6] = 2 × 10−5 M; μ = 0.10 M KCl; T = 298.2 K; pH range = 2.1–10.2; 5.0 vol % methanol aqueous solution.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC5037427&req=5

f5: Spectrophotometric titration curves for uranyl with L1H6, conditions: [UO22+] = [L1H6] = 2 × 10−5 M; μ = 0.10 M KCl; T = 298.2 K; pH range = 2.1–10.2; 5.0 vol % methanol aqueous solution.
Mentions: The uranyl affinities of ligands L1–3H6 were determined by performing spectrophotometric titrations using a 1:1 metal to ligand ratio to avoid the decomposition of free ligand at high pH values. Maintaining this ratio may also ensure the formation of mononuclear complexes. The poor solubility of the uranyl complexes requires 2 × 10−5 M analyte and 5 vol % starting methanol for solvating the neutral uranyl complexes during titration. The uranyl titration spectra with L1–3H6 ligands generally exhibit similar absorption spectra within 250–400 nm, with a maximum absorption within 280–350 nm range and subtle shoulder at long wavelengths (Fig. 5 and Figures S5 and S6). These features resemble those of the free ligands and are attributed to π → π* transitions. The uranyl complexes routinely form [UO2(L1–3H4)] have been generated at pH 4.5, uranyl titration with all ligands displayed increased intensity from pH 4.5 to pH 7.5 for L1H6, pH 8.1 for L2H6, and pH 8.4 for L3H6. These finding indicated the deprotonation of more acidic two protons of the ligands and complexation of the uranyl ion [UO2(L1–3H2)]2−. Subsequently, the intensity rapidly decreased until around pH 9.0 and slowly increased until around pH 10.0 with red shift of the absorption peaks. This result revealed the complete deprotonation of the ligands and binding to the uranyl ion [UO2(L1–3)]4−. The acid titrations (pH 4.6 to 2.0) were also carried out for each ligand. The intensity decreased until around pH 3.0 and slowly increased until around pH 2.0 with blue shift of the absorption peaks, which indicated that the protonation of the ligands and binding to the uranyl ion [UO2(L1–3H5)]+.

View Article: PubMed Central - PubMed

ABSTRACT

A series of novel hexadentate enterobactin analogues, which contain three catechol chelating moieties attached to different molecular scaffolds with flexible alkyl chain lengths, were prepared. The solution thermodynamic stabilities of the complexes with uranyl, ferric(III), and zinc(II) ions were then investigated. The hexadentate ligands demonstrate effective binding ability to uranyl ion, and the average uranyl affinities are two orders of magnitude higher than 2,3-dihydroxy-N1,N4-bis[(1,2-hydroxypyridinone-6-carboxamide)ethyl]terephthalamide [TMA(2Li-1,2-HOPO)2] ligand with similar denticity. The high affinity of hexadentate ligands could be due to the presence of the flexible scaffold, which favors the geometric agreement between the ligand and the uranyl coordination preference. The hexadentate ligands also exhibit higher antiradical efficiency than butylated hydroxyanisole (BHA). These results provide a basis for further studies on the potential applications of hexadentate ligands as therapeutic chelating agents.

No MeSH data available.


Related in: MedlinePlus