Abstract
Iron(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (FeTPPS) is used as non-physiological metalloporphyrin model for the natural iron (III)-protoporphyrin IX (FePPIX) resulting from hemoglobin degradation to investigate ligand binding reactions in aqueous solution. Studies were conducted on the interaction of FeTPPS with Chloroquine, Quinine, and Quinidine, which are historically the most common quinoline-based drugs used to treat malaria, an infectious disease afflicting several hundred millions every year worldwide, mainly in tropical regions. Using UV-Visible spectrophotometry, the binding reaction was studied at pH 7.40 in purely aqueous solution, and in aqueous solution containing NaNO3 at concentration of 0.1 M. Fitted titration curves obtained were in agreement with experimental data according to a formation scheme of 1:1 complex (1 FeTPPS μ-oxo-dimer: 1 Antimalarial). Values of apparent binding constant (K) obtained were between 4.3 × 103 M-1 to 7.59 × 104 M-1, demonstrating that FeTPPS and the antimalarials formed stable complexes. The stability of the complex decreased when NaNO3 was added to the solution. This ionic strength dependence was ascribed to electrostatic effects. Quinine and Chloroquine interacted with FeTPPS stronger than Quinidine did. Chloroquine showed the strongest affinity to FeTPPS. These findings revealed the influence of steric and stereochemical factors. Molecular electrostatic potentials (MEP) calculated with Hartree-Fock theory argue in favor of π-π and electrostatic interactions between reaction partners as driving forces for the complex formation. In the case of FeTPPS: Chloroquine interaction, it is suggested that an intramolecular hydrogen bond is formed between phenyl and quinuclidine N-H+ as additional force stabilizing the complex. Analysis of crystallographic data using the Cambridge Structural Database (CSD) gave evidence of the hydrogen bond formation between phenyl and N-H+ groups in 370 structures.
Highlights
Porphyrins and their derivatives are well-investigated molecules because of numerous potential applications from molecular electronics, over sensors and information storage elements, to medical agents [1] [2]
We report the results of the interaction of the iron porphyrin FeTPPS with Chloroquine, Quinine and Quinidine in pure aqueous solution and in aqueous solution containing NaNO3
We can see that (Figure 3) no absorption of quinoline-based antimalarials was observed in the visible region as illustrated with Chloroquine, whereas the spectrum of FeTPPS has a marked peak in the Soret Band around 413 nm and a small peak around 565nm (Figure 3)
Summary
Porphyrins and their derivatives are well-investigated molecules because of numerous potential applications from molecular electronics, over sensors and information storage elements, to medical agents [1] [2]. The binding of FePPIX and its derivate Iron(III)-deuteroporphyrin IX (FeDPIX) to quinoline-based antimalarials Chloroquine, Quinine and Quinidine (Figure 2) have been demonstrated in vitro using mixtures of water with ethylene glycol, propylene glycol and DMSO [4] [11] [12] [15] [16] [17] [18]. Quantitative studies of the interaction of the iron (III) porphyrin FePPIX in pure aqueous solution, the physiological medium, are hampered by the tendency of FePPIX to form aggregates considerably larger than dimers. We report the results of the interaction of the iron porphyrin FeTPPS with Chloroquine, Quinine and Quinidine in pure aqueous solution and in aqueous solution containing NaNO3. Complexes of FeTPPS with Nitric Oxide and Per-O-methylated-Cyclodextrin have been used as primary models for FePPIX in ferrihemoproteins [5] [6]
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