Interaction of Iron(III)-5,10,15,20-Tetrakis (4-Sulfonatophenyl) Porphyrin with Chloroquine, Quinine and Quinidine

摘要

Iron(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (FeTPPS) is used as non-physiological metalloporphyrin model for the natural iron (III)-pro style="font-family:Verdana;">toporphyrin 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 world style="font-family:;" "=""> style="font-family:Verdana;">wide, 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 NaNO _{style="font-family:Verdana;">3} style="font-family:Verdana;"> at concentration of 0.1 style="font-family:Verdana;"> style="font-family:;" "=""> style="font-family:Verdana;">M. Fitted titration curves obtained were in agreement with experimental data according to a formation scheme of 1:1 complex (1 FeTPPS style="font-family:Verdana;">μ style="font-family:Verdana;">-oxo-dimer: 1 Antimalarial). Values of apparent binding constant (K) obtained were between 4.3 style="font-family:Verdana;"> style="font-family:Verdana;">× style="font-family:Verdana;"> style="font-family:;" "=""> style="font-family:Verdana;">10 style="font-family:Verdana;">3 style="font-family:Verdana;"> M style="font-family:Verdana;">-1 style="font-family:Verdana;"> to 7.59 style="font-family:Verdana;"> style="font-family:Verdana;">× style="font-family:Verdana;"> style="font-family:;" "=""> style="font-family:Verdana;">10 style="font-family:Verdana;">4 style="font-family:Verdana;"> M style="font-family:Verdana;">-1 style="font-family:Verdana;">, demonstrating that FeTPPS and the antimalarials formed stable complexes. The stability of the complex decreased when NaNO _{style="font-family:Verdana;">3} style="font-family:Verdana;"> 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? src="Edit_39638446-767f-4ddd-9a9e-42279ee88d61.bmp" alt="" />?and quinuclidine N-H style="font-family:Verdana;">+ style="font-family:Verdana;"> 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? src="Edit_7bd9aa0d-1b99-47e5-bd73-fcaf3ffbb33a.bmp" alt="" />?and N-H style="font-family:Verdana;">+ style="font-family:Verdana;"> groups in 370 structures.