Author(s): Jerzy Leszczynski
This chapter reviews the results of molecular modeling of iodine-containing drugs. They are active ingredients of mixtures that in aqueous solutions consist of molecular iodine, bio-organic ligands, and potassium and lithium halogenides. In these drugs molecular iodine is in such an active form that after oral administration it minimizes toxic effects in humans. Previously it was shown that the active complex (AC) of the drugs contains molecular iodine that is located inside α-helix of dextrin and is coordinated by lithium halides and polypeptides (LiI5-α-dextrin polypeptide). In these types of complexes the electronic structure of the I2 molecule is different from the electronic structure of I2 in complexes with organic ligands, or in its free state. Interestingly, in the AC the molecular iodine exhibits acceptor properties with respect to polypeptides, and donor properties with respect to lithium halide. Our group was the first to propose the molecular model of active complexes of the iodine-containing drugs. This was based on the results of calculations performed using the DFT-B3PW91/midi approach. Model system of the water-glycine KI3-LiCl-ethanol was considered in this study. The calculations of the spectral parameters of the proposed structures are in good agreement with the experimental data of UV and IR spectral investigations. We have shown that α-dextrins ensure the presence in the studied mixtures of the three active centers located within the α-dextrin helix: molecular iodine coordinated lithium halogenides and polypeptides, triiodide, and lithium halogenides. Using UV spectroscopy, the interaction of α-dextrin-LiCl(I)-I2-polypeptid with the AGA nucleotide triplet was investigated. Comparison of the quantum chemical calculations carried out for electronic transitions obtained for the structure that models the interaction of α-dextrin-LiCl(I)-I2-polypeptid with the nucleotide triplet indicates that the DNA nucleotides can displace polypeptide and form stable complexes with molecular iodine and lithium halogenides. In such structures, molecular iodine binds both the nucleotide triplet and lithium halogenides. We have shown that the presence of molecular iodine is vital for activity of compounds that inhibit the active site of HIV-1 integrase. Iodine prevents the active site of integrase from the formation of a complex with HIV DNA and inhibits the active complex of integrase and viral DNA, becoming the center of another nucleoprotein complex, and binding together the active site of integrase and viral DNA.