Synthesis, Structural Characterization, and Computational Studies of Novel Diiodine Adducts with the Heterocyclic Thioamides N-Methylbenzothiazole-2-thione and Benzimidazole-2-thione:  Implications with the Mechanism of Action of Antithyroid Drugs

• Published in: Inorganic chemistry 2005-11, Vol.44 (23), p.8617-8627
• Main Authors: Corban, Ghada J, Hadjikakou, Sotiris K, Hadjiliadis, Nick, Kubicki, Maciej, Tiekink, Edward R. T, Butler, Ian S, Drougas, Evangelos, Kosmas, Agnie M
• Format: Article
• Language: English
• Subjects: Antithyroid Agents - chemistry; Antithyroid Agents - pharmacology; Benzimidazoles - chemical synthesis; Benzimidazoles - chemistry; Benzothiazoles - chemical synthesis; Benzothiazoles - chemistry; Conductometry; Crystallography, X-Ray; Iodine - chemistry; Models, Molecular; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Spectrum Analysis, Raman
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/ic0484396

Reaction of N-methylbenzothiazole-2-thione (C8H7NS2 or NMBZT) with diiodine produced the charge-transfer (ct) complex [(NMBZT)·I2] (1). NMBZT reacts with diiodine in the presence of FeCl3 in a molar ratio of 3:6:1 and forms the ionic complex {[(NMBZT)2I+]·[FeCl4]-} (2) together with {[(NMBZT)2I+]·[I7]-} (2a) iodonium salt. The reaction of benzimidazole-2-thione (C7H6N2S or MBZIM) with diiodine on the other hand results in the formation of the ct {[(MBZIM)2I]+[I3]-}·[(MBZIM)·I2] (3) compound. The compounds have been characterized by elemental analyses, DTA-TG, FT-Raman, FT-IR, UV−vis, and 1H NMR spectroscopies, and X-ray crystal structure determinations. Compound 1, C8H7I2NS2, is orthorhombic with a space group Pna21 and a = 12.5147(13) Å, b = 22.536(3) Å, c = 4.2994(5) Å, and Z = 4. Compound 2, C16H14Cl4FeIN2S4, is monoclinic, space group C2/c, a = 35.781(2) Å, b = 7.4761(5) Å, c = 18.4677(12) Å, β = 107.219(1)°, and Z = 8. Compound 3, C21H18I6N6S3, monoclinic, space group P21/n, a = 14.0652(11) Å, b = 22.536(3) Å, c = 4.2994(5) Å, β = 99.635(7)°, and Z = 4, consists of two component moieties cocrystallized, one neutral which contains the benzimidazole-2-thione (MBIZM) ligand bonded with an iodine atom through sulfur, forming a compound with a “spoke” structure [(MBZIM)I2] 3a, while the other is the ionic complex {[(MBZII)2I+}·[I3]-} (3b). The X-ray crystal structure of 1 shows a bond between the thione-sulfur atom and one of the iodine atoms in an essentially planar arrangement. In the cation of 2, an iodine is coordinated by two thione-sulfur atoms in a linear arrangement but the molecule is not planar. For the first time in the solid state a spoke−ionic mixed complex has been characterized in 3. One component of the structure is a molecular diiodine adduct, i.e., [(MBZIM)I2] (3a), with a linear coordination geometry in a decidedly planar arrangement, and the other component is an ionic adduct {[(MBZIM)2I]+·[I3]-} (3b) with the cation having an arrangement similar to that found for 1. Theoretical calculations using density functional (DFT) and ab initio Hartree−Fock theory have been carried out for 1 and 3a,b. The results are consistent with the experimental data. Conclusions on the behavior of a thioamide, when used as an antithyroid drug, have also been made.