Nick Hadjiliadis

A foreword highlighting the 12th Eurasia Conference on Chemical Sciences, EuAsC2S-12, held at Corfu, Greece.

Crystals of Ph3SnCl (1) were grown from a methanol/acetonitrile solution. Compounds [Ph3SnOH]n (2) and [(Ph2Sn)4Cl2O2(OH)2] (3) were crystallized from diethyl ether/methanol/acetonitrile and hot acetone/water solutions respectively, of the white precipitation, formed by adding KOH to solutions of 1 and [Ph2SnCl2] in 1 : 1 and 1 : 2 molar ratios respectively. Complex 1 was characterized by X-ray crystallography. X-ray structure determination of compounds 2 and 3 confirmed the previously reported identities. The molecular structure of 1, reported here, is a new polymorphic form of the known one for Ph3SnCl. Four independent [Ph3SnCl] molecules constitute the crystal structure of 1. The moieties are packed in two pairs in a tail-to-tail arrangement. Complexes 1–3 were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (human cervical), MCF-7 (breast, estrogen receptor (ER) positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (kidney carcinoma), 786-O (renal adenocarcinoma), K1 (thyroid carcinoma), and the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) versus, the normal immortalized human mammary gland epithelial cell line MTSV17 with a sulforhodamine B (SRB) assay. The results show potent cytotoxic activity of the complexes against all cell lines used, which was superior to that of cisplatin (CDDP). Compounds 1–3 showed higher activity against breast cancer cells MCF-7 (ER positive) than against of MDA-MB-231 (ER negative). These findings prompted us to search for possible interaction of these complexes with other cellular elements of fundamental importance in cell proliferation. The influence of these complexes 1–3 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX), as well as their binding affinity towards calf thymus-DNA, were kinetically and theoretically studied.

New antimony(III) chloride complexes with heterocyclic thioamides, thiourea (TU), 2-mercapto-5-methyl-benzimidazole (MMBZIM), 3-methyl-2-mercaptobenzothiazole (MMBZT), 2-mercaptopyrimidine (PMT), 2-mercaptopyridine (PYT) of formulae [SbCl₃(TU)₂] (1), [SbCl₃(MMBZIM)₂] (2), [SbCl₃(MMBZT)₂] (3), [SbCl₃(PMT)₂] (4), [SbCl₃(μ ₂-S)(PYT)₂] (5) were synthesized and characterized by elemental analysis, FT-IR and FT-Raman spectroscopies, and TG-DTA analysis. The crystal structure of 5 was also determined by X-ray diffraction. [C₁₀H₁₀Cl₃N₂S₂Sb] (5) crystallizes in space group C2/c, with a = 25.0169(10) Å, b = 9.7952(3) Å, c = 12.9329(5) Å, β = 109.702(4)°, and Z = 8. Crystals of 5 grown from acetonitrile solutions adopt a square-pyramidal geometry. The equatorial plane is formed by three chlorides and one sulfur atom from the thione ligand while the second sulfur is axial. The complexes were evaluated for their biological activities and compared with [SbCl₃(MMI)₂] (6) (MMI = 2-mercapto-1-methylimidazole) and other isostructural ones. The complexes showed moderate cytostatic activity against murine leukemia cells (L1210), murine mammary carcinoma cells (FM3A), human T-lymphocyte (Molt4/C8, CEM), and human cervix carcinoma (HeLa) cells. The chloro and iodo derivatives show better cytostatic activity than the bromo ones.

Ionic salts with the formulae {3[ΗBPMTU]⁺ · 3[X]⁻ · nH₂O} (BPMTU = 1,3-bis(3-pyridylmethyl)-2-thiourea, X = Cl⁻ and n = 1.5 (1), X = Br⁻and n = 1 (2), X = I⁻ and n = 1 (3)) were synthesized. The compounds have been characterized by elemental anaylses, TG-DTA, FT-IR, far-IR, Raman, ESI–MS and ¹H, ¹³C-NMR spectroscopic methods, and X-ray powder diffraction techniques. The crystal structures of 1 and 2 have also been determined by X-ray diffraction at 120(2) and 100(2) K, respectively. In 1, weak lp(Cl⁻) → σ*(O–Η) hyperconjugative interactions and OH ··· Cl⁻ hydrogen-bonding interactions lead to the formation of 1-D zigzag tetrameric complexes consisting of four chlorides bridged by four waters. Two oxygens of the bridging waters are also coordinated to Cl⁻ of the complex forming a parallelogram-shaped ring. Two chlorides are also anchored by NH ··· Cl⁻ hydrogen bonds in the free space between four tetrameric complexes. Heating 1 at 100°C for 4 h does not remove lattice water and the framework structure is retained. In 2, NH ··· Br⁻ hydrogen-bonding interactions stabilize the supramolecular architecture. In this case, however, only two bromides are bridged by one water through OH ··· Br⁻ hydrogen bonds. The supramolecular interactions existing in the crystal packing of the ionic salts have been analyzed at the density functional theories and ab initio CCSD(T) levels of the theory.

The reaction of di-iodine with N-methyl-2-mercapto-benzothiazole (NMBZT) in the presence of ferric tetra-phenyl-porphyrin chloride (FeTPPCl) in 6 ∶ 3 ∶ 1 (I₂ ∶ thioamide ∶ FeTPPCl) molar ratio yields a mixture of products consisting of the iodonium {[(NMBZT)₂I]⁺·[(I₇)⁻]}_n salt, 1, and the FeTPPCl complex, 2. The compounds were characterized by X-ray diffraction analysis. The crystal structure of 1 was identical to the one already published, while of compound 2 at 294(1) K re-evaluates previous work on it. The inhibition activity of the thioamide ligands (N-methyl-2-mercapto-benzothiazole (NMBZT), 2-mercapto-benzothiazole (MBZT), 5-chloro-2-mercapto benzothiazole (CMBZT), 2-mercaptothiazolidine (MTZT), 2-mercaptopyridine (PySH), thiourea (TU), 1,3-bis(3-pyridyl-methyl)-2-thiourea (PyTU), 2-mercapto-3,4,5,6-tetrahydropyrimidine (THP), 2-mercaptopyrimidine (PmSH), 6-propyl-2-thiouracil (PTU), 6-methyl-2-thiouracil (MTU), di-thiouracil-2,4 (DTUC), 2-mercapto-4-methyl-pyrimidine hydro chloride (MPmCl), methimazole (MMI), 2-mercapto-benzimidazole (BZIM), 5-nitro-2-mercapto-benzimidazole (NiMBZIM), 5-methyl-2-mercapto-benzimidazole (MBZIM), 2-hydroxy-pyrimidine (PmOH), 2-hydroxypyridine (PyOH)) against the catalytic oxidation of iodides by H₂O₂ in the presence of FeTPPCl (a model of the active site of Thyroid Peroxidase (TPO)) was measured as a result of the yield of I₃ ⁻ resulting from the oxidation of I⁻ and was also evaluated theoretically using electronic structure calculation methods (DFT). The compounds exhibiting high and intermediate degree of inhibition (between 27% and 17%) are MBZT, MMI, PySH, NMBZT, PmSH, MBZIM, NiBZIM and MTZT. The kinetic study of inhibition of lactoperoxidase (LPO) (a model of TPO) is based on the assessment of LPO activity in the presence of its inhibitors—the thioamide compounds. LPO activity can be assayed by measuring guaiacol (gua) peroxidation to tetraguaiacol in the presence of H₂O₂ . The results illustrated that the lowest IC₅₀ values (<10 μM) required for the LPO inhibition were exhibited by DTUC, NiMBZIM, MBZT, PySH thioamides. Low concentrations between 10 and 30 μM are obtained in the case of CMBZT, BZIM, MPmCl, PmSH, MBZIM, and MMI. DFT calculations of the geometric and energetic profiles threw light on the mechanism of the inhibition process by the thioamide compounds scrutinizing all crucial reaction steps and are in agreement with the experimental results.