Antikanser Aktiviteye Sahip Kondanse Triazol Türevlerinin Kristal Yapılarının X-Işını Toz Kırınımı Yöntemiyle Belirlenmesi

Abstract

The results of the anticancer activity studies on 1,2,4-triazoles and their fused derivatives showed promising results. Epidemiological studies have shown a reduction in the incidence of cancer in individuals using long-term, regular nonsteroidal antiinflammatory (NSAI) drugs (ibuprofen, flurbiprofen, naproxen). In this thesis the crystal structures of new anticancer active fused triazole derivates compounds carrying NSAI drugs residuals were determined by X-ray powder diffraction method. The compounds structurally analyzed are divided into two groups. The first group of the compounds (Compound 1, Compound 6 and Compound 7) contain 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines ring system, the second group of the compounds (Compound 2, Compound 3, Compound 4 and Compound 5) contain 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles ring system and functional groups. The functional groups of the compounds contain stoichiometric oxygen, carbon, fluorine, ibuprofen, chlorine, sulfur and/or hydrogen. The synchrotron measurements of the Compound 1, Compound 2, Compound 3 and Compound 4 samples were done at the beamline 11-BM at Argonne National Laboratory through the mail-in program. The laboratory X-ray powder diffraction data of the Compound 5, Compound 6 and Compound 7 samples were collected with “Bruker D8 Advance” X–ray diffractometer. The stages of crystal structure determination from X-ray powder diffraction data which were followed are: data collection, unit cell determination and space group assignment (indexing), whole pattern decomposition (Pawley or LeBail refinement), structure solution by using simulated annealing method and Rietveld refinement. At the indexing stage TOPAS 4.2, McMaille, DICVOL, ITO and EXPO programs were used. At the structure solution stage, the indexing solutions obtained by TOPAS 4.2 were used, the structure solutions were applied via DASH or FOX programs with simulated annealing method. The fragments of the molecules for the structure solutions were prepared with the Avogadro or Gaussian program. The Rietveld refinements were performed with FullProf or TOPAS academic program by using soft restraints for bond lengths, bond angles and sometimes for planar groups. By help of using soft restraints in the Rietveld refinements, chemical reasonable structure solutions were obtained. After the Rietveld refinements of the crystal structures, good agreements between calculated and experimental powder diffraction patterns were obtained with acceptable R-factors and χ2 values. The Compound 2 and Compound 3, Compound 6 and Compound 7 were found isostructural. Especially the crystal structures obtained from limited laboratory X-ray powder diffraction data were intended to verify by theoretical methods. The experimental and optimized structures were compared and similar structures were observed. The results of the study of the Compound 1, Compound 2 and Compound 3 were published in 2017 at “Powder Diffraction” journal.