Date on Master's Thesis/Doctoral Dissertation

12-2011

Document Type

Doctoral Dissertation

Degree Name

Ph. D.

Department

Chemistry

Committee Chair

Buchanan, Robert Martin

Author's Keywords

Benzimidazole; Cisplatin; Metal complexes; Pyridine complexes; Pt (II) complexes - antitumor; Transition metal

Subject

Benzimidazoles; Cisplatin; Pyridine

Abstract

This study expands our efforts to make a new class of Pt (II) compounds analogous to cisplatin and its derivatives using sterically hindered ligands. Pt compounds in this series have been synthesized using specially designed pyridine and benzimidazole ligands. These heterocycles, amide functionalized at position 2 with aryl and alkyl pendants, rapidly change their mode of coordination depending on the pH of the medium. These ligands, synthesized using condensation chemistry, also coordinate to Co(II), Ni(H), Cu(lI), and Zn(1I) generally as anionic bis-chelates through the benzimidazole nitrogen and the carbonyl oxygen, creating a four-coordinate complex with the exception of an unusual trigonal bipyramidal Zn(H) complex. I H NMR temperature studies reveal that these ligands interconvert between imide and amide isomers and that electron withdrawing pendants favor amide isomers. Crystal structures of Co(II) and Ni(1I) complexes of N-( I-methylbenzimidazol-2-yl)cyclohexanecarboxamide, for example, show two ligands bind per metal ion when reacted with acetate and nitrate salts. The bischelates of these Ni(1I) complexes also show expansions of their coordination spheres from four to five-coordinate. Furthermore, these Ni(II) bis-chelated complexes possess square planar or distorted 4-coordinate geometries. The synthesis and properties of several new Pt (II) complexes containing these ligands will be presented. A second generation and novel complex class containing metal-binding, linker and recognition domains is reported. Both classes of Pt complexes were obtained using a synthetic methodology which favors the cis isomers. The second generation complex crystallizes in the monoclinic space group P2dn with lattice dimensions a = 17.7393(5) A, b = 11.4632(3) A, c = 19.3959(5) A and ~ = 99.794(3)°. These complexes have been characterized using physical methods that include X-ray crystallography, IH &13C NMR, Mass spectrometry, UV and IR spectroscopies. Complexes similar in structure to cisplatin and carboplatin show varying cytotoxic properties toward different cancer cell lines. Additionally, some of these new Pt complexes show comparable and promising cytotoxicity against prostate cancer cell lines.

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