Syntheses and characterizations of ruthenium complexes as antitumor agents and osmium dinitrogen complexes

Abstract

This thesis is divided into two main parts. The first part is concerned with the synthesis and characterization of some ruthenium complexes that are potential antitumor agents. In the second part, the synthesis and characterization of some osmium µ-dinitrogen complexes bearing salen ligands are described. In part one, new ruthenium complexes containing 2,2’-bi-2-imidazoline (biml) and bis(1-pyrazolyl)methane (bpm), trans-[RuIII(biml)2(Cl)2]PF6, cis-[RuII(biml)2(DMSO)2](ClO4)2, mer-[RuIII(Cl)3(DMSO)(bpm)] and [RuIII(acac)2(bpm)]BF4 have been prepared. The complexes have been characterized by IR, elemental analysis, electrospray ionization mass spectrometry (ESI-MS), UV-Vis, 1H NMR and cyclic voltammetry. X-ray crystallographic studies revealed that all the dimethyl sulfoxide ligands are S-bonded. A series of ruthenium monocarbonyl complexes have also been synthesized from [RuII(CO)(H2O)(Cl)2]n. The structures of mer-[RuII(pz)3(CO)(Cl)2] and cis-[RuII(cyclen)(CO)(Cl)]Cl (pz = pyrazole, cyclen = 1,4,7,10-tetraazacyclododecane) have been determined by X-ray crystallography. In addition, by using [RuII(CO)3(Cl)2]2 as the starting material, a number of ruthenium tricarbonyl complexes, [RuII(CO)3(L1)(Cl)] (L1 = bis(1-pyrazolyl)methane, ethylenediamine, picolinate, quinaldate and 5-chloro-8-quinolinolate) have been prepared. The structures of these complexes have been determined by X-ray crystallography, and three CO ligands are in facial coordination. Furthermore, the X-ray structures of trans-[RuIII(5mepz)4(Cl)2]Cl and [RuII(5mepz)6](Cl)2 have been resolved. The cytotoxicities of some of the ruthenium complexes have been examined using human carcinoma cell lines. The Ru(III) complexes containing four pyrazole and its derivatives show high cytotoxicities and anti-angiogenic properties. Besides, trans-[RuIII(biml)2(Cl)2]PF6 has higher potency than cis-[RuII(biml)2(DMSO)2](ClO4)2. Conversely, it is found that the carbonyl complexes do not have significant cytotoxicities. In the second part, a series of novel osmium µ-dinitrogen complexes, cis-,cis-[{OsII.5(salchda)(L2)}2(µ-N2)]PF6, have been synthesized by ligand-induced N···N coupling reaction of [OsVI(N)(salchda)(H2O)]PF6 (salchda = N,N'-bis(salicylidene)-o-cyclohexyldiamine dianions) (L2 = pyrazole, 3-methylpyrazole, 3,5-dimethylpyrazole, imidazole, 1-methylimidazole, 2-methylimidazole, 4-methylimidazole, 1,2-dimethylimidazole, 2-methyl-2-oxazoline and 4-methylthiazole). These complexes have been characterized by IR, elemental analysis, electrospray ionization mass spectrometry (ESI−MS) and UV-Vis-NIR. The cyclic voltammetry of these complexes exhibit reversible OsIII,III/OsIII,II and OsIII,II/OsII,II couples. The ν(N≡N) of these complexes occur at around 1960 cm-1 and show the expected shift to lower frequency upon 15N labelling. The pyrazole and 4-methylthiazole complexes have been characterized by X-ray crystallography. Their N≡N distances are 1.150(16) and 1.164(5) Å respectively. These mixed-valance complexes have also been characterized by UV-Vis-NIR spectroscopy. The structure of cis-,cis-[{OsIII(salchda)(4metz)}2(µ-N2)](PF6)2 (4metz = 4-methylthiazole) has been determined by X-ray crystallography and the N≡N distance is 1.156(12) Å. A monomeric complexes, trans-[OsIII(salchda)(4metz)(CH3CN)]PF6, has been synthesized and characterized by X-ray crystallography. It exhibits reversible OsIV/III and OsIII/II couples in the cyclic voltammetry.