Tungsten(0), palladium(II), and ruthenium(II) complexes with bio-compatible ligands for potential antitumor applications

In the past few decades, the use of transition metal complexes has contributed a great deal to currently used methods of treating diseases such as cancer. The discovery of chemotherapeutic drugs such as cisplatin have stimulated research to create complexes of platinum and of other metals that have better anticancer activity, improved drug delivery, and decreased toxicity to the patient. The ability of a potential antitumor complex to accomplish these goals will hinge not only on the identity of the metal center but on the choice of ligands that are bound to it.;Binuclear complexes that can bind to DNA twice will offer an inherent stability not afforded to mononuclear alternatives such as cisplatin. Several such binuclear complexes with palladium(II) have been synthesized and characterized. Substitution reactions of two of these complexes, Pd2(hdta) 2Cl2 and Pd2(egta)2Cl2, with inosine and 5'-guanosine monophosphate, a DNA nucleotide, have been performed and will be discussed herein. It was found that palladium(II) prefers to bind to N-7 sites on the purine, and substitution of a second nucleobase is not as facile as the first.;The second major project focuses on Group VI pentacarbonyl complexes with biologically relevant molecules that provide insight into the preferred sites of metallation for softer metal centers, such as tungsten(0). The synthesis and characterization of tungsten, molybdenum, and chromium pentacarbonyl complexes of pyrazine, pyrimidine, and triazine are discussed. Also, the tungsten(0) coordination sites of DNA bases guanosine, adenosine, and cytosine have been discerned, with the tungsten center coordinating to all available sp 2 nitrogen donors on the nucleobase. Finally, the unusual reaction of tungsten(0) pentacarbonyl with ribose itself, to form a Fischer carbene complex, will be investigated and a mechanism of reaction proposed.;Finally, ruthenium nitrosyls have captured great interest recently because the controlled release of nitric oxide via photochemical excitation can potentially be used for antitumor purposes. The third project covers characterization by NMR, IR, and ESI-MS of ruthenium(II) nitrosyl complexes of 2,2' -bipyridine and 2,2'-bis(4,5dimethylimidazole). The bis-substituted complexes of both ligands were found to exhibit differing fragmentation behavior under ESI-MS conditions, with respect to NO loss.