Synthesis and DNA binding of CIS and TRANS-RuCl2 (DMSO)4

The synthesis of both cis and rrans-RuCIJDMSO)J has been reported in literature, and is currently the only way of acquiring these compounds. Because these rnetallo­ drugs have shown similar antirumor properties to cisplatin, they are currently under investigation for use in clinical trials as potential chemotherapeutics. It is believed that these drugs act in a way similar to cisplatin by causing intrastrand crosslinking of adjacent guanine residues in DNA. In an auempt to better understand any RulDNA interaction for these compounds, both cis and rrans-RuCl2(DMSO)J were synthesized with reasonable yields (-40%). The compounds were then characterized by nuclear magnetic resonance (NMR), combustion elemental analysis (CHN), and ultraviolet­ visible spectroscopy (UV -Vis). These compounds were then reacted in aqueous solution with various types of DNA (calf thymus, nucleosides, and a synthetic 11 base oligonucleotide). The products of these reactions were separated and collected using either two different types of high performance liquid chromatography (HPLC), ethanol precipitation, or centrifugation filtration. Collected products were then analyzed using inductively coupled plasma atomic emission spectroscopy (lCP-AES) and electrospray ionization mass spectrometry (ESI-MS). Reactions with calf thymus DNA proved very hard to work with and only allowed for some indications of the reaction kinetics. Focus was then directed towards nucleosides and the II base oligonucleotide. No Ru-bound DNA was seen using ESI-MS, but the HPLC traces did indicate some RulDNA interaction. HPLC data suggested that this interaction may be reversible over time. The solution chemistry of me compounds was examined and compared to previous reports. It was discovered that the presence of phosphate buffer in solution with cis'-RuCI2(DMSO)J causes the formation of a ruthenium/phosphate dimer of proposed molecular formula Ru2POiDMSOMH20 )x. If this dimer is formed inside cells, it may be partially responsible for the lower antitumor activity of cis-Ru02(DMSO)J compared to trans­ RuCl,(DMSO)4' CV of Author Thomas F, urrun \ \ ' '1 , raised in Gardn r. i\'I A b. his parents D:1\ id P. and Margaret C. O-Hearn Curran . He attended Gardner High School an came to CoIL)\.' ollege in the fall of 1998. Thomas majored in Physics as well a~ Chemistry-Biochemistry and \\ as a three time Dana Scholar. He vas e lected to the physics national honors <ociei v. ' igma Pi Sigma. and the national honors society Phi Bela Kappa, He began \\ orking for Dr. Shari U, Dunham during January or .200 I and continued \\ ar k on this project unti l graduating in the spring of .2002. During t i c fall of his ~ .nior year he harv estcd a d er in Unity Maine \\ ith a M. TC score of 166 7 ,). worthy of a top _00 ranking in t aine ~ skull and antler record t ook.