Roles of protons and structure in electron-transfer reactions of DNA and RNA.

摘要

The electron-transfer chemistry of DNA is a well-studied phenomenon; however, the mechanism of electron transfer is still unclear. Similar base oxidation pathways are thought to occur in both DNA and RNA; yet the electron-transfer chemistry of RNA has been studied in far less detail than that of DNA. Here, we study the role protons have on the electron-transfer chemistry of DNA to help identify its mechanism. We also examine how transition metal complexes can better characterize the structure of nucleotides, how those structures influence electron-transfer chemistry, and the specificities of oxidation.;The transition metal complexes that are being studied include the following ruthenium complexes, which have different binding modes and electronic properties: Ru(bpy)32+ (bpy = bipyridine), Ru(tpy)(bpy)O 2+ (tpy = 2,2',2"-terpyridine), Ru(bpz)32+ (bpz = 2,2'-bipyrazyl), and Ru(bpy)2(dppz)2+ (dppz = dipyrido [3,2-a:2',3'-c] phenazine). For proton-DNA studies, we will be using a simple DNA strand consisting of fifteen base pairs for comparison of the electrochemical techniques of cyclic voltammetry and digital simulation with the flash-quench technique. In order to better compare the electron-transfer chemistry that is occurring in both DNA and RNA, we will be using sequences based off of the human ferritin iron responsive elements (IREs) RNA. The human ferritin IRE RNA is a well-studied hairpin loop RNA that has a primary role in the regulation of ferritin and iron in the cell. Our lab has also developed a mutated ferritin IRE (MIRE), which has a more rigid structure but still contains the hairpin loop feature. The DNA used for comparison is based off of the template used for the transcription of IRE RNA and MIRE RNA.;After the ruthenium complexes' oxidation of DNA is confirmed and specified, these complexes' oxidation will be tested on RNA. Here, we show that transition metal complexes can oxidize RNA very similarly to DNA. We also show that some of these complexes, depending on their electronic properties, can footprint small molecules or proteins bound to RNA, which is useful for drug targeting-RNA studies. These oxidation studies of various nucleotides are also important due to their implications in aging, cancer, atherosclerosis, and neurological disorders.