Infrared Multiple Photon Dissociation Action Spectroscopy of Sodium Cationized Halouracils: Effects of Sodium Cationization on Gas-Phase Conformation

摘要

The 5-halouracils and a variety of their complexes with metal cations have been shown to exhibit antitumor and antiviral activities. The cause of this activity is likely their ability to inhibit proper replication of DNA in tumors and infected cells. Currently 5-flourouracil is the most active agent employed in chemotherapy of colorectal cancer. While, there are also investigations into the ability of 5- and 6-haloruacils to control damage to healthy tissues during radiation therapy. The mechanisms for the antitumor and antiviral action of the halouracils are not well understood. As such the properties and characteristics of halouracils are of great interest in pharmaceutical research. The presence of metal cations in biological systems influences the conformational behavior of DNA by neutralizing the overall negative charge on DNA. Alkali metal cations including sodium do not frequently form covalent bonds, thus interactions are controlled by their noncovalent interactions. To better understand the influence of halogenation and noncovalent interactions with sodium cations on the gas-phase conformation of uracil, a comprehensive study on the structures and stability of all possible tautomers of the halouracils and sodium cation halouracil complexes has been undertaken here. The halouracils investigated in this study include: 5-fluorouracil (5FU), 5-chlorouracil (5ClU), 5-bromouracil (5BrU), 5-iodouracil (5IU), and 6-chlorouracil (6ClU), to allow examination of the identity and position of the halogen substituent on the structure and sodium cation binding affinities.