More

Abstract: The goal of this research was to design and study new systems of light activated molecules to deliver therapeutic agents. The impact of structural variation on spectroscopic properties as well as changes in photoinduced release of therapeutic molecules is reported herein. Chapter 2 reports complexes with the general structure [(bpy)2Ru(BL)Mn(CO)3Br](PF6)2 where the BL = 2,3-bis(2-pyridyl)pyrazine (dpp) and 2,2?-bipyrimidine (bpm) and bpy = 2,2?-bipyridine. Each of the bidentate bridging ligands exhibit different degrees of π-accepting ability when bridging two metal cations. The impact of the choice of bridging ligand on the photoactivated release of both CO and singlet oxygen (1O2) is reported. This report is the first example of a Ru(II),Mn(I) bimetallic complex with photoactivity in the phototherapy window (600 – 900 nm). The complexes were found to be stable in the dark and only released CO and singlet oxygen upon exposure to visible light. Chapter 3 extends the types of photoactivity of the complexes to include photoactivated DNA intercalation, along with CO release and 1O2 production. The framework used in this study was [(bpy)2Ru(tpphz)Mn(CO)3Br](PF6)2 where bpy = 2,2?-bipyridine and tpphz = tetrapyrido[3,2-a:2′,3′-c:3′′,2′′-h:2′′′,3′′′- j]phenazine. The previously studied [Ru(bpy)2(tpphz)](PF6)2 complex has the ability to intercalate between the base pairs of DNA, which can inhibit cell proliferation, as well as a high production efficiency of singlet oxygen when exposed to light. This study used the 4 framework studied in chapter 2 and incorporated the tpphz as a bridging ligand component. The purpose of this study was to test if the addition of the Mn moiety would continue to allow interaction of the tpphz to DNA or inhibit it. The study found that the complex is stable in the dark and inhibits DNA intercalation in the dark. When exposed to visible light, the Mn component dissociates from the complex, freeing the tpphz to then intercalate into DNA. To the best of our knowledge, this is only the second reported photoactivated intercalative binding of an inorganic complex to DNA. Chapter 4 investigates the structure of the Mn(I) component on the energy of light required for photoactivation. A series of Mn(I) monometallic and bimetallic complexes were investigated for their ability to release CO when exposed to visible light. The framework studied was fac-[Mn(BL)(CO)3Br] and fac-[Br(CO)3Mn(BL)Mn(CO)3Br] for the monoand bimetallic complexes respectively where BL = 2,3-Bis(2-pyridyl)-pyrazine (dpp), 2,3-Bis(2-pyridyl)quinoxaline (dpq), and 2,3-bis(2-pyridyl)benzoquinoxaline (dpb). The bridging ligands, which have increasing π-accepting ability from dpp ? dpq ? dpb, allowed for lower energy absorbance and lower energy light required to release the CO. All of these complexes were able to release all CO molecules using visible light, which extended into the phototherapy window for some of the structures studied.