Radical mediated autoxidation is a pervasive phenomenon in commercial (i.e. rubbers, fuels, lubricants, etc.) and biological contexts (i.e. lipid peroxidation associated with neurodegeneration, cancer, and aging), which can be strategically managed with radical-trapping antioxidants (RTAs). While various phenol and polyphenol RTAs have enjoyed much academic fanfare, particularly in biochemical circles, there are other RTA scaffolds that tend to be overlooked despite possessing rather promising activity. Among these seldom studied RTA scaffolds is that of the tricyclic aromatic amine phenoxazine. The inherent reactivity of phenoxazines as RTAs was explored using a quantitative linear free energy approach. A library of phenoxazines was synthesized and Hammett correlations developed between BDE/(log kinhPhCl)/Eo and the electrophilicity substituent parameters (Σ σp+) served to unambiguously demonstrate that phenoxazine RTAs collectively represent the most reactive family of RTAs yet reported. The high inherent reactivity of phenoxazine RTAs towards peroxyl radicals necessitated the co- development of an approach to enable the accurate prediction of kinhPhCl based on the inhibition rate constants measured in hydrogen-bond accepting solvent mixtures containing chlorobenzene, 1,4-dioxane, and/or dimethylsulfoxide. The catalytic antioxidant activity of phenoxazines was established in hexadecane autoxidations at elevated temperatures, where they demonstrated superior activity to industry standard alkylated diphenylamine (ADPA), but also an inferiority to phenothiazine. These results combined with amine/nitroxide monitoring experiments serve to re-emphasize some current design considerations for high-temperature RTAs while challenging others. Lastly the activity of these as inhibitors of lipid peroxidation was assessed in liposomes and mammalian cell culture. The kinetics of peroxyl radical-trapping of the various phenoxazines in phosphatidylcholine liposomes enabled the quantitation of H- bonding interactions to the phosphate head groups of the phospholipids on RTA activity – which diminish the kinetics by up to two orders of magnitude relative to non-H- bonding hydrocarbons. The potency of these phenoxazines to subvert ferroptosis corresponds well with their inhibition activity in liposomes which further affirms the role that non-enzymatic autoxidation plays in this form of cell death.

This thesis reports the synthesis of new near infrared dyes in three chapters. The first two chapters outline the synthetic procedure for synthesizing mono- and pentamethine cyanine dyes. The initial chapter encompasses the synthesis of asymmetric monomethine dyes with red-shifted optical properties. The second chapter involves the synthesis and assessment of new symmetrical quinolin-4-yl and phenanthridin-6-yl pentamethine dyes as potential oxidative DNA cleavage agents. The last chapter of the thesis details the synthesis and evaluation of new phenoxizinum dyes as contrast agents for insulunomia, a pancreatic cancer. Furthermore, all new compounds were characterized via NMR and their coherent optical properties were obtained.

Autoxidation is a radical mediated chain-process that involves initiation, propagation, branching and termination reactions and is responsible for the spontaneous peroxidation of hydrocarbons, formally appearing as RH + O₂ → ROOH. Autoxidation is a consequentially damaging process in many domains, ranging from materials to automotive transportation to biology and medicine. One of the key intermediates in the propagation of autoxidation is the peroxyl radical (ROO•) which can be targeted by radical-trapping antioxidants (RTAs) that promote chain-termination, mitigating the damage of autoxidation. Chapter 1 lays out the fundamental chemistry of both autoxidation and RTAs as well as a history of the rational design of phenol and diarylamine-type RTAs. Lipid-peroxidation (i.e. autoxidation) is a key feature of ferroptosis which is a form of cell death that has been associated with many serious conditions such as ALS, Alzheimer's, Huntington's and Parkinson's disease, and lipid-soluble RTAs such as Vitamin E have been shown to acutely suppress ferroptosis. An aspect of RTA chemistry that has not been well studied/understood hitherto is their kinetic behaviour in phospholipid membranes, and we hypothesized that this would be a very relevant consideration for designing compounds that target lipid-peroxidation and ferroptosis. In Chapter 2 we systematically examine the kinetic behaviour for a series of hindered and unhindered phenolic RTAs in various mediums, particularly in phosphatidylcholine (PC) liposomes. The key chemical interaction in the PC membrane that fundamentally changed the observed kinetics of the phenolic RTAs is a very strong hydrogen-bonding interaction with the phosphate-diester headgroup that suppresses the phenols' ability to trap ROO•, an effect that was previously overlooked. In Chapter 3 we further expanded/validated the model by studying over 40 phenoxazine (PNX) and phenothiazine-based (PTZ) RTAs, which showed the quantitative/predictive capabilities of the H-bonding effect. By introducing a water-soluble co-antioxidant, Vitamin C (ascorbate), we were able to study many features of the PNX/PTZ radical intermediates with respect to their reactivity and dynamics. The PNX/PTZ were far more persistent than the Vitamin E analogue 2,2,5,7,8-pentamethyl-6-chromanol (PMC), meaning that they catalytically trapped lipid-peroxyls far more efficiently (i.e., higher turnover number). Additionally, there is strong evidence suggesting that the PNX/ascorbate synergism is a diffusion-controlled process. The study was further expanded to biological models. Ferroptosis in vitro was inhibited by every single one of these compounds, and there was a general positive correlation between RTA kinetics (kᵢₙₕ) and ferroptosis rescue potency (EC₅₀) as well as a positive correlation between lipophilicity (logP) and ferroptosis rescue potency. A lead PNX compound, 3-trifluoromethyl-8-tert-butylphenoxazine, was identified in this study on the basis of superior potency and metabolic stability. When used to treat mice with GPx4 deletion in kidneys, an in vivo model of ferroptosis, it was found to extend the life of the mice in a statistically significant fashion compared to the vehicle control. In Chapter 4 there is further elaboration on the dynamics of PNX/ascorbate synergy and a demonstration of the early works toward developing a drug-like-PNX ferroptosis inhibitor, based on the conclusions from the work in Chapter 3. In Chapters 5 and 6 the research is focused on the development novel RTAs for the application of inhibiting autoxidation in lubricants in high temperature environments. Heavy machinery and most transportation technologies require lubrication to aid safe and efficient movement, and these lubricants/greases are highly susceptible to autoxidation. Large quantities of RTA additives are expended to extend the service life of these materials and there is a constant appetite for innovation to find new and improved RTAs for improved economics and competitiveness. In Chapter 5 the behaviour of PNX and PTZ in a simulated high temperature lubricant autoxidations are analyzed, revealing that PNX is highly susceptible to direct O₂-mediated oxidation due to its rapid electron-transfer kinetics, while PTZ is far more resilient despite both compounds having nearly identical oxidation potentials. In Chapter 6, in this same context, previously unreported substituent effects are analyzed which significantly enhance the period of inhibition (tᵢₙₕ) for PTZ compounds. Particular alkyl substituents on the PTZ can increase the number of chains-trapped at high temperatures by fortuitous substituent oxidation that promotes termination, substantially improving their atom-economy. These findings prompt a broader critique of putative catalytic RTA mechanisms which have been taken for granted for nearly three decades.

Today, smart innovation has become an essential part of human life; thus, contemporary technologies are always looking for intelligent, responsive, and efficient materials to satisfy these demands. Consequently, synthetic "metals" or, more precisely, intrinsically conducting polymers (CPs) have begun to find a place as valuable and practical materials for a new generation of devices. Amongst all intrinsic conducting polymers, polyaniline (PANI) has attracted significant attention due to its outstanding air and moisture stability, simple preparation technique, and high electrical conductivity (chapter I). Chapter II represents the synthesis of a new PANI derivative that contains a phenoxazine unit co-polymerized with p-phenylenediamine derivatives by the Buchwald/Hartwig reaction. These polymers are soluble in many common organic solvents, which permit their full characterization and allow for solution processing. The polymers' optical properties mimicked PANI; however, they were more electrochemically stable and soluble compared to PANI. In addition, the analogous PANI emeraldine base forms a large bathochromic shift in the absorption spectra upon acidic doping to form analogues of PANI emeraldine salts. Chapter III describes our strategy to prepare economical, electrochemically stable, and processable PANI derivatives from carbazole and 1,4-aryldiamines for supercapacitor device. The polymers exhibit good solubility in various organic solvents, enabling a scalable spray-coating method to fabricate electrodes. The polymers were used to fabricate electrodes for supercapacitor devices and exhibit a maximum area capacitance of 64.8 mF cm−2 and specific capacitance of 319 F g−1 at a current density of 0.2 mA cm−2. Chapter IV MXene has been recently widely applied to energy storage devices due to its metallic conductivity and excellent electrochemical Activities. However, MXene sheets suffer from the restacking phenomena during cycling. Restacking restricts the ion diffusions and storage capability between the MXene layers, which lowers the accessible surface area. The restacking phenomena of MXene sheets was shown to be eliminated by the deposition of conductive polymers on the surface of MXene sheets.

This thesis gives a detailed description of the design and synthesis of new organic sensitizers for Dye sensitized Solar Cells (DSCs). It is divided in 7 chapters, where the first gives an introduction to the field of DSCs and the synthesis of organic sensitizers. Chapters 2 to 6 deal with the work of the author, starting with the first publication and the other following in chronological order. The thesis is completed with some concluding remarks (chapter 7). The DSC is a fairly new solar cell concept, also known as the Grätzel cell, after its inventor Michael Grätzel. It uses a dye (sensitizer) to capture the incident light. The dye is chemically connected to a porous layer of a wide band-gap semiconductor. The separation of light absorption and charge separation is different from the conventional Si-based solar cells. Therefore, it does not require the very high purity materials necessary for the Si-solar cells. This opens up the possibility of easier manufacturing for future large scale production. Since the groundbreaking work reported in 1991, the interest within the field has grown rapidly. Large companies have taken up their own research and new companies have started with their focus on the DSC. So far the highest solar energy to electricity conversion efficiencies have reached ~12%. The sensitizers in this thesis are based on triphenylamine or phenoxazine as the electron donating part in the molecule. A conjugated linker allows the electrons to flow from the donor to the acceptor, which will enable the electrons to inject into the semiconductor once they are excited. Changing the structure by introducing substituents, extending the conjugation and exchanging parts of the molecule, will influence the performance of the solar cell. By analyzing the performance, one can evaluate the importance of each component in the structure and thereby gain more insight into the complex nature of the dye sensitized solar cell. / QC 20110505