Browsing by Subject "Photochemistry"

The ability of photocatalytic nanoparticles (NPs) to produce reactive oxygen species (ROS) has inspired research into several new applications and technologies, including water purification, contaminant remediation, and self-cleaning surface coatings. As a result, NPs continue to be incorporated into a wide variety of increasingly complex products. With the increased use of NPs and nano-enabled products and their subsequent disposal, NPs will make their way into the environment. Currently, many unanswered questions remain concerning how changes to the NP surface chemistry that occur in natural waters will impact reactivity. This work seeks to investigate potential influences on photoreactivity – specifically the impact of functionalization, the influence of anions, and interactions with biological objects - so that ROS generation in natural aquatic environments may be better understood.

To this aim, titanium dioxide nanoparticles (TiO2) and fullerene nanoparticles (FNPs) were studied in terms of their reactive endpoints: ROS generation measured through the use of fluorescent or spectroscopic probe compounds, virus and bacterial inactivation, and contaminant degradation. Physical characterization of NPs included light scattering, electron microscopy and electrophoretic mobility. These systematic investigations into the effect of functionalization, sorption, and aggregation on NP aggregate structure, size, and reactivity improve our understanding of trends that impact nanoparticle reactivity.

Engineered functionalization of FNPs was shown to impact NP aggregation, ROS generation, and viral affinity. Fullerene cage derivatization can lead to a greater affinity for the aqueous phase, smaller mean aggregate size, and a more open aggregate structure, favoring greater rates of ROS production. At the same time however, fullerene derivatization also decreases the 1O2 quantum yield and may either increase or decrease the affinity for a biological surface. These results suggest that the biological impact of fullerenes will be influenced by changes in the type of surface functionalization and extent of cage derivatization, potentially increasing the ROS generation rate and facilitating closer association with biological targets.

Investigations into anion sorption onto the surface of TiO2 indicate that reactivity will be strongly influenced by the waters they are introduced into. The type and concentration of anion impacted both aggregate state and reactivity to varying degrees. Specific interactions due to inner sphere ligand exchange with phosphate and carbonate have been shown to stabilize NPs. As a result, waters containing chloride or nitrate may have little impact on inherent reactivity but will reduce NP transport via aggregation, while waters containing even low levels of phosphate and carbonate may decrease “acute” reactivity but stabilize NPs such that their lifetime in the water column is increased.

Finally, ROS delivery in a multicomponent system was studied under the paradigm of pesticide degradation. The presence of bacteria or chlorpyrifos in solution significantly decreased bulk ROS measurements, with almost no OH detected when both were present. However, the presence of bacteria had no observable impact on the rate of chlorpyrifos degradation, nor chlorpyrifos on bacterial inactivation. These results imply that investigating reactivity in simplified systems may significantly over or underestimate photocatalytic efficiency in realistic environments, depending on the surface affinity of a given target.

This dissertation demonstrates that the reactivity of a system is largely determined by NP surface chemistry. Altering the NP surface, either intentionally or incidentally, produces significant changes in reactivity and aggregate characteristics. Additionally, the photocatalytic impact of the ROS generated by a NP depends on the characteristics of potential targets as well as on the characteristics of the NP itself. These are complicating factors, and the myriad potential exposure conditions, endpoints, and environmental systems to be considered for even a single NP highlight the need for functional assays that employ environmentally relevant conditions if risk assessments for engineered NPs are to be made in a timely fashion so as not to be outpaced by, or impede, technological advances.

Synthetic technologies can enable transformation of polarizable carbon–carbon (C=C) bonds and typically inert carbon–hydrogen (C–H) bonds into value-added diverse functional groups. Such technologies streamline access to complex molecules. In recent years, nitrogen-centered oxidants have garnered significant attention as a result of their ability to engage in selective and predictable synthetic transformations of these groups. Within this broad class of reactions, herein disclosed are investigations into two complementary approaches to access and utilize nitrogen-centered oxidants. Of these, the first approach advances iron nitrenoids to affect substrate-limited aziridination reactions of carbon–carbon double bonds. Specifically, Chapter two documents a best-in-class method that relies on limiting quantities of electronically varied styrene substrates to furnish synthetically useful aziridines in moderate to good yields under mild conditions. Subsequently, an orthogonal approach is developed – one that demonstrates the viability sulfamate esters as precursors to radical intermediates that template C–H functionalization reactions, with a focus on two group-transfer processes. Through this research, sulfamate esters have been identified as precursors to a modern class of nitrogen-centered oxidants, sulfamyl radicals. To enable broader usage, Chapter three discloses a new general and mild method to access substrates for this approach, employing inexpensive readily available sulfur trioxide sources with a wide range of ubiquitous amine and alcohol starting materials. The method relies on activation of a common intermediate, a sulfamic acid salt, to generate a large variety of N, O-disubstituted sulfamate esters and sulfamides. Studies described in Chapters four and five have resulted in mild strategies to generate sulfamyl radicals from sulfamate esters. These sulfamyl radicals engage in a rare, 1,6-hydrogen-atom transfer processes to affect position-selective C(3)-functionalization of aliphatic C–H bonds. More specifically, in Chapter four, this rare property is harnessed to establish a C(3)-selective xanthylation process. Enabled by visible-light, xanthylation of primary, secondary, and tertiary centers has been demonstrated with exquisite site selectivity. This investigation confirms the scientific insight that N-functionalized sulfamate esters enable complementary site selectivity to the previously known methods employing nitrogen-centered radicals. Additionally, this C(3)-xanthylation reaction can be combined with known technologies to affect formal C(sp3)–H azidation, thiolation, trifluoromethylthiolation, deuteration, allylation, and vinylation to generate molecular diversity from a common intermediate. Building on this foundation, Chapter five documents a photoredox-mediated method to generate the requisite sulfamyl radicals for site-selective carbon-carbon and carbon-oxygen bond forming processes. These investigations are the first of their kind to generate sulfamyl radicals from non-pre-oxidized sulfamate esters. These nitrogen-centered sulfamyl radicals, through the sulfamate-templated 1,6-HAT process, furnish secondary and tertiary carbon-centered radicals which can be trapped by Michael acceptors for a formal C(3)-alkylation. This process yields products with diastereoselectivity when engaging complex small molecules and enantioenriched Michael acceptors. Thereby, photoredox-mediated C(3)-selective alkylation process affords complementary position selectivity to that was achieved using known photoredox–mediated carbon-carbon bond-forming reactions. Finally, Chapter six describes electrochemical methods to generate the key sulfamyl radicals. Through this research, the first example of direct anodic oxidation of sulfamate ester anions is disclosed. The resultant sulfamyl radicals are utilized to affect novel C(3)-hydroxylation reactions. The electrochemical method is further extended to affect N-alkylation of sulfamate esters and sulfamides. Together, conceptual innovations have facilitated mild methods to access the nitrogen-centered oxidants for the functionalization of carbon–carbon (C=C) bond and radical-mediated functionalization of remote C(3)-aliphatic C–H bonds. These investigations enable synthetic disconnections that would be infeasible using previously established methods and provide efficient access to new chemical space.

Alcohols are ubiquitous motifs in the constellation of organic molecules. Given their prevalence in the world around us, new synthetic methods for forging new bonds on alcohols and preparing biologically active alcohol derivatives provide toolkits to solve challenging problems in organic chemistry. First, new bond-forming reactions with alcohols streamline access to complex alcoholic scaffolds commonly found in natural products and pharmaceuticals. Second, commercial and synthetic availabilities of alcohols offer rapid entry to new chemical space or expansion of pre-existing chemical space for biologically active molecules. My dissertation meets these motivations by masking alcohols as sulfamate esters, which are useful traceless linkers for C–H functionalizations and heteroatom-rich bioactive molecules.

The first part of my dissertation describes photochemically mediated, nickel-catalyzed γ-C(sp3)–H (hetero)arylation reaction between sulfamate esters and (hetero)aryl bromides to affect traditionally challenging net C(sp2)–C(sp3) cross-coupling reactions. Hitherto, there were no general methods that convert γ-C(sp3)–H bonds of aliphatic alcohols into γ-C(sp3)–C(sp2) bonds under mild photochemical conditions. Fortunately, this transformation was realized by photochemically generating nitrogen-centered free radical intermediate and introducing nickel catalyst to orchestrate radical relay/C(sp2)–C(sp3) cross-coupling cascade reaction. The second part of my dissertation applies sulfamate esters in the arenas of medicinal chemistry and biochemistry. Herein, these heteroatom-enriched masked alcohols were surveyed as a novel class of small molecule ligands for targeting disease-relevant non-coding RNAs. Informed by machine learning and rational molecular design, I developed a new generation of sulfamate esters that should herald a new chemical space for RNA therapeutics.