The non-sustainable nature of fossil fuels as feedstocks for valuable chemicals, combined with the environmental damage caused by their extraction and combustion, increases the need for the development of a bio-based economy. While industry and public opinion are slowly shifting towards acceptance of this change, efficient technologies for the depolymerization and subsequent separation of lignocellulosic biomass fall short of the ever-increasing demand. In particular, there are currently no efficient, sustainable mass scale methods to convert lignin, the most abundant source of aromatic molecules on Earth. The use of oxovanadium(V) catalyst complexes to aerobically cleave C‒C bonds has been demonstrated previously and remains an attractive option for incorporation into a sustainable bio-based economy. Two new triphenoxyamine oxovanadium(V) catalysts with reduced steric bulk and electron density at the metal center (vs. previously reported complexes) have been synthesized for aerobic oxidative diol C‒C bond cleavage. These complexes were found to cleave less activated and more complex substrates than previous generations, including cyclic diols and polyalcohols. Several insights into the reaction pathways of this class of complex were elucidated through a series of kinetic studies. Experimentally, the rate of C‒C bond cleavage of both pinacol and hydrobenzoin was determined to be unaffected by substitution of the O‒H bonds with deuterium, suggesting that currently proposed mechanisms need to be revised. Multiple catalytic regimes were observed during anaerobic reaction, which were not altered significantly by the brief addition of O2. A series of density functional theory calculations revealed a plausible mechanism for the trialkoxy complex that did not involve a proton transfer in the rate determining step, instead suggesting that ligand-arm dissociation-reassociation play a significant role in the reaction. In a second project, new bisphenoxyamine-N-appended base ligand with less steric hindrance and electron density at the metal center, has been synthesized utilizing similar design principles gained from work with triphenoxyamine catalysts. When reacting with lignin model compound 1,2-diphenyl-2-methoxyethanol, this new complex displays a higher selectivity towards aldehydes and esters (relative to previous bisphenoxyamine-N-appended ligands), leading to a higher rate of C‒C bond cleavage. Investigations into the mechanism of bisphenoxy complexes, as well as the role of the N-appended base in reactivity, were performed using substrate pre-complexed bisphenoxy compounds. Thermolysis at 60 and 100 °C produced almost exclusively oxidative C‒H bond cleavage product benzyl methyl ether, with evidence for overoxidation product benzoic acid observed. Thermolysis of labelled substrate pre-complexed revealed that N-appended base may impede C‒C cleavage of 1,2-diphenyl-2-methoxyethanol by forcing the methyl ether away from the oxovanadium(V) center. Through the use of these multidentate phenoxyamine ligands, advances have been made towards sustainable oxovanadium catalysis in the pursuit of efficient and selective lignocellulosic disassembly for a sustainable bio-based economy.

Functional Dendritic Structures from Bile Acids: Supramolelcular Hosts, Light Harvesters and Drug Carriers Chapter 1. An Overview of Functional Dendrimers. Dendrimers are welldefined, hyperbranched macromolecules that are prepared by highly controlled iterative methodologies. The ability to modulate the size, molecular weight, chemical functionalities and the position and number of functional groups in dendrimers make them promising candidates for a wide variety of applications. In this chapter, three areas 1) hostguest chemistry 2) light harvesting and 3) drug delivery, where dendrimers are increasingly finding applications, are discussed with selected examples. Chapter 2. Hydroxyl Terminated Dendritic Oligomers from Bile Acids: Synthesis and Properties. Bile acids are excellent building blocks for dendritic construction because of their many interesting features. They are readily available, chiral, facial amphiphiles with complementary functionalities. Moreover, due to the large size of the bile acid units, a dendritic structure consisting of only a few such repeat units can have an extended structure with multiple functionalizable groups. (figure 1) The high reactivity of the chloroacetyl group has been exploited for the synthesis of bile acid based first and second-generation dendrons with glycolate linkers and multiple hydroxyl groups. The synthesis involves only a few steps and avoids the use of protecting groups for the terminal hydroxyl groups. The synthesis of a bile acid tetramer is shown here as an example (Figure 1). Carboxyl protected cholic acid was reacted with chloroacetylchloride to generate the trischloroacetylated derivative. This compound on reaction with excess of sodium cholate generated the tetramer with nine hydroxyl groups via displacement of the chlorides. In order to synthesize higher generation dendritic structures, perchloroacetylated firstgeneration dendrons were first synthesized. These were subsequently reacted with excess of sodium deoxcholate to generated secondgeneration dendrons with multiple hydroxyl groups (Figure 2). All the compounds were characterized by H NMR, C NMR, IR, ESIMS/MALDI-TOF, HPLC and elemental analysis(wherever possible) Figure 2. Structure of tridecamer. These dendritic structures with facially amphiphilic bile acid backbones on the periphery were able to solubilize cresol red, a hydrophilic dye, in a nonpolar solvent, thus exhibiting reverse micellar characteristics. Chapter 3. Multiple Naproxen Appended Bile Acid Dendrimers as Light Harvesters and Drug Carriers. Part I. Synthesis and Characterization. Using the same synthetic strategy as in Chapter 2, bile acid based dendritic structures appended with multiple bioactive (S)naproxens were generated as potential drug carriers. The construction of these dendrimers was accomplished using per(chloroacetylated) bile acid dendrons and conveniently displacing all the chlorides with naproxen units. Since naproxen is photoactive with a high fluorescence quantum Figure 3. Structures of secondgeneration dendrimers and a monomer with multiple naproxens. yield, the photophysical properties of these multichromophoric dendrimers could be further explored (Figure 3). By functionalizing the carboxyl group on the side chain with an anthracenyl moiety the energy transfer properties of these dendrimers could be studied. In this section the synthesis of first and secondgeneration dendritic structures with multiple naproxen units at the periphery and benzyl/anthracenyl moiety on the side chain are described (Figure 3). Model compounds using monomeric bile acid units were synthesized for comparison with the dendritic structures. All the compounds were characterized by H NMR, C NMR, IR, ESIMS/MALDITOF, HPLC and elemental analysis (wherever possible). Part II: Absorption, Fluorescence and Intramolelcular Energy Tranfer Studies. Absorption studies showed that the molar extinction coefficients increase linearly with increasing number of naproxen units and the absorption spectra of anthracenyl moiety remain unchanged in all the dendritic systems. These indicated the absence of ground state interaction between the chromophores. In the 275-290 nm absorption region, the molar extinction coefficient of naproxen is much greater than that of the 9-anthracenylmethyl chromophore. Hence excitation in this region would mainly excite the naphthalene chromophore. Upon excitation at 275 nm, there was predominant emission from the anthracenyl moiety in the dendritic structures (containing both chromophores) and the fluorescence intensity increased with increasing number of naproxens(Figure4). This indicated that the dendrimers act as efficient light harvesters with energy transfer from naproxen to anthracene (intramolecular nature of the energy transfer was confirmed through control experiments). (Figure 4: Refer PDF File) The fluorescence and energy-transfer properties were further investigated by time-resolved fluorescence spectroscopy. The presence of fast decay component(s) in the naproxen decay in dendritic structures (containing both chromophores) indicates that its fluorescence is quenched in the presence of anthracene due to energy transfer ((λex 275 nm, λem 350 nm (Figure 5). This was further confirmed by monitoring the fluorescence of the sensitized anthracenyl chromophore (λex 275 nm, λem 436 nm) which exhibited a fast rise comparable to he quenched naproxen lifetime(s). The efficiency of energy transfer was estimated by donor quenching by both steadystate and timeresolved techniques. The dendritic structures exhibited high energy transfer efficiencies (~ 70 – 90 %) with the net efficiency decreasing from the first to second-generation. Part III. In vitro Study of Hydrolysis of Naproxen Appended Bile Acid Prodrugs by Chemical and Enzymatic Methods. The naproxen appended bile acid dendrimers consist of hydrolyzable ester and glycolate linkers. Hence the chemical stability and enzymatic degradation with possible release of naproxen was studied. Two compounds, monomer appended with two naproxens and trimer with four naproxens have been used for the initial investigations (Figure 6). The compounds were found to be highly stable towards chemical hydrolysis and did not show any hydrolysis in phosphate buffer, pH = 7.4 even after 7 days. Since the compounds were not soluble in water, Arabic gum and TritonX were used for emulsification. Figure 6. Structures of monomer and trimer. (Refer PDF File) The enzymatic hydrolysis of the compounds was then studied using Candida Rugosa Lipase. In both cases, there was slow hydrolysis of the substrate and intermediates were formed (with release of free naproxen) which were detected by HPLC (reverse phase column with a UV detector). The trimer underwent much slower hydrolysis compared to the monomer. The intermediates were characterized by absorption and mass (ESIMSQTOF) spectrometry.

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