The chemical modification of carbohydrates has been used extensively in order to investigate specificity of binding in biological processes. Inclusion of one or more fluorine atoms into a carbohydrate molecule can have minimal impact upon molecular recognition due to the small size of the fluorine atom, making fluorinated carbohydrate analogues an important class of biological probes.

Thesis (Ph.D)--Civil and Environmental Engineering, Georgia Institute of Technology, 2008. / Committee Chair: Saunders, F. Michael; Committee Member: Huang, Ching-Hua; Committee Member: Hughes, Joseph; Committee Member: Loeffler, Frank; Committee Member: Pullman, Gerald; Committee Member: Spain, Jim. Part of the SMARTech Electronic Thesis and Dissertation Collection.

A novel class of potential positron emission tomography (PET) radiotracers for imaging aminopeptidase N (also known as APN or CD13) and cannabinoid type 1 (CB1) receptors were designed and synthesised with an efficient chemical strategy. Both targets have remarkable diagnostic and therapeutic potential, in fact the CD13 receptors are over-expressed during tumour angiogenesis and the CB1 receptors are highly expressed in the brain playing important functions in several pathophysiological processes. The target compounds were obtained by means of oxime-bio-conjugation between fluoro-deoxy-carbohydrates, used as prosthetic groups, and hydroxylamine-functionalised cyclic NGR (asparagine-glycine-arginine) motif sequences for CD13 receptor and rimonabant-type pyrazoles for the CB1 receptor. In particular, aminooxy-cyclic NGR peptides were conjugated with the novel prosthetic group 5-FDR (5-fluoro-5-deoxy-D-ribose) and the aminooxy- pyrazole-type cannabinoid molecules were conjugated with both 5-FDR and with FDG (2-fluoro-2-deoxy-D-glucose). 5-FDR proved to be superior to FDG, as the bioconjugation reaction occurred in milder conditions (room temperature vs 100 °C) and at faster rate. Furthermore, we observed that the rate of the oxime bond formation depends on the solubility of the aminooxy-functionalized core used. In fact, the bioconjugation with hydrophilic cyclic aminooxy-NGR peptides was faster than in the case of lipophilic aminooxy-pyrazoles (10 min vs 20-30 min). The receptor affinity is decreased in the case of the CB1 receptors after conjugation with the fluoro-carbohydrates. This is not observed with the conjugated NGR peptides, which maintain similar affinity for the CD13 receptor compared with the unconjugated NGR. In conclusion, we have developed an efficient strategy for the synthesis of a novel class of CD13 ligands, which may be also produced in radiofluorinated form, and explored a novel bioconjugation strategy for CB1 receptor ligands. Both may have important applications in the development of PET tracers.

Aquatic plants of the family Lemnaceae (e.g., duckweed) actively uptake, metabolize, and sequester pollutants in natural and engineered wetland systems. Numerous interrelated processes contribute to pollutant removal in wetlands; of these processes, interactions between organic pollutants and aquatic plants may be least understood. Research focused on (1) understanding parameters that affected uptake of fluorinated organic pollutants by Lemnaceae, (2) identifying plant processes involved in removal of wastewater-associated organic pollutants by Lemnaceae, and (3) assessing use of Lemnaceae callus cultures in understanding toxicity and metabolism of fluorinated organic pollutants by Lemnaceae. Through active plant uptake, Lemna minor rapidly removed 13 fluorinated phenols, with pseudo-first order rate constants of 0.20±0.04 d-1 to 0.84±0.07 d-1. Uptake rates depended on substituent type (i.e., trifluoromethyl- vs. fluoro-) and position, with slowest removal rates for di-ortho-substituted fluorophenols. Uptake rates decreased with increasing concentrations of fluorinated phenols; assessments of inhibition of plant oxygen production in conjugation with concentration studies indicated that concentration affected uptake rates even when Lemnaceae was not inhibited. Additionally, temperature dependencies of fluorinated phenol uptake by Lemnaceae were well represented by Arrhenius relationships; however, effects of temperature on plant activity were also observed in trends of uptake rates with temperature. Increasing uptake with decreasing concentration and increasing temperature, in addition to effects of plant inhibition, plant activity, and sorption on uptake, strongly emphasized the importance of plant metabolism in uptake of fluorinated phenols by Lemnaceae. Active plant uptake of wastewater-associated organic pollutants affected fate of fluoxetine, triclosan, and 2,4-dichlorophenoxyacetic acid, while passive plant removal processes contributed to fate of four of six wastewater derived organic pollutants. Consequently, plant-associated processes were important components of fate for over 50% of experimental wastewater-associated organic pollutants. Furthermore, assessments with Lemnaceae callus cultures indicated that callus cultures were generally more susceptible to inhibitory responses to fluorinated phenols than were Lemnaceae plants; however, metabolism of 3-trifluormethylphenol in Lemnaceae callus cultures and plants was similar, indicating that callus cultures may be valuable in plant metabolism studies. Research advances understanding of fate of organic pollutants in wetland systems, and thus has important implications for water quality, ecosystem health, and human health.

The synthesis of fluorinated cellulose derivatives was pursued for the purpose of investigating the effects of fluorine on the interfacial properties of cellulose derivatives, in multiphase materials. Synthetic approaches included: 1) the replacement of hydroxyl groups on cellulose with fluorine using fluoride displacement chemistry, or direct, one step fluorination 2) the replacement of hydroxyl groups on hydroxypropyl cellulose, HPC, with direct one step fluorinating agents, or 3) the conventional derivatization of cellulose with prefluorinated agents. Fluoride displacement of cellulose sulfonate esters was plagued low yields, and was therefore ineffective. Direct cellulose fluorination with aminofluorosulfur, and aminofluorocarbon reagents was effective for the surface fluorination of cellulose. However, the bulk, homogeneous fluorination of cellulose was complicated by side reactions that often precluded fluorination. Cellulose dissolved in DMAC/LiCI underwent simultaneous chlorination, and branching reactions when treated with dialkylaminosulfur trifluoride, DAST. Branching resulted from an anhydrous HF catalyzed trans-glycosidation reaction, which produced mainly (3-1,6 branching. Serendipitously, this discovery allows for the first known synthesis of long chain branched cellulose derivatives, with increased molar mass, and increased polydispersity. Treatment of HPC with DAST and FAR gave good levels of fluorination; however, the HF catalyzed gelation was always a complicating factor. The lower reactivity of FAR allowed for partial control of gelation with the use of nonnucleophilic bases. The easiest way to introduce fluorine was to perform conventional derivatization using prefluorinated reagents such as for the synthesis of fluorobenzyl cellulose. Mixed benzyl ethers of controlled fluorine content were made by altering the ratio of pfluorobenzyl chloride to benzyl chloride during reaction. 2-Dimensional NMR techniques were used to identify most proton and carbon resonances of cellulose and amylose fluorobenzyl ethers. Thermal analysis, solution analysis, and l3C spin-lattice relaxation experiments were used to compare the rod-like and coil-like behavior of the fluorobenzyl cellulose and amylose. Polycaprolactone, PCL, was blended with tri-O-benzylated cellulose with different degrees of fluorination. PCL was found to be immiscible with all derivatives, of fluorine contents from 0 % to as high as 11.7%. PCL did display some degree of mechanical compatibility with all derivatives. The greatest compatibility was found with benzylated cellulose having fluorine contents slightly below the maximum. It was found that no specific interactions were occurring between peL and fluorobenzyl cellulose. The enhanced compatibility of the mixed fluorobenzyl/benzyl cellulose ethers was postulated to arise from intramolecular interactions, which served to enhance the mixing of the copolymeric mixed benzyl ethers with PCL. / Ph. D.