Reevaluation of organosulfur heats of formation resulted in the conclusion that the sulfur-sulfur bond of aliphatic disulfides is nearly 15 Kcal/mole stronger than the disulfide carbon-sulfur bond energy. Semi-empirical calculations using AM1, MNDO and MINDO/3 from the AMPAC program package confirmed these results and clarified their relative impact on organosulfide and disulfide properties. / Existing organoselenium bond energy data were also reevaluated and erroneous assumptions discovered. New bond energy estimates were made via a new procedure. It was concluded that the selenium-selenium bond is also stronger than the selenium-carbon of aliphatic diselenides. / The above results led to the conclusion that loss of molecular dichalcogen from molecules such as disulfides or diselenides is favored over the stepwise loss of a single chalcogen by about 40 Kcal/mol. Loss of molecular diselenium from dibenzyl diselenide is reported. The average carbon-selenium bond energy of the latter is calculated to be only 27 Kcal/mol. / The preparation of 2-thiatriselenides (RSeSSeR) and 2,3-dithiatetraselenides (RSeSSSeR) has been achieved from selenosilanes. The products were characterized by $ sp{77}$Se NMR and the trends of chemical shifts were analyzed. / The preparation of the first selenium transfer reagents, including the first unsymmetrical chalcogen transfer reagent, is reported. Their use to effect the synthesis of 2-selenatrisulfides (RSSeSR) is also reported. Low temperature $ sp{77}$Se NMR was used to elucidate the reaction mechanism and characterize several intermediates such as selenuranes, selenonium ions and azole selenides. In addition, 2,3-diselenatetrasulfides (RSSeSeSR) were characterized by $ sp{77}$Se NMR.

Nucleic acids are responsible for the storage of genetic information and directly participate in gene replication, transcription and expression, and thereby the control of nucleic acids leads to the regulation of genetic information flow and gene expression. Meanwhile, many non-coding RNAs are in-volved in signal transduction directly. Moreover, nucleic acid-based therapeutic strategies have been lead to drug candidates and are effective tools in drug discovery and disease study at the molecular level as well as the genetic level. Consequently, the 3D crystal structure study and related functional research on natural and unnatural nucleic acids have become very popular area, expanding their potential appli-cation in medicinal and biological chemistry. Since oxygen, sulfur, selenium and tellurium are in the same elemental family (VIA) in the peri-odic table, we anticipate that oxygen atoms in nucleic acids can most likely be replaced with the other chalcogen atoms without causing significant perturbations. Owing to the special K edge and unique properties of selenium, our lab has completed the chemical and enzymatic synthesis of unnatural nucle- ic acids with selenium substitutions at various positions. The selenium functionality in nucleic acid is es-sential for nucleic acids’ structural determination at the atomic level. Additionally this novel elemental feature (atomic size and electronic nature) provides nucleic acids with unique properties. In addition, the selenium derivatization can facilitate crystal growth. Other chalcogen elements are applicable as well to modify nucleic acid, generating some special biofunctions, like the application of phosphorthioate oligonucleotide in gene therapy. This dissertation will outline the chalcogen elements (especially selenium) modifications of nucleic acids, including syntheses strategies, structure studies and potential therapeutic applications. Our research work here tries to show that (1) Selenium functionality is able to facilitate the crystal structure determination, by both helping solve phase problem and accel-erating crystal growth; (2) Selenium functionality can generate special capability to nucleic acids, like improved base pair fidelity, novel atomic interactions and feasibility to be biological chemistry probe; (3) Selenium derivatized oligonucleotides are extraordinary good candidates for gene therapy discovery, considering its stability under nuclease environment. In general, these atom-specific replacements gen-erate a new paradigm of nucleic acids. INDEX WORDS: Nucleic acid, Selenium, X-ray crystal structure, Biofunction, Therapeutics

ABSTRACT This work examined the role of micro-organisms in the biogeochemical cycling of selenium within the benthic ecosystem of Lake Macquarie, a coastal lake in New South Wales with a history of anthropogenic heavy metal contamination. Certain micro-organisms possess the ability to oxidise or reduce selenium (Fleming and Alexander, 1973; Doran and Alexander, 1977), and microbial volatilisation of selenium from contaminated sediments and soils utilising naturally-occurring microflora has been shown in overseas research (Thompson-Eagle and Frankenberger, 1992) to be a potentially effective remediation strategy. In examining the impact of micro-organisms upon the oxidation state of selenium in Lake Macquarie sediments, this work also investigated and characterised selenium (and heavy metal) concentrations, speciation and geochemical phase associations (an indicator of potential bioavailability) in the sediments. Seven distinct bacterial species indigenous to Lake Macquarie were identified in this work with the ability to reduce selenium as selenite to elemental selenium, and selenium as selenate to organic forms of selenium, including volatile methylated selenium compounds. Metabolic parameters calculated for these organisms compared favourably with those reported in the literature by other researchers. Mixed populations of sediment micro-organisms were also isolated and studied in this work for their selenite and selenate reduction abilities. Total reduction of added selenite at levels up to 100 mg/L was recorded for a number of the organisms studied in this work. A maximum specific uptake rate for selenite of 3040 mgSe(IV).(gcells)-1.(h)-1 for one isolate (Shewanella putrefaciens) was determined, exceeding rates reported in the literature by other authors. Use of the indigenous micro-organisms from Lake Macquarie for the bioremediation of selenium containing waste streams was also examined in this work and selenium reduction in an immobilised cell reactor was demonstrated with such organisms. Concentrations, speciation, sediment core profiles and geochemical phase associations for selenium were determined for sediment samples collected at a variety of sites throughout Lake Macquarie and from Wyee Creek, a selenium-impacted fluvial input to the lake. The maximum concentration of selenium obtained in this work for the lake proper was 4.04 mg/kg, considerably lower than values reported over a decade ago (Batley, 1987) but consistent with reported reductions of selenium input into the lake from the lead-zinc smelter. Selective extraction methodology (Tessier et al. and BCR methods) studied geochemical phase association of selenium in Lake Macquarie sediments and found up to 44% of selenium was in bioavailable forms. Of interest and environmental concern was levels of selenium found in sediments of Wyee Creek, which previously received overflows from the ash dam associated with the Vales Point Power Station. Sediment selenium levels of up to 300 mg/kg were determined for this creek. These were an order of magnitude or more greater than those recorded for the lake itself and are of concern as to the potential impact on benthic organisms and those animals, including humans, who consume them. While this work can only provide a 'snapshot' of conditions within Lake Macquarie at the time of the sampling events recorded herein, it does make several important contributions to the understanding of selenium biogeochemistry in Lake Macquarie. These include: presentation of the hypothesis that selenium levels in surficial sediments being deposited in the north of the lake have decreased in recent years as a result of selenium reduction measures undertaken by the lead-zinc smelter; determination that up to 44% of selenium in surficial sediments from the lake is associated with sediment phases in which selenium has the potential to become remobilized and hence possibly bioavailable; and documentation of selenium concentrations in Wyee Creek, identifying the area as having selenium concentrations an order of magnitude or more greater than the lake itself. Concerning the role played by microorganisms in the biogeochemical cycling of selenium in Lake Macquarie, this work has: identified individual isolated and mixed cultures of bacteria that can reduce selenium as selenite to lower oxidation states; identified individual isolated and mixed cultures of bacteria that can reduce selenium as selenate to lower oxidation states; identified volatile methylated selenium compounds in the headspace gases of microorganisms reducing selenate; determined Minimum Inhibitory Concentrations for selenate and selenite for organisms isolated from Lake Macquarie; identified casein hydrolysate as a preferred carbon source for selenium reducing microorganisms from Lake Macquarie; and demonstrated that bioremediation of selenium contaminated waste streams using indigenous organisms from Lake Macquarie is feasible on the laboratory scale. Further research areas suggested by this work include: additional investigations of elevated selenium levels in Wyee Creek sediments; determination of the role of microbes in in-situ selenium reduction; and optimisation of selenium biotreatment/bioremediation of selenium-containing waste streams and sediments. In summary, this work, in rejecting the null hypothesis that the oxidation states of selenium in sediments from Lake Macquarie, NSW, are independent of microbial activity and accepting the alternate hypothesis that these oxidation states are not independent of microbial activity, contributes to the understanding of the role of microorganisms in the biogeochemical cycling of selenium, having applicability to both the specific ecosystem of Lake Macquarie, NSW, and also to selenium cycling in the environment in general. In addition, this work has identified selenium contamination in Wyee Creek, one of the fluvial inputs to Lake Macquarie, which was previously been undocumented in the literature and which may pose significant potential risk to humans and the ecosystem due to sediment selenium levels one or more orders of magnitude higher than those recorded in the lake itself. Finally, this work has also identified a number of microorganisms indigenous to Lake Macquarie with the ability to reduce selenium from toxic, mobile forms to less toxic, immobile or volatile forms, and these organisms have been shown to have the potential for use in treatment of selenium contaminated waste streams and also in the bioremediation of selenium-contaminated sediments.

Thesis (Ph.D.)--University of Western Sydney, Nepean, 1998. / Includes bibliographies.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniversitet, 2007. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xv, 162 p. : ill. (some col.), maps (some col.). Includes abstract. Includes bibliographical references (p. 157-162).

Thesis (M.S.)--University of Alabama at Birmingham, 2007. / Description based on contents viewed Oct. 3, 2008; title from PDF t.p. Includes bibliographical references (p. 39-53).

Thesis (M. Sc.(Agric.))(Animal Science)--University of Pretoria, 2004. / Title from opening screen (viewed March 14, 2005). Summaries in Afrikaans and English. Includes bibliographical references.

Thesis (MMedVet (Bov.))-University of Pretoria, 1998. / Includes bibliographical references.