The first part of this thesis describes the efficient synthesis of several hypervalent iodine(III) compounds. Electron-rich diaryliodonium salts have been synthesized in a one-pot procedure, employing mCPBA as the oxidant. Both symmetric and unsymmetric diaryliodonium tosylates can be isolated in high yields. An in situ anion exchange also enables the synthesis of previously unobtainable diaryliodonium triflates. A large-scale protocol for the synthesis of a derivative of Koser’s reagent, that is an isolable intermediate in the diaryliodonium tosylate synthesis, is furthermore described. The large-scale synthesis is performed in neat TFE, which can be recovered and recycled. This is very desirable from an environmental point of view. One of the few described syntheses of enantiopure diaryliodonium salts is discussed. Three different enantiopure diaryliodonium salts bearing electron-rich substituents are synthesized in moderate to high yields. The synthesis of these three salts shows the challenge in the preparation of electron-rich substituted unsymmetric salts. The second part of the thesis describes the application of both symmetric and unsymmetric diaryliodonium salts in organic synthesis. A metal-free efficient and fast method for the synthesis of diaryl ethers from diaryliodonium salts has been developed. The substrate scope is wide as both the phenol and the diaryliodonium salt can be varied. Products such as halogenated ethers, ortho-substituted ethers and bulky ethers, that are difficult to obtain with metal-catalyzed procedures, are readily prepared. The mild protocol allows arylation of racemization-prone a-amino acid derivatives without loss of enantiomeric excess. A chemoselectivity investigation was conducted, in which unsymmetric diaryliodonium salts were employed in the arylation of three different nucleophiles in order to understand the different factors that influence which aryl moiety that is transferred to the nucleophile. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Accepted. Paper 5: Submitted. Paper 6: Manuscript.</p>

In the research reported in this dissertation, the concept of classic conjugate imaging, a non-tomographic nuclear medicine technique, is modified such that activity of a radiopharmaceutical distribution in the striata can be estimated. A mathematical model is developed that extended the application of classic conjugate imaging to estimation of two distinct and aligned activity distributions. Error analysis of the mathematical model is performed to characterize the accuracy of the model and to benchmark the limitations of the model. Phantom experiments are performed to demonstrate the practical application of the model and to evaluate its accuracy. A Monte Carlo simulation model of conjugate imaging of activity uptake in the striata of a primate is developed to evaluate the accuracy of the modified conjugate imaging technique as applied in the use of a dedicate conjugate imaging system. In addition, the simulation model is used to determine and characterize the shielding design of the small field of view gamma cameras comprising the dedicated conjugate imaging system. The application of scatter correction is investigated to address the downscatter of high-energy photon emissions into the photopeak window and the inclusion of scattered primary photons in the photopeak window. In this dissertation, it is shown that the modified conjugate imaging technique developed can be used to estimate accurately activity uptake in each of two distinct and aligned activity distributions. The accuracy of the technique is shown to be comparable to that of clinical quantitative SPECT. The modified conjugate imaging technique used with the dedicated conjugate imaging system may, therefore, be a viable quantitative nuclear medicine technique for activity estimation of radiopharmaceutical uptake in the striata of Parkinsonian and schizophrenic patients. The portability and low cost relative to SPECT systems make a dedicated conjugate imaging system advantageous for clinics with Parkinsonian and schizophrenic patients, who are unable to travel due to physical or mental limitation.

A series of laboratory and field investigations were carried out to elucidate the importance of natural organic matter in aquatic systems, i.e., trace element scavenging (e.g., 234Th) by exopolymeric substances (EPS), formation of biofilms, as well as interactions with 129I. A method involving cross flow ultrafiltration, followed by a three-step cartridge soaking and stirred-cell diafiltration, was developed for isolating EPS from phytoplankton cultures, especially in seawater media. EPS isolated from a marine diatom, Amphora sp. was then subjected to semi-quantitative (e.g., carbohydrate, proteins) and quantitative analysis (e.g., neutral sugars, acidic sugars, sulfate). It appeared that Th (IV) binding by EPS was dominated by the acidic polysaccharides of fraction. For EPS of biofilms collected from polluted streams, hydrophobic proteins were the most abundant components in EPS, followed by more hydrophilic carbohydrates. However, chemical composition of carbohydrates or proteins, i.e., monosaccharides and amino acids, respectively, varied with environmental conditions and substrata applied, which suggests that the formation of biofilms on different substrates is regulated by specific properties of microorganisms, environmental conditions and nature of substratum. No correlation between relative hydrophobicity of substratum and development of biofilm was found in this study. A sensitive and rapid GC-MS method was developed to enable the determination of isotopic ratios (129I/127I) of speciated iodine in natural waters. At the F-area of the Savannah River Site (SRS), iodine species in the groundwater consisted of 48.8 percent iodide, 27.3 percent iodate and 23.9 percent organo-iodine. Each of these iodine species exhibited vastly different transport behavior in the column experiments using surface soil from the SRS. Results demonstrated that mobility of iodine species depended greatly on the iodine concentration, mostly due to the limited sorptive capacity for anions of the soil. EPS, especially enzymes (e.g., haloperoxidases) could facilitate the incorporation of iodide to natural organic carbon. At high input concentrations of iodate (78.7 μM), iodate was found to be completely reduced and subsequently followed the transport behavior of iodide. The marked reduction of iodate was probably associated with natural organic carbon and facilitated by bacteria, besides inorganic reductants (e.g., Fe2 ) in sediments and pore water.

Pyrazoles have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The electrophilic cyclization of the acetylenic hydrazones initiated by molecular iodine could provide new ways of synthesizing biologically active 4-iodopyrazole derivatives, which are important precursors for the synthesis of highly substituted pyrazole derivatives. For this reason, we investigated the synthesis of 4-iodopyrazole derivatives, such as 1-aryl- 5-alkyl/aryl-4-iodopyrazoles, starting from phenylhydrazine and ,-acetylenic aldehyde derivatives. Initially, ,-acetylenic aldehydes were synthesized by formylation reaction of corresponding alkynes with DMF. Then, hydrazone derivatives of these aldehydes were prepared by heating them with phenylhydrazine in a neat manner at 55 &deg / C for 5 h. Finally, acetylenic phenyl hydrazone derivatives were subjected to electrophilic cyclization by treating with excess molecular iodine at 80 &deg / C for 3 h. Although electrophilic cyclization is commonly used in organic chemistry, it has not been employed for the cyclization of acetylenic phenyl hydrazones to pyrazole derivatives. Under optimized conditions, these reactions afforded 1-aryl-5-alkyl/aryl-4-iodopyrazole derivatives in moderate to good yields as the single or the major product of the reactions. In some cases, 1-aryl-5-alkyl/arylpyrazole derivatives resulted from these reactions as minor products. In conclusion, 4-iodopyrazole derivatives were synthesized for the first time directly from acyclic starting materials, ,-acetylenic phenylhydrazones and iodine, via electrophilic cyclization.

Quinolines have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess. The incorporation of the essential structural features of quinolines with a ferrocene moiety could provide new derivatives with unexpected and/or enhanced biological activities since several ferrocene derivatives have already been shown to be active against a number of tumors. For this reason, we investigated the synthesis of ferrocenyl-substituted quinolines, such as 2-ferrocenylquinoline, by employing the molecular iodine catalyzed reaction between enolizable aldehydes and ferrocenyl imines, which were prepared by the condensation reactions of ferrocenecarboxaldehyde with aniline derivatives. As anticipated, these reactions produced 2-ferrocenylquinoline derivatives. By employing this ethodology, we synthesized 2-ferrocenylquinoline, 6-chloro-2-ferrocenylquinoline, 6-bromo-2-ferrocenyl-quinoline, 2-ferrocenyl-7-methylquinoline and 2-ferrocenyl-3,7-dimethylquinoline. Due to the ready availability of ferrocenylimines and aldehydes, this practical onepot method represents a versatile synthesis of ferrocenyl-substituted quinolines.

Understanding future climate requires observations of trace species that can significantly influence the chemical or radiative properties of the atmosphere. The development of optical instruments, utilizing laser-systems as high-resolution light sources, for making in situ observations of trace species from either airborne- or ground-based platforms and results from field campaigns are presented. Glyoxal, the smallest \(\alpha\)-dicarbonyl, is a common product during the oxidation of volatile organic compounds. An instrument using the technique of laser-induced phosphorescence was developed to measure glyoxal at the part per trillion by volume (pptv) level from a tower in a forest canopy. The instrument was deployed as part of the Community Atmosphere-Biosphere INteractions EXperiment. The instrumental limit of detection is 3 pptv with a 1-minute acquisition time. Nearly continuous measurements of glyoxal ranging between 5 – 75 pptv were acquired throughout the campaign and vertical gradients in the forest canopy were found to be driven by elevated temperature. A sensitive instrument using laser-induced fluorescence detection was developed and deployed into remote marine environments to measure iodine monoxide (IO) where the mixing ratio is on the order of 1 – 5 pptv. The challenges and solutions of operating in this environment and results from the field and laboratory are discussed. Laboratory experiments show that IO can be generated from Laminaria digitata, a subtidal kelp species, in the presence of ozone. Observations of the isotopic composition of condensed and vapor water above a large summertime tropical convective system obtained by Hoxotope and ICOS instruments during the TC4 campaign are used to analyze the role of convection in the lower tropical transition layer (TTL). Regions of ice that are characteristic of either convective lofting or in situ condensation are encountered above an active deep tropical convective system. Ice is an important component of water transport models in the TTL, yet its isotopic composition is a relatively unconstrained parameter. The implications from the direct observations of the isotopic composition of ice during convection is explored with respect to transport models of water in the TTL. / Chemistry and Chemical Biology

This thesis addresses the synthesis of organic compounds, some of them are derivatives of compounds with DNA binding properties, for potential use in targeted nuclide therapy. The compounds synthesized therefore also need to contain potent nuclides. Here the nuclides considered are the radionuclide 125I, and the stable isotope 10B, which becomes radioactive upon neutron activation. 125I is an Auger-electron emitter, which emits particles that can travel only about 1-2 µm through human tissue and hence has to be delivered to the cancer cell nucleus to cause DNA damage. Neutron activated 10B emits highly cell killing α-particles and 7Li3+ ions, the application of which in Boron Nuclide Capture Therapy (BNCT) has proven very promising. The thesis can be divided into three parts: i) A nido-carborate, 7-(3´-ammoniopropyl)-7,8-dicarba-nido-undecaborate(-1), has been synthesized and radioiodinated for use as a pendant group for attachment of 125I to tumor-seeking macromolecules. Radiolabeling was achieved in greater than 95% yield. ii) Both enantiomers of m-carboranylalanine, a carborane analogue of phenylalanine, have been prepared in high enantiomeric excess, and are of potential interest in BNCT. The synthesis involved amination of the N-acyl derivative formed from [3-(1,7-dicarba-closo-dodecarborane(12)-1-yl)-2-propanoic acid and Oppolzer’s camphor sultam. iii) Derivatives of the DNA intercalating compounds 9-aminoacridine, daunorubicin and doxorubicin have been synthesized and labeled with 125I. The 9-aminoacridines were synthesised with a variety of functional groups such as carboxyl, amino and hydroxyl. The anthracylines daunorubicin and doxorubicin are efficient chemotherapeutic agents; the synthesis routes of ester, amide and amine derivatives of these compounds are presented. The Chloramine T method was used for the radioiodinations, and the radioiodination precursors of both the acridine and the anthracycline derivatives, were made to contain either a trimethylstannyl group or a phenolic substituent. In the former case the trimethylstannyl group was replaced by 125I, and in the latter case, the compounds were radiolabeled directly at the o- position to the phenolic hydroxyl group. Both methods gave high radiolabeling yields.

Tyrimo tikslas - išanalizuoti priešinės liaukos vėžiu sergančių pacientų, 2007–2010 metais gydytų brachiterapija, radioaktyviojo Jodo-125 šaltinių implantavimo kokybę ir nepageidaujamą poveikį. Įvade išdėstomi tyrimo tikslai bei uždaviniai, pateikiama literatūros apžvalga, kurioje apibendrinamos pagrindinės su nagrinėjama tema susijusios problemos. Atskirame skyriuje aprašyta tyrimo metodika. Disertacijoje išnagrinėta laisvų ir skirtingais atstumais į grandinėlę sujungtų Jodo-125 šaltinių implantavimo kokybės skirtumais gydant priešinės liaukos vėžį bei dozimetrijos po implantacijos atlikimo laiko įtaką implantacijos rezultatų vertinimui. Atskirai analizuotas nepageidaujamas gydymo poveikis. Įvertinti su priešinės liaukos vėžio gydymu Jodo-125 šaltiniais susiję šlapinimosi sutrikimai, išanalizuoti erekcijos sutrikimai ir juos sukeliančtys veiksniai po Jodo-125 šaltinių implantavimo, nustatytos kraujavimo iš tiesiosios žarnos dažnio sąsajos su klinikiniais ir dozimetriniais parametrais. / Aim of this study - to analyze implant quality and treatment toxicity in prostate cancer patients, treated with Iodine-125 seeds brachytherapy during the perios of 2007 – 2010 years. Initial dissertation chapters covers study aims and objectives. Literature data about prostate brachytherapy with Iodine-125 seeds are analysed. Material and methods are thorougly described. Data about implant quality differences in prostate cancer patients, treated with loose and linked seeds, are presented. Influence of postimplant dosimetry time to evaluation of Iodine-125 implantation results is analysed. Another part of this work is dedicated to toxicity of Iodine-125 seeds brachytherapy. Various aspects of treatment side effects are evaluated urinary disorders and erectile dysfunction. Association of risk of rectal bleeding after Iodine–125 brachytherapy with clinical and dosimetry parameters is assesed.

La famille des composés halogènes et inter-halogènes représentent des solides moléculaires adoptant des phases denses communes avec des solides moléculaires diatomiques comme l’azote et l’hydrogène. Parmi les transformations structurales et électroniques induites sous haute pression et observées dans ces solides, on note, entre autres, la dissociation moléculaire et la métallisation. De plus, l’étude des phases denses de l’iode a permis récemment l’observation d’une structure cristalline possédant une modulation dite incommensurable, c’est-à-dire une modulation possédant une périodicité différente de celle de la structure cristalline, jetant ainsi une lumière nouvelle sur le processus de dissociation moléculaire dans les solides halogènes. Dans ce mémoire, on propose d’étudier les changements structuraux dans monobromure d’iode (IBr), un composé inter-halogène possédant des propriétés structurales semblables à celles de deux composés halogènes, soit l’iode (I2) et le brome (Br2) sous leur forme solide. Des expériences de diffraction des rayons X de poudres en utilisant un rayonnement synchrotron ont été réalisées à température ambiante sur l’IBr en variant la pression jusqu’aux environs de 60 GPa. La nature chimique particulière du composé IBr a nécessité la mise au point de techniques de chargement d’échantillon destinées à préserver l’intégrité chimique de la substance utilisée. On rapporte également l’observation d’une phase de l’IBr présentant une modulation incommensurable. Les phases observées dans l’IBr permettent d’établir des parallèles avec les phases denses rapportées dans I2 et Br2 par le biais d’un modèle phénoménologique décrivant la séquence structurale des solides halogènes sous forme condensée.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv. / Härtill 4 uppsatser.