Indiana University-Purdue University Indianapolis (IUPUI) / The purpose of this study is to further investigate the effect of using six different light source types with different light output intensities on the parameters of a mathematical model that predicts the DOC in VLDC’s. In this equation: D = Dp In(E0/Ec), D is the depth of cure in millimeters, E is the curing energy in J/cm2, Ec is the critical curing energy for the composite to reach a gel layer, and Dp is a characteristic coefficient. Three LED and three halogen dental curing units with different light output intensities were used to cure three shades (B1, A3, D3) of a hybrid resin composite. The exposure duration was at the intervals of 10, 20, 30, and 40 seconds for each sample setting. ISO scraping technique was performed to measure the depth of cure of each sample. Regression analysis was used to assess the fit of the proposed mathematical model D = Dp In(E0/Ec) to the experimental data obtained in this study. 72 For all the shade-light combinations; A3, B1, and D3 had significantly different regression lines (P < 0.05) with significantly higher Dp and Ec for B1 than A3 and D3. The only exceptions were for the Ec values between B1 and D3 in Allegro, Astralis 5, and Visilux 2 groups; and the Ec between A3 and B1 in Allegro group. The Dp and Ec parameters didn’t show significant differences between A3 and D3 shades in all the groups. Also, most of the significant differences for Dp values occurred in the B1 shade-light combinations; however, none of the D3 shade-light combinations showed significant differences for Dp. Several factors play combined influential effects on the kinetics of polymerization and depth of cure in VLDC’s. The shade has a more dominant effect on both parameters Dp and Ec than the curing light type or source output intensity. As we cure lighter shades “B1,” the effect of using different lights with different output intensities on the two parameters Dp and Ec will be greater and more significant than for darker shades “A3 or D3.” The clinical significance drawn from this study is that clinicians should recognize that using curing lights w/ increased output intensities doesn’t absolutely increase the DOC of VLDC’s especially with the darker shades.

No description available.

<p> In or der to study the mechanism of their conversio~ into hydrazides and thiohydrazides, a number of hydrazidic halides were treated with compounds containing a nucleophilic oxygen or sulfur atom. </p> <p> The initial products of these reactions were formed from the displacement of the (alpha)-halogen atom of the hydrazidic halide. In cases where there was sufficient activation the group attached to oxygen or sulfur was transferred to nitrogen in the presence of base. </p> <p> Some hydrazides and thiohydrazides containing displace-able groups in the 2-position of an N-aryl ring yielded benzoxadiazines and benzothiadiazines respectively under basic conditions. The reactions exhibited the characteristics of bimolecular nμcleophilic aromatic substitutions. The synthesis of four novel heterocyclic ring systems is described. </p> / Thesis / Doctor of Philosophy (PhD)

No description available.

No description available.

Der Cr2O3 ist einer der wichtigsten Katalysatoren im Chlor/Fluor (Cl/F) Austauschreaktionen für die Produktion von chlorofluorocarbon (CFC) Alternativen. Es wird als ein ausgezeichneter heterogener Katalysator für Fluorierung Reaktionen gegründet. Die Dismutierung von CCl2F2 wurde verwendet, um die Wirkung von Halogenierung von Chrom(III) Oxyd auf Cl/F-Austauschreaktionen zu untersuchen und um den Unterschied zwischen den inaktiven und aktiven Katalysatoren herauszufinden. Die heterogenen Reaktionen wurden in einem tubular-flow Ni Reaktor und auch unter simulierten Reaktionsbedingungen in einem Reaktor durchgeführt, wo nach der Reaktion die Photoelektronspektroskopie (XPS) und die Auger-Elektronspektroskopie (XAES) Analysen konnte direkt ohne Luftkontakt, unter so genannt "in - situ" Bedingungen gefolgt werden. Es wurde gezeigt, dass die Probleme der Behandlung von Cr (III) 2p Photoelektronenspektren so gelöst werden können, dass ihnen relevante Daten für die chemische Charakterisierung von Oberflächen entnommen werden können. Hochaufgelöste Photoelektronspektroskopie von Cr2O3 Pulverproben zeigte deutlich die Existenz von spektralen Strukturen, die mit Multiplet-Aufspaltungen im jeweiligen Cr 2p Spektrum verbunden sind. Das Spektrum kann durch eine Peakfit-Analyse vertieft interpretiert werden in dem die Anfangswerte für die Peakparameter der Multiplet-Strukturen den jeweiligen Cr L2,3 XANES Spektren entnommen werden. Vom theoretischen Gesichtspunkt sollte dasselbe Verfahren auch eine Analyse der Cr 2p Photoelektronenspektren von alpha-CrF3, CrCl3 und anderen Chrom (III) Verbindungen ermöglichen. Die Unterschiede, die im Experiment für die Cr2O3, alpha-CrF3 und CrCl Photoelektronenspektren beobachtet werden, deuten auf die Tatsache, dass, obwohl in all diesen Fällen dieselben Multiplet-Aufspaltungen für Cr3+ erwartet werden, individuelle Einflüsse der Symmetrie und Ligandenfelder die Endgestalt des jeweiligen Cr 2p Photoelektronenspektrums definieren. Eine Analyse von Cr 3s Spektren kann zusätzlich wertvolle Finger-print Informationen zu chemischen Zuständen von Chrom in Cr (III) Verbindungen erbringen. Sowohl ex-situ als auch ´´in-situ´´ ESCA zeigen, dass sobald CCl2F2 zu Cr2O3 an 390 °C geführt wird, Fluorierung sowie Chlorierung an der Katalysator-Oberfläche findet statt. Wenn die XPS Oberflächenzusammensetzung etwa 4 Atom - % Fluorierung und 6 Atom - %-Chlorierung erreicht, wird die maximale katalytische Aktivität erhalten. Die längeren Reaktionszeiten ändern bedeutsam die erhaltene Oberflächenzusammensetzung von aktiviertem Chrom(III) Oxyd nicht. Der Fluorierung und Chlorierung von Chrom(III) Oxyd wurden weiter durch verschiedenen HF und HCl Behandlungen ebenso untersucht. Die aktivierten Chrom(III) Oxyd Proben und Referenzproben mit der weithin bekannten chemischen Struktur wurden auch durch Kantennahe Röntegenabsorptionsuntersuchungen (XANES), Flugzeit-statischesekundärionenmassenspektroskopie (TOF-SSIMS), Rasterelektronenmikroskopie (SEM), Fluor-Festkörper-NMR, Pyridin-FTIR, Nasschemie (F und Cl) Analyse, Pulver Röntgensbeugung (XRD) und Oberflächen (BET) Analyse untersucht. Die Ergebnisse der Referenzproben Cr2O3, Cr (OH) 3, CrF2 (OH), CrF3.3H2O, Alpha-CrF3, Beta-CrF3 und CrCl3 und aktivierte Cr2O3 Proben wurden verglichen. Die angewandten Charakterisierungsmethoden schlagen vor, dass die Bildung der Chrom-Oxydchlorid-Fluorid-Arten, bzw. Chrom-Oxyd Halogenide, an der Oberfläche ist genügend die katalytische Aktivität zu versorgen. Die Anwesenheit jedes CrF3 und/oder CrCl3 Phasen auf den aktivierten Chrom(III) Oxyd Proben wurde nicht entdeckt. / The Cr2O3 is one of the most important catalysts in the chlorine/fluorine (Cl/F) exchange reactions for the production of chlorofluorocarbon (CFC) alternatives. It is established as an excellent heterogeneous catalyst for fluorination reactions. The dismutation of CCl2F2 was used to probe the effect of halogenation of chromia on Cl/F exchange reactions in order to find out the difference between the inactive and active catalysts. The heterogeneous reactions were performed in a continuous flow Ni reactor and also under simulated reaction conditions in a reactor where after the reaction the X-ray photoelectron spectroscopy (XPS) and the X-ray excited Auger electron spectroscopy (XAES) analyses could be followed directly without air contact, under so called ´´in-situ´´ conditions. In order to be able to apply the Cr(III) 2p XPS analysis in the proper manner the spectroscopic features of the chromium(III) compounds of O, F and Cl were re-investigated. Latest generation of XPS spectrometers, which are able to analyze non-conductive powders with ultimate energy resolution, were used to reveal multiplet splitting features and satellite emission in the Cr 2p spectra. The energy positions of the multiplets were determined by total electron yield (TEY)- X-ray absorption near edge structure (XANES) spectroscopy. Using both high resolution XPS and XANES spectra a peak-fit analysis, which is also applicable for normally resolved Cr 2p XPS spectrum, was proposed. In order to overcome the known background problem by drawing the background in the broad Cr 2p window including the high binding energy satellite, a modified Shirley background, which is a combination of a linear and Shirley function, was used. Moreover, the spectroscopic features of the Cr(III) 3s XPS spectrum, which is relatively simpler than the Cr 2p one, were also surveyed. An alternative chemical analysis was proposed by using chemical state plots for Cr 3s. Both ex- and in-situ ESCA show that as soon as Cr2O3 is conducted to CCl2F2 at 390 °C fluorination as well as chlorination takes place at the catalyst surface. When the XPS surface composition reaches approximately 4 atom-% fluorination and 6 atom-% chlorination, maximum catalytic activity is obtained. Applying longer reaction times do not change significantly the obtained surface composition of the activated chromia. The fluorination and chlorination of chromia was further investigated by various HF and HCl treatments as well. The activated chromia samples and reference samples with well known chemical structure were also characterized by XANES, time of flight - static secondary ion mass spectroscopy (TOF-SSIMS), scanning electron microscopy (SEM), fluorine solid state NMR, pyridine-FTIR, wet chemical (F and Cl) analysis, X-ray powder diffraction (XRD) and surface area (BET) analysis. The results for the references Cr2O3, Cr(OH)3, CrF2(OH), CrF3.3H2O, alpha-CrF3, beta-CrF3 and CrCl3 and activated Cr2O3 samples were compared. The applied characterization methods suggest that the formation of chromium oxide chloride fluoride species, e.g. chromium oxide halides, at the surface is sufficient to provide catalytic activity. The presence of any CrF3 and/or CrCl3 phases on the activated chromia samples was not detected.

Aluminiumfluorid (HS-AlF3), das mit Hilfe des Sol-Gel-Verfahrens unter nicht-wässrigen Bedingungen hergestellt wird, weist eine extrem große Oberfläche und eine hohe Lewis-Acidität auf, die mit den stärksten bekannten Lewis-Säuren wie SbF5 und ACF vergleichbar ist. Diese ungewöhnlichen Eigenschaften werden im Ergebnis einer neuen Sol-Gel-Synthese erhalten, die die Fluorolyse eines Aluminium-Alkoxids durch wasserfreien Fluorwasserstoff in organischen Lösungsmitteln zur Grundlage hat. Das zunächst in einer amorphen, katalytisch inaktiven Vorstufe mit großer Oberfläche gebildete Gel wird nach anschließender Trocknung mit gasförmigen Fluorierungsmitteln nachfluoriert, wobei die aktive Form des HS-AlF3 erhalten wird. Im Rahmen der vorliegenden Arbeit wurden alle Schritte dieses Syntheseweges untersucht und die Ergebnisse einschließlich einer detaillierten Analyse der erhaltenen Materialien diskutiert. Des Weiteren wurde HS-AlF3 durch eine Imprägnierungs-Methode auf das Trägermaterial Al2O3 aufgetragen, wobei verschiedene Beladungen mit HS-AlF3 getestet wurden. Die Eigenschaften des HS-AlF3/Al2O3 als Lewis-Säure-Katalysator wurden mittels der Dismutierung von CHClF2 und der Isomerisierung von CBrF2CBrFCF3 bestimmt. Die Herstellung von AlFyOx mit Hilfe des Sol-Gel-Verfahrens ist ebenfalls beschrieben, wobei das Produkt amorph ist und eine große Oberfläche von bis zu 240 m2/g aufweist. / Aluminum fluoride (HS-AlF3) prepared via sol-gel synthesis route under non-aqueous conditions exhibits high surface area and an extremely strong Lewis acidity, comparable with some of the strongest known Lewis acids such as SbF5 and ACF. The basis of its unusual properties is the sol-gel fluorination of aluminum alkoxide with anhydrous HF in organic solvents yielding first an amorphous catalytically inactive precursor with high surface area, which can be dried and eventually post-fluorinated to get HS-AlF3. In this thesis, all steps of the synthesis route were thoroughly investigated. The results of these investigations together with detailed analysis of the obtained materials are reported and discussed. HS-AlF3 supported on Al2O3 with different HS-AlF3 loadings was prepared by wet impregnation method. The properties of the HS-AlF3/Al2O3 samples as Lewis acid catalyst were evaluated for CHClF2 dismutation and CBrF2CBrFCF3 isomerization. The preparation of AlFyOx via sol-gel method is also reported. AlFyOx prepared is amorphous and have high surface are up to 240 m2/g.

Nesta pesquisa foi avaliado a resistência flexural, a microinfiltração e o grau de conversão de uma resina composta micro-híbrida fotoativada por laser de argônio e luz halógena. Para o teste de resistência flexural e grau de conversão foram preparadas cinco amostras de 25 X 2 X 2mm de acordo com a norma ISO 4049. Os parâmetros de fotoativação utilizados em todas as etapas do trabalho foram: luz halógena (500mW/cm2) por 20 segudos, laser de argônio (250mW) por 10 e 20 segundos. As amostras foram lixadas com a seqüência de granulações 500, 800, 1000, 1200, 2500 e 4000. Os espécimes eram armazenados em água destilada, em recipiente escuro, em estufa a 37ºC por 24 horas e eram submetidos ao ensaio de resistência flexural (Máquina de Ensaios Mecânicos - Modelo 4411 ? Instron) em velocidade de 1mm/min. Para o estudo da microinfiltração foram utilizados dentes incisivos bovinos (n=20), As cavidades eram preparadas com brocas Carbide #330 com 4mm (altura) X 3mm (largura) X 2mm (profundidade). Os dentes eram então restaurados, e recebiam acabamento e polimento e em seguida eram armazenados em água destilada, em estufa a 37ºC por 24 horas. As amostras foram submetidas ao processo de termociclagem (500 ciclos de 30 segundos - 6ºC e 60ºC). Após a termociclagem, os ápices dos dentes eram selados com IRM e adesivo a base de cianoacrilato e imersos em fucsina básica a 0,5% por 24 horas, em estufa a 37ºC. A análise do grau de conversão foi feita com o Espectrômetro FT-Raman RFS 100/S (Bruker). Para o teste de resistência flexural foi realizado o teste de análise de variância, que mostrou não haver diferença estatisticamente significante entre as fontes fotoativadoras estudadas (p>0,05). A microinfiltração das margens oclusais (em esmalte) e gengivais (em dentina) dos três grupos foram analisadas separadamente por meio do teste de Mann-Whitney. Houve diferença estatisticamente significante ao nível de 5% entre esmalte e dentina, sendo que em todos os grupos a microinfiltração em dentina foi maior que em esmalte. O teste nãoparamétrico Kruskall-Wallis foi utilizado separadamente nas comparações entre as fontes para as análises do grau de microinfiltração em esmalte e dentina. Não houve diferença estatisticamente significante em ambas as comparações, sendo o valor de H= 0,1283 para esmalte e de H=2,3083 para em dentina. Para a análise do grau de conversão foi realizada a análise de variância (ANOVA) entre os grupos. Não houve diferença estatisticamente significante entre as fontes. Diante dos resultados obtidos, pode-se afirmar que o laser de argônio apresentou qualidade de fotoativação semelhante à da luz halógena e que nenhuma fonte ativadora estudada foi capaz de evitar a microinfiltração. / In the research was evaluated the flexural strength, the microleakage and the degree of conversion of a micro-hybrid composite resin photocured with argon laser and halogen lamp. For both flexural test and degree of conversion analysis five bar samples of composite resin (25 X 2 X 2mm) were prepared and polymerized following the ISO 4049. The light cured unit halogen was used with 500mW/cm2 for 20 seconds and the argon laser with 250mW for 10 and 20 seconds. After curing, samples were removed from the molds, polished using silicon carbide paper up to 4000 grit-number and stored in distilled water in dark environment at 37oC for 24 hours. The flexural property was quantified by a three-point loading test (Model 4411, Instron Corp., Canton, MA) with a cross-head speed of 1,0mm/min. To microleakage test sixty bovine incisors were used to prepare standardized class V cavities that were restored and polished. The specimens were stored in water for 24 hours at 37oC and thermocycled 500 times between water baths kept at 5 oC and 55 oC. After thermocycling, specimens were immersed in a aqueous solution of basic fuchsin for 24 hours. Longitudinal sections of each restoration were obtained and examined with a stereomicroscope for qualitive evaluation of microleakage. FTRaman RFS 100/S spectrometer (Bruker) was used to analyse the degree of conversion. The ANOVA test showed that there were no statistically significant difference of the flexural setrength between the photo-activation types evaluated in the flexural study. Microleakage data was statistically analysed by Mann-Whitney and Kruskall-Wallis tests. Enamel margins resulted in statistical lower degree of leakage than dentin margins. There was no statistically significant difference between the three types of photo-curing studied. The ANOVA test also showed that there were no statistically significant difference of the degree of conversion between the studied groups. According to the methodology used in this research it was concluded that the argon laser is a posible alternative for photocuring, providing the same quality of polymerization as do the halogen lamp. None of the photocured units tested in this study completely eliminated microleakage.

Det finns fortfarande för många hushåll i Sverige som använder mest glödljus för belysning, i form av glödlampor eller halogenlampor. Detta orsakar en väsentlig del av det onödiga överskott av koldioxidutsläpp som är en av orsakerna till den globala uppvärmningen. Därför avser detta examensarbete att försöka skapa en grönare miljö genom att studera och uppmärksamma faktorer som påverkar val av ljuskällor i belysningssammanhang. Syftet med examensarbetet är att få en ökad förståelse för hur LED-ljuset upplevs i hemmiljö. Arbetet ska visa hur LED-ljuskällans nuvarande kvalité bedöms utifrån individuella rumsupplevelser samt om ytterligare kvalitetsförbättringar behövs. Detta görs för att kunna vända allmänhetens inställning i en mer positiv riktning gentemot LED, vilket kan bidra till en mer ekologiskt hållbar miljö. För att undersöka hur LED fungerar i hemmiljö genomfördes en experimentell studie med syfte att besvara följande frågor: hur upplevs LED-ljusets kvalité jämfört med halogenljusets, hur tror man att det egna välmåendet påverkas av halogenljus respektive LED-ljus, hur påverkas rumsupplevelsen och rumskaraktären om halogenljus ersätts med LED-ljus och finns det några skillnader mellan ljusdesigners och icke ljusdesigners upplevelse av halogenljus och LED-ljus i hemmiljö? Det byggdes upp två likadana försöksrum som hade samma förutsättningar både storleksmässigt, inredningsmässigt och belysningsmässigt. Den enda skillnaden var de installerade ljuskällorna, då det användes halogenlampor i det ena rummet och LED-lampor i det andra rummet. En enkätundersökning genomfördes, resultatet analyserades och en utförlig rumsanalys gjordes. Resultatet visade att ljuset, oavsett ljuskälla, påverkade deltagarnas välmående och rumsupplevelse på olika sätt, beroende på vilken yrkesgrupp de tillhörde. Det visade sig också att skillnaden i ljuskvalitén mellan halogenljus och LED-ljus inte längre är omfattande. Dagens LED-lampor utvecklas alltså positivt och är redan en värdig ersättare till glöd- och halogenlampor. / There are still too many households in Sweden that use mostly incandescent light for lighting, using incandescent or halogen bulbs. This causes a substantial part of the unnecessary surplus of carbon-dioxide that is one of the reasons for global warming. Therefore, this degree project aims to promote a greener environment by studying and paying attention to factors that have an influence in the lighting context. The purpose of this degree project is to gain a better understanding of how the LED light is experienced in a home environment. The work will show how LED light source's current quality is evaluated based on individual room experiences, and if additional quality improvements are needed. The objective is to turn the public's attitude in a more positive direction where LED can contribute to a more ecologically sustainable environment. To investigate how LEDs are perceived in home environments an experimental study was performed which was based on the following research questions: How is LED light quality experienced compared to halogen light, how is personal wellbeing perceived in relationship to halogen and LED light, how are room experience and room character affected if halogen light is replaced by LED light in a home environment and are there any differences in these experiences between lighting designers and non lighting designers? Two identical test-rooms were used. They were identical in size, interior design and lighting design. Halogen bulbs were used in one room and LED lights were used in the other room. A survey was used to get answers to the questions above. The results have been analyzed and detailed room analysis was also made. The results showed that the light, regardless of light-source, influenced the participant's well-being and their room experience in different ways, depending on the occupational group they belonged to. It was also found that the difference in quality of light between halogen light and LED light is no longer significant. The presently available LED lights are improving and are worthy replacements for incandescent and halogen lamps.

Thyroid hormones, which are secreted by the thyroid gland, are one of the most important halogenated compounds in the body. Thyroid hormones control almost every processes in the body including growth, body temperature, protein synthesis, carbohydrate and fat metabolism, heart rate, and cardiovascular, renal and brain function. Thyroid gland secretes L-thyroxine or 3,3',5,5'-tetraiodothyronine (T4) as a prohormone. While the biologically active hormone 3,3',5-triiodothyronine (T3) is produced by selective phenolic ring deiodination of T4, selective tyrosyl ring deiodination of T4 produces a biologically less active metabolite 3,3',5'-triiodothyronine (rT3). Tyrosyl and phenolic ring deiodination of T3 and rT3, respectively, also produces a biologically inactive metabolite 3,3'-diiodothyronine (3,3'-T2). Regioselective deiodinations of thyroid hormones are catalysed by three isoforms of a selenoenzyme iodothyronine deiodinase (DIO1, DIO2, DIO3). DIO1 can remove iodine from both the tyrosyl and phenolic rings of thyroid hormones, whereas DIO2 and DIO3 are selective towards phenolic and tyrosyl ring, respectively. Although the Figure 1. (A) Deiodination of thyroid hormones by iodothyronine deiodinases (DIOs) (A) and naphthyl-based selenium and/or sulphur compounds (B). mystery behind the origin of regioselectivity of deiodination by DIOs remains unsolved, formation of halogen bonding between selenium in the active site of DIOs and iodine of thyroid hormones has been widely accepted as the mechanism of deiodination. Halogen bonding, a noncovalent interaction between halogen and an electron donor such as nitrogen, oxygen, sulphur, selenium etc., elongates the C-I bond and impart a carbanionic character on the carbon atom that gets protonated after the removal of iodide. Apart from the deiodination, thyroid hormones also undergo decarboxylation, oxidative deamination, sulphate-conjugation to form iodothyronamines, iodothyroaetic acids and sulphated thyroid hormones, respectively. Figure 2. (A) Proposed mechanism of deiodination of thyroid hormones by deiodinase mimics. (B) Halogenation of uracil- and cytosine-containing nucleosides by hypohalous acid (HOX). Recently, naphthyl-based selenium/sulphur-containing compounds, such as compound 1 (Figure 1B), have been reported to mediate the selective tyrosyl ring deiodination of T4 and T3 to form rT3 and 3,3'-T2, respectively. Interestingly, replacement of the selenol moiety in compound 1 with a thiol decreases the activity, whereas replacement of the thiol moiety with another selenol dramatically increases the deiodination activity. Based on the detailed experimental and theoretical investigations, a mechanism involving the Se···I halogen bonding was proposed (Figure 2A). In addition to the halogen bonding between selenium and iodine atom, chalcogen bonding between two nearby chalcogen atoms was also shown to be important for the deiodination activity. Another important class of halogenated compounds in the body are the halogenated nucleosides. Myeloperoxidase and eosinophil peroxidase are heme-containing enzymes, which can convert halide ions (X¯) into a toxic reactive halogen species hypohalous acid (HOX) in presence of hydrogen peroxide (H2O2). Uracil- and cytosine-containing nucleosides are known to undergo halogenation at the 5-position of the nucleobase to form the halogenated nucleosides (Figure 2B). Interestingly, halogenated nucleosides such as 5-halo-2'-deoxyuridine are known to be incorporated in the DNA of dividing cells essentially substituting for thymidine. Incorporation of halogenated nucleosides into the DNA leads to mutagenesis, carcinogenesis and loss of genome integrity. Thymidylate synthase (TSase), the key enzyme involved in the biosynthesis of 2'-deoxythmidine-5'-monophosphate (dTMP) from 2'-deoxyuridine-5'-monophosphate (dUMP), can catalyse the dehalogenation of halogenated nucleotides in presence of external thiols. This thesis consists of five chapters. The first chapter provides a general introduction to halogen bonding, thyroid hormones and halogenated nucleosides. This chapter also briefly describes the halogen bond-mediated biochemical and biomimetic deiodinations of thyroid hormones by iodothyronine deiodinases and naphthyl-based organoselenium compounds. Dehalogenation of halogenated nucleotides by thymidylate synthase and thiol-based small molecules has also been discussed in this chapter. The second chapter of this thesis contains the regioselective deiodination of iodothyronamines (TAMs) by deiodinases mimics. TAMs are the endogenous metabolites produced by the decarboxylation of β-alanine side chain of thyroid hormones (THs). 3,3',5-triiodothyronamine (T3AM) and 3,5-diiodothyronamine (3,5-T2AM) undergoes selective tyrosyl ring deiodination by deiodinase mimics to form 3,3'-diiodothyronamine (3,3'-T2AM) and 3-iodothyronamine (3-T1AM), respectively. Interestingly, when the initial rates of deiodinations of T3 and T3AM were compared, deiodination of T3 was found to be several fold faster than that of T3AM under identical reaction conditions. To understand the ability of the iodine atoms to form Figure 3. (A) HPLC chromatogram of deiodination of T3. (B) Proposed mode of interaction of dimeric T3 and monomeric T3AM with organoselenium compounds. halogen bonding, a model selenolate (MeSe¯) was optimized with the T3 and T3AM. Although both T3 and T3AM forms the expected Se···I halogen bonding with MeSe¯, the strength of halogen bonding was found to be less for T3AM than T3. Furthermore, detailed kinetic and spectroscopic studies indicate that T3 and T3AM exist as dimeric and monomeric species in solution. The dimerization of T3 in solution was shown to have remarkable impact on the activation energy and pre-exponential factor of the deiodination reactions. Single crystal X-Ray crystallography and theoretical calculations indicated that in addition to Se···I halogen bonding, I···I halogen bonding may play an important role in the deodination of thyroid hormones by deiodinase mimics. Furthermore, the presence of heteroatoms such as nitrogen, oxygen and sulphur in the close proximity of one of the selenium atoms of deiodinase mimics was shown to have significant effect on the rate of deiodination reactions. The third chapter of the thesis focusses on the conformational polymorphism and conformation-dependent halogen bonding of L-thyroxine. Synthetic version of L-thyroxine (T4) is a life-saver for millions of people who are suffering from hypothyroidism, a thyroidal disorder recognised by low levels of T4 and elevated levels of TSH in blood plasma. Synthetic version of L-thyroxine is available in the Figure 4. Ball and stick model of the single crystal X-Ray structure of the conformational polymorphs of L-thyroxine. Form I and Form II was exclusively crystallized from methanol and acetonitrile, respectively. Water molecules are omitted for clarity. market with various brand names. However, adverse effects have been observed in the patients when they switch their brand of thyroxine. Based on these observations, the American Thyroid Association (ATA), the Endocrine Society (TES), and the American Association of Clinical Endocrinologists (AACE) declared that the different brands of T4 are not bioequivalent, thus leading to differences in the bioavailability of the drug. We have shown that the commercially available thyroxine exists in at least two stable forms (Form I and Form II) with different three-dimensional structures (Figure 4). These two forms exhibit different intermolecular interactions in crystal packing, spectral behaviours, thermal stabilities, optical activity and very interestingly, different solubility in acidic and basic pH. At pH 4, solubility of Form I is about 42% and 45% greater than that of Form II and bulk T4, respectively, whereas at pH 9, the solubility of Form II is about 38% and 42% higher than that of Form I and bulk T4, respectively. As T4 is a narrow therapeutic index drug, these differences in solubility may have remarkable impact on the bioavailability of the drug. In addition to this, we have shown that the ability of the iodine atoms in the C-I bonds to form halogen bond with donor atoms can be altered by changing the relative orientation of tyrosyl and phenolic rings in T4. In the fourth chapter, the three-dimensional structures and conformations of thyroid hormones (THs) and iodothyronamines (TAMs) are discussed. TAMs, the endogenous decarboxylated metabolites of THs, exhibit different binding affinities to the transport proteins and iodothyronine deiodinases (DIOs) compared to the THs. Figure 5. Change in the structure and conformations of thyroid hormones and iodothyronamines with the decarboxylation of amino acid side chain and deiodination of phenolic and tyrosyl ring. Furthermore, the substrate specificities of DIOs have been found to be dependent on the position of iodine atoms on the phenolic and tyrosyl ring of TAMs and THs. Single crystal X-ray structures of TAMs indicate that decarboxylation of amino acid side chain of THs induces significant changes in the structure and conformation. Furthermore, the positional isomers of THs and TAMs exhibit remarkably different conformations, which may have significant effect on the binding of these metabolites to the active site of DIOs. In addition to the structure and conformations, different categories of the intermolecular halogen···halogen (X···X) interactions in the crystal packing of THs and TAMs have also been discussed. Natural bond orbital (NBO) analysis have been done on the halogen-bonded geometries to understand the electronic nature of these interactions. In the fifth chapter, the dehalogenation of halogenated nucleosides and nucleobases by naphthyl-based sulphur/selenium compounds is discussed. Purine and pyrimidine nucleosides are halogenated at various positions of the aromatic ring by different peroxidases such as myeloperoxidase and eosinophil peroxidase present in the white blood cells. Incorporation of the halogenated nucleosides into the DNA of replicating cells leads to DNA-strand breaks, mutagenesis, carcinogenesis and loss of Figure 6. (A) Dehalogenation of halogenated nucleosides. Effect of base-pairing wih adenine and guanine on the deiodination of IU (B) and debromination of BrU (C) by compound 2. genome integrity. We have shown that the naphthalene-based organoselenium compounds such as compound 2 can mediate the dehalogenation of 5-iodo-2'-deoxyuridine (5-IdUd) and 5-bromo-2'-deoxyuridine (5-BrdUd) to produce 2'-deoxyuridine (dUd) (Figure 6A). The deiodination of 5-IdUd was found to be faster than the debromination of 5-BrdUd by compound 2. The mechanism of dehalogenation of halogenated nucleosides by compound 2 was found to be dependent on the nature of halogen. While the deiodination of 5-IdUd by compound 2 follow halogen bond-mediated pathway like thyroid hormones, debromination of 5-BrdUd follow a Michael addition-elimination pathway. Similar results were obtained when 5-iodo-2'-deoxycytidine (5-IdCd) or 5-bromo-2'-deoxycytidine (5-BrdCd) was used as substrate for dehalogenation reaction. Base-pairing of 5-iodouracil (IU) and 5-bromouracil (5-BrU) with adenine and guanine has a significant effect on the rate of dehalogenations of IU and BrU by compound 2 (Figure 6B and 6C).