Tartaric acid is a dicarboxylic acid naturally present in grapes, and has many application areas with its salts. It can be produced synthetically, manufactured as a by-product in wine industry, or can be recovered by electrodialysis and solvent extraction methods. Since, ion exchange is one of the oldest processing techniques for the recovery and purification of valuable materials, it can be applied to obtain this valuable organic acid. In this study it is aimed to investigate the effects of resin basicity, initial concentration, and initial pH of the solution on ion exchange equilibrium. The model tartaric acid solutions were prepared for the equilibrium analysis with two different anion exchange resins in a batch type system. A shaker bath at 28 oC with 300-rpm agitation rate was used. The weakly basic resin Lewatit MP62, and strongly basic resin Lewatit M511, which are in polystyrene structure, was obtained from the producer Bayer AG. In the analysis, Shimadzu PDA Detector at 210 nm with Waters Atlantis dC18 column was used. 20 mM NaH2PO4 at pH = 2.7 was introduced to the HPLC as the mobile phase at 0.5 ml/min flow rate. In the investigation of the resin basicity, MP62 presented better performance than M511. The equilibrium experiments were performed at three different initial acid concentrations (0.01, 0.02, and 0.10 M) for both resin, and in the pH ranges pH &lt / pKa1, pKa1 &lt / pH &lt / pKa2, and pKa2 &lt / pH for weakly basic resin, and in the pH ranges pH &lt / pKa1, pKa1 &lt / pH &lt / pKa2 for strongly basic resin at each concentration. Results show that the pH of the solution is a more important parameter than the initial concentration that affects the ion exchange equilibrium. Also, Langmuir and Freundlich isotherms were plotted, and it was shown that they were in good agreement with the experimental data especially for the systems that are at low total ion concentrations.

In this study two polychelatogens for borate and a polyelectrolyte for chromate retention (R) were designed for investigating the effect of pH and loading (g metal /g polymer) on the separation performances of the synthesized polymers using continuous polymer enhanced ultrafiltration. Increase in pH increased the retention of borate for all of the synthesized polymers. Decrease in the loading resulted in an enhancement in boron retention with PNSM and PNSL. When COP was utilized, retentions remained almost constant after a certain loading, probably due to possible adverse effects of high polymer concentrations on polymer conformation in aqueous solutions. Decrease in loading caused an increase in the retention of chromate until a loading of 0.01. After that a slight decrease was observed. Maximum Cr (VI) retention was obtained as 0.70 for a loading of 0.01 and a pH of 4. Effect of crowding on Cr(VI) retention was also investigated. It was observed that retention does not only depend on the loading but also on the concentrations of both Cr (VI) and PDAM. Effect of the presence of competing anions such as chloride and sulfate on the retention of chromate was investigated to see the effect of competing anion charge to the selectivity of the synthesized polyelectrolyte. Addition of both anions decreased the retention of Cr(VI) . Divalent sulfate decreased the retention more than monovalent chloride indicating that charge of the anion may be the predominant variable in the retention of chromate using PDAM. Finally, dynamic and static light scattering measurements were performed to investigate the conformational changes in the structure of the synthesized polymers at different pH values as well as in the presence of boron in the solution. In this study, it is shown that PEUF can be successfully applied to for boron and Cr (VI) retention with the synthesized polymers. Satisfactory retention values were obtained both for boron and Cr (VI). Even if the retention of Cr (VI) decreased with the addition of high amount of competing anions, significant Cr (VI) retentions could be obtained.

The thiourea derivatives have become a main focus of research in asymmetric synthesis as an organocatalyst in recent years. In the first part, the thiourea catalysts are synthesized starting from easily available L-tartaric acid and application of the catalysts to some addition reactions showed no significant asymmetric induction. A number of HDAC inhibitors have been developed as anti-cancer agent at the present time.In the second part, some aryl butenoic acid derivatives are synthesized as HDAC inhibitors starting from substituted benzaldehyde and pyruvic acid. The HDAC activity studies showed comparable results with known molecules. In the last part, some acyl phosphonates are synthesized and addition of ethylcyanoformate to acyl phosphonates furnished the products in good yields.

Dysfunction of Mitochondrial Respiratory Chain in Rostral Ventrolateral Medulla During Experimental Endotoxemia Sepsis is a complex pathophysiologic state resulting from an exaggerated whole-body inflammatory response to infection or injury. Metabolic disturbances, abnormal regulation of blood flow and diminished utilization of oxygen at the cellular level may account for tissue damage and lead to multiple organ failure and death. As the primary site of cellular energy generation is the mitochondrion, it presents itself as an important target for the septic cascade. In this regard, the notion that bioenergetic failure due to mitochondrial dysfunction contributes to organ failure during sepsis has received attention. We established the low frequency fluctuations in the systemic arterial pressure signals are related to the sympathetic neurogenic vasomotor tone, and reflect the functional integrity of the brain stem. Their origin is subsequently traced to the premotor sympathetic neurons at the rostral ventrolateral medulla (RVLM), whose neuronal activity is intimately related to the ¡§life-and-death¡¨ process. Based on a rat model of experimental endotoxemia that provides continuous information on changes in neuronal activity in the RVLM, the present study was undertaken to evaluate whether changes in mitochondrial respiratory functions are associated with death arising from sepsis. We also evaluated the efficacy of a new water-soluble coenzyme Q10 (CoQ10, ubiquinone) formula in the protection against fatality during endotoxemia by microinjection into bilateral RVLM. Dysfunction of Mitochondrial Respiratory Chain in Rostral Ventrolateral Medulla During Experimental Endotoxemia in the Rat We investigated the functional changes in mitochondrial respiratory chain at the RVLM in an experimental model of endotoxemia that mimics systemic inflammatory response syndrome. Experiments were carried out in adult male Sprague-Dawley rats that were maintained under propofol anesthesia. Intravenous administration of E. coli lipopolysaccharide (LPS; 30 mg/kg) induced progressive hypotension, with death ensued within 4 hours. The sequence of cardiovascular events during this LPS-induced endotoxemia can be divided into a reduction (Phase I), followed by an augmentation (Phase II; ¡§pro-life¡¨ phase) and a secondary decrease (Phase III; ¡§pro-death¡¨ phase) in the power density of the vasomotor components (0-0.8 Hz) of systemic arterial pressure (SAP) signals. Enzyme assay revealed significant decrease of the activity of NADH cytochrome c reductase (Complex I+III) and cytochrome c oxidase (Complex IV) in the RVLM during all 3 phases of endotoxemia. On the other hand, the activity of succinate cytochrome c reductase (Complex II+III) remained unaltered. Neuroprotective Effects of Coenzyme Q10 at Rostral ventrolateral Medulla Against Fatality During Experimental Endotoxemia in the Rat CoQ10 is a highly mobile electron carrier in the mitochondrial respiratory chain that also acts as an antioxidant. We evaluated the neuroprotective efficacy of CoQ10 against fatality in an experimental model of endotoxemia, using a novel water-soluble formulation of this quinone derivative. In Sprague-Dawley rats maintained under propofol anesthesia, intravenous administration of E. coli LPS (30 mg/kg) induced experimental endotoxemia. Pretreatment by microinjection bilaterally of CoQ10 (1 or 2 mg) into RVLM significantly diminished mortality, prolonged survival time, and reduced the slope or magnitude of the LPS-induced hypotension. CoQ10 pretreatment also significantly prolonged the duration of Phase II endotoxemia and augmented the total power density of the vasomotor components of SAP signals in Phase II endotoxemia. The increase in superoxide anion production induced by LPS at the RVLM during Phases II and III endotoxemia was also significantly blunted. Conclusion The present study revealed that selective dysfunction of respiratory enzyme Complexes I and IV in the mitochondrial respiratory chain at the RVLM is closely associated with fatal endotoxemia. CoQ10 provides neuroprotection against fatality during endotoxemia by acting on the RVLM. We further found that a reduction in superoxide anion produced during endotoxemia at the RVLM may be one of the mechanisms that underlie the elicited neuroprotection of CoQ10. These findings therefore open a new direction for future development of therapeutic strategy in this critical, complicated and highly fatal condition known as sepsis.

Ziel dieser Arbeit ist die Abtrennung von monovalenten Anionen wie Chlorid, Fluorid, Bromid und Nitrat aus hochkonzentrierten alkalischen wässrigen Lösungen, die als Matrix zweiwertigen Anionen (Carbonat und Sulfat) besitzen. Nach Auswertung der Literatur eignen sich vor allem die Verfahren Ionenaustausch und Nanofiltration für diesen Zweck. Die untersuchten Ionenaustauscher weisen eine geringe Selektivität für die einwertigen Anionen auf, so dass die für einwertige Anionen nutzbare Kapazität mit steigendem Gehalt an zweiwertigen Anionen sinkt. Dabei steigt die Kapazität in der Reihenfolge Fluorid→Chlorid→Bromid→Nitrat. Die beobachteten Selektivitäten bei der Nanofiltration steigen in der gleichen Reihenfolge, wobei die Trennrate zwischen ein- und zweiwertigen Anionen vom Membrantyp abhängt. Es konnte ein Zusammenhang zwischen den Kapazitäten der untersuchten stark basischen Anionenaustauscher für monovalente Anionen und den Rückhalten für diese Anionen bei den Nanofiltrationsmembranen mit den Ionenhydratationsparametern festgestellt werden.

The study of the binding and recognition of anions has emerged as a significant branch of supramolecular chemistry over the past 20 years. Of particular interest is the binding in aqueous media of industrially or biologically relevant anions including fluoride, pyrophosphate, and terephthalate. To date, most anion recognition using synthetic systems has been accomplished with small molecule receptors operating in organic media. We believe the challenge of sensing and binding anionic species in aqueous media could be addressed through polymers. This is due to their solubility, which can be tuned by judicious selection of the appropriate polymer backbone. Further, polymers can be cross-linked (forming interchain bonds) to produce insoluble materials that are attractive for use as filter materials for liquids and gases. The polymer network can also act as a net to strip away the solvent shell of the anions, leading to increased sensitivity toward hydrated analytes. In addition, the multi-valency due to multiple binding sites in a polymer can lead to increased affinities for analytes. This dissertation details the author’s work focused on the preparation of anion receptor-containing polymers and their subsequent evaluation as both sensors for the fluoride anion and as extractants for bisanions under conditions of liquid-liquid extraction. Chapter 1 gives a brief review of the challenges of anion binding and a primer on the field of sensing and extracting anions using polymeric systems. Chapter 2 describes our work incorporating three quinoxaline-based anion receptors into poly(methyl methacrylate) polymers and their sensing of anionic targets. Chapter 3 describes our work incorporating calix[4]pyrrole anion receptors into poly(methyl methacrylate) polymers. These polymeric systems were found to undergo reversible crosslinking in organic media when combined with certain ditopic anions. Chapter 4 describes our work to investigate chemopreventives of prostate cancer based on the phytochemicals 6-gingerol and 6-shogaol. The mechanism of action was linked to the inhibition of inflammation pathways. Derivatives of 6-shogaol were synthesized and their ability to inhibit prostate cancer cell growth was evaluated. Chapter 5 details all the syntheses and characterization data of the compounds discussed in this dissertation, as well as spectra from titrations and extraction studies. / text

The cation&ndash;&pi; interaction has been long-established to play an important role in molecular recognition, supramolecular chemistry, and molecular biology. In contrast, its potential application in small-molecule catalysis, especially as a selectivity-determining factor in asymmetric synthesis has been overlooked until very recently. This dissertation begins with an extensive literature review on the state-of-the-art research on the application of cation&ndash;&pi; interactions in non-enzymatic catalysis of organic and organometallic transformations. The research in this field has been largely inspired and guided by the related biosynthetic systems incorporating the same type of interactions.</p> / Chemistry and Chemical Biology

Per- and polyfluoroalkyl substances (PFASs) are chemicals that have been used for over 50 years. They are both hydrophobic and hydrophilic, which make them useful in a wide range of products, both in the domestic and industrial market. Recently, the global attention on PFASs has increased due to their possible harmful health effects on humans. Furthermore, PFASs have been detected in drinking water sources all over the world. Conventional treatment processes in drinking water treatment plants (DWTPs) are not able to remove PFASs. Therefore, more research is required to find efficient removal techniques for these compounds. The aim of this study was to investigate the removal efficiency of PFASs using two different adsorption techniques, anion exchange (AE) with the resin Purolite A-600, and granular activated carbon (GAC) of type Filtrasorb®400. The experiments were performed in laboratory batch-scale, at Swedish University of Agriculture (SLU), and column tests in pilot-scale, at Bäcklösa DWTP in Uppsala. The PFASs showed a high sorption potential to AE and GAC. However, the removal efficiency differed depending on the perfluorocarbon chain length, functional group, and concentration level. For the AE, in average 92 % of the PFASs were removed in the end of the batch experiments while the average removal efficiency in the column experiment was 86 %. In the batch experiments treated with GAC on average 55 % of the PFASs were removed in the end of the experiments while the column experiment had the average removal efficiency of 86 %. There was an increase in the removal efficiency with increasing perfluorocarbon chain length in the column experiments. However, in the batch experiments, the adsorption of PFASs decreased with an increasing chain length, except for the highest PFAS concentration level (5000 ng L-1) treated with AE and the lowest PFAS concentration level (200 ng L-1) treated with GAC. In the column experiments, the perfluoroalkane sulfonates (PFSAs) were slightly better removed than perfluoroalkyl carboxylates (PFCAs) with an average removal efficiency of 97 % for AE and 91 % for GAC compared to 67 % and 82 % for AE and GAC, respectively. In the batch experiments, there was no clear trend between the removal efficiency and functional group. Overall, the pilot-scale experiments removed the PFASs relatively well even after 42 days (on average, 86 % for both AE and GAC). The lowest removal capacity in the column experiments was seen for the shorter chained PFSAs (in average 46 % for ≤C6 PFCAs using AE and 75 % for ≤C7 PFCAs using GAC). More efficient treatment techniques are needed to minimise the PFAS concentrations in drinking water and the potential human. / Per- och polyfluorerade alkylsubstanser (PFASs) är kemikalier som har används globalt under de senaste 50 åren. Tack vare att de är uppbygda av både en hydrofob och en hydrofil del är de ytaktiva (s.k. surfaktanter) och har ett brett användningsområde, både för industri- och hushållsprodukter. På senare år har dessa ämnen fått uppmärksamhet på grund av att exponering för PFASs har visats kunna medföra hälsorisker. PFASs har upptäckts i dricksvatten på många håll i världen, men flera av de konventionella reningsmetoderna för dricksvatten är inte effektiva för PFASs och därför finns ett behov av mer forskning och kunskap inom vattenberedningsområdet. I denna studie undersöktes reningseffektiviteten för PFASs hos två adsorptionstekniker; i) anjonbyte (AE) med Purolite A-600 och ii) granulerat aktivt kol (GAC) med Filtrasorb®400. Studien utformades så att inverkan av kolkedjans längd, molekylens funktionella grupp samt koncentrationsnivån av PFASs kunde utvärderas. Experimenten utfördes både i liten skala genom försök i bägare på Sveriges lantbruksuniversitet (SLU) och i något större skala i en pilotanläggning med kolonnexperiment på Bäcklösa dricksvattenverk i Uppsala.  Båda reningsmetoderna visade god effekvititet för avlägsnandet av PFASs i dricksvatten. I slutet av bägarexperimenten var i medeltal 92 % och 55 % av PFASs eliminerade för de prover behandlade med AE respektive GAC. Reningseffektivititen för kolonnexperimenten var i medeltal 86 % för båda metoderna. Reningsgraden var beroende av längden på den perfluorerade kolkedjan. I kolonnexperimenten visades att ökad kedjelängd ledde till ökad reningseffektivitet, medan bägarexperimenten visade på motsatt trend, med undantag för prover behandlades med AE och PFAS-koncentration 5000 ng L-1 samt prover behandlade med GAC och PFAS-koncentration 200 ng L-1. Reningseffektiviteten varierade också beroende på funktionell grupp, d.v.s. beroende på om det var en sulfonat eller en karboxylat. I kolonnexperimenten avlägsnades de perfluorerade alkylsulfonaterna (PFSAs) i något högre grad (97 % och 91 %; AE och GAC) än karboxylaterna (PFCAs; 67 % och 82 %; AE och GAC). För bägarexperimenten hittades dock inget tydligt motsvarande samband. Sammanfattningsvis renades PFASs från dricksvattnet i kolonnexperimenten relativt väl även i slutet av experimentent (efter 42 dagar). De sämst renade PFAS ämnena var de med kortare kolkedja. Efter 42 dagar hade PFCAs med kolkedjelängd ≤C6 renats bort med 46 % (AE) och på PFCAs med kolkedjelängd ≤C7 med 75 % (GAC). Behovet av bättre reningsmetoder för dessa PFASs är därför stort.

Biofuel is a renewable and sustainable energy source with near-neutral carbon footprint. Algae are an ideal feedstock for biofuel production because they reproduce quickly and have high oil. Algae can be cultivated in non-arable land, and would not impact the food supply. Unfortunately, processing algae into biofuel is more expensive than land crops due to the large volumes of dilute algal suspension that must be harvested and concentrated. In order to improve algae-based biofuel economics, resins were developed that reduce costs associated with water pumping and transport. Hydrophobic resins were developed for binding oil out of an algal suspension so that the residual biomass could be recovered without solvent contamination. Binding behavior displayed lipid species specificity, and binding capacity was improved by ethanol treatment of the biomass. Algae was harvested by binding to anion exchange resin and directly converted into biodiesel. One-step, room temperature in situ transesterification of algae yielded nearly as much biodiesel as two-step, heated transesterification of dried biomass. Elution with transesterification reagent also regenerated the resin for subsequent algal binding. Functionalized resins were developed with high algal binding capacity at neutral pH. Binding was easily reversed, as treatment with buffer with pH higher than pKa of the resin functional group removed the algae and regenerated the resin for subsequent use. The resin bound 10% of its weight in algae and released it as a 100-fold concentrated suspension. The polymers developed can be scaled up for commercial processes and reduce algal harvesting and concentration costs. / text

Cerebral ischemia occurs when blood flow to the brain is insufficient to meet metabolic demand. This can result from cerebral artery occlusion that interrupts blood flow, limits CNS supply of oxygen and glucose, and causes an infarction/ischemic stroke. Ischemia initiates a cascade of molecular events in neurons and cerebrovascular endothelial cells including energy depletion, dissipation of ion gradients, calcium overload, excitotoxicity, oxidative stress, and accumulation of ions and fluid. Blood-brain barrier (BBB) disruption is associated with cerebral ischemia and leads to vasogenic edema, a primary cause of stroke-associated mortality. To date, only a single drug has received US Food and Drug Administration (FDA) approval for treatment of acute ischemia/reperfusion injury, recombinant tissue plasminogen activator (rt-PA). While rt-PA therapy restores perfusion to ischemic brain, considerable tissue damage occurs when cerebral blood flow is re-established. Therefore, there is a critical need for novel therapeutic approaches that can "rescue" salvageable brain tissue and/or protect BBB integrity during cerebral hypoxia and subsequent reoxygenation stress (H/R). One approach that may enable neural tissue rescue following H/R is CNS delivery of drugs with brain protective effects such as HMG-CoA reductase inhibitors (i.e., statins). Our present in vivo data demonstrates that atorvastatin, a commonly prescribed statin, attenuates poly (ADP-ribose) polymerase (PARP) cleavage in the brain following H/R, suggesting neuroprotective efficacy. However, atorvastatin use as a CNS therapeutic is limited by poor blood-brain barrier (BBB) penetration. Therefore, we examined regulation and functional expression of the known statin transporter Oatp1a4 at the BBB under H/R conditions. In rat brain microvessels H/R (6% O₂, 60 min followed by 21% O₂, 10 min) increased Oatp1a4 expression. Brain uptake of taurocholate (i.e., Oap1a4 probe substrate) and atorvastatin were reduced by Oatp inhibitors (i.e., estrone-3-sulfate, fexofenadine), suggesting involvement of Oatp1a4 in brain drug delivery. Pharmacological inhibition of TGF-β/ALK5 signaling with the selective inhibitor SB431542 increased Oatp1a4 functional expression, suggesting a role for TGF-β/ALK5 signaling in Oatp1a4 regulation. Taken together, our novel data show that targeting an endogenous BBB drug uptake transporter (i.e., Oatp1a4) may be a viable approach for optimizing CNS drug delivery for treatment of diseases with an H/R component.