Guest Intercalation Into Metal Halide Inorganic-Organic Layered Perovskite Hybrid Solids And Hydrothermal Synthesis Of Tin Oxide Spheres

The work presented in this thesis is divided into two research areas. In part I, the synthesis and guest intercalation of inorganic-organic metal halide ammonium layered perovskites is discussed. Comparisons are made between the solid matrix before and after the intercalations, and all solids are characterized using thermogravimetric analysis (TGA) and powder X-ray diffraction (XRD). In part II, “templateree” hydrothermal synthesis of tin oxide spheres in the presence of different ortho-substituted anilines is discussed. The aim is to determine whether there are differences in the structures, shapes and surface morphology of the tin oxide spheres that correspond to the identity/shape of the ortho-substituent on the anilines. Solids were characterized by XRD, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques

Novel chelating agents for zirconium-89-positron emission tomography (PET) imaging: Synthesis, DFT calculation, radiolabeling, and in vitro and in vivo complex stability

We report the synthesis and evaluation of novel chelating agents for zirconium-89

Studies on Hexahapto-Dibenzo[A,E]Cyclooctatetraene Complexes of Chromiumtricarbonyl and Cationic Manganesetricarbonyl

Mono- and dinuclear chromiumtricarbonyl and manganesetricarbonyl complexes of dibenzo[a,e]cyclooctatetraene (DBCOT) were synthesized and characterized. In the bis(chromiumtricarbonyl)DBCOT synthesis, the main product was the syn,anti isomer where the two Cr(CO)3 moieties coordinate to opposite faces of the DBCOT backbone. This complex exhibits three dynamic processes in solution. A ring inversion of the organic skeleton occurs while the two chromiumtricarbonyl moieties undergo tripod rotation. This is the first study where eight-membered ring inversion is studied for a pi-coordinated metallic system. The rate of inversion at various temperatures was determined by 1H NMR line shape analysis at two different field strengths (300 and 600 MHz). Compared with other cyclooctatetraene compounds reported, there is a large positive entropy of activation and a relatively high enthalpy of activation in this system. DFT calculations, using the B3LYP/6-31G** basis set, were performed to gain a better understanding of the experimental results. It is proposed that free rotation of both Cr(CO)3 groups in the planar transition state are responsible for the large entropy of activation for ring inversion in hexahapto,hexahapto-dibenzo[a,e]cyclooctatetraene-syn,anti-bis(tricarbonylchromium). The relatively large enthalpy of activation is due to a stabilizing interaction between the endo carbonyl groups on the syn-Cr(CO)3 and the remote arene. In the monometallic DBCOT complexes, the metal can either be inside or outside the tub conformation. Interestingly, the crystal structures show opposite orientations for the isoelectronic chromium and manganese systems. The Cr(CO)3 group is positioned anti relative to the DBCOT backbone while the Mn(CO)3+ is syn. It should be noted that the optimized gas phase geometries obtained through DFT calculations agree with the crystallographic results. Electrochemical studies were performed to investigate the change in redox behavior associated with coordination of mono and bis-chromium units to the DBCOT backbone. Four new organometallic crystal structures are reported in this dissertation. Different tripod orientations, DBCOT backbone angles, and metal orientation relative to the interior of the organic skeleton are found. C-H...O, C-H...pi, and charge assisted C-H...F hydrogen bonding interactions were observed in the solid state packing. The structural motifs found suggest these complexes could serve as organometallic synthons in supramolecular chemistry

Do the Th17 Cells Play a Role in the Pathogenesis of Leptospirosis?

Objectives. The aim of this study was to determine the level of five different pro- and anti-inflammatory cytokines to study the inflammatory response of leptospirosis. Materials and methods. The serum cytokine levels of IL-10, IL-17A, IL-21, IL-23, and TNF-α were investigated in 57 patients with leptospirosis and 12 healthy controls using a commercially available ELISA kit (Mabtech, Sweden). Statistical analysis was done using Graphpad Prism. Results. Elevation of serum IL-10 and IL-17A levels and significant elevation of serum IL-21 (p=0.002), IL-23 (p=0.002), and TNF-α (p=0.039) were observed among leptospirosis patients compared to the healthy control group. The two major complications observed among these patients were renal failure and liver involvement. Renal failure was significantly associated with elevation of IL-21 and IL-23, while patients with liver involvement had a significant elevation of IL-21, IL-23, and TNF-α. Conclusion. Elevation of IL-17A together with the significant elevation of IL-21 and IL-23 suggests a possible involvement of Th17 cells in the immunopathogenesis of leptospirosis

Divalent 2-(4-Hydroxyphenyl)benzothiazole Bifunctional Chelators for 64Cu PET Imaging in Alzheimer’s Disease

Herein we report a new series of divalent 2-(4-hydroxyphenyl)benzothiazole bifunctional chelators (BFCs) with high affinity for amyloid β aggregates and favorable lipophilicity for blood-brain barrier (BBB) penetration. The addition of an alkyl carboxylate ester pendant arm offers high binding affinity towards Cu(II). The novel BFCs form stable 64Cu-radiolabeled complexes and exhibit promising partition coefficient (log D) values of 1.05-1.85. Among the five compounds tested, the 64Cu-YW-15 complex exhibits significant staining of amyloid β plaques in ex vivo autoradiography studies. In addition, biodistribution studies show that 64Cu-YW-15-Me exhibits elevated brain uptake (0.89 ± 0.25 %ID/g) in transgenic AD versus wild type mice

Benzothiazole Carboxylate Diester Bifunctional Chelators for 64Cu PET Imaging in Alzheimer’s Disease

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms enable high binding affinity towards Cu(II). The BFCs form stable 64Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, the 64Cu-YW-1 and 64Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies

Metal-Chelating Benzothiazole Multifunctional Compounds for the Modulation and 64Cu PET Imaging of Aβ Aggregation

While Alzheimer’s Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Ab aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Ab aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Ab oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 %ID/g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD