Synthesis and characterization of Ruthenium complexes

In this project, [Cp*RuCl2]2 has been used as the starting material to prepare two new Ruthenium complexes. [Cp*RuCl2]2 reacts with the C6H8S2 (NHCS) ligand only in acetonitrile, to form Cp*RuCl2{NHCS} cleanly, according to observations. [Cp*RuCl2]2 was also used to prepare Cp*RuCl2S2CNMe2 according to literature procedures, which was then made to react with the NHCS ligand, to form [Cp*RuCl2S2CNMe2{NHCS}]. 1H and 13C NMR spectroscopy, together with Mass Spectroscopic Methods were used to characterize the products. At the point of submission, diffraction quality crystals are being grown to determine the absolute structure of the products.Bachelor of Science in Chemistry and Biological Chemistr

A reactivity-based 18F-labeled probe for PET imaging of oxidative stress in chemotherapy-induced cardiotoxicity

[Image: see text] Oxidative stress underlies the pathology of many human diseases, including the doxorubicin-induced off-target cardiotoxicity in cancer chemotherapies. Since current diagnostic procedures are only capable of monitoring cardiac function, a noninvasive means of detecting biochemical changes in redox status prior to irreversible functional changes is highly desirable for both early diagnosis and prognosis. We designed a novel (18)F-labeled molecular probe, (18)F-FPBT, for the direct detection of superoxide in vivo using positron emission tomography (PET). (18)F-FPBT was radiosynthesized in one step by nucleophilic radiofluorination. In vitro, (18)F-FPBT showed rapid and selective oxidation by superoxide (around 60% in 5 min) compared to other physiological ROS. In healthy mice and rats, (18)F-FBPT is distributed to all major organs in the first few minutes post injection and is rapidly cleared via both renal and hepatobiliary routes with minimal background retention in the heart. In a rat model of doxorubicin-induced cardiotoxicity, (18)F-FBPT showed significantly higher (P < 0.05) uptake in the hearts of treated animals compared to healthy controls. These results warrant further optimization of (18)F-FBPT for clinical translation

Modulation of Lymphocyte Potassium Channel KV1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated KV1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to KV1.3, causing current run-down by a phosphatidylinositol 4,5-bisphosphate-dependent mechanism. EgK5 exhibits selectivity for KV1.3 over other channels, receptors, transporters, and enzymes. EgK5 suppresses antigen-triggered proliferation of effector memory T cells, a subset enriched among pathogenic autoreactive T cells in autoimmune disease. PET-CT imaging with 18F-labeled EgK5 shows accumulation of the peptide in large and small joints of rodents. In keeping with its arthrotropism, EgK5 treats disease in a rat model of rheumatoid arthritis. It was also effective in treating disease in a rat model of atopic dermatitis. No signs of toxicity are observed at 10-100 times the in vivo dose. EgK5 shows promise for clinical development as a therapeutic for autoimmune diseases