Development of luminescent probes for ultrasensitive detection of biopolymers, their complexes, and living cells

New luminescent probes with enhanced brightness convenient for bioconjugation were synthesized and tested in major biological applications including the detection of nucleic acids and living cells. The first project used luminescent lanthanide ion probes that take advantage of hyper-sensitive acquisition of their long-lived emission signal in time- resolved mode, which avoids short-lived background fluorescence of the medium. Two model carbostyril fluorophores (cs 124-CH3 and cs 124-CF3) were modified by inclusion of two spacers (diamino and bi-phenyl) for the attachment of amine and thiol reactive cross-linking groups. In this project, time-resolved measurements are presented for spectroscopy and microscopy. The probes were synthesized, then characterized by UV/VIS, NMR, mass spectrometry and then validated in various biological applications. DNA detection using luminescently labeled molecular beacons hybridization probes was performed with sensitivity less then 1 pM, which is about 100 fold higher then that for conventional fluorescent probes. Further 30-fold increase in detection sensitivity was achieved by tethering multiple lanthanide probes to a carrier molecule, avidin. The resulting avidin conjugates were used for imaging of living cells employing time-gated fluorescent microscopy. Six thiol-reactive derivatives of the lanthanide ion probes with bromoacetamido- and maleimido- cross-linking groups were synthesized. It was found that maleimido-compounds displayed exceptional reactivity instantaneously coupling to thiols at physiological conditions at micromolar thiol concentrations. The second part of the project included the development of light-emitting diagnostic molecules for the detection of human microbial pathogens. The approach employs fluorescently labeled antibiotics, which retain high specificity towards pathogens and render them fluorescent after binding to their cellular targets. These studies present that the obtained derivative 7- aminoDDAO is ~2.8 fold brighter than its predecessor DDAO, with excitation and emission maxima located in the spectral area where body tissues are the most transparent (λem= 680 nm). Using near-infrared emitting dyes, this approach presents non-invasive tomographic detection of the pathogens in the living body, thereby enabling swift and efficient therapies. The desired NIR probes were synthesized and validated in a collaboration study by detection of fungal infections in mice

Development of pharmacophore and CoMFA studies for sigma2 receptor ligands

This study describes the development of a pharmacophore and CoMIFA model for sigma 2 (σ2) receptor ligands. CoMFA studies were performed for 32 bioactive σ2 receptor ligands using the radioligand [H 3] (+) DTG in the presence of pentazocine. The pharmacophore was derived using Distance Comparisons (DISCOtech) from eight partially to highly active ~2 receptor ligands. All 32 compounds were calculated in three methods: AMi, HFI3~21G*, and B3LYP/3~21G* methods. These methods run in Gaussian 98 determined the geometry optimization and electrostatic charges for each molecule. CoMFA maps were developed using SYBYL ver. 7.2 to compare the electrostatic and steric properties of each calculation and molecule. With leave-one-out cross validation, the numbers of optimal components was determined. No cross validation was performed in a training set using the optimal components for each analysis. After the completion of a test set, it was verified that CoMIFA models derived from HF/3~21G* optimized geometries and atomic charges are more reliable in predicting the bioactivities of σ2 receptor ligands. Using the HF/3~21G* analysis, new active σ2 receptor ligands were designed and pK i values were predicted. It was determined that active σ2 receptor ligands require localization on the benzene ring contributed through an electron withdrawing group

Preparation of aqueous anionic poly(urethane-urea) dispersions. Influence of the incorporation of acrylic, polycarbonate and perfluoro-oligoether diols on the dispersion and polymer properties

Aqueous poly(urethane‐urea) dispersions were prepared by the prepolymer mixing technique, without using any organic solvent. This work focused on the incorporation into the prepolymer chain of specific macrodiols bearing acrylic, polycarbonate and perfluoro‐oligoether chains, in conjunction with a poly(propylene oxide) diol (Mn = 1000). All the dispersions were synthesized with a fixed NCO/OH ratio, using α,α,α′,α′‐tetramethyl‐1,3‐xylylene diisocayanate, a fixed proportion of emulsifying agent (dimethylol propionic acid, neutralized with triethylamine) and the same chain extender (1,2‐ethylene diamine). The properties of both the dispersions and the dried polymer films were characterized as a function of the nature of the specific incorporated diol and its proportion in the polymer chain, in order to establish criteria leading to an optimized performance in terms of particle size, viscosity, and polymer film properties

Isocyanurate Formation During Oxazolidinone Synthesis from Epoxides and Isocyanates Catalysed by a Chromium(Salphen) Complex

Chromium(salphen) complex 10 is found to be a catalyst for the preparation of oxazolidinones from epoxides and isocyanates. Using the optimal reaction conditions (1.5 mol % of chromium(salphen) complex 10 at 80 °C in toluene for 4 hours), six epoxides were reacted with five isocyanates, providing 15 oxazolidinones in up to 90 % yield. With electron-deficient isocyanates, cyclotrimerisation of the isocyanate to the corresponding isocyanurates is a competing reaction, showing the importance of matching catalyst activity to that of the substrates

Identity of Intermarium – West

Prezentowany tekst jest wprowadzeniem do rozprawy o formowaniu się Międzymorza, którego kraje w XIX oraz XX wieku pozbawione były bytu politycznego i suwerenności. Stało się to przyczyną uformowania specyfi cznej tożsamości w napięciu między demokracją Zachodu i samodzierżawiem Rosji. Społeczności Międzymorza nie brały zatem udziału w kształtowaniu struktur nowożytnych państw narodowych w XIX stuleciu. Tekst wprowadza w problematykę włączania krajów Międzymorza w zachodni system polityczny po przemianach 1989 roku.The presented text is an introduction to the study of the formation of the Intermarium, which in the 19th and 20th centuries included countries that lacked political existence or had limited sovereinty. This fact has now conditioned the identity of these peoples in the space between Western democracy and Russian autocracy. The peoples of the Intermarium were under the dominance of other countries, so they did not participate in the formation of modern nation-states in the 19th century. The text is an attempt to outline the formation of the political system of Western Europe (Latin), which constituted the starting point for the countries of the Intermarium in creating their own political systems (after 1989)