Approaches to the synthesis of chiral and amino-substituted BODIPY dyes

PhD ThesisBoron dipyrromethenes (BODIPYs) have attracted considerable attention due to their fluorescence properties, including high fluorescence quantum yields and absorption coefficients, good photochemical stability and narrow absorption and emission bandwidths. Because of these properties, they have found extensive use for in vivo imaging, analyte sensing, photodynamic therapy, solar cells and light harvesting arrays. This thesis is divided in two parts. Part one covers the synthesis of functionalised chiral BODIPYs whilst part two involves investigations into the synthesis and application of aminoBODIPY via metal catalysed amination reactions. Four approaches to the synthesis of novel chiral BODIPY dyes were investigated. The axially chiral BODIPY dye with C2-symmetry I was synthesised via Suzuki coupling of the corresponding 2,6-dibromoBODIPY with 2-methoxyphenyl boronic acid. The unsymmetrical axially chiral BODIPY II was synthesized via Suzuki coupling of the corresponding 2-bromoBODIPY with phenyl boronic acid. Unfortunately, attempted resolution of these chiral systems by analytical chiral HPLC was unsuccessful. The new helically chiral BODIPYs IIIa-c were synthesised. Resolution of racemic helically chiral BODIPYs IIIa and IIIb was successfully accomplished by preparative chiral HPLC. Abstract ii Electronic circular dichroism (ECD) spectra of both (M) and (P) isomers of IIIa and IIIb were measured by Prof. W. Herrebout (University of Antwerp). Comparison of the measured and computationally predicted ECD spectra allowed the absolute configuration of each of the enantiomeric samples of IIIa-b to be established. The CPL spectra of both (M) and (P) isomers of IIIa and IIIb were recorded by Prof. R. D. Peacock (University of Glasgow). The |glum| of IIIa at 637 nm is 0.0043 and IIIb at 675 nm is 0.0042, which are among the largest so far reported for a simple BODIPY fluorophore in solution. We designed and synthesized the mono-strapped BODIPY V scaffold via sequential regioselective functionalisation of the unsymmetrical BODIPY IV. Resolution of N,N,F,O-BODIPY V by analytical chiral HPLC gave two peaks confirming that single enantiomers of this compound should be accessible. The 8-anisyl-substituted BODIPY VI was synthesized using a standard synthetic route, regioselective iodination with ICl then gave the 2-iodo-substituted BODIPY VII. We unexpectedly found that copper catalysed nucleophilic substitution of the 2-iodoBODIPY VII produced the 3-amino BODIPYs VIIIa-n in good yield. The reactions occurred successfully for a range of primary and secondary alkyl and aryl amines and even with benzamide, albeit in low yield. 2-aminoBODIPYs Xa-e have been prepared successfully via Buchwald–Hartwig amination of the 2-iodoBODIPY IX (fully blocked). The presence of the nitrogen group Abstract iii in the 2-position gives a broadened red-shifted absorption maximum and quenched fluorescence. This palladium catalysed amination was used to prepare the 2-nitroaniline-substituted BODIPY XI. Reduction of the nitro group by hydrogenation gave the novel fluorescencequenched 2-aminoaniline-substituted BODIPY XII. Reaction of this compound with triphosgene gave the corresponding benzimidazolone-substituted BODIPY XIII. The bright yellow fluorescence of the triphosgene reaction product XIII can be easily visualized by the naked eye. The detection limit for phosgene was determined to be 160 nM in solution at room temperature.Taibah Universit

Dopamine-Dependent Task Performance over the Menstrual Cycle

Estradiol (E2) has been found to influence dopamine (DA) activity in the nonhuman animal brain. While there has been very little research performed looking at E2’s effects on DA-related cognitive function in humans, recent research found that women tested during high E2 phases of the menstrual cycle had significantly better performance on a DA-dependent spatial working memory task, than women tested during the lowest E2 phase. The current study utilized the natural hormone fluctuations that occur over the menstrual cycle to determine if E2 is associated with DA-dependent task performance. Using a repeated measures design, 47 women completed a battery of tasks, including 3 that are known to depend heavily on DA. The results showed that DA-dependent task performance was significantly associated with menstrual cycle phase. These findings provide preliminary evidence that variations in E2 over the menstrual cycle can affect central DA function in humans

Supersymmetric Higgs pair discovery prospects at hadron colliders

We study the potential of hadron colliders in the search for the pair production of neutral Higgs bosons in the framework of the Minimal Supersymmetric Standard Model. Using analytical expressions for the relevant amplitudes, we perform a detailed signal and background analysis, working out efficient kinematical cuts for the extraction of the signal. The important role of squark loop contributions to the signal is emphasised. If the signal is sufficiently enhanced by these contributions, it could even be observable at the next run of the upgraded Tevatron collider in the near future. At the LHC the pair production of light and heavy Higgs bosons might be detectable simultaneously.Comment: 5 pages, hep99, 6 figures; Presented at the International Europhysics Conference on High Energy Physics, Tampere, Finland, 15-21 July 199

(Re)thinking patient education and preparation in nuclear medicine and radiology departments: perspectives from technologists and recent-graduates

Patient-centered approach is gaining prominence in several areas of Medicine and is increasingly considered as an important paradigm for the provision of quality healthcare. The communication established between health professionals and patients in hospitals became increasingly seen as fundamental and to be valued, namely in areas such as Radiology (RD) or Nuclear Medicine (NM). Patient education is therefore a common practice in the NM and RD departments, mainly due to the lack of knowledge about this kind of procedures, which is believed to be a reality, based on our empirical evidence and on data not yet published. The aim of this study is to characterize current practices used in patient education in Portuguese Departments of Nuclear Medicine and Radiology.info:eu-repo/semantics/publishedVersio

Short-Term Forecasting of GDP Using Large Monthly Datasets: A Pseudo Real-Time Forecast Evaluation Exercise

This paper evaluates different models for the short-term forecasting of real GDP growth in ten selected European countries and the euro area as a whole. Purely quarterly models are compared with models designed to exploit early releases of monthly indicators for the nowcast and forecast of quarterly GDP growth. Amongst the latter, we consider small bridge equations and forecast equations in which the bridging between monthly and quarterly data is achieved through a regression on factors extracted from large monthly datasets. The forecasting exercise is performed in a simulated real-time context, which takes account of publication lags in the individual series. In general, we find that models that exploit monthly information outperform models that use purely quarterly data and, amongst the former, factor models perform best.Bridge models, Dynamic factor models, real-time data flow model

THE IMPACT OF NEW TARGETING METHODS IN THE CANCER THERAPY

Rapid development has achieved in treating tumor to stop malignant cell growth and metastasis in the past decade. Numerous researches have emerged to increase potency and efficacy with novel methods for drug delivery. The main objective of this literature review was to illustrate the impact of current new targeting methods to other previous delivering systems to select the most appropriate method in cancer therapy. This review first gave a brief summary of cancer structure and highlighted the main roles of targeting systems. Different types of delivering systems have been addressed in this literature review with focusing on the latest carrier derived from malarial protein. The remarkable advantages and main limitations of the later have been also discussed. PubMed and Science Direct were the main search engines that have been used as information sources to prepare this review. Articles related to cancer targeting system, active and passive processes, current nanoparticles, antibody carriers, and current novel cancer carriers were used as sources in this review. Important points from many references published in the last decade (2008-2018) were selected and included. Several targeting methods were introduced to enhance the efficacy and tolerability of the toxic drug by active and passive processes, but there is still no conclusive carrier without certain drawbacks. A combination of targeting methods probably shows the most appropriate choice for increasing selectivity and safety of anticancer drugs via reducing the concentration of carriers used

Short-term forecasting of GDP using large monthly datasets: a pseudo real-time forecast evaluation exercise.

This paper evaluates different models for the short-term forecasting of real GDP growth in ten selected European countries and the euro area as a whole. Purely quarterly models are compared with models designed to exploit early releases of monthly indicators for the nowcast and forecast of quarterly GDP growth. Amongst the latter, we consider small bridge equations and forecast equations in which the bridging between monthly and quarterly data is achieved through a regression on factors extracted from large monthly datasets. The forecasting exercise is performed in a simulated real-time context, which takes account of publication lags in the individual series. In general, we find that models that exploit monthly information outperform models that use purely quarterly data and, amongst the former, factor models perform best.Bridge models ; Dynamic factor models ; real-time data flow.

To shift, or not to shift: Adequate selection of an internal standard in mass-shift approaches using tandem ICP-mass spectrometry (ICP-MS/MS)

The use of an internal standard to correct for potential matrix effects and instrument instability is common practice in ICP-MS. However, with the introduction of a new generation of ICP-MS instrumentation with a tandem mass spectrometry configuration (ICP-MS/MS), the use of chemical resolution in a mass-shift approach has become much more popular, suggesting that the appropriate selection of an internal standard needs revision. In this particular case, it needs to be decided whether the internal standard should also be subjected to a mass-shift or can simply be monitored on-mass ("to shift, or not to shift"). In this work, 17 elements covering a wide range of masses (24-205 amu) and ionization energies (3.89-9.39 eV) were measured via on-mass and/or mass-shift strategies, and the corresponding atomic ions and reaction product ions were monitored during various systematic experiments. For mass-shifting, an NH3/He gas mixture was used to obtain NH3-based reaction product ions (cluster formation). Product ion scanning (PIS) was used for assessing the differences in reactivity between the different analytes and for the identification of the best suited reaction product ions. It was found that the use of chemical resolution can significantly affect the short-term signal stability and that ion signals measured on-mass are not affected in the same way as those measured mass-shifted. Variations affecting the signal intensities of both atomic and reaction product ions can be attributed to the ion-molecule chemistry occurring within the collision/reaction cell and were found to be related with some degree of initial instability in the cell and differences in reactivity. The use of a sufficiently long stabilization time, however, avoids or at least mitigates such differences in the behavior between signals monitored on-mass and after mass-shifting, respectively. Furthermore, the introduction of cell disturbances, such as those generated after quickly switching between different sets of operating conditions in a multi-tune method, revealed significant differences in signal behavior between atomic and reaction product ions, potentially hampering the use of an internal standard monitored on-mass when the analysis is based on an analyte monitored after mass-shifting. However, the use of a reasonable waiting time again greatly mitigates such differences, with the duration of this stabilization time depending on the magnitude of the cell disturbances (e.g., switch between vented and pressurized mode or only between pressurized modes using different gas flow rates). In addition, also the effect of varying different instrument settings (plasma power, torch position, and gas and liquid flow rates) was evaluated, but no remarkable differences were found between signals monitored on-mass and those mass-shifted. Interestingly, a statistical evaluation of the influence of the different settings on the signal intensities of all ions monitored did not reveal the a priori important role of some properties traditionally suggested for adequate selection of analyte/internal standard pairs, such as mass number or ionization energy, as also suggested in other recent studies. © The Royal Society of Chemistry

The use and relevance of gonad protection shields in children during hips radiography

Considering that ionizing radiation effects are cumulative and the gonads are particularly sensitive to these effects, and also the clinical importance of pelvic radiographs in children, the excess of radiation exposure to the gonads must be avoided. The purpose of this study is to demonstrate the relevance of the correct use of gonad protection shields and to evaluate their use on the hip radiographs performed in a reference clinical institution, through the retrospective analysis of pelvic radiographic images performed in children. According the image quality assessment, 20 (40%) patients were unprotected and gonads shields were incorrectly placed in 24 (80%) patients.Dado que os efeitos da radiação ionizante são cumulativos e as gónadas são particularmente sensíveis a estes efeitos, e também pela importância clínica das radiografias pélvicas nas crianças, deve evitar-se a exposição excessiva da região gonadal à radiação. Neste estudo, pretende-se demonstrar a relevância da correcta utilização da protecção gonadal e avaliar a sua utilização em radiografias da bacia. Através da análise retrospectiva de imagens radiográficas da bacia realizadas em crianças, concluiu-se que não foi utilizada a protecção gonadal em 20 (40%) pacientes, e estas foram incorrectamente colocadas em 24 (80%) pacientes