The European Strategy Forum on Research Infrastructures (ESFRI) has selected in 2006 a proposal based on ultra-intense laser fields with intensities reaching up to 10-10 W cm called 'ELI' for Extreme Light Infrastructure. The construction of a large-scale laser-centred, distributed pan-European research infrastructure, involving beyond the state-of-the-art ultra-short and ultra-intense laser technologies, received the approval for funding in 2011-2012. The three pillars of the ELI facility are being built in Czech Republic, Hungary and Romania. The Romanian pillar is ELI-Nuclear Physics (ELI-NP). The new facility is intended to serve a broad national, European and International science community. Its mission covers scientific research at the frontier of knowledge involving two domains. The first one is laser-driven experiments related to nuclear physics, strong-field quantum electrodynamics and associated vacuum effects. The second is based on a Compton backscattering high-brilliance and intense low-energy gamma beam (<20 MeV), a marriage of laser and accelerator technology which will allow us to investigate nuclear structure and reactions as well as nuclear astrophysics with unprecedented resolution and accuracy. In addition to fundamental themes, a large number of applications with significant societal impact are being developed. The ELI-NP research centre will be located in Măgurele near Bucharest, Romania. The project is implemented by 'Horia Hulubei' National Institute for Physics and Nuclear Engineering (IFIN-HH). The project started in January 2013 and the new facility will be fully operational by the end of 2019. After a short introduction to multi-PW lasers and multi-MeV brilliant gamma beam scientific and technical description of the future ELI-NP facility as well as the present status of its implementation of ELI-NP, will be presented. The science and examples of societal applications at reach with these electromagnetic probes with much improved performances provided at this new facility will be discussed with a special focus on day-one experiments and associated novel instrumentation.
IntroductionPhenothiazines when exposed to white light or to UV radiation undergo a variety of reactions that result in degradation of parental compound and formation of new species. This process is slow and may be sped up with exposure to high energy light such as that produced by a laser.MethodsVarying concentrations of Chlorpromazine Hydrochloride (CPZ) (2–20 mg/mL in distilled water) were exposed to 266 nm laser beam (time intervals: 1–24 hrs). At distinct intervals the irradiation products were evaluated by spectrophotometry between 200–1500 nm, Thin Layer Chromatography, High Pressure Liquid Chromatography (HPLC) - Diode Array Detection, HPLC tandem mass spectrometry, and for activity against the CPZ sensitive test organism Staphylococcus aureus ATCC 25923.ResultsCPZ exposure to 266 nm laser beam of given energy levels yielded species, whose number increased with duration of exposure. Although the major species produced were Promazine (PZ), hydroxypromazine or PZ sulfoxide, and CPZ sulfoxide, over 200 compounds were generated with exposure of 20 mg/mL of CPZ for 24 hrs. Evaluation of the irradiation products indicated that the bioactivity against the test organism increased despite the total disappearance of CPZ, that is due, most probably, to one or more new species that remain yet unidentified.ConclusionsExposure of CPZ to a high energy (6.5 mJ) 266 nm laser beam yields rapidly a large number of new and stable species. For biological grade phenothiazines (in other words knowing the impurities in the samples: solvent and solute) this process may be reproducible because one can control within reasonably low experimental errors: the concentration of the parent compound, the laser beam wavelength and average energy, as well as the duration of the exposure time. Because the process is “clean” and rapid, it may offer advantages over the pyrogenically based methods for the production of derivatives.
Whereas exposure of combinations of a phenothiazine and bacterium to incoherent UV increases the activity of the phenothiazine, exposure of the phenothiazine alone does not yield an increase of its activity. Because the laser beam energy is greater than that produced by the incoherent UV sources, exposure of phenothiazines to specific lasers may yield molecules with altered activities over that of the unexposed parent. Chlorpromazine, thioridazine and promethazine active against bacteria were exposed to two distinct lasers for varying periods of time. Absorption and fluorescence spectra were conducted prior to and post-exposure and the products of laser exposure evaluated for activity against a Staphylococcus aureus ATCC strain via a disk susceptibility assay. Exposure to lasers alters the absorption/fluorescence spectra of the phenothiazines; reduces the activity of thioridazine against the test bacterium; produces a highly active chlorpromazine compound against the test organism. Exposure of phenothiazines to lasers alters their structure that results in altered activity against a bacterium. This is the first report that lasers can alter the physico-chemico characteristics to the extent that altered bioactivity results. Exposure to lasers is expected to yield compounds that are difficult to make via chemical manipulation methods. A survey of selected patents of interest, even co-lateral for the subject of this article is shortly made.
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