RESUMEN
Best resolutions in X-ray focusing are obtained to date by using diffractive lenses called Fresnel zone plates (FZPs). Their further improvement is nevertheless hindered by fundamental limitations in the employed manufacturing techniques. Here, we show a novel method to fabricate FZPs based on multilayer deposition with atomic layer deposition (ALD) and subsequent sectioning with focused ion beam (FIB). For the first time a multilayer FZP working in the soft X-ray range was prepared and could achieve the best resolution obtained so far for multilayer FZPs by resolving features below 39nm in size in a scanning soft X-ray microscope. The new technique presents high potential for high resolution microscopy in both the soft and hard X-ray range.
RESUMEN
The intramolecular degrees of freedom contributing to the ultrafast excited-state intramolecular proton transfer of 1-hydroxy-2-acetonaphthone are determined. Thereto, resonance Raman studies are combined with transient absorption measurements with 30-fs time resolution. Enhanced Raman intensity is found in coordinates that are dominantly associated with deformations and bond length changes in the naphthalene chromophore. This indicates that the primary changes after the optical excitation are a geometric relaxation of the chromophore. A ringing of the molecule after the ultrafast proton transfer is observed by the transient absorption measurements. It reveals the nuclear coordinates contributing to the reaction path beyond the Franck-Condon region. There, planar H-chelate ring deformations changing the donor-acceptor distance are found to dominate. The difference in the observed vibrational signatures indicates a significant turn in the reaction path.
RESUMEN
Surface-enhanced Raman spectroscopy (SERS) has been applied to characterize the interaction of 6-mercaptopurine-ribose (6MPR), an active drug used in chemotherapy of acute lymphoblastic leukemia, with a model biological substrate at therapeutic concentrations and as function of the pH value. Therefore, a detailed vibrational analysis of crystalline and solvated (6MPR) based on Density Functional Theory (DFT) calculations of the thion and thiol tautomers has been performed. 6MPR adopts the thion tautomeric form in the polycrystalline state. The SERS spectra of 6MPR and 6-mercaptopurine (6MP) recorded on silver colloid provided evidence that the ribose derivative shows different adsorption behavior compared with the free base. Under acidic conditions, the adsorption of 6MPR on the metal surface via the N7 and possibly S atoms was proposed to have a perpendicular orientation, while 6MP is probably adsorbed through the N9 and N3 atoms. Under basic conditions both molecules are adsorbed through the N1 and possibly S atoms, but 6MP has a more tilted orientation on the silver colloidal surface while 6MPR adopts a perpendicular orientation. The reorientation of the 6MPR molecule on the surface starts at pH 8 while in the case of 6MP the reorientation starts around pH 6. Under basic conditions, the presence of the anionic molecular species for both molecules is suggested. The deprotonation of 6MP is completed at pH 8 while the deprotonation of the riboside is finished at pH 10. For low drug concentrations under neutral conditions and for pH values 8 and 9, 6MPR interacts with the substrate through both N7 and N1 atoms, possibly forming two differently adsorbed species, while for 6MP only one species adsorbed via N1 was evidenced.
Asunto(s)
Antimetabolitos Antineoplásicos/química , Mercaptopurina/química , Tioinosina/química , Adsorción , Coloides , Humanos , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Estructura Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Plata , Espectrometría Raman/métodosRESUMEN
Quinolones are important gyrase inhibitors. Even though they are used as active agents in many antibiotics, the detailed mechanism of action on a molecular level is so far not known. It is of greatest interest to shed light on this drug-target interaction to provide useful information in the fight against growing resistances and obtain new insights for the development of new powerful drugs. To reach this goal, on a first step it is essential to understand the structural characteristics of the drugs and the effects that are caused by the environment in detail. In this work we report on Raman spectroscopical investigations of a variety of gyrase inhibitors (nalidixic acid, oxolinic acid, cinoxacin, flumequine, norfloxacin, ciprofloxacin, lomefloxacin, ofloxacin, enoxacin, sarafloxacin and moxifloxacin) by means of micro-Raman spectroscopy excited with various excitation wavelengths, both in the off-resonance region (532, 633, 830 and 1064 nm) and in the resonance region (resonance Raman spectroscopy at 244, 257 and 275 nm). Furthermore DFT calculations were performed to assign the vibrational modes, as well as for an identification of intramolecular hydrogen bonding motifs. The effect of small changes in the drug environment was studied by adding successively small amounts of water until physiological low concentrations of the drugs in aqueous solution were obtained. At these low concentrations resonance Raman spectroscopy proved to be a useful and sensitive technique. Supplementary information was obtained from IR and UV/vis spectroscopy.
Asunto(s)
Fluoroquinolonas/química , Espectrometría Raman/métodos , Compuestos Aza/química , Cinoxacino/química , Ciprofloxacina/análogos & derivados , Ciprofloxacina/química , Girasa de ADN/metabolismo , ADN Bacteriano/metabolismo , Enoxacino/química , Inhibidores Enzimáticos/farmacología , Enlace de Hidrógeno , Concentración de Iones de Hidrógeno , Modelos Químicos , Modelos Moleculares , Modelos Teóricos , Moxifloxacino , Ácido Nalidíxico/química , Norfloxacino/química , Ofloxacino/química , Ácido Oxolínico/química , Quinolinas/química , Quinolonas/química , Espectrofotometría Infrarroja , Temperatura , Rayos Ultravioleta , Vibración , Agua/químicaRESUMEN
The surface enhanced Raman spectroscopy (SERS) spectrum of caffeine is recorded on a silver colloid at different pH values. It is discussed on the basis of the SERS "surface selection rules" in order to characterize its vibrational behavior on such a biological artificial model. To improve the previous assignments in the Raman spectrum and for a reliable, detailed analysis of SERS spectra, density functional theory calculations (structural parameters, harmonic vibrational wavenumbers, total electron density, and natural population analysis of the molecule) are performed for the anhydrous form of caffeine and the results are discussed. The predicted geometry and vibrational Raman spectra are in good agreement with the experimental data. The flat orientation of the mainly chemisorbed caffeine attached through the pi electrons and the lone pair of nonmethylated N atoms of the imidazole ring are proposed to occur at neutral and basic pH values. At acid pH values caffeine is probably adsorbed on the Ag surface through one or both oxygen atoms, more probably through the O atom of the conjugated carbonyl group with an end-on orientation. However, the changes in the overall SERS spectral pattern seem to indicate the electromagnetic mechanism as being the dominant one.