Two-photon chemistry of tetrahydrofuran in clathrate hydrates.

High-lying electronic states hold the potential for new and unusual photochemical reactions. However, for conventional single-photon excitation in the condensed phase, reaching these states is often not possible because the vacuum-ultraviolet (VUV) light required is competitively absorbed by the surrounding matrix rather than the molecule of interest. Here, this hurdle is overcome by leveraging nonresonant two-photon absorption (2PA) at 265 nm to achieve preferential photolysis of tetrahydrofuran (THF) trapped within a clathrate hydrate network at 77 K. Electron spin resonance (ESR) spectroscopy enables direct observation and identification of otherwise short-lived organic radicals stabilized by the clathrate cages, providing clues into the rapid dynamics that immediately follow photoexcitation. 2PA induces extensive fragmentation of enclathrated THF yielding 1-alkyl, acyl, allyl and methyl radicals-a stark departure from the reactive motifs commonly reported in γ-irradiated hydrates. We speculate on the undetected transient dynamics and explore the potential role of trapped electrons generated from water and THF. This demonstration of nonresonant two-photon chemistry presents an alternative approach to targeted condensed phase photochemistry in the VUV energy range.

Observation of Electric-Field-Induced Liberation of Guest Molecules from Clathrate Hydrate.

Clathrate hydrates can store a high density of guest molecules in cages. However, as a gas-storage material, the controllable release of guests therefrom is still challenging. Here we report on the utilization of an electric field as a control agent. Attenuated total reflectance surface-enhanced infrared absorption spectroscopy (ATR-SEIRAS) is used to investigate the release of tetrahydrofuran (THF) from the clathrate in the electrochemical double layer (EDL). When voltage is applied, the ATR-SEIRA signal from encaged THF rapidly decreases, and the water characteristic O-H absorption peak exhibits an appreciable blue-shift. Our measurements indicate a transformation of the hydrate lattice to a less H-bonded configuration at the electrode surface. In combination with previous experimental results on the orientation of water molecules in the EDL, we propose that the strong electric field in the EDL aligns the water molecules of the clathrate and distorts the hydrate lattice structure enough to release the trapped guest molecules.

Ultrafast X-ray absorption study of longitudinal-transverse phonon coupling in electrolyte aqueous solution.

Ultrafast X-ray absorption spectroscopy is applied to study the conversion of longitudinal to transverse phonons in aqueous solution. Permanganate solutes serve as X-ray probe molecules that permit the measurement of the conversion of 13.5 GHz, longitudinal phonons to 27 GHz, transverse phonons that propagate with high-frequency sound speed. The experimental results, combined with QM/MM MD simulations, show that the hydrogen bond network around the charged solutes has a glass-like stiffness that persists for at least tens of picoseconds.

Ultrafast X-ray measurements of the glass-like, high-frequency stiffness of aqueous solutions.

The ultrafast dynamics of the domains surrounding solutes in aqueous solution were measured using laser-generating GHz phonons inside of 30 mM ferrocyanide solutions and the resulting molecular motions of the solutes and their hydrogen-bonded solvation shells were detected using ultrafast X-ray absorption spectroscopy (UXAS). The measurements of the phonon dynamics around the solutes showed that the domains had a glass-like stiffness on a timescale of tens of picoseconds.

X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (<1 cm diameter) has proven elusive. Better, more specific, and more sensitive detection methods are therefore urgently needed. Here we discuss the application of a newly developed x-ray imaging technique called Spatial Frequency Heterodyne Imaging (SFHI) for the early detection of HCC. SFHI uses x-rays scattered by an object to form an image and is more sensitive than conventional absorption-based x-radiography. We show that tissues labeled in vivo with gold nanoparticle contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

Picosecond-resolved X-ray absorption spectroscopy at low signal contrast using a hard X-ray streak camera.

A picosecond-resolving hard-X-ray streak camera has been in operation for several years at Sector 7 of the Advanced Photon Source (APS). Several upgrades have been implemented over the past few years to optimize integration into the beamline, reduce the timing jitter, and improve the signal-to-noise ratio. These include the development of X-ray optics for focusing the X-rays into the sample and the entrance slit of the streak camera, and measures to minimize the amount of laser light needed to generate the deflection-voltage ramp. For the latter, the photoconductive switch generating the deflection ramp was replaced with microwave power electronics. With these, the streak camera operates routinely at 88 MHz repetition rate, thus making it compatible with all of the APS fill patterns including use of all the X-rays in the 324-bunch mode. Sample data are shown to demonstrate the performance.

A highly sensitive x-ray imaging modality for hepatocellular carcinoma detection in vitro.

Innovations that improve sensitivity and reduce cost are of paramount importance in diagnostic imaging. The novel x-ray imaging modality called spatial frequency heterodyne imaging (SFHI) is based on a linear arrangement of x-ray source, tissue, and x-ray detector, much like that of a conventional x-ray imaging apparatus. However, SFHI rests on a complete paradigm reversal compared to conventional x-ray absorption-based radiology: while scattered x-rays are carefully rejected in absorption-based x-ray radiology to enhance the image contrast, SFHI forms images exclusively from x-rays scattered by the tissue. In this study we use numerical processing to produce x-ray scatter images of hepatocellular carcinoma labeled with a nanoparticle contrast agent. We subsequently compare the sensitivity of SFHI in this application to that of both conventional x-ray imaging and magnetic resonance imaging (MRI). Although SFHI is still in the early stages of its development, our results show that the sensitivity of SFHI is an order of magnitude greater than that of absorption-based x-ray imaging and approximately equal to that of MRI. As x-ray imaging modalities typically have lower installation and service costs compared to MRI, SFHI could become a cost effective alternative to MRI, particularly in areas of the world with inadequate availability of MRI facilities.

X-ray focusing scheme with continuously variable lens.

A novel hybrid X-ray focusing scheme was developed for operation of the X-ray streak camera at the Advanced Photon Source: an X-ray lens focuses vertically from a long distance of 16 m and produces an extended focus that has a small footprint on an inexpensive sagittal mirror. A patented method is used to continuously adjust the focal length of the lens and compensate for chromatic dispersion in energy scans.

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents.

Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size.

X-ray spatial harmonic imaging of phase objects.

Refractive index gradients in materials or at material interfaces lead to x-ray diffraction. Interference of this radiation with adjacent x-ray waves causes phase contrast that can be used for imaging purposes if an x-ray source with sufficient spatial coherence is used. The imaging modality presented here uses hard x radiation diffracted at interfaces, but requires only little spatial coherence. We report experiments showing, first, that image contrast is not diminished by motional blurring, and second, that contrast can be increased by orders of magnitude relative to in-line x-ray phase-contrast imaging. These properties substantially broaden the applicability of phase-sensitive imaging to moving samples and very weak density gradients.

Nanomaterials for X-ray imaging: gold nanoparticle enhancement of X-ray scatter imaging of hepatocellular carcinoma.

We present the development of a new imaging technique for the early diagnosis of hepatocellular carcinoma that utilizes surface-modified gold nanoparticles in combination with X-ray imaging. Tissues labeled with these electron-dense particles show enhanced X-ray scattering over normal tissues, distinguishing cells containing gold nanoparticles from cells without gold in X-ray scatter images. Our results suggest that this novel approach could enable the in vivo detection of tumors as small as a few millimeters in size.

Picosecond X-ray absorption measurements of the ligand substitution dynamics of Fe(CO)5 in ethanol.

Ultrafast X-ray absorption near edge spectroscopy has been carried out for photo excited iron pentacarbonyl in ethanol with 2 picosecond resolution. A temporal resolution limited dissociation process was observed, followed by the formation of the mono-substituted complex Fe(CO)(4)EtOH within a few tens of picoseconds. The measurements have been carried out with a newly developed X-ray absorption instrument at station 7 ID-C of the Advanced Photon Source. The results show that single picosecond temporal resolution can be achieved at a synchrotron beam line.

X-ray phase contrast imaging: Transmission functions separable in cylindrical coordinates.

A Fresnel-Kirchhoff integral can be used to calculate x-ray phase contrast images when the transmission function is known. Here expressions for image intensity are derived for objects with axial symmetry for an x-ray source with non-vanishing dimensions. An expression for the image intensity is given for an x-ray source whose intensity distribution is described by a Gaussian function, from which an expression for the limiting case of a point source of radiation is found. The expressions for image intensity are evaluated for cases where the magnification is substantially greater than one, as would be employed in biological imaging. Experiments using a microfocus x-ray tube and charge coupled device camera are reported to determine the capability of the method for imaging small spherical objects, such as gold particles, which might find application as contrast agents in biomedical imaging.

Low density contrast agents for x-ray phase contrast imaging: the use of ambient air for x-ray angiography of excised murine liver tissue.

We report a new preparative method for providing contrast through reduction in electron density that is uniquely suited for propagation-based differential x-ray phase contrast imaging. The method, which results in an air or fluid filled vasculature, makes possible visualization of the smallest microvessels, roughly down to 15 microm, in an excised murine liver, while preserving the tissue for subsequent histological workup. We show the utility of spatial frequency filtering for increasing the visibility of minute features characteristic of phase contrast imaging, and the capability of tomographic reconstruction to reveal microvessel structure and three-dimensional visualization of the sample. The effect of water evaporation from livers during x-ray imaging on the visibility of blood vessels is delineated. The deformed vascular tree in a cancerous murine liver is imaged.

Structure of solvated Fe(CO)5: complex formation during solvation in alcohols.

The equilibrium structure of iron pentacarbonyl, Fe(CO)5, solvated in various alcohols has been investigated by Fourier transform infrared (FTIR) measurements and density functional theory calculations. This system was studied because it is prototypical of a larger class of monometallic systems, which are electronically saturated but not sterically crowded. Upon solvation, the Fe(CO)5 is not just surrounded by a solvation shell. Instead, solute-solvent complexes are formed with the oxygen of the alcohol oriented toward an axial ligand of the Fe(CO)5 giving a formation energy on the order of -5 kJ/mol. This complexation is not a chemical reaction but rather a "preassembly" of the solute molecules with a single solvent molecule. For instance, at room temperature the interaction between Fe(CO)5 and ethanol results in 87% of all Fe(CO)5 molecules being complexated with a single ethanol molecule. This complexation was found in all the alcohol systems studied in this paper. The stability of these complexes was found to depend on the alcohol chain length and branching. The observed complexation mechanism is accompanied by an electron density shift from the complexed alcohol molecule toward Fe(CO)5 where it induces a dipole moment. The finding that Fe(CO)5 forms a complex with the hydroxyl group of a single solvent molecule might have significant implications for ligand substitution reactions. This implies that ligand substitution reactions do not have to proceed via a dissociative mechanism. Instead, the reaction might proceed through a concerted mechanism with the leaving CO simultaneously being replaced by the incoming alcohol that was complexed to Fe(CO)5 prior to the photoexcitation.

Ultrafast x-ray pulses emitted from a liquid mercury laser target.

We report the generation of ultrashort, hard-x-ray pulses from a liquid mercury target irradiated by 5 kHz laser pulses. The new x-ray source is designed for time-resolved x-ray absorption spectroscopy as well as imaging applications. This marks the first laser-driven plasma x-ray source that continuously recycles the target material, facilitating maintenance-free operation. Theoretical calculations show mercury targets emit shorter x-ray pulses than targets of lighter elements under identical illumination and x-ray detection conditions.

X-ray phase-contrast imaging: transmission functions separable in Cartesian coordinates.

In-line, x-ray phase-contrast imaging is responsive to both phase changes and absorption as the x radiation traverses a body. Expressions are derived for phase-contrast imaging of objects having transmission functions separable in Cartesian coordinates. Starting from the Fresnel-Kirchhoff integral formula for image formation, an expression is found for the phase-contrast image produced by an x-ray source with nonvanishing dimensions. This expression is evaluated in limiting cases where the source-to-object distance is large, where the source acts as a point source, and where the weak phase approximation is valid. The integral expression for the image is evaluated for objects with simple geometrical shapes, showing the influence of the source dimensions on the visibility of phase-contrast features. The expressions derived here are evaluated for cases where the magnification is substantially greater than one as would be employed in biological imaging. Experiments are reported using the in-line phase-contrast imaging method with a microfocus x-ray source and a CCD camera.

Ultrafast tabletop laser-pump-x-ray probe measurement of solvated Fe(CN)6 4-.

We report on the first ultrafast laser-pump-picosecond x-ray probe measurements of solvated transition metal complexes carried out with a tabletop ultrafast laser-driven plasma x-ray source. The x-ray absorption fine structure (XAFS) spectra of Fe(CN)(6) (4-) solvated in water have been measured before and tens of picoseconds after photoexcitation with ultrashort UV laser pulses. The XAFS spectra after photoexcitation exhibits a K-edge shift indicating the increase of the iron-ligand distances. Reference spectra of Fe(CN)(6) (4-) and Fe(CN)(6) (3-) measured at a synchrotron source yield structural data that show static solvation-induced bond length changes of the metal complexes.

Acoustically modulated x-ray phase contrast imaging.

We report the use of ultrasonic radiation pressure with phase contrast x-ray imaging to give an image proportional to the space derivative of a conventional phase contrast image in the direction of propagation of an ultrasonic beam. Intense ultrasound is used to exert forces on objects within a body giving displacements of the order of tens to hundreds of microns. Subtraction of images made with and without the ultrasound field gives an image that removes low spatial frequency features and highlights high frequency features. The method acts as an acoustic 'contrast agent' for phase contrast x-ray imaging, which in soft tissue acts to highlight small density changes.