Investigation into the subambient behavior of aqueous mannitol solutions using temperature-controlled Raman microscopy.

The aim was twofold; to demonstrate the ability of temperature-controlled Raman microscopy (TRM) to locate mannitol within a frozen system and determine its form; to investigate the annealing behavior of mannitol solutions at -30 degrees C. The different polymorphic forms of anhydrous mannitol as well as the hemihydrate and amorphous form were prepared and characterized using crystal or powder X-ray diffractometry (XRD) as appropriate and Raman microscopy. Mannitol solutions (3% w/v) were cooled before annealing at -30 degrees C. TRM was used to map the frozen systems during annealing and was able to differentiate between the different forms of mannitol and revealed the location of both beta and delta polymorphic forms within the structure of the frozen material for the first time. TRM also confirmed that the crystalline mannitol is preferentially deposited at the edge of the frozen drop, forming a rim that thickens upon annealing. While there is no preference for one form initially, the study has revealed that the mannitol preferentially transforms to the beta form with time. TRM has enabled observation of spatially resolved behavior of mannitol during the annealing process for the first time. The technique has clear potential for studying other crystallization processes, with particular advantage for frozen systems.

The use of Raman microscopy to determine and localize vitamin E in biological samples.

Alpha-tocopherol (aT), the predominant form of vitamin E in mammals, is thought to prevent oxidation of polyunsaturated fatty acids. In the lung, aT is perceived to be accumulated in alveolar type II cells and secreted together with surfactant into the epithelial lining fluid. Conventionally, determination of aT and related compounds requires extraction with organic solvents. This study describes a new method to determine and image the distribution of aT and related compounds within cells and tissue sections using the light-scattering technique of Raman microscopy to enable high spatial as well as spectral resolution. This study compared the nondestructive analysis by Raman microscopy of vitamin E, in particular aT, in biological samples with data obtained using conventional HPLC analysis. Raman spectra were acquired at spatial resolutions of 2-0.8 microm. Multivariate analysis techniques were used for analyses and construction of corresponding maps showing the distribution of aT, alpha-tocopherol quinone (aTQ), and other constituents (hemes, proteins, DNA, and surfactant lipids). A combination of images enabled identification of colocalized constituents (heme/aTQ and aT/surfactant lipids). Our data demonstrate the ability of Raman microscopy to discriminate between different tocopherols and oxidation products in biological specimens without sample destruction. By enabling the visualization of lipid-protein interactions, Raman microscopy offers a novel method of investigating biological characterization of lipid-soluble compounds, including those that may be embedded in biological membranes such as aT.

Raman scattering and FT-IR spectroscopic studies on dithienylethene switches--towards non-destructive optical readout.

The non-destructive readout of photochromic memory materials based on the dithienylethene unit both by IR spectroscopy and Raman scattering is explored. A representative series of C5-substituted thienyl hexahydro- and hexafluoro-cyclopentene based photochromes was investigated to explore the effect and potential usefulness of substitution for the development of multicomponent memory materials. The effect of the deposition method on the photochemistry of solid materials containing photochromic dithienylcyclopentene switches was also explored. Photoconversion in the solid state to the closed form was found to be low when starting from the open form, but, in contrast, ring opening to the open state from the closed form was found to be complete. The effect was found to be due to inner filter rather than conformational phenomena. Characteristic vibrational bands for the central dithienyl core are assigned and a comparison made of the vibrational spectroscopic properties of the perhydro- and perfluoro switches. The data enable the determination of the photoconversion achievable in the solid state as well as some assessment of the influence of the deposition method on the photoconversion. The potential of Raman spectroscopy as a method of achieving non-destructive optical readout is demonstrated through the large differences in absolute Raman scattering intensity between the open and closed states, when monitored at wavelengths which do not result in photochemical ring opening.

Tracking the distribution of "ecstasy" tablets by Raman composition profiling: a large scale feasibility study.

Here we report the results of the largest study yet carried out on composition profiling of seized "ecstasy" tablets by Raman spectroscopy. Approximately 1500 tablets from different seizures in N. Ireland were analysed and even though practically all the tablets contained MDMA as active constituent, there were very significant differences in their Raman spectra, which were due to variations in both the nature and concentration of the excipients used and/or the degree of hydration of the MDMA. The ratios of the peak heights of the prominent drug bands at 810 cm(-1) and 716 cm(-1) (which vary with hydration state of the drug), and the drug band at 810 cm(-1) against the largest clearly discernible excipient band in the spectrum were measured for all the samples. It was found that there was sufficient variation in composition in the general sample population to make any matches between batches of tablets taken from different seizures significant, rather than the result of random chance. Despite the large number of different batches of tablets examined in this study, only two examples of indistinguishable sets of tablets were found and in only one of these had the two batches of tablets been seized at different times. Finally, the fact that there are many examples of batches of tablets (particularly in different batches taken from single seizures) in which the differences between each set are sufficiently small that they appear to arise only from random variations within a standard manufacturing method implies that, with more extensive data, it may be possible to recognize the "signature" of tablets prepared by major manufacturers.