Assigning a structural motif using spontaneous molecular dipole orientation in thin films.

Spontaneous orientation of molecular dipoles has been observed to produce bulk electric fields, termed 'spontelectric' fields, in a broad variety of molecular solid thin films formed by condensation from the gas phase. Such spontelectric fields are found in cis-methyl formate (cis-MF) and the present work combines observation of these fields with high quality ab initio studies of cis-MF monomers and dimers. This enables a prediction of the structural motif within the unit cell of the crystalline phase of solid cis-MF, showing it to be a non-polar dimer. Dimer formation at deposition temperatures of >90 K is therefore cited to contribute to the observed collapse of the spontelectric field at these temperatures. This is the first time that such a structural prediction has been made using observations of spontelectric behaviour as a key indicator.

Non-linear and non-local behaviour in spontaneously electrical solids.

Using reflection-absorption infrared spectroscopy (RAIRS), we show that solids displaying spontaneous dipole orientation possess quite general non-local and non-linear characteristics, exemplified through their internal electric fields. The most graphic illustration of this, uncovered originally through electron beam studies, may be found in films of cis-methyl formate (cis-MF), for which data demonstrated the counter-intuitive property that the degree of dipole order in the film does not monotonically decrease as the temperature of deposition rises, but rather increases sharply above ∼77 K. Here we show how RAIRS provides independent evidence to support this conclusion. These new data confirm (i) that the behaviour of spontelectrics is governed by an expression for the degree of dipole orientation, which is continuous in temperature, but with a discontinuity in the derivative, and (ii) that the temperature of deposition associated with this discontinuity matches the temperature above which dipole order switches from the expected reduction with temperature to an increase with temperature.

Wannier-Mott Excitons in Nanoscale Molecular Ices.

The absorption of light to create Wannier-Mott excitons is a fundamental feature dictating the optical and photovoltaic properties of low band gap, high permittivity semiconductors. Such excitons, with an electron-hole separation an order of magnitude greater than lattice dimensions, are largely limited to these semiconductors but here we find evidence of Wannier-Mott exciton formation in solid carbon monoxide (CO) with a band gap of >8 eV and a low electrical permittivity. This is established through the observation that a change of a few degrees K in deposition temperature can shift the electronic absorption spectra of solid CO by several hundred wave numbers, coupled with the recent discovery that deposition of CO leads to the spontaneous formation of electric fields within the film. These so-called spontelectric fields, here approaching 4×10^{7} V m^{-1}, are strongly temperature dependent. We find that a simple electrostatic model reproduces the observed temperature dependent spectral shifts based on the Stark effect on a hole and electron residing several nm apart, identifying the presence of Wannier-Mott excitons. The spontelectric effect in CO simultaneously explains the long-standing enigma of the sensitivity of vacuum ultraviolet spectra to the deposition temperature.

Sarcopenia and change in body composition following maximal androgen suppression with abiraterone in men with castration-resistant prostate cancer.

BACKGROUND: Standard medical castration reduces muscle mass. We sought to characterize body composition changes in men undergoing maximal androgen suppression with and without exogenous gluocorticoids. METHODS: Cross-sectional areas of total fat, visceral fat and muscle were measured on serial CT scans in a post-hoc analysis of patients treated in Phase I/II trials with abiraterone followed by abiraterone and dexamethasone 0.5 mg daily. Linear mixed regression models were used to account for variations in time-on-treatment and baseline body mass index (BMI). RESULTS: Fifty-five patients received a median of 7.5 months abiraterone followed by 5.4 months abiraterone and dexamethasone. Muscle loss was observed on single-agent abiraterone (maximal in patients with baseline BMI >30, -4.3%), but no further loss was observed after addition of dexamethasone. Loss of visceral fat was also observed on single-agent abiraterone, (baseline BMI >30 patients -19.6%). In contrast, addition of dexamethasone led to an increase in central visceral and total fat and BMI in all the patients. INTERPRETATION: Maximal androgen suppression was associated with loss of muscle and visceral fat. Addition of low dose dexamethasone resulted in significant increases in visceral and total fat. These changes could have important quality-of-life implications for men treated with abiraterone.

Following the surface response of caffeine cocrystals to controlled humidity storage by atomic force microscopy.

Active pharmaceutical ingredient (API) stability in solid state tablet formulation is frequently a function of the relative humidity (RH) environment in which the drug is stored. Caffeine is one such problematic API. Previously reported caffeine cocrystals, however, were found to offer increased resistance to caffeine hydrate formation. Here we report on the use of atomic force microscopy (AFM) to image the surface of two caffeine cocrystal systems to look for differences between the surface and bulk response of the cocrystal to storage in controlled humidity environments. Bulk responses have previously been assessed by powder X-ray diffraction. With AFM, pinning sites were identified at step edges on caffeine/oxalic acid, with these sites leading to non-uniform step movement on going from ambient to 0% RH. At RH >75%, areas of fresh crystal growth were seen on the cocrystal surface. In the case of caffeine/malonic acid the cocrystals were observed to absorb water anisotropically after storage at 75% RH for 2 days, affecting the surface topography of the cocrystal. These results show that AFM expands on the data gathered by bulk analytical techniques, such as powder X-ray diffraction, by providing localised surface information. This surface information may be important for better predicting API stability in isolation and at a solid state API-excipient interface.