Rapid comparison of diacetylmorphine on banknotes by tandem mass spectrometry

A procedure is described for the determination of the distribution of the contamination of banknotes with controlled drugs using tandem mass spectrometry. The method is illustrated using diacetylmorphine, which is the major active component of heroin. A series of banknotes is introduced into the mass spectrometer and the intensities of two product ions (m/z 328 and 268) derived from the precursor protonated molecule (m/z 370) are recorded. A banknote is considered contaminated if it shows a significant peak for both product ions, and if the ratio of intensities of these two peaks falls within accepted limits. The distribution of diacetylmorphine on sterling banknotes taken from general circulation within the UK can be modelled by an arcsin (square root) transformation of the data or by a log transformation of the data with a higher proportion of contamination. The two models were found to be in close agreement, predicting an upper limit (at 99.9% confidence) of contamination on banknotes from general circulation between 9 and 10%. The percentage contamination in a case study was calculated and compared to the background distribution using the two models proposed. This comparison revealed that the contamination present in the case study was inconsistent with that present on banknotes in general circulation.     

Freely available conformer generation methods: how good are they?

Conformer generation has important implications in cheminformatics, particularly in computational drug discovery where the quality of conformer generation software may affect the outcome of a virtual screening exercise. We examine the performance of four freely available small molecule conformer generation tools (Balloon, Confab, Frog2, and RDKit) alongside a commercial tool (MOE). The aim of this study is 3-fold: (i) to identify which tools most accurately reproduce experimentally determined structures; (ii) to examine the diversity of the generated conformational set; and (iii) to benchmark the computational time expended. These aspects were tested using a set of 708 drug-like molecules assembled from the OMEGA validation set and the Astex Diverse Set. These molecules have varying physicochemical properties and at least one known X-ray crystal structure. We found that RDKit and Confab are statistically better than other methods at generating low rmsd conformers to the known structure. RDKit is particularly suited for less flexible molecules while Confab, with its systematic approach, is able to generate conformers which are geometrically closer to the experimentally determined structure for molecules with a large number of rotatable bonds (≥10). In our tests RDKit also resulted as the second fastest method after Frog2. In order to enhance the performance of RDKit, we developed a postprocessing algorithm to build a diverse and representative set of conformers which also contains a close conformer to the known structure. Our analysis indicates that, with postprocessing, RDKit is a valid free alternative to commercial, proprietary software.     

Electrochemistry at carbon nanotube forests: sidewalls and closed ends allow fast electron transfer

The electrochemical properties of the closed ends and sidewalls of pristine carbon nanotube forests are investigated directly using a nanopipet electrochemical cell. Both are shown to promote fast electron transfer, without any activation or processing of the carbon nanotube material required, in contrast to the current model in the literature.