The generation of a novel polyoxometalate-based 3D framework following picolinate-chelation of tungsten and potassium centres

A new polyoxometalate-based 3D framework K(5)Na[K(2){Dy(H(2)O)(3)}(2){As(2)W(19)O(68)}{WO(2)(pic)}(2)] (1) (pic = 2-picolinate), composed of picolinate-functionalised dysprosium-containing tungstoarsenates and distorted potassium-picolinate cubane units, has been synthesised from the polyoxometalate precursor [As(2)W(19)O(67)(H(2)O)](14-).     

Using consensus-shape clustering to identify promiscuous ligands and protein targets and to choose the right query for shape-based virtual screening

Ligand-based shape matching approaches have become established as important and popular virtual screening (VS) techniques. However, despite their relative success, many authors have discussed how best to choose the initial query compounds and which of their conformations should be used. Furthermore, it is increasingly the case that pharmaceutical companies have multiple ligands for a given target and these may bind in different ways to the same pocket. Conversely, a given ligand can sometimes bind to multiple targets, and this is clearly of great importance when considering drug side-effects. We recently introduced the notion of spherical harmonic-based "consensus shapes" to help deal with these questions. Here, we apply a consensus shape clustering approach to the 40 protein-ligand targets in the DUD data set using PARASURF/PARAFIT. Results from clustering show that in some cases the ligands for a given target are split into two subgroups which could suggest they bind to different subsites of the same target. In other cases, our clustering approach sometimes groups together ligands from different targets, and this suggests that those ligands could bind to the same targets. Hence spherical harmonic-based clustering can rapidly give cross-docking information while avoiding the expense of performing all-against-all docking calculations. We also report on the effect of the query conformation on the performance of shape-based screening of the DUD data set and the potential gain in screening performance by using consensus shapes calculated in different ways. We provide details of our analysis of shape-based screening using both PARASURF/PARAFIT and ROCS, and we compare the results obtained with shape-based and conventional docking approaches using MSSH/SHEF and GOLD. The utility of each type of query is analyzed using commonly reported statistics such as enrichment factors (EF) and receiver-operator-characteristic (ROC) plots as well as other early performance metrics.     

Terahertz probe of individual subwavelength objects in a water environment

Terahertz (THz) spectroscopy and imaging have been heralded for some time as potentially revolutionary techniques for biomedical applications. Label‐free detection of molecules and recognition of molecular events are often mentioned as the most exciting possibilities. A crucial practical goal, however, is the ability to perform such measurements on tiny amounts of biological fluids or even on individual organic structures. Living cells, for instance, have diameters at most of some tens of micrometers, i.e. at least λ/10 even for few‐THz radiation. Furthermore, all analyses relevant for a biological perspective must be performed in a water environment, which presents a strong absorption across the whole THz spectral range, severely limiting the penetration of the electromagnetic field. Here, it is shown how both issues can be overcome with a lab‐on‐a‐chip approach based on a microfluidic platform coupled to a plasmonic antenna. Using a quantum cascade laser as THz illumination source, liquid volumes down to the picoliter range are probed, and direct operation on individual 10‐µm diameter microparticles flowing in water is shown. The present demonstration opens the way to the development of THz biosensing of individual living cells and small probe volumes.     

A microfabricated graphitic carbon column for high performance liquid chromatography

We report the first development of a novel, planar, microfluidic, graphitic carbon separations column utilizing an array of graphitic micropillars of diamond cross-section as the chromatographic stationary phase. 795 nm femtosecond laser ablation was employed to subtractively machine fluidic architectures and a micropillared array in a planar, graphitic substrate as a monolithic structure. A sample injector was integrated on-chip, together with fluid-flow distribution architectures to minimize band-broadening and ensure sample equi-distribution across the micro-pillared column width. The separations chip was interfaced directly to the ESI probe of a Thermofisher Surveyor mass spectrometer, enabling the detection of test-mixture analytes following their differential retention on the micro-pillared graphitic column, thus demonstrating the exciting potential of this novel separations format. Importantly, unlike porous, graphitic microspheres, the temperature and pressure resilience of the microfluidic device potentially enables use in subcritical H(2)O chromatography.     

Line strength and collisional broadening studies of hydrogen sulphide in the 1.58 μm region using diode laser spectroscopy

High resolution diode laser spectroscopy has been applied to the detection of hydrogen sulphide at ppm levels utilizing different transitions within the region of the ν ₁+ν ₂+ν ₃ and 2ν ₁+ν ₂ combination bands around 1.58 μm. Suitable lines in this spectral region have been identified, and absolute absorption cross sections have been determined through single-pass absorption spectroscopy and confirmed in the Doppler linewidth regime using cavity enhanced absorption spectroscopy (CEAS). The desire for a sensitive system potentially applicable to H₂S sensing at atmospheric pressure has led to an investigation on suitable transitions using wavelength modulation spectroscopy (WMS). The set-up sensitivity has been calculated as 1.73×10⁻⁸ cm⁻¹ s^1/2, and probing the strongest line at 1576.29 nm a minimum detectable concentration of 700 ppb under atmospheric conditions has been achieved. Furthermore, pressure broadening coefficients for a variety of buffer gasses have been measured and correlated to the intermolecular potentials governing the collision process; the H₂S–H₂S dimer well depth is estimated to be 7.06±0.09 kJ mol⁻¹.