Phosphoramidate analogues of diribonucleoside monophosphates

The synthesis of thio, seleno, and imino analogues of diribonucleoside phosphoramidates is described.     

Directed ortho metalation-boronation and Suzuki-Miyaura cross coupling of pyridine derivatives: a one-pot protocol to substituted azabiaryls

A general method for the synthesis of azabiaryls 19a-t by a one-pot procedure involving a Directed ortho metalation (DoM)-boronation-Suzuki-Miyaura cross coupling sequence is described. Aside from the three isomeric pyridyl carboxamides 15a-c, chloro-, fluoro-, and O-carbamoyl pyridines are adapted to this method providing a range of azabiaryls (Table 2). The method has an advantage in that it avoids the recognized difficult isolation of pyridyl boronic acids and their instability toward deboronation. The efficient synthesis of hydroxypicolinamides 12-14 (Scheme 3) by a one-pot metalation-boronation-oxidation sequence with the LDA-B(OiPr)3 in situ procedure that avoids self-condensation of incipient ortho-metalated species (Scheme 2) is delineated. The conversion of azabiaryls 19b,e,h,l into azafluorenones 20b,e,h,l by a directed remote metalation protocol is demonstrated (Table 3). A comprehensive survey of pyridyl boronates, of considerable interest in contemporary heterocyclic synthetic chemistry, is given (Figure 1).     

Chemically resistant microfluidic valves from Viton® membranes bonded to COC and PMMA

We present a reliable technique for irreversibly bonding chemically inert Viton? membranes to PMMA and COC substrates to produce microfluidic devices with integrated elastomeric structures. Viton? is widely used in commercially available valves and has several advantages when compared to other elastomeric membranes currently utilised in microfluidic valves (e.g. PDMS), such as high solvent resistance, low porosity and high temperature tolerance. The bond strength was sufficient to withstand a fluid pressure of 400 kPa (PMMA/Viton?) and 310 kPa (COC/Viton?) before leakage or burst failure, which is sufficient for most microfluidic applications. We demonstrate and characterise on-chip pneumatic Viton? microvalves on PMMA and COC substrates. We also provide a detailed method for bonding fluorinated Viton? elastomer, a highly chemically compatible material, to PMMA and COC polymers. This allows the production of microfluidic devices able to handle a wide range of chemically harsh fluids and broadens the scope of the microfluidic platform concept.     

Nanomolar detection with high sensitivity microfluidic absorption cells manufactured in tinted PMMA for chemical analysis

We describe a novel, cost effective and simple technique for the manufacture of high sensitivity absorption cells for microfluidic analytical systems. The cells are made from tinted polymethyl methacrylate (PMMA) in which microfluidic channels are fabricated. Two windows (typically 250 μm thick, resulting in little optical power loss) are formed at either end of the channel through which light is coupled. Unwanted stray light from the emitter passes through a greater thickness of the tinted substrate (typically the length of the cell) and is preferentially absorbed. In effect, this creates a pin-hole configuration over the length of the absorption cell, providing improved performances (sensitivity, S/N ratios, baseline noise and limit of detection) when used as an absorption cell compared to clear substrates. The method is used to achieve a LOD of 20 nM with a colourimetric iron assay and a LOD of 0.22 milli-absorption units with a pH assay.