Examples of a new class of zwitterionic, ''right-hand side'' merocyanines containing a cyanodicyanomethylidenedihydrofuran electron acceptor have been prepared. As well as allowing for the facile synthesis of these chromophores, our synthetic methodology enables considerable variation in both the donor moiety as well as the extent of conjugation between the donor and acceptor systems. As expected, all of these ''right-hand side'' systems are negatively solvatochromic, with the difference between l max (polar vs. nonpolar solvents) increasing with the extent of conjugation. In accord with expectations, hyper-Raleigh scattering (HRS) measurements confirm that molecules with the greatest conjugation pathway (for e.g. 21c, 23c) have the largest first hyperpolarisabilites, b o . In addition, our HRS evaluation indicates that the 4-quinolinylidene donor nucleus is superior to both the 4-pyridinylidene and benzothiazolylidene systems. The figures of merit, m (calc) .b o(measured) , that we obtain for some of these compounds, are of a similar magnitude to the best ''left hand side'' examples reported in the literature. In order to demonstrate the versatility of our synthetic technique, representative polymer-tetherable derivatives of these compounds have been prepared, as have the corresponding TDI-based polyurethanes.

ImmH (1) and DADMe-ImmH (2) are potent inhibitors of human purine nucleoside phoshorylase (PNP), developed by us and currently in clinical trials for the treatment of a variety of T-cell related diseases. Compounds 1 and 2 were used as templates for the design and synthesis of a series of acyclic immucillin analogues (8-38) in order to identify simplified alternatives to 1 and 2. SerMe-ImmG (8) and DATMe-ImmG (9) displayed the lowest inhibition constants of 2.1 and 3.4 pM, respectively, vs PNP. It was postulated that the flexible natures of 8 and 9 enabled them to adopt conformations resembling those of 1 and 2 within the active site of PNP and that the positioning of two hydroxyl groups was critical for picomolar activity. SerMe-ImmH (10, K d = 5.2 pM) was shown to be orally available in mice with a long biological residence time on blood PNP.

International audienceRock—Eval HI values for coals vary with rank and do not give a direct measurement of oil potential. However, oils from coals are characteristically paraffinic and can be considered to derive from a polymethylene (PM) component, so the PM content should provide an estimate of the paraffinic oil potential. A trend apparently representing lignin evolution has been identified on the Van Krevelen diagram which permits the relative proportions of carbon in lignin and PM to be determined for coals that approximate a mixture of these two components, such as the members of the New Zealand (NZ) Coal Band. On the basis of this compositional model, HI values can be calibrated to provide an alternative estimate of the paraffinic oil potential. A maximum in HI is generally reached in coals near the onset of oil generation, at Rank(S) 12 (R. ca. 0.7%), from which it is suggested that the PM contri¬bution can be obtained using the formula HIpm = 1.15HIma„-172 for the suite of NZ coals examined. The onset of oil expulsion can be identified from a variety of geochemical measurements, and occurs in the Rank(S) range ca. 12.0 — 14.5 (Ro ca. 0.7-1.1%) for coals with paraffinic oil potentials exceeding ca. 40 mg HC/g TOC. Data from Taranaki Basin coals correlate well with the theoretical relationship between BI/HIPM and HIpm, using bitumen index (BI = S 1/TOC) values of 10 mg HC/g TOC at the start of oil generation (i.e. bitumen inherited from diagenesis) and 40 mg HC/g TOC at the onset of oil expulsion, suggesting the HIpm model is reasonably accurate for members of the NZ Coal Band. Kinetic modelling of paraffinic oil generation from vitrinite-rich coals may be best approximated by consideration of PM degradation alone

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