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Computational modeling has been performed on the cross-linking mechanism of partially substituted melamine reacting with poly(vinyl alcohol). Ab initio calculations were performed with density functional theory employing the BLYP functional and double numerical DND basis set. The mechanism, general acid catalysis, has been modeled with respect to structures, protonation, and reaction with a polymer. Protonation of the oxygen is required initially, followed by liberation of methanol. The reaction can take one of two pathways after methanol liberation. The conjugate base of the weak acid can abstract a proton, generating a Schiff-base intermediate. The O-H on the polymer then adds to the C-N double bond, producing the polymer-melamine bond. The alternative is that the polymer adds to the charged melamine, using the specific acid catalysis mechanism. After polymer addition, the proton is abstracted, producing the product.

The use of triethylsilane as a carbocation scavenger in the presence of trifluoroacetic acid in dichloromethane leads to increased yields, decreased reaction times, simple work-up and improved selectivity for the deprotection of t-butyl ester and t-butoxycarbonyl sites in protected amino-acids and peptides in the presence of other acid-sensitive protecting groups such as the benzyloxycarbonyl, 9-fluorenylmethoxycarbonyl, O- and S-benzyl and t-butylthio groups.

Trypanothione reductase, an essential component of the anti-oxidant defences of parasitic trypanosomes and Leishmania, differs markedly from the equivalent host enzyme, glutathione reductase, in the binding site for the disulphide substrate. Molecular modelling of this region suggested that certain tricyclic compounds might bind selectively to trypanothione reductase without inhibiting host glutathione reductase. This was confirmed by testing 30 phenothiazine and tricyclic antidepressants, of which clomipramine was found to be the most potent, with a K(i) of 6 microM, competitive with respect to trypanothione. Many of these compounds have been noted previously to have anti-trypanosomal and anti-leishmanial activity and thus they can serve as lead structures for rational drug design.

The synthesis and chemical characterisation of a range of substrate analogues for trypanothione reductase are described, with the spermidine portion of trypanothione replaced by the 3-dimethylaminopropylamide moiety. Using 1-hydroxybenzotriazole/N-hydroxysuccinimide coupling, products were obtained which had a range of replacements of the gamma-glutamyl groups of the enzyme substrate. The materials were characterised by FPLC, 1H/13C NMR spectroscopy and FAB mass spectroscopy.