Diffuse and polarization functions have been optimized for the LANL2DZ basis set for elements in groups 14-17. The optimized exponents are in most cases similar to those optimized with different effective core potentials, valence basis sets, or computational models. The average of the LANL2DZ results for different models is taken to be the best generalized set of exponents. The extended basis set gives good results (average deviation from experiment 0.11 eV) for atomic electron affinities with the B3LYP model, but is consistently low with the MP2 model. The extended basis set gives similar performance to the all-electron 6-31+G(d) basis set in calculations of vibrational frequencies and bond energies in selected main-group compounds, and is intermediate in speed between the 6-31+G(d) basis set and the unmodified LANL2DZ basis set.

Three phosphinate salts (5), (6) and (7) were prepared as potential inhibitors of the enzyme pantothenate synthetase. The synthesis of compound (5) utilises a (diethoxymethyl)-protected phosphinate (8) as a new reagent for the formation of unsymmetrical phosphinic acids and esters. Initial P-alkylation of (8) followed by a selective deprotection sequence yields intermediate P-H phosphinates (16) and (21) which can be P-alkylated a second time. Enzyme assays have been performed with the target compound and the results are discussed.

The toxicity of ethoxyquin (EQ) to rat kidney was examined in males which were either weanling or adult at the beginning of the experiment, and also in adult females. Female rats were much less susceptible to the toxic effects of EQ than males of the same age. In males damage to the cortex, mainly as an acceleration of the normal ageing process, was similar in both age groups, but rats exposed to EQ as weanlings also suffered from extensive papillary necrosis. Male rats were more prone than females to proteinuria, which was greatly exacerbated by EQ in both age groups. Thus there is very little evidence of nephrotoxicity in adult female rats on exposure to EQ at 0.5% in the diet for 26 weeks. In males, the initial age of the animal, as well as the length of treatment, influences the extent of damage.

Pyruvate dehydrogenase is already well known as a site of action of pesticides, although the compounds that act there are either nonspecific or rather weak inhibitors. In the present study a series of acyl phosphinates has been prepared as potential mechanism-based inhibitors of the enzyme. Some of these are very powerful inhibitors and are also herbicidal, and a substantial body of evidence is presented to support the view that susceptible plants die as a direct result of the enzyme inhibition. Further synthesis has led to the discovery that certain derivatives of the inhibitors (which are presumably converted to the parent phosphinate in vivo) are also good herbicides, and one of these (an acetal) has been extensively evaluated in the field. Although this compound appeared to have insufficient commercial potential, the results of the study encourage the view that biochemical design of agrochemicals will be successful.

AbstractAn attempt has been made to design a herbicide by synthesising active site directed irreversible inhibitors for the peroxidase‐catalysed oxidation of indolyl‐3‐acetic acid (IAA). A variety of substituted indoles were prepared and found to bind reversibly to the enzyme, but none produced any progressive inhibition, nor showed any herbicidal activity. This may be related to the fact that the inhibitors can be degraded by peroxidase in vitro since, if this occurred in the plant, the compounds could not then interfere with IAA oxidation.