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The ground-state electronic structures of K3V(ox)3.3H2O, Na3V(ox)3.5H2O, and NaMgAl1-xVx(ox)3.9H2O (0xor= 1, ox = C2O42-) have been studied by Fourier-transform electronic absorption and inelastic neutron scattering spectroscopies. High-resolution absorption spectra of the 3Gamma(t2g2) --1Gamma(t2g2) spin-forbidden electronic origins and inelastic neutron scattering measurements of the pseudo-octahedral [V(ox)3]3- complex anion below 30 K exhibit both axial and rhombic components to the zero-field-splittings (ZFSs). Analysis of the ground-state ZFS using the conventional S = 1 spin Hamiltonian reveals that the axial ZFS component changes sign from positive values for K3V(ox)3.3H2O (D approximately +5.3 cm-1) and Na3V(ox)3.5H2O (D approximately +7.2 cm-1) to negative values for NaMgAl1-xVx(ox)3.9H2O (D approximately -9.8 cm-1 for x = 0.013, and D approximately -12.7 cm-1 for x = 1) with an additional rhombic component, |E|, that varies between approximately 0.8 and approximately 2 cm-1. On the basis of existing crystallographic data, this phenomenon can be identified as due to variations in the axial and rhombic ligand fields resulting from outer-sphere H-bonding between crystalline water molecules and the oxalate ligands. Spectroscopic evidence of a crystallographic phase change is also observed for K3V(ox)3.3Y2O (Y = H or D) with three distinct lattice sites below 30 K, each with a unique ground-state electronic structure.

Pilocarpine isosteres have been synthesized and characterized with regard to their in vitro muscarinic properties. The results indicate that the carbonyl oxygen of the lactone function of pilocarpine is of primary importance for agonist activity with the ether oxygen being of lesser or secondary importance. An X-ray structure determination for the hydrogen O,O'-ditoluoyltartrate salt of thiolactone pilocarpine isostere 2a has been performed. This compound has an unusual pharmacological profile exhibiting M1-agonist selectivity as well ass presynaptic antagonism. As a result this compound is also viewed as having therapeutic potential for Alzheimer's disease. A model for the binding of pilocarpine and other muscarinic agonists to the third transmembrane helix of the human m1 muscarinic receptor has been developed.

Crystal structure analyses have been carried out for lithium enolates of the following three esters: tert-butyl propionate ((Z)-1), tert-butyl2-methylpropionate (2), and methyl 3,3-dimethylbutanoate ((Z)-3). Enolates (Z)-1 and 2 are dimeric (with one TMEDA per Li atom), whereas (2)-3 is tetrameric (with one THF per Li atom). The Z configuration of 1 and 3 established by X-ray analysis is in agreement with that assigned by Ireland. From a detailed analysis of the geometry of the ester enolate grouping, the reaction path trajectory for the breakdown of this type of molecule can be derived. The implication of ketenes as intermediates, suggested by this analysis, could be confirmed chemically. In spite of the central importance of ester enolates as reactive intermediates in synthetic organic chemistry, very little is known about the actual structures of the metallated species involved. This lack of information is largely attributable to the low stability of ester enolates in general. In fact, the structures of only two metal derivatives of esters have been established by X-ray analysis: one is the Reformatksy reagent derived from tert-butyl bromoacetate,2 and the other is a lithium derivative of the highly acidic penta- kis(methoxycarbonyl)cyclopentadiene.3 Neverthless, it has been more than 10 years since the Lochmann4 and Rathke5 groups described the isolation of pure lithium derivatives of esters as solid substances. The analysis of these compounds was at that time limited to what could be achieved by IR and NMR spectroscopy; the deduction was that they are to be formulated as enolates. Deprotonation of esters of the type RR'CH-COOR" with LDA (lithium diisopropylamide) gives in principle (E)- or (Z)-con- figurated enolates, shown as (E)-1 and (Z)-1 for the example of

The enantiomers of three 5-methyl-2-pyrrolidone analogues of the muscarinic agent oxotremorine (1) were synthesized. The pyrrolidine derivative (R)-13 was an antagonist to carbachol in the guinea pig ileum and also showed central and peripheral antimuscarinic activity in vivo. It was more potent and more selective than atropine in antagonizing the central effects of 1. The dimethylamino analogue (R)-14 and the trimethylammonium salt (R)-15 were potent agonists in the guinea pig ileum. (R)-14 showed both central muscarinic (hypothermia) and central antimuscarinic activity (antagonism of oxotremorine-induced tremor) in vivo. The R enantiomers of 13-15 were considerably more potent than the S enantiomers in vivo and in vitro irrespective of whether agonist or antagonist activity was measured. From a comparison of the contribution of the methyl group at the chiral center to the overall affinities, it is suggested that agonists and antagonists in this series bind in an essentially identical manner to the muscarinic receptor.