Using medicinal chemistry to solve an old medical mystery.

The logic behind the traditional medicinal chemistry technique of designing a synthetic enzyme substrate to mimic a natural one is used to uncover the identity of the unknown cause of two legacy industrial diseases by comparing the reported symptoms to two side effects of a modern synthetic.

33S NMR spectra of sulfonium salts: calculated and experimental.

33S NMR chemical shifts were calculated by the scaled DFT and EMPI approaches for the fluoride, chloride and bromide of trimethylsulfonium ion (1) and S-methyltetrahydrothiophenium ion (2), in addition to the free cations. Experimental values were obtained for the iodides of 1 (delta +48, CS2 = 0 ppm) and 2 (delta +95), and were found to agree with the calculated values well within the standard deviation of 35 ppm (3.5% of the shielding range) established in earlier work for a great variety of sulfur compounds.

Bonding and 33S NMR chemical shielding in the thiophosphoryl group.

B3LYP and MP2 calculations at the 6-311 + G(nd,p) level (with n = 2 for second-row elements and n = 1 otherwise) were carried out using the atoms-in-molecules (AIM) approach to characterize the thiophosphoryl bond. A series of R(3)PS molecules were studied and compared with the corresponding R(3)PO systems. As with the phosphoryl bond, one cannot distinguish the thiophosphoryl bond from a standard P=S double bond by comparing bond distances.

Phospholes with Reduced Pyramidal Character from Steric Crowding. 2. Photoelectron Spectral Evidence for Some Electron Delocalization in 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole.

Photoelectron spectroscopy has been explored as a tool to measure the flattening of the phosphorus pyramid in a phosphole as caused by a large, sterically demanding P-substituent. Earlier PE spectra had shown no difference in ionization energies (IE) for simple phospholes and their tetrahydro derivatives (both around 8.0-8.

Phospholes with Reduced Pyramidal Character from Steric Crowding. 1. Synthesis and NMR Characterization of 1-(2,4-Di-tert-butyl-6-methylphenyl)-3-methylphosphole.

The sterically crowded 1-(2,4-di-tert-butyl-6-methylphenyl)-3-methylphosphole was synthesized by dehydrohalogenation of the corresponding 3,4-dibromophospholane, in order to probe the possibility that the steric congestion would cause some flattening of the phosphorus pyramid and an increase in electron delocalization. The phosphole was a recrystallizable solid with (31)P NMR delta 1.8.

Generation of Ethyl Metathiophosphate by Thermal Fragmentation of O-Ethyl N-Substituted Phosphoramidothioates.

O-Ethyl N-1-adamantylphosphoramidothioate was synthesized and found to fragment on heating in inert solvents to form the pyrophosphate AdNHP(S)(OEt)OP(S)(OEt)OH. The proposed mechanism involves an elimination of the amine portion with release of ethyl metathiophosphate (EtOP(S)O), as was confirmed in previous work for the comparable structure with oxygen. This transient compound then phosphorylates the starting phosphoramidothioate.