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The mechanism of action of rifamycins against bacterial DNA-dependent RNA polymerase has been explained on the basis of the spatial arrangement of four oxygens which can form hydrogen bonds with the enzyme. Structural descriptors are derived from X-ray diffraction crystal structures of 25 active and nonactive rifamycins. Principal component analysis is used to find the combination of structural parameters which better discriminate between active and nonactive rifamycins. Two possible mechanisms of molecular rearrangement are described which can convert nonactive into active conformations. The energy involved for conformational rearrangements is studied by molecular modeling techniques. Methyl C34 is found to play a key role for determining the geometry of the pharmacophore. Rifamycin O, reported to be active, is obtained by oxidation of rifamycin B and is studied by X-ray single-crystal diffractometry, by solution IR and NMR spectroscopy, and by thermal analysis. Surprisingly the oxidation process is totally stereospecific, and an explanation is given based on solution spectroscopic evidence. The conformation found in the solid state is typical of nonactive compounds, and molecular mechanics calculations show that a molecular rearrangement to the active conformation would require about 15 kcal/mol. Thermal analysis confirms that rifamycin O has a sterically constrained conformation. Therefore, it is likely that the antibiotic activity of rifamycin O is due either to chemical modification prior to reaching the enzyme or to conformational activation.

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Tetraphenyldibismuth, Bi2Ph4, is best prepared by the reaction of BiPhzl with 1 equivalent of sodium in liquid ammonia, followed by extraction with toluene and recrystallization from anhydrous ethanol. It is sensitive to air and slightly thermochromic. The crystal and molecular structure was solved by X-ray diffraction methods: triclinic, space group P i , with a = 7.865( 4), b = 11.444( 5), c = 6.257(3) A, a = 105.24(4), f3 = 94.20(7), y = 96.52( 6)", and Z = 1 ; R = 0.0560 for 1 097 absorption-corrected reflections having I z 30(/). The molecule has a staggered trans conformation, with a bismuthbismuth distance of 2.990(2) A. Tetraphenyldibismuth reacts promptly with di-iodine to give BiPh21, and with p-benzoquinone, elemental sulphur, and diazomethane to give the corresponding products of bismuth (111) resulting from oxidative insertion into the bismuth-bismuth bond.Almost 50 years ago Paneth and Loleit l reported the first experimental evidence of the existence of 'bisdimethylbismuth,' formed by the reaction of methyl radicals, generated2 by heating tetramethyl-lead, with elemental bismuth. The exis-