No abstract

No abstract

Muon-spin-rotation and relaxation (tbSR) studies of the organic compounds (TMTSF)q-X (X = PFs, NOs, and C104) at ambient pressure are reported. We observe spin-density-wave (SDW) states in all three compounds under zero external magnetic field. The onset of the SDW is extremely sharp, which may indicate a first-order transition. The sublattice magnetization (or SDW amplitude) in the PFs compound exhibits significant reduction with increasing temperature at low temperatures, which demonstrates the existence of collective low-energy excitations, in addition to the single-particle excitations across the SDW gap. The large spin-wave sti6'ness we observe in this system is incompatible with a Heisenberg model for a localized spin system; this demonstrates the importance of using an itinerant-electron picture to describe the magnetic behavior of this system. The broad distribution of local magnetic fields deduced from the @SRtime spectra is consistent with that expected from an incommensurate SDW. The magnitude of the internal Geld at T -+ 0 is approximately the same for the three systems, suggesting a common SDW amplitude in these systems. Transverse-field @SR measurements in the relaxed-state C104 system show no visible enhancement of the relaxation rate in the superconducting state down to 0.1 K, providing a lower limit for the superconducting penetration depth A br ) 12 000 A.

Two naturally occurring metabolites of progesterone, 3 alpha-hydroxy-5 alpha- and 5 beta-pregnan-20-one (1 and 2), are potent allosteric modulators of the GABAA receptor. Their therapeutic potential as anxiolytics, anticonvulsants, and sedative/hypnotics is limited by rapid metabolism. To avoid these shortcomings, a series of 3 beta-substituted derivatives of 1 and 2 was prepared. Small lipophilic groups generally maintain potency in both the 5 alpha- and 5 beta-series as determined by inhibition of [35S]TBPS binding. In the 5 alpha-series, 3 beta-ethyl, -propyl, -trifluoromethyl and -(benzyloxy)methyl, as well as substituents of the form 3 beta-XCH2, where X is Cl, Br, or I or contains unsaturation, show limited efficacy in inhibiting [35S]TBPS binding. In the 5 beta-series, the unsubstituted parent 2 is a two-component inhibitor, whereas all of the 3 beta-substituted derivatives of 2 inhibit TBPS via a single class of binding sites. In addition, all of the 3-substituted 5 beta-sterols tested are full inhibitors of [35S]TBPS binding. Electrophysiological measurements using alpha 1 beta 2 gamma 2L receptors expressed in oocytes show that 3 beta-methyl- and 3 beta-(azidomethyl)-3 alpha-hydroxy-5 alpha-pregnan-20-one (6 and 22, respectively) are potent full efficacy modulators and that 3 alpha-hydroxy-3 beta-(trifluoromethyl)-5 alpha-pregnan -20-one (24) is a low-efficacy modulator, confirming the results obtained from [35S]TBPS binding. These results indicate that modification of the 3 beta-position in 1 and 2 maintains activity at the neuroactive steroid site on the GABAA receptor. In animal studies, compound 6 (CCD 1042) is an orally active anticonvulsant, while the naturally occurring progesterone metabolites 1 and 2 are inactive when administered orally, suggesting that 3 beta-substitution slows metabolism of the 3-hydroxyl, resulting in orally bioavailable steroid modulators of the GABAA receptor.