Synthetic and structural studies on [Fe2(SR)2(CN)x(CO)6-x](x-) as active site models for Fe-only hydrogenases.

A series of models for the active site (H-cluster) of the iron-only hydrogenase enzymes (Fe-only H2-ases) were prepared. Treatment of MeCN solutions of Fe2(SR)2(CO)6 with 2 equiv of Et4NCN gave [Fe2(SR)2(CN)2(CO)4](2-) compounds. IR spectra of the dicyanides feature four nu(CO) bands between 1965 and 1870 cm(-1) and two nu(CN) bands at 2077 and 2033 cm(-1). For alkyl derivatives, both diequatorial and axial-equatorial isomers were observed by NMR analysis. Also prepared were a series of dithiolate derivatives (Et4N)2[Fe2(SR)2(CN)2(CO)4], where (SR)2 = S(CH2)2S, S(CH2)3S. Reaction of Et4NCN with Fe2(S-t-Bu)2(CO)6 gave initially [Fe2(S-t-Bu)2(CN)2(CO)4](2-), which comproportionated to give [Fe2(S-t-Bu)2(CN)(CO)5](-). The mechanism of the CN(-)-for-CO substitution was probed as follows: (i) excess CN(-) with a 1:1 mixture of Fe2(SMe)2(CO)6 and Fe2(SC6H4Me)2(CO)6 gave no mixed thiolates, (ii) treatment of Fe2(S2C3H6)(CO)6 with Me3NO followed by Et4NCN gave (Et4N)[Fe2(S2C3H6)(CN)(CO)5], which is a well-behaved salt, (iii) treatment of Fe2(S2C3H6)(CO)6 with Et4NCN in the presence of excess PMe3 gave (Et4N)[Fe2(S2C3H6)(CN)(CO)4(PMe3)] much more rapidly than the reaction of PMe3 with (Et4N)[Fe2(S2C3H6)(CN)(CO)5], and (iv) a competition experiment showed that Et4NCN reacts with Fe2(S2C3H6)(CO)6 more rapidly than with (Et4N)[Fe2(S2C3H6)(CN)(CO)5]. Salts of [Fe2(SR)2(CN)2(CO)4](2-) (for (SR)2 = (SMe)2 and S2C2H4) and the monocyanides [Fe2(S2C3H6)(CN)(CO)5](-) and [Fe2(S-t-Bu)2(CN)(CO)5](-) were characterized crystallographically; in each case, the Fe-CO distances were approximately 10% shorter than the Fe-CN distances. The oxidation potentials for Fe2(S2C3H6)(CO)4L2 become milder for L = CO, followed by MeNC, PMe3, and CN(-); the range is approximately 1.3 V. In water,oxidation of [Fe2(S2C3H6)(CN)2(CO)4](2-) occurs irreversibly at -0.12 V (Ag/AgCl) and is coupled to a second oxidation.

Clinical evaluation of pain during subcutaneous injections of low molecular weight heparins in healthy volunteers.

In order to compare the intensity and the duration of the pain following the subcutaneous injection of low molecular weight heparins, 0.4 ml nadroparin, 0.4 ml enoxaparin and 0.4 ml placebo (NaCl 0.9%) were administered at 1 week intervals to 12 healthy volunteers in a randomised, double-blind, three-period study. Pain was assessed by visual analogue and verbal category scales. Based on visual analogue scale scores, nadroparin resulted in significantly less pain than enoxaprin at 1 and 5 min after injection (6.2 +/- 2.6 mm vs 21.9 +/- 5.9 mm; P < 0.05 and 3.5 + 1.5 mm vs 14.3 +/- 4 mm; P < 0.05, respectively, mean +/- s.e. mean). Similar results were obtained using verbal category scale. Confidence interval testing for difference between groups showed that nadroparin injection resulted in less pain than enoxaparin at 1 min (-15.8: -31.2 to -0.4 mm).

Conversion of androgen to estrogen by the rat fetal and neonatal female gonad: effects of dcAMP and FSH.

Female gonads of fetal (on days 14.5, 16.5, 18.5 and 20.5 postcoitum) and neonatal rats (on days 4.5 and 8.5 postpartum) were cultured in Medium 199 in the presence of [3H]testosterone and the conversion into [3H]estrone and [3H]estradiol was estimated. Formation of both estrogens was found in all fetal and neonatal ovaries explanted in control medium. Dibutyryl cAMP (1 mM) had a clear-cut stimulatory effect as early as 16.5 days postcoitum, but had little or no effect at 8.5 days postpartum. In contrast, ovine or rat FSH (0.3 or 1 microgram/ml, respectively) increased the aromatase activity only from 20.5 days postcoitum. The effects of FSH and dibutyryl cAMP were more obvious after preculture for 48 h in control medium. These results indicate that: a biochemical sex differentiation, revealed by the difference in aromatase activity levels between ovaries and testes or other tissues occurs in female gonads as early as 14.5 days postcoitum; aromatase activity in the ovaries increases markedly after birth; functional FSH receptors are absent before 20.5 days postcoitum in the ovaries.