Enhancing electron affinity and tuning band gap in donor-acceptor organic semiconductors by benzothiadiazole directed C-H borylation.

Electrophilic borylation using BCl3 and benzothiadiazole to direct the C-H functionalisation of an adjacent aromatic unit produces fused boracyclic materials with minimally changed HOMO energy levels but significantly reduced LUMO energy levels. In situ alkylation and arylation at boron using Al(alkyl)3 or Zn(aryl)2 is facile and affords boracycles that possess excellent stability towards protic solvents, including water, and display large bathochromic shifts leading to far red/NIR emission in the solid state with quantum yields of up to 34%. Solution fabricated OLEDs with far red/NIR electroluminescence are reported with EQEs > 0.4%.

Potential steroidal antiestrogens.

A series of analogues of 17beta-estradiol has been synthesized and the compounds have been tested, using sucrose density gradient analysis, for their ability to compete with [6,7-3H]-17beta-estradiol for the estrogen-receptor protein from mouse uterine homogenates. Active compounds were also tested for antiuterotrophic activity in immature rats and/or mice. 3,17beta-Dihydroxy-6-phenylestra-1,3,5(10),6-tetraene (14) was the most active new compound in the in vitro test suppressing the binding of 17beta-estradiol by 34 and 87%, respectively, at molar ratios of 1 and 3.16. It was significantly more potent than the intermediate 6-oxoestradiol (4) which produced a 52% inhibition of binding at a molar ratio of 3.16. The thiosemicarbazone of 6-oxoestradiol (17) and the derived 3,17beta-dihydroxy-6-(2-imino-4-oxothiazolidinyl-1-imino)estra-1,3,5(10)-triene (19) produced, respectively, only 46 and 16% inhibition of binding at a molar ratio of 10. Introduction of a 1-methyl substituent into either 6-oxo or 6-phenyl compounds reduced affinity for the receptor significantly (compounds 5 and 15) and conversion of the 3-OH into a beta-dialkylaminoethoxy group virtually destroyed all binding activity (compounds 2, 6, 10, and 11). At a molar ratio of 10 compound 14 failed to suppress the uterine weight response of immature rats to 17beta-estradiol, whereas compound 15, at a molar ratio of 200, produced a significant increase in the uterine weight of immature rats but not of immature mice even at a molar ratio of 1000.

Conformations and "nictinic" activites of cyclic analogues of choline aryl ether.

The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the minimum torsional angles about the aryl-oxygen gond geing 20, 20, 80, and 27 degrees, respectively. Since the piperidinium compound stimulates ganglia, it is concluded the either planarity of the aryl--O--C system is not essential for this type of activity or receptor interaction can involve appreciable bond distortion. The absence of ganglion-stimulant activity in the remaining compounds indicates the need for a transoid arrangement of the O--C--C--N+ system.

Oestrogenic, anti-oestrogenic and fertility effects of some triphenylethanes and triphenylethylenes related to ethamoxytriphetol (MER 25).

Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and antioestrogenic activity in mice, and three of the compounds, alpha-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-alpha-phenyl-beta-4-methoxyphenyl-ethanol (IV), alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-bibenzyl (V) and alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-stilbene (VI), were tested for their effects on fertility in mice. 2 Orthomethylation reduces oestrogenic and/or anti-oestrogenic activity compared with the reported activities of non-methylated analogues. 3 The anti-oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti-oestrogens, V and VI, did not affect fertility in mice.

Evidence for the metabolic activation of non-steroidal antioestrogens: a study of structure-activity relationships.

1 The oestrogenic and antioestrogenic activities of tamoxifen and monohydroxytamoxifen have been compared with those of para-methoxy, -methyl, -fluoro, and -chloro tamoxifen in the 3 day immature rat uterine weight test.2 The oestrogenic activity of mestranol, a steroid with low oestrogen receptor binding affinity which is believed to be demethylated to ethinyl oestradiol before exerting its effects, was less potent than ethinyl oestradiol when assayed in the 3 day immature rat uterine weight test. Similarly, para-methoxytamoxifen was less active than monohydroxytamoxifen in oestrogenic and antioestrogenic tests.3 The introduction of a para-methoxy group into tamoxifen did not affect oestrogenic or antioestrogenic activity.4 All the derivatives of tamoxifen were partial oestrogen agonists when compared with oestradiol benzoate in the 3 d immature rat uterine weight test. All test compounds inhibited the uterotrophic activity of oestradiol benzoate (0.16 mug daily) in a dose-related manner. The order of potency was: monohydroxytamoxifen > tamoxifen identical with methoxytamoxifen > p-fluoro identical with p-chloro identical with p-methyltamoxifen.5 Tamoxifen was approximately equiactive with its p-methyl, p-fluoro and p-chloro derivatives in the ability to inhibit [(3)H]-oestradiol binding to rat uterine oestrogen receptors in vitro.6 Tamoxifen was approximately equiactive with its p-methyl and p-fluoro derivatives in the ability to inhibit vaginal cornification of ovariectomized rats upon intravaginal administration with oestradiol (3.2 ng total dose).7 Since tamoxifen in vivo was more active as a partial oestrogen agonist and antagonist than the para substituted fluoro, chloro and methyl derivatives that cannot undergo metabolic hydroxylation to monohydroxytamoxifen, whereas the antioestrogenic activity of the compounds upon local application in the vaginal cornification test was equivalent as was their ability to inhibit [(3)H]-oestradiol-17beta binding to the oestrogen receptor in vitro, it is suggested that at low doses; i.e. over the range of the partial agonist dose-response curve, the biological activity of tamoxifen is the net result of the activities of the parent compound and its metabolites.8 The results demonstrate that metabolic activation of non-steroidal antioestrogens is only an advantage and not a requirement for antioestrogenic activity.

Improved pertussis toxin production by Bordetella pertussis through adjusting the growth medium's ionic composition.

Ionic composition and total ionic concentration of the growth medium were important factors in limiting productivities in aerated reactors used for the production of pertussis toxin and other antigens by Bordetella pertussis. Salt concentration has opposing effects on cell growth of wild-type B. pertussis and specific toxin formation. Sodium ion concentrations below 140 mM correlated with a precipitous decline in specific yields of pertussis toxin, an otherwise growth-associated product. High salt concentrations in the medium resulted in lower final cell concentrations but did not affect initial growth rates. A new medium is proposed that allows a 60 to 70% increase in both cell and toxin yields by replacing the sodium chloride in the 'cyclodextrin liquid' (CL) medium with additional monosodium glutamate which provides both the sodium and the carbon and energy source.

The determination of traces of formaldehyde.

An extensive critical review of the methods utilized to determine trace formaldehyde concentrations is presented. The methods are grouped under the physical techniques employed and are discussed with reference to interfering agents, sensitivity, reagent stability and analysis time. The applicability of the procedures is considered for routine monitoring of occupational and environmental exposure to gaseous formaldehyde.

Indirect determination of organic compounds by atomic-absorption spectrophotometry.

A review of the published methods for analysis of organic compounds by atomic-absorption spectrophotometry is given. Most of the applications are based on precipitation of metal compounds or solvent extraction of metal chelates or ion-association complexes. Although many of the methods offer great sensitivity, simplicity, and speed of analysis, few have been widely accepted by analysts, but some have proved to be satisfactory in field trials.

Application of a mathematical model for two component receptor binding to two high affinity oestrogen binding sites in nuclei from DMBA rat mammary tumours.

Saturation binding of [3H]oestradiol has been determined using exchange conditions, on nuclei from DMBA tumours from rats treated prior to sacrifice with oestradiol and tamoxifen alone or in combination. Application of a model to the binding data enabled the amounts (C2) and apparent dissociation constants (Kdapp) of a second lower affinity binding component to be determined as well as the amount of a higher affinity site (C1) and its dissociation constant (Kd1). Kdapp did not change significantly with any pretreatment but 2 h after oestradiol (5 micrograms) and after tamoxifen alone there was a significant decrease in Kd compared with control. It is suggested that the difference in Kd of the higher affinity binding sites in control and 2 h oestradiol treated animals may be due to the loss of an essential co-factor, possibly cytosolic, when nuclei are isolated in the absence of ligand.