Tatiana Cantillana

Dichlorido(di-2-pyridylamine)mercury(II).

In the molecule of the title compound, [HgCl2(C10H9N3)], the HgII atom is four-coordinated in a distorted tetrahedral configuration by two N atoms from the chelating di-2-pyridylamine ligand and by two Cl atoms. In the crystal structure, intermolecular N—H⋯Cl hydrogen bonds link the molecules into centrosymmetric dimers. There is a π–π contact between the pyridine rings [centroid–centroid distance = 3.896 (5) Å].

Olfactory mucosal toxicity screening and multivariate QSAR modeling for chlorinated benzene derivatives.

The olfactory mucosa (OM) is an important target for metabolism-dependent toxicity of drugs and chemicals. Several OM toxicants share a 2,6-dichlorinated benzene structure. The herbicides dichlobenil (2,6-dichlorobenzonitrile) and chlorthiamide (2,6-dichlorothiobenzamide) and the environmental dichlobenil metabolite 2,6-dichlorobenzamide all induce toxicity in the OM following covalent binding in the Bowman’s glands. In addition, we have shown that 2,6-dichlorophenyl methylsulfone targets the Bowman’s glands and is probably the most potent OM toxicant so far described. These findings suggest that the 2,6-positioning of chlorines in combination with an electron-withdrawing group in the primary position of the benzene ring is an arrangement that facilitates OM toxicity. This study examined the physicochemical characteristics of the 2,6-dichlorinated OM toxicants. A number of 2,6-dichlorinated benzene derivatives with various types of substituents in primary position were tested for OM toxicity in mice. In addition, some other 2,6- and 2,5-substituted benzene derivatives were examined. Two novel OM toxicants, 2,6-dichlorobenzaldehyde oxime and 2,6-dichloronitrobenzene, were identified. By the use of partial least squares projection to latent structures with discriminant analysis (PLS-DA) a preliminary quantitative structure-activity relationship (QSAR) model was built also using reported OM toxicity data. Physicochemical properties positively correlated with olfactory mucosal toxicity were identified as molecular dipolar momentum and the electronic properties of the substituent. Inversely correlated descriptors were variables describing the hydrophobicity, electronic properties of the molecule such as electron affinity and the electronic charge on the primary carbon. In conclusion, this preliminary PLS-DA model shows that a 2,6-dichlorinated benzene derivative with a large, polar, and strong electron-withdrawing substituent in the primary position has the potential of being a potent OM toxicant in mice.

Chiral effects in adrenocorticolytic action of o,p'-DDD (mitotane) in human adrenal cells

Adrenocortical carcinoma (ACC) is a rare malignant disease with poor prognosis. The main pharmacological choice, o,p′-DDD (mitotane), produces severe adverse effects. Since o,p′-DDD is a chiral molecule and stereoisomers frequently possess different pharmacokinetic and/or pharmacodynamic properties, we isolated the two o,p′-DDD enantiomers, (R)-(+)-o,p′-DDD and (S)-(–)-o,p′-DDD, and determined their absolute structures. The effects of each enantiomer on cell viability and on cortisol and dehydroepiandrosterone (DHEA) secretion in the human adrenocortical cell line H295R were assessed. We also assayed the o,p′-DDD racemate and the m,p′- and p,p′-isomers. The results show small but statistically significant differences in activity of the o,p′-DDD enantiomers for all parameters tested. The three DDD isomers were equally potent in decreasing cell viability, but p,p′-DDD affected hormone secretion slightly less than the o,p′- and m,p′-isomers. The small chiral differences in direct effects on target cells alone do not warrant single enantiomer administration, but might reach importance in conjunction with possible stereochemical effects on pharmacokinetic processes in vivo.

(2S)-1,1-Dichloro-2-(2-chloro-phen-yl)-2-(4-chloro-phen-yl)ethane.

The title compound, C14H10Cl4, is easily crystallized while the other enantiomorph only forms an oil upon crystallization attempts. The title compound has a considerably higher density, ρ ≃ 1.562 Mg m−3 compared to the racemic substance, ρ ≃ 1.514 Mg m−3. This is supported by the fact there are two intermolecular halogen–halogen contacts in the title compound compared with only one the racemic compound. The dihedral angle between the two phenyl rings is 76.83 (5)°

Total Diet Studies in Sweden: Monitoring Dietary Exposure to Persistent Organic Pollutants by a Market Basket Approach

In Sweden, market basket studies (MBS) have been conducted in 1999, 2005, and 2010 by the use of similar methods, with the ambition to follow a 5-year scheme. Data on the mean Swedish consumption of common foods on the market were obtained from national food production and trade statistics, and listed food items were purchased from five major Swedish grocery chains and grouped into, at minimum, 12 different food groups (e.g. cereals, meat, fish, and dairy products). By the use of MBS methods, the Swedish mean exposure of both nutrients and potentially hazardous substances could be followed. Among other substances, POPs, such as PCBs, DDT, dioxins, and brominated flame retardants (e.g. PBDEs and HBCD) have been analysed. The data obtained are well suited for time trend studies, and could be used, e.g. in validation of other methods for exposure assessment.

Synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE) via Newman-Kwart rearrangement - A precursor for synthesis of radiolabeled and unlabeled alkylsulfonyl-DDEs

For the first time, a pathway for synthesis of 2-(4-chlorophenyl)-2-(4-chloro-3-thiophenol)-1,1-dichloroethene (3-SH-DDE), is presented. The compound is of particular interest as a precursor for synthesis of alkylsulfonyl-DDE containing different alkyl groups to discover structural activity relationships, and to promote synthesis of radiolabeled methylsulfonyl-DDE. 2-Chloro-5-methylphenol was first methylated and further oxidized to the corresponding benzoic acid. The acid was reduced to the corresponding aldehyde (4-chloro-3-methoxy benzaldehyde) via 4-chloro-3-methoxy-benzene methanol. A lead/aluminium bimetal system was used to carry out the reductive addition of tetrachloromethane to 4-chloro-3-methoxy benzaldehyde to obtain 2,2,2-trichloro-1-(4-chloro-3-methoxyphenyl)ethanol, the desired starting material to synthesize the DDT-analogue (2-(4-chlorophenyl)-2-(4-chloro-3-methoxy-phenyl)-1,1,1-trichloroethane). Elimination of hydrochloric acid and removal of the methyl group led to the 3-OH-DDE. The Newman-Kwart rearrangement was applied to convert 3-OH-DDE to 3-SH-DDE via the dimethylcarbamothioate derivative. 3-SH-DDE is then used as a precursor for the radiolabel synthesis. The overall yield to acquire 3-SH-DDE after 11 steps was 3%. The step with the lowest yield was the DDT-analog synthesis with a yield of 30%. All other step had a yield of >50%. 3-SH-DDE was methylated with (14)C-labeled iodomethane and oxidized by hydrogen peroxide to obtain 3-[(14)C]MeSO(2)-DDE in an overall yield of 30%.