Methyl sulfone (MeSO2-) and hydroxylated (OH-) metabolites of polychlorinated biphenyls (PCBs) have emerged as important classes of environmental contaminants in wildlife and humans. The detection of persistent MeSO2-PCBs was first shown in tissues of Baltic grey seal in the mid-1970s. In the last decade the detection and quantification of these metabolites in biota has gained momentum. MeSO2-PCBs are one of the major classes of organochlorine contaminants in humans and several marine and a few terrestrial mammal species. A number of studies have demonstrated the toxicological potential of MeSO2-PCBs including tissue selective retention via non-covalent protein binding, induction of cytochrome P450 enzymes, and endocrine-related effects. More recently OH-PCBs have gained greater scientific notoriety in environmental toxicology as a consequence of the capability of certain OH-PCB congeners to bind with the thyroxine transport protein, transthyretin, and their interaction with thyroid and estrogen hormone receptors. Research on environmentally persistent MeSO2-PCBs and OH-PCB metabolites reported in the last two decades is presented, discussed and summarized. Topics include the relative importance and mechanisms of biochemical formation in the context of PCB biotransformation, physico-chemical properties, and chemical synthesis, nomenclature and analysis. The chemical analysis summary encompasses tissue extraction, compound separation and methods of detection. MeSO2-PCB and OH-PCB toxicokinetics are addressed such as species- and congener-specific formation and clearance, persistence in biota and tissue specific retention. The known biological and toxicological activities of these PCB metabolites are also summarized.

Methyl Sulfone and Hydroxylated Metabolites of Polychlorinated Biphenyls

By using fragments endowed with interesting and complementary properties for the treatment of Alzheimer’s disease (AD), a new family of tacrine–4-oxo-4H-chromene hybrids has been designed, synthesized, and evaluated biologically. The tacrine fragment was selected for its inhibition of cholinesterases, and the flavonoid scaffold derived from 4-oxo-4H -chromene was chosen for its radical capture and β-secretase 1 (BACE-1) inhibitory activities. At nano- and picomolar concentrations, the new tacrine–4-oxo-4H-chromene hybrids inhibit human acetyl- and butyrylcholinesterase (h-AChE and h-BuChE), being more potent than the parent inhibitor, tacrine. They are also potent inhibitors of human BACE-1, better than the parent flavonoid, apigenin. They show interesting antioxidant properties and could be able to penetrate into the CNS according to the in vitro PAMPA-BBB assay. Among the hybrids investigated, 6-hydroxy-4-oxo- N-{10-[(1,2,3,4-tetrahydroacridin-9-yl)amino]decyl}-4 H-chromene-2-carboxamide (19) shows pote...

New tacrine-4-oxo-4H-chromene hybrids as multifunctional agents for the treatment of Alzheimer's disease, with cholinergic, antioxidant, and β-amyloid-reducing properties.

A series of four subphthalocyanine-C(60) fullerene dyads have been prepared through axial functionalization of the macrocycle with m-hydroxybenzaldehyde and a subsequent dipolar cycloaddition reaction. The subphthalocyanine moiety has been peripherally functionalized with substituents of different electronic character, namely fluorine or iodine atoms and ether or amino groups, thus reaching a control over its electron-donating properties. This is evidenced in cyclic voltammetry experiments by a progressive shift to lower potentials, by ca. 200 mV, of the first oxidation event of the SubPc unit in the dyads. As a consequence, the energy level of the SubPc(*)(+)-C(60)(*)(-) charge-transfer state may be tuned so as to compete with energy transfer deactivation pathways upon selective excitation of the SubPc component. For instance, excitation of those systems where the level of the radical pair lies high in energy triggers a sequence of exergonic photophysical events that comprise (i) nearly quantitative singlet-singlet energy transfer to the C(60) moiety, (ii) fullerene intersystem crossing, and (iii) triplet-triplet energy transfer back to the SubPc. On the contrary, the stabilization of the SubPc(*)(+)-C(60)(*)(-) radical pair state by increasing the polarity of the medium or by lowering the donor-acceptor redox gap causes charge transfer to dominate. In the case of 1c in benzonitrile, the thus formed radical pair has a lifetime of 0.65 ns and decays via the energetically lower lying triplet excited state. Further stabilization is achieved for dyad 1d, whose charge-transfer state would lie now below both triplets. The radical pair lifetime consequently increases in more than 2 orders of magnitude with respect to 1c and presents a significant stabilization in less polar solvents, revealing a low reorganization energy for this kind of SubPc-C(60) systems.

Subphthalocyanines: Tuneable Molecular Scaffolds for Intramolecular Electron and Energy Transfer Processes

A range of nematogenic materials which incorporate a 2,6-disubstituted naphthyl moiety and a terminal cyano-substituent have been synthesized by using palladium-catalysed cross-coupling procedures involving arylboronic acids and alkynylzinc reagents with aryl iodides, bromides and trifluoromethanesulphonates (triflates). The compounds have very high nematic phase stability, but their melting points are also quite high. The birefringences were measured using an extrapolation technique and the values were found to be between 0·26 and 0·42.

The synthesis and high optical birefringence of nematogens incorporating 2,6-disubstituted naphthalenes and terminal cyano-substituent

A subazaporphyrin (SubAP), tert-butylated and crowned subphthalocyanines (tBSubPc and SubCRPc), a μ-oxo dimer of tert-butylated SubPc {(tBSubPc)2O}, a subnaphthalocyanine (SubNc), and monosubstituted type unsymmetrical phthalocyanine (Pc) and naphthalocyanine (Nc) analogues have been synthesized. In particular, unsymmetrical Pc's and Nc's have been prepared in moderate yields by the ring expansion reaction of structurally distorted SubPc's and SubNc's with isoindolediimine derivatives in dimethyl sulfoxide−chloronaphthalene (or chlorobenzenes or aromatic hydrocarbons such as toluene and xylene) mixtures. The compounds have been characterized by electronic absorption, magnetic circular dichroism (MCD), fluorescence emission, and nuclear magnetic resonance spectroscopy. Both the Soret bands and Q-bands shift to longer wavelength and gain intensity in the order SubAP, SubPc, and SubNc. Fluorescence quantum yields and lifetimes generally decrease with decreasing molecular symmetry. Circular dichroism and NMR ...

Synthesis, Spectroscopy, and Molecular Orbital Calculations of Subazaporphyrins, Subphthalocyanines, Subnaphthalocyanines, and Compounds Derived Therefrom by Ring Expansion1

J.F.W. McOmie

Papers

Demethylation of aryl methyl ethers by boron tribromide