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In this paper, we report the first systematic experimental and theoretical investigation of the electric field induced second harmonic response of some tetrathia[7]helicene-based NLOphores. We studied six model compounds carrying the NO2, CHCHCN, and COCF3 units as accepting groups on both the terminal thiophene positions as well as on the central benzene ring of the helicene backbone. These groups, known to be of medium and medium-strong accepting strength, allow tuning of both the electronic and structural properties of the helicenes studied. This experimental/theoretical study should set a milestone in addressing new structure-properties relationship of this class of nonconventional chiral chromophores able to show second order as well as third order NLO phenomena.

We report here the synthesis and cell-proliferation properties of derivatives of the breast cancer drug tamoxifen, in which the -O(CH(2))(2)N(CH(3))(2) side chain, responsible for the drug's antiestrogenic properties, has been modified by a ferrocenyl moiety. We recently reported the diphenol compound 5, in which this amino chain had been replaced with an acyl-ferrocenyl (-O(CH(2))(2)C(O)[(eta(5)-C(5)H(4))FeCp]) group, and which showed antiproliferative effects against both the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. We now report the results of a structure-activity relationship (SAR) study, in which the lateral chain length has been varied, the ketone group has been omitted, and the number of phenol groups has been varied. Compounds 1-4, with a side chain lacking the carbonyl function (-O(CH(2))(n)[(eta(5)-C(5)H(4))FeCp], n = 1-4) and which show a decreasing affinity for ERalpha (ER = estrogen receptor) with increasing chain length, act as estrogens on MCF-7 cells, and mild cytotoxics on PC-3 prostate cancer cells, with IC(50) values around 10 microM. The two monophenolic derivatives of 2, 2 a and 2 b, which show a reduced affinity for ERalpha compared to 2, are also estrogenic, but are only slightly cytotoxic. Finally, we have reexamined compound 5 and discovered that its antiproliferative effect against the MCF-7 cell line does not arise from antiestrogenicity as we had originally suspected, but by means of a cytotoxic pathway. This compound is also sensitive to the number of phenol groups as cell death is diminished when one of the hydroxyl groups is omitted (5 a and 5 b). Molecular modeling studies of the ligand-ERalpha binding stability are broadly consistent with the experimental binding affinity results for compounds 2, 2 a, 2 b, 5, 5 a, and 5 b. Electrochemical experiments show that 1-4, 2 a, and 2 b are stable to oxidation on the electrochemical timescale, unlike 5, 5 a, and 5 b, and that cytotoxicity is related to less positive phenol oxidation potentials. The SAR study shows that the presence of a ketone group and two phenol groups is necessary for strong receptor binding and cytotoxic effects, and that all compounds are estrogenic, despite the presence of a bulky side chain.

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We have designed and synthesised a new organometallic molecule containing three ferrocene groups for use as a highly sensitive electrochemical marker in biological assays. This trisferrocene derivative was conjugated to different PNA monomers, and the electrochemical activities of the conjugates were extensively investigated in organic solvents, in view of their potential diagnostic applications. The results showed that the introduction of a trisferrocene unit on the PNA monomer triples the current signal in comparison with the monoferrocene-labelled one. Despite their greater molecular complexity, trisferrocene-conjugated PNA monomers are even more electrochemically active than the reference ferrocene. By using differential pulse voltammetry (DPV), the detection limit can reach 10(-8) M in acetonitrile solution. These results are a good premise for the use of the trisferrocene unit as an effective electrochemical probe for biomolecules.