Improving triplet-triplet-annihilation based upconversion systems by tuning their topological structure.

Materials capable to perform upconversion of light transform the photon spectrum and can be used to increase the efficiency of solar cells by upconverting sub-bandgap photons, increasing the density of photons able to generate an electron-hole pair in the cell. Incoherent solar radiation suffices to activate upconverters based on sensitized triplet-triplet annihilation, which makes them particularly suited for this task. This process requires two molecular species, sensitizers absorbing low energy photons, and emitters generating higher frequency photons. Successful implementations exist in solutions and solids. However, solid upconverters exhibit lower efficiency than those in solution, which poses a serious problem for real applications. In the present work, we suggest a new strategy to increase the efficiency of sensitized upconverters that exploits the solid nature of the material. We show that an upconversion model system with molecules distributed as clusters outperforms a system with a random distribution of molecules, as used in current upconverters. Our simulations reveal a high potential for improvement of upconverter systems by exploring different structural configurations of the molecules. The implementation of advanced structures can push the performance of solid upconverters further towards the theoretical limit and a step closer to technological application of low power upconversion.

Efficiency scaling of non-coherent upconversion in a one-dimensional model system.

A very promising approach to obtain efficient upconversion of light is the use of triplet-triplet annihilation of excitations in molecular systems. In real materials, besides upconversion, many other physical processes take place--fluorescence, phosphorescence, non-radiative decay, annihilation, diffusion--and compete with upconversion. The main objective of this work is to design a proof of principle model that can be used to shed light on the interplay between these processes. Ultimately, we want to establish general principles that may guide experimentalists toward the design of solid state materials with maximum efficiency. Here we show, in a one-dimensional model system, that upconversion can be optimized by varying the ratio between the two molecular species used in triplet-triplet-annihilation based upconversion systems, even in the presence of undesired losses through phosphorescence, non-radiative decay, or annihilation. We derive scaling laws for this ratio and for the maximum efficiency of upconversion, as a function of the diffusion rate J, as well as of the creation and of the decay rate of the excitations.

Hydrogen-deuterium exchange reactions of aromatic compounds and heterocycles by NaBD4-activated rhodium, platinum and palladium catalysts.

Conventional thermal and microwave conditions were compared for hydrogen-deuterium (H/D) exchange reactions of aminobenzoic acids catalysed by NaBD(4)-activated Pd/C or RhCl(3) with D(2)O as the deuterium source. We also investigated different NaBD(4)-activated metal catalysts (including Pd/C, RhCl(3) and Pt/C) under microwave conditions for an efficient H/D exchange of aromatic and heterocyclic compounds. Even higher deuterium incorporations were obtained for Pd/C and Pt/C catalyst mixtures due to the previously observed synergistic effect. Finally, we have applied these optimised conditions for one-step syntheses of the MS standards of several pharmaceutically active compounds.

Benzothiepin-derived molecular scaffolds for estrogen receptor modulators: synthesis and antagonistic effects in breast cancer cells.

A series of novel benzothiepin-derived compounds are described as potent selective modulators of the human estrogen receptor (SERMs). The objective of the study is to evaluate the antiproliferative effects of the compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the traditional triarylethylene arrangement exemplified by tamoxifen, conformationally restrained through the incorporation of the benzothiepin ring system. The compounds demonstrated potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity. The compounds exhibited low nanomolar binding affinity for the estrogen receptor (ER) with some specificity for ERbeta, and also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzothiepin molecular scaffold is explored through a brief computational structure-activity relationship investigation with molecular simulation.

The renaissance of H/D exchange.

The increasing demand for stable isotopically labeled compounds has led to an increased interest in H/D-exchange reactions at carbon centers. Today deuterium-labeled compounds are used as internal standards in mass spectrometry or to help elucidate mechanistic theories. Access to these deuterated compounds takes place significantly more efficiently and more cost effectively by exchange of hydrogen by deuterium in the target molecule than by classical synthesis. This Review will concentrate on the preparative application of the H/D-exchange reaction in the preparation of deuterium-labeled compounds. Advances over the last ten years are brought together and critically evaluated.

Estrogenic and antiestrogenic activities of 2,4-diphenylfuran-based ligands of estrogen receptors alpha and beta.

The estrogen receptor (ER) exists in two isoforms ERalpha and ERbeta with a different distribution in the body and different functions which are not clearly identified yet. Thus, it is desirable to have both agonists and antagonists with selectivity for one or the other ER isoform available. In a previous study we showed that 2,5-diphenylfurans can be converted into pure antiestrogens with preference for ERalpha. When the arrangement of the phenyl rings was altered to a 2,4-substitution, the alpha-selectivity was lost as demonstrated by comparative assays using recombinant human ERalpha and ERbeta. 3,5-Dialkyl-2,4-bis(4-hydroxyphenylfurans) were shown to act as agonists with preference for ERbeta. Replacement of one of the alkyl groups by the [(pentylsulfanyl)propyl]aminohexyl side chain afforded estrogen antagonists without receptor selectivity. These derivatives were characterized as pure antiestrogens in transcription and proliferation assays in ER+ MCF-7 breast cancer cells. The most potent antagonists displayed IC50 values of ca. 20 nM (fulvestrant 4 nM). The data showed that the 2,4-arrangement of the phenyl rings in the furan structure increases the binding affinity for ERbeta in comparison to the isomeric 2,5-diphenylfurans but does not lead to a pure antagonist with selectivity for ERbeta.

2,5-Diphenylfuran-based pure antiestrogens with selectivity for the estrogen receptor alpha.

The estrogen receptor alpha (ERalpha) is understood to play an important role in the progression of breast cancer. Therefore, pure antiestrogens with a preference for this receptor form are of interest as new agents for the treatment of this malignancy. Several chemical structures with selective binding affinity for ERalpha have been identified and might be useful for the synthesis of ERalpha-selective pure antiestrogens. In this study we applied the 2,5-diphenylfuran system which is closely related to the triphenylfurans described by others. Various side chains with amino and/or sulfur functions were linked to C3 to convert the furans to estrogen antagonists without residual estrogenic activity. The degree of alpha-selectivity which ranges from 2.5- to 236-fold is strongly influenced by the alkyl group at C4. Antiestrogenic potency was determined in MCF-7/2a breast cancer cells stably transfected with a luciferase gene under the control of an ERE. The 2,5-bis(4-hydroxyphenyl)furan with an ethyl substituent and a 6-[N-methyl-N-(3-pentylthiopropyl)amino]hexyl side chain exerted the strongest antiestrogenic effect in this series with an IC(50) value of 50 nM in cells stimulated with 1 nM estradiol. The RBA values of this derivative were 18% (ERalpha) and 3.4% (ERbeta) of estradiol, respectively. It inhibited the growth of wild-type MCF-7 cells with an IC(50) value of 22 nM. The data show that the 2,5-diphenylfuran system is appropriate for the development of pure antiestrogens with preference for ERalpha.