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There is significant current interest in the development of fluorescent sensors for the physiologically relevant chloride ion. In this study we report a new squaramide-based chloride sensor, derived from ethyl ortho aminobenzoate, whose emission intensity increases by nearly 40% upon chloride binding. The intramolecularly hydrogen bonded squaramide exhibited a blue-shifted excitation spectrum relative to its absorption spectrum, and its emission displayed excitation wavelength dependence. These unusual characteristics were attributed to the existence of two ground state conformers for the unbound squaramide; an intramolecular hydrogen bonded conformer which undergoes non-radiative decay and a non-hydrogen bonded non-planar conformer from which emission occurs. Using computational investigations we identified two nearly degenerate excited states arising from two different charge transfer pathways with the squaramide nitrogen atom as the donor and either the cyclobutene dione ring or the ortho substituted N-phenyl ring functioning as acceptors. In the unbound squaramide, this competition between the two charge transfer pathways decreases fluorescence intensity. Chloride binding, suppresses charge transfer into the cyclobutene dione ring thereby enhancing emission intensity. Our study contributes to an increased understanding of the excited states of squaramides and could facilitate their use in the development of new sensors.

New azulene derivatives containing resonantly electron withdrawing formyl and resonantly electron donating fluorine substituents on the seven- as well as the five-member ring have been prepared. Systematic color changes as a result of perturbation of HOMO, LUMO, and LUMO + 1 energies were discussed. Corresponding excited-state properties related to S2-fluorescence were determined.

The ligand-binding pockets of estrogen receptor alpha and beta (ERα and ERβ) appear to have subpockets of different size and flexibility. To find ligands that will discriminate between the two ER subtypes on the basis of affinity or efficacy, we have prepared compounds of varying size, shape and structure. We have evaluated the binding affinity of these compounds and their potency and efficacy as transcriptional activators through ERα and ERβ. In this manner, we have identified a number of ligands that show pronounced ER subtype selectivity. These studies also highlight the eclectic structure–activity relationships of estrogens and the challenges inherent in developing computational methods for the prediction of estrogenic activity.

Nuclear receptors function as ligand-regulated transcription factors and modulate the expression of sets of genes in response to varying concentrations of ligands. The ligand modulators can be endogenous metabolites that function as hormones, or they can be exogenous substances, such as pharmaceutical agents or environmental substances of natural or man-made origin, which in some cases can cause endocrine disruption. Ligands modulate nuclear receptor activity by binding to their ligand-binding domains and stabilizing conformations that lead either to transcriptional activation or repression. The ligand-binding pocket is somewhat flexible, and binding affinities can be measured over a 10-million-fold range (i.e., with equilibrium dissociation constant values ranging from ca. 0.01 nM to 100 μM). Thus, it is not surprising that by binding a large variety of structures, some nuclear receptors can appear to be promiscuous; however, when affinity is considered, the binding patterns are more restricted. The spectrum of ligands that bind to the estrogen receptor has been most thoroughly investigated. Those from natural sources include natural products in food, such as soy isoflavones and whole grain lignans, as well as microbial products and components from wood. Aside from pharmaceuticals, man-made estrogen ligands can be found in industrial products, such as alkyl phenols from nonionic detergents, bisphenols from plastics, indicator dye impurities, polymer chemicals, and chlorinated aromatics and pesticides. Exogenous ligands are also known for the androgen and progesterone receptors. While it is possible that endocrine disruption can result from exogenous chemicals acting directly as ligands for the nuclear receptors, endocrine disruption needs to be considered in the broader context; thus, compounds also need to be assessed for their effects at other levels, such as on endogenous hormone production, transport, metabolism, and clearance, and at points in signal transduction cascades that are beyond the ligand-receptor interaction.

The UV−visible−near-IR absorption spectra, S2 → S0 fluorescence quantum yields and S2 fluorescence lifetimes of 1-fluoroazulene, 1,3-difluoroazulene, and several of their alkyl-substituted derivatives have been measured at room temperature in up to six solvents, benzene, dichloromethane, ethanol, acetonitrile, n-hexane, and perfluoro-n-hexane. The quantum yields (up to 0.2) and lifetimes (up to 9.5 ns) of the S2 state of 1,3-difluoroazulene are exceptionally largethe largest ever reported for an upper excited singlet state of a polyatomic molecule with a closed-shell ground state. The nonradiative rate constants for the decay of the S2 states of these molecules in these solvents and of azulene, 1,3-dichloroazulene and 1,3-dibromoazulene, determined previously, have been analyzed in terms of the weak coupling case of radiationless transition theory. The data show that the nonradiative rate constants for the S2 states of azulene, 1-fluoroazulene, and 1,3-difluoroazulene in the nonpolar solvents follow the l...

Tertiary aryl squaramides were synthesized by using copper catalyzed C-N bond-formation with L-proline as the ligand. Symmetrical diaryl squaramides could be prepared in a one-pot reaction by using excess aryl bromide with varying yields. Unsymmetrical derivatives were prepared by sequential arylation. Yields of the diarylated products were highly sensitive to steric effects.

Incorporating red-shifted retinal analogues, such as azulenic retinals, into bacterioopsin provides a method to evaluate the low-energy limit for bacteriorhodopsin (bR) proton-pumping activity. We report results of nanosecond time-resolved studies of three azulenic bR analogues. In contrast to a recent report on an azulenic bR analogue (Druzhko et al., 1996),4 we conclude that such pigments do not exhibit photocycles (no detectable intermediates) and suspect that the preferred direction of deactivation is internal conversion to the low-lying forbidden S1 state of the azulene chromophore. We further demonstrated that for slow-binding bR analogues, the samples can easily be contaminated with small amounts of native bR.