Stimuli Response of Eu3+-Based Metallo-Supramolecular Polymers toward Pharmaceutical Amines.

Metallo-supramolecular polymers offer a highly controllable platform for sensing. Their modular characteristics obtained by the ability of varying both building blocks, the metal ion and the organic ligand, provide tunability of their optical and chemical properties. Specifically, polymers based on lanthanide ions and conjugated aromatic ligands exhibit enhanced luminescence properties that can be altered by external stimulation. Herein, using europium-based polymers, we demonstrate the ability to detect different pharmaceutical amines, including in complex biological media, based on their luminescence quenching efficiency as a result of their polymer dissociation capacity. A combination of absorption, luminescence, and NMR measurements reveals combined static and dynamic quenching mechanisms that enable selective sensing of strong basic amines with high pKa values.

Effective neutralization of chemical warfare agents (HD, VX) by Me-DABCOF: a small molecule with dual action.

The ability of mono N-methyl-1,4-diazabicyclo[2.2.2]octane fluoride (Me-DABCOF, 1) to act as a bifunctional reagent that effectively and universally neutralizes both the persistent and extremely toxic blister agent HD and the nerve agent VX in nearly neutral aqueous solution, alumina powder or a hydrogel formulation, is described.

Oxidative Detoxification of Sulfur-Containing Chemical Warfare Agents by Electrophilic Iodine.

Mild oxidation of sulfur-containing chemical warfare agents was performed in organic medium by electrophilic iodine reagents. Kinetic experiments on sulfur mustard (HD) showed rapid ( t1/2 < 3 min) and selective oxidation to the nonvesicant sulfoxide product (HD-SO) in acetonitrile or propylene carbonate solutions (9% water added) containing excess N-iodosuccinimide (NIS). Molecular iodine solutions in these solvents led to similar results as with NIS but at much slower rates ( t1/2 ∼ 90 min). Higher donor number solvents, such as THF, DMF, or DMSO, showed slower rates with both iodine and NIS. The oxidation of the nerve agent O-ethyl- S-2-( N,N-diisopropylaminoethyl)methylphosphonothioate (VX) selectively to the nontoxic ethyl methylphosphonic acid product exhibited fast rates ( t1/2 = 6 min) using NIS in DMSO solution. In all other solvents tested with VX, rates were slower ( t1/2 ∼ 30-70 min). Oxidation experiments under the same conditions with chloroethyl ethyl sulfide (HD simulant) and O,S-diethyl methylphosphonothioate (VX simulant) led to much faster reaction rates. These transformations are believed to proceed through electrophilic iodine attack on the sulfur moiety and display solvent dependency based on the agents' structural and chemical properties.

Synthesis, Characterization, and Reactivity of Thermally Stable Anhydrous Quaternary Ammonium Fluorides.

The synthesis and properties of a new class of anhydrous quaternary ammonium fluorides, based on the rigid skeleton azabicyclo[2.2.2]octane, is described. Compounds 2a-d were easily prepared by passing the corresponding ammonium iodides over fluoride-based resin followed by drying their hydrated form at 100 or 140 °C under reduced pressure. The stability (experimental and theoretical study), solubility, reactivity, and characterization by solution and solid-state MAS NMR are discussed.

Chemoselective N-Difluoromethylation of Functionalized Tertiary Amines.

A practical, convenient, and general method for the difluoromethylation of tertiary amines, using diethyl bromodifluoromethylphosphonate and fluoride, is described. This commercially available phosphonate smoothly reacts with a fluoride ion to liberate a difluorocarbene intermediate that in the presence of a proton source and a tertiary amine generates the corresponding α-difluoromethylammonium compound in good to excellent yields. Despite the involvement of a difluorocarbene intermediate, this difluoromethylation occurs almost exclusively on the nitrogen atom with diverse molecular structures, including drugs, surfactants, chiral phase transfer catalysts, polymers, ionic liquids, and other fine chemicals. A preliminary assessment of the effects that an α-difluoromethyl groupT has on hydrogen bonding and logP of quaternary ammonium salts is also described.

Ultrafast excited-state proton transfer to the solvent occurs on a hundred-femtosecond time-scale.

Steady-state and ultrafast time-resolved techniques were used to study a newly synthesized photoacid, phenol-carboxyether dipicolinium cyanine dye, QCy9. We found that the excited-state proton transfer (ESPT) to water occurs at the remarkably short time of about 100 fs, k(PT) ≈ 1 × 10(13) s(-1), the fastest rate reported up to now. On the basis of the Förster-cycle, the pK(a)* value is estimated to be -8.5 ± 0.4. In previous studies, we reported the photoacidity of another superphotoacid, the QCy7 for which we found an ESPT rate constant of ~1.25 × 10(12) s(-1), one-eighth that of the QCy9 compound. We found a kinetic isotope effect of the ESPT of about two.

Enzyme-mediated nutrient release: glucose-precursor activation by ß-galactosidase to induce bacterial growth.

Bacteria will gain an advantage if they are able to metabolize nutrients that are inaccessible for other bacteria. To demonstrate this principle, we developed a simple model system, which mimics how bacteria exploit natural carbon sources. A masked glucose precursor that is activated by ß-galactosidase was used as a carbon source for bacterial growth in a glucose-deficient medium. No bacterial growth was observed in the presence of control substances in which ß-galactosidase mediated cleavage did not lead to glucose release. This study represents a proof-of-principle example in which a bacterium can grow in a nutrient-free medium by inducible, enzyme-mediated nutrient release from a precursor.

"Donor-two-acceptor" dye design: a distinct gateway to NIR fluorescence.

The detection of chemical or biological analytes upon molecular reactions relies increasingly on fluorescence methods, and there is a demand for more sensitive, more specific, and more versatile fluorescent molecules. We have designed long wavelength fluorogenic probes with a turn-ON mechanism based on a donor-two-acceptor π-electron system that can undergo an internal charge transfer to form new fluorochromes with longer π-electron systems. Several latent donors and multiple acceptor molecules were incorporated into the probe modular structure to generate versatile dye compounds. This new library of dyes had fluorescence emission in the near-infrared (NIR) region. Computational studies reproduced the observed experimental trends well and suggest factors responsible for high fluorescence of the donor-two-acceptor active form and the low fluorescence observed from the latent form. Confocal images of HeLa cells indicate a lysosomal penetration pathway of a selected dye. The ability of these dyes to emit NIR fluorescence through a turn-ON activation mechanism makes them promising candidate probes for in vivo imaging applications.

Ultrafast proton transfer of three novel quinone cyanine photoacids.

Steady-state and time-resolved emission techniques were used to study the photoprotolytic properties of three recently synthesized strong quinone cyanine photoacids (QCy7 and its sulfonated derivatives). The rate coefficient of the excited-state proton transfer (ESPT), k(PT), of the three dyes is roughly 1.5 × 10(12) s(-1), a high value that is comparable to the solvation dynamics rate of large polar organic molecules in H(2)O and D(2)O. It is twice as fast as the proton transfer rate between two adjacent water molecules in liquid water. We found that, as expected, two of the sulfonated photoacids geminately recombines with the proton at an elevated rate. The accelerated geminate recombination process of the sulfonated derivatives is different from a simple diffusion process of protons. The ESPT rate coefficient of these molecules is the highest recorded thus far.

Ultrafast excited-state intermolecular proton transfer of cyanine fluorochrome dyes.

Steady-state and time-resolved emission spectroscopy techniques were employed to study the excited-state proton transfer (ESPT) to water and D(2)O from QCy7, a recently synthesized near-infrared (NIR)-emissive dye with a fluorescence band maximum at 700 nm. We found that the ESPT rate constant, k(PT), of QCy7 excited from its protonated form, ROH, is ~1.5 × 10(12) s(-1). This is the highest ever reported value in the literature thus far, and it is comparable to the reciprocal of the longest solvation dynamics time component in water, τ(S) = 0.8 ps. We found a kinetic isotope effect (KIE) on the ESPT rate of ~1.7. This value is lower than that of weaker photoacids, which usually have KIE value of ~3, but comparable to the KIE on proton diffusion in water of ~1.45, for which the average time of proton transfer between adjacent water molecules is similar to that of QCy7.

A unique paradigm for a Turn-ON near-infrared cyanine-based probe: noninvasive intravital optical imaging of hydrogen peroxide.

The development of highly sensitive fluorescent probes in combination with innovative optical techniques is a promising strategy for intravital noninvasive quantitative imaging. Cyanine fluorochromes belong to a superfamily of dyes that have attracted substantial attention in probe design for molecular imaging. We have developed a novel paradigm to introduce a Turn-ON mechanism in cyanine molecules, based on a distinctive change in their π-electrons system. Our new cyanine fluorochrome is synthesized through a simple two-step procedure and has an unprecedented high fluorescence quantum yield of 16% and large extinction coefficient of 52,000 M(-1)cm(-1). The synthetic strategy allows one to prepare probes for various analytes by introducing a specific triggering group on the probe molecule. The probe was equipped with a corresponding trigger and demonstrated efficient imaging of endogenous hydrogen peroxide, produced in an acute lipopolysaccharide-induced inflammation model in mice. This approach provides, for the first time, an available methodology to prepare modular molecular Turn-ON probes that can release an active cyanine fluorophore upon reaction with specific analyte.