1,2,3-Triazoles: Controlled Switches in Logic Gate Applications.

A 1,2,3-triazole-based chemosensor is used for selective switching in logic gate operations through colorimetric and fluorometric response mechanisms. The molecular probe synthesized via "click chemistry" resulted in a non-fluorescent 1,4-diaryl-1,2,3-triazole with a phenol moiety (PTP). However, upon sensing fluoride, it TURNS ON the molecule's fluorescence. The TURN-OFF order occurs through fluorescence quenching of the sensor when metal ions, e.g., Cu2+, and Zn2+, are added to the PTP-fluoride ensemble. A detailed characterization using Nuclear Magnetic Resonance (NMR) spectroscopy in a sequential titration study substantiated the photophysical characteristics of PTP through UV-Vis absorption and fluorescence profiles. A combination of fluorescence OFF-ON-OFF sequences provides evidence of 1,2,3-triazoles being controlled switches applicable to multimodal logic operations. The "INH" gate was constructed based on the fluorescence output of PTP when the inputs are F- and Zn2+. The "IMP" and "OR" gates were created on the colorimetric output responses using the probe's absorption with multiple inputs (F- and Zn2+ or Cu2+). The PTP sensor is the best example of the "Write-Read-Erase-Read" mimic.

Exploring the Effects of Various Polymeric Backbones on the Performance of a Hydroxyaromatic 1,2,3-Triazole Anion Sensor.

Polymeric chemosensors are vital sensing tools because of higher sensitivity compared to their monomeric counterparts and tunable mechanical properties. This study focuses on the incorporation of a hydroxyaromatic 1,2,3-triazole sensor, 2-(4-phenyl 1H-1,2,3-triazol-1-yl)phenol (PTP), into polymers. By itself, the triazole has a selective, fluorometric response to the fluoride, acetate, and dihydrogen phosphate anions, and is most responsive to fluoride. Current investigations probe the suitability of various polymeric backbones for the retention and enhancement of the triazole's sensing capabilities. Backbones derived from acrylic acid, methyl methacrylate, divinylbenzene, and styrene were explored. UV-illumination, Nuclear Magnetic Resonance (NMR) titration, and ultraviolet-visible (UV-Vis) absorption and fluorescence spectroscopy studies are used to investigate the performance of newly synthesized polymers and the derivatives of PTP that serve as the polymers' precursors. Among the polymers investigated, copolymers with styrene proved best; these systems retained the sensing capabilities and were amenable to tuning for sensitivity.

Rationally designed phenanthrene derivatized triazole as a dual chemosensor for fluoride and copper recognition.

A 1,2,3-triazole chemosensor containing phenanthrene and phenol moieties (PhTP) was efficiently synthesized via copper (I)-catalyzed azide-alkyne cycloaddition, "click chemistry". PhTP is a dual analyte sensor for fluoride and copper (II) ions in homogeneous medium. Deprotonation of the phenolic OH proton by the fluoride ion is responsible for a change in fluorescence color from blue (PhTP) to yellowish-orange (PhTP-fluoride adduct), while a charge transfer between the triazole nitrogen of the chemosensor and Cu2+ revealed a turn-off fluorescence output. The detection capability of PhTP was analyzed with a series of anions (F-, Cl-, Br-, I-, H2PO4-, ClO4-, OAc-, BF4-) and cations (Fe3+, Fe2+, Cu2+, Ag+, Cr3+, Al3+, Co2+, Ni2+, Cd2+, Zn2+). With anions, competitive fluorescence responses under UV lamp were observed for acetate and dihydrogen phosphate anions, but maximum response from fluoride ion was substantiated from steady state absorption and fluorescence experiments. With cations, PhTP displayed a selective and sensitive recognition towards Cu2+ ion through spectral modulation in absorption spectroscopy and a turn-off fluorescence response. Nuclear magnetic resonance (NMR) spectroscopic titration studies supported the results obtained through photophysical studies and provided evidence for the ion-binding sites on the probe.

Structure-activity relationships of organofluorine inhibitors of ß-amyloid self-assembly.

A broad group of structurally diverse small organofluorine compounds were synthesized and evaluated as inhibitors of ß-amyloid (Aß) self-assembly. The main goal was to generate a diverse library of compounds with the same functional group and to observe general structural features that characterize inhibitors of Aß oligomer and fibril formation, ultimately identifying structures for further focused inhibitor design. The common structural motifs in these compounds are CF(3) -C-OH and CF(3) -C-NH groups that were proposed to be binding units in our previous studies. A broad range of potential small-molecule inhibitors were synthesized by combining various carbocyclic and heteroaromatic rings with an array of substituents, generating a total of 106 molecules. The compounds were tested by standard methods such as thioflavin-T fluorescence spectroscopy for monitoring fibril formation, biotinyl Aß(1-42) single-site streptavidin-based assays for observing oligomer formation, and atomic force microscopy for morphological studies. These assays revealed a number of structures that show significant inhibition against either Aß fibril or oligomer formation. A detailed analysis of the structure-activity relationship of anti-fibril and -oligomer properties is provided. These data present further experimental evidence for the distinct nature of fibril versus oligomer formation and indicate that the interaction of the Aß peptide with chiral small molecules is not stereospecific in nature.

Enantioselective Friedel-Crafts reaction of indoles with trifluoroacetaldehyde catalyzed by Cinchona alkaloids.

The first direct asymmetric synthetic preparation of trifluoro-1-(indol-3-yl)ethanols (TFIEs) is described by an enantioselective organocatalytic method from indoles and inexpensive trifluoroacetaldehyde methyl hemiacetal. The reaction is catalyzed by hydroquinine to produce TFIEs in an almost quantitative yield and with enantioselectivities up to 75% at room temperature. The enantioselectivity is strongly dependent on the concentration of substrates and catalyst due to the competitive noncatalyzed reaction.

Isomerization mechanism in hydrazone-based rotary switches: lateral shift, rotation, or tautomerization?

Two intramolecularly hydrogen-bonded arylhydrazone (aryl = phenyl or naphthyl) molecular switches have been synthesized, and their full and reversible switching between the E and Z configurations have been demonstrated. These chemically controlled configurational rotary switches exist primarily as the E isomer at equilibrium and can be switched to the protonated Z configuration (Z-H(+)) by the addition of trifluoroacetic acid. The protonation of the pyridine moiety in the switch induces a rotation around the hydrazone C=N double bond, leading to isomerization. Treating Z-H(+) with base (K(2)CO(3)) yields a mixture of E and "metastable" Z isomers. The latter thermally equilibrates to reinstate the initial isomer ratio. The rate of the Z → E isomerization process showed small changes as a function of solvent polarity, indicating that the isomerization might be going through the inversion mechanism (nonpolar transition state). However, the plot of the logarithm of the rate constant k vs the Dimroth parameter (E(T)) gave a linear fit, demonstrating the involvement of a polar transition state (rotation mechanism). These two seemingly contradicting kinetic data were not enough to determine whether the isomerization mechanism goes through the rotation or inversion pathways. The highly negative entropy values obtained for both the forward (E → Z-H(+)) and backward (Z → E) processes strongly suggest that the isomerization involves a polarized transition state that is highly organized (possibly involving a high degree of solvent organization), and hence it proceeds via a rotation mechanism as opposed to inversion. Computations of the Z ↔ E isomerization using density functional theory (DFT) at the M06/cc-pVTZ level and natural bond orbital (NBO) wave function analyses have shown that the favorable isomerization mechanism in these hydrogen-bonded systems is hydrazone-azo tautomerization followed by rotation around a C-N single bond, as opposed to the more common rotation mechanism around the C=N double bond.

A pH activated configurational rotary switch: controlling the E/Z isomerization in hydrazones.

The replacement of one of the carbonyl groups in a 1,2,3-triketone-2-naphthylhydrazone with a pyridine ring yields an original molecular switch that can be switched fully, effectively, and reversibly between the E and Z configurations. This hydrazone-based, pH-controlled, molecular switch is the first example of a chemically controlled configurational rotary switch. The bistable switch exists primarily (97%) as the E configuration in solution and can be converted quantitatively to the Z-H(+) configuration upon treatment with trifluoroacetic acid. When Z-H(+) is passed over a plug of K(2)CO(3), the "metastable" Z configuration is observed using (1)H NMR spectroscopy, which thermally equilibrates to give back the E configuration. The rate of this process is dependent on the polarity of the solvent, indicating that the E/Z isomerization takes place via a rotation around the hydrazone C=N bond.

Microwave-Assisted Preparation of Trifluoroacetaldehyde (Fluoral): Isolation and Applications.

A novel method for the preparation of trifluoroacetaldehyde (fluoral, TFAc, CF(3)CHO) from commercially available trifluoroacetaldehyde ethylhemiacetal (TFAE) by microwave irradiation is described. The isolation, characterization and reaction of fluoral with various nucleophiles were studied to verify the diverse applicability of this new method.

SYNTHESIS OF TRIFLUOROMETHYL-IMINES BY SOLID ACID/SUPERACID CATALYZED MICROWAVE ASSISTED APPROACH.

A new solid acid/superacid catalyzed microwave assisted synthesis of trifluoromethyl-imines is described. Various α,α,α-trifluoromethylketones react readily with primary amines to produce the corresponding imines. Two different strategies have been employed; one is the application of microwave irradiation coupled with solvent-free solid acid catalysis. The other method, for highly deactivated substrates includes the use of a pressure vessel at 175 °C temperature, with solid superacid catalysis. Using the solid acid K-10 montmorillonite or the superacidic perfluorinated resinsulfonic acid Nafion-H, a wide variety of trifluoromethylated imines have been synthesized using the above methods. The products have been isolated in good to excellent yields and high selectivities. This new environmentally friendly synthetic methodology provides significantly higher yields than traditional methods during relatively short reaction times for the preparation of the target compounds.