Click Synthesis of Tweezer Dyads for H-Bond Assisted Cooperativity in Tandem Uncaging Systems.

"Tandem" uncaging systems, in which a photolabile protecting group (PPG) is sensitized by an energy-harvesting antenna, may increase the photosensitivity of PPGs by several orders of magnitude for two-photon (2P) photorelease. Yet, they remain poorly accessible because of arduous multi-step synthesis. In this work, we design efficient tandem uncaging systems by (i) using a convenient assembly of the building blocks relying on click chemistry, (ii) H-bonding induced proximity thus facilitating (iii) photoinduced electron transfer (PeT) as a cooperative mechanism. A strong two-photon absorber electron-donating quadrupolar antenna and various electron-accepting PPGs (mDEAC, MNI or MDNI) were clicked stepwise onto a "tweezer-shaped" pyrido-2,6-dicarboxylate platform whose H-bonding and p-stacking abilities were exploited to keep the antenna and the PPGs in close proximity. The different electron acceptor ability of the PPGs led to dyads with wildly different behaviors. Whilst the MDNI and MNI dyads showed poor dark stability or no photo-uncaging ability due to their too high electron accepting character, the mDEAC dyad benefited from optimum redox potentials to promote PeT and slow down charge recombination, resulting in enhanced uncaging quantum yield (Fu=0.38) compared to mDEAC (Fu=0.014). The unique resulted in large 2P photo-sensitivity in the near-infrared window (240 GM at 710 nm).

Product Detection of the CH(X2Π) Radical Reaction with Cyclopentadiene: A Novel Route to Benzene.

The reaction of the methylidyne radical (CH(X2Π)) with cyclopentadiene (c-C5H6) is studied in the gas phase at 4 Torr and 373 K using a multiplexed photoionization mass spectrometer. Under multiple collision conditions, the dominant product channel observed is the formation of C6H6 + H. Fitting the photoionization spectrum using reference spectra allows for isomeric resolution of C6H6 isomers, where benzene is the largest contributor with a relative branching fraction of 90 (±5)%. Several other C6H6 isomers are found to have smaller contributions, including fulvene with a branching fraction of 8 (±5)%. Master Equation calculations for four different entrance channels on the C6H7 potential energy surface are performed to explore the competition between CH cycloaddition to a C═C bond vs CH insertion into C-H bonds of cyclopentadiene. Previous studies on CH addition to unsaturated hydrocarbons show little evidence for the C-H insertion pathway. The present computed branching fractions support benzene as the sole cyclic product from CH cycloaddition, whereas fulvene is the dominant product from two of the three pathways for CH insertion into the C-H bonds of cyclopentadiene. The combination of experiment with Master Equation calculations implies that insertion must account for ∼10 (±5)% of the overall CH + cyclopentadiene mechanism.

Hydrophilic Fluorescent Nanoprodrug of Paclitaxel for Glioblastoma Chemotherapy.

Highly water-soluble, nontoxic organic nanoparticles on which paclitaxel (PTX), a hydrophobic anticancer drug, has been covalently bound via an ester linkage (4.5% of total weight) have been prepared for the treatment of glioblastoma. These soft fluorescent organic nanoparticles (FONPs), obtained from citric acid and diethylenetriamine by microwave-assisted condensation, show suitable size (Ø = 17-30 nm), remarkable solubility in water, softness as well as strong blue fluorescence in an aqueous environment that are fully retained in cell culture medium. Moreover, these FONPs were demonstrated to show in vitro safety and preferential internalization in glioblastoma cells through caveolin/lipid raft-mediated endocytosis. The PTX-conjugated FONPs retain excellent solubility in water and remain stable in water (no leaching), while they showed anticancer activity against glioblastoma cells in two-dimensional and three-dimensional culture. PTX-specific effects on microtubules reveal that PTX is intracellularly released from the nanocarriers in its active form, in relation with an intracellular-promoted lysis of the ester linkage. As such, these hydrophilic prodrug formulations hold major promise as biocompatible nanotools for drug delivery.

Product Detection of the CH Radical Reactions with Ammonia and Methyl-Substituted Amines.

Reactions of the methylidyne (CH) radical with ammonia (NH3), methylamine (CH3NH2), dimethylamine ((CH3)2NH), and trimethylamine ((CH3)3N) have been investigated under multiple collision conditions at 373 K and 4 Torr. The reaction products are detected by using soft photoionization coupled to orthogonal acceleration time-of-flight mass spectrometry at the Advanced Light Source (ALS) synchrotron. Kinetic traces are employed to discriminate between CH reaction products and products from secondary or slower reactions. Branching ratios for isomers produced at a given mass and formed by a single reaction are obtained by fitting the observed photoionization spectra to linear combinations of pure compound spectra. The reaction of the CH radical with ammonia is found to form mainly imine, HN═CH2, in line with an addition-elimination mechanism. The singly methyl-substituted imine is detected for the CH reactions with methylamine, dimethylamine, and trimethylamine. Dimethylimine isomers are formed by the reaction of CH with dimethylamine, while trimethylimine is formed by the CH reaction with trimethylamine. Overall, the temporal profiles of the products are not consistent with the formation of aminocarbene products in the reaction flow tube. In the case of the reactions with methylamine and dimethylamine, product formation is assigned to an addition-elimination mechanism similar to that proposed for the CH reaction with ammonia. However, this mechanism cannot explain the products detected by the reaction with trimethylamine. A C-H insertion pathway may become more probable as the number of methyl groups increases.

Cooperative Veratryle and Nitroindoline Cages for Two-Photon Uncaging in the NIR.

Tandem uncaging systems in which a two-photon absorbing module and a cage moiety, linked via a phosphorous clip, that act together by Förster resonance energy transfer (FRET) have been developed. A library of these compounds, using different linkers and cages (7-nitroindolinyl or nitroveratryl) has been synthesized. The investigation of their uncaging and two-photon absorption properties demonstrates the scope and versatility of the engineering strategy towards efficient two-photon cages and reveals surprising cooperative and topological effects. The interactions between the 2PA module and the caging moiety are found to promote cooperative effects on the 2PA response while additional processes that enhance the uncaging efficiency are operative in well-oriented nitroindoline-derived dyads. These synergic effects combine to lead to record two-photon uncaging cross-section values (i.e., up to 20 GM) for uncaging of carboxylic acids.

Fluorescent periodic mesoporous organosilica nanoparticles dual-functionalized via click chemistry for two-photon photodynamic therapy in cells.

The synthesis of ethenylene-based periodic mesoporous organosilica nanoparticles for two-photon imaging and photodynamic therapy of breast cancer cells is described. A dedicated two-photon absorbing fluorophore possessing four triethoxysilyl groups and having large two-photon absorption in the near IR region, and azidopropyltriethoxysilane were incorporated into the structure. The mesoporous nanoparticles of 100 nm diameter were further functionalized by means of click chemistry with a propargylated fluorescent bromo-quinoline photosensitizer able to generate singlet oxygen. The photophysical properties and two-photon absorption properties of the nanoparticles were investigated evidencing complementary contribution of the two dyes. Both dyes contribute to the two-photon absorption response of the mesoporous nanoparticles while efficient FRET from the two-photon fluorophore to the quinoline sensitizer is observed. The dual-functionalized nanoparticles were incubated with MCF-7 breast cancer cells. Two-photon confocal imaging demonstrated the endocytosis of the nanoparticles within cancer cells. Moreover, brief two-photon irradiation (3 scans of 1.57 s) at 760 nm at high laser power (3 W) was shown to induce 40% of cancer cell death demonstrating the potential of the dual-functionalized mesoporous organosilica nanoparticles for two-photon photodynamic therapy.

Flow tube studies of the C((3)P) reactions with ethylene and propylene.

Product detection studies of C((3)P) atom reactions with ethylene, C2H4(X(1)Ag) and propylene, C3H6(X(1)A') are carried out in a flow tube reactor at 332 K and 4 Torr (553.3 Pa) under multiple collision conditions. Ground state carbon atoms are generated by 193 nm laser photolysis of carbon suboxide, C3O2 in a buffer of helium. Thermalized reaction products are detected using tunable VUV photoionization and time of flight mass spectrometry. For C((3)P) + ethylene, propargyl (C3H3) is detected as the only molecular product in agreement with previous studies on this reaction. The temporal profiles of the detected ions are used to discriminate C((3)P) reaction products from side reaction products. For C((3)P) + propylene, two reaction channels are identified through the detection of methyl (CH3) and propargyl (C3H3) radicals for the first channel and C4H5 for the second one. Franck-Condon Factor simulations are employed to infer the C4H5-isomer distribution. The measured 1 : 4 ratio for the i-C4H5 isomer relative to the methylpropargyl isomers is similar to the C4H5 isomer distribution observed in low-pressure flames and differs from crossed molecular beams data. The accuracy of these isomer distributions is discussed in view of large uncertainties on the photoionization spectra of the pure C4H5 isomers.

Cooperative dyads for two-photon uncaging.

A series of dyads that combine a photolabile protecting group (PPG) 4,5-dimethoxy-2-nitrobenzyl and different bis-donor or bis-acceptor dissymmetric chromophores acting as two-photon (2P) absorbers were synthesized. Even for low energy transfer efficiency from the 2PA subunit to the uncaging one, improvement of the 2P uncaging sensitivity in the NIR is achieved as compared to isolated PPG. Moreover enhancement of the 2PA response is achieved by tuning the electronic dissymmetry of the 2PA subunit and the arrangement of the complementary subunits in the dyads.

The rate of the F + H2 reaction at very low temperatures.

The prototypical F + H2 â†’ HF + H reaction possesses a substantial energetic barrier (~800 K) and might therefore be expected to slow to a negligible rate at low temperatures. It is, however, the only source of interstellar HF, which has been detected in a wide range of cold (10-100 K) environments. In fact, the reaction does take place efficiently at low temperatures due to quantum-mechanical tunnelling. Rate constant measurements at such temperatures have essentially been limited to fast barrierless reactions, such as those between two radicals. Using uniform supersonic hydrogen flows we can now report direct experimental measurements of the rate of this reaction down to a temperature of 11 K, in remarkable agreement with state-of-the-art quantum reactive scattering calculations. The results will allow a stronger link to be made between observations of interstellar HF and the abundance of the most common interstellar molecule, H2, and hence a more accurate estimation of the total mass of astronomical objects.

Tandem triad systems based on FRET for two-photon induced release of glutamate.

Tandem systems allowing enhanced two-photon (2P) absorption in a wavelength range permitting coupling of the primary excitation by energy transfer to an intramolecular cage known to have fragmentation properties suited to photolysis in neuroscience is demonstrated to lead to a 10-fold improvement in the 2P photolysis cross-section at experimentally compatible wavelengths.

Synthesis of the beta-rhamnopyranosides and the 6-deoxy-beta-mannoheptopyranosides.

A review is presented of the development of methods for the synthesis of beta-rhamnopyranosides and the related 6-deoxy-beta-mannoheptopyranosides based on the 4,6-O-alkylidene directed synthesis of mannopyranosides and their 6-thia derivatives followed by selective reduction at the 6-position. Applications to total synthesis of complex bacterial oligosaccharides containing the title moieties are presented.

Low temperature kinetics, crossed beam dynamics and theoretical studies of the reaction S((1)D) + CH4 and low temperature kinetics of S((1)D) + C2H2.

The reaction between sulfur atoms in the first electronically excited state, S((1)D), and methane (CH(4)), has been investigated in a complementary fashion in (a) crossed-beam dynamics experiments with mass spectrometric detection and time-of-flight (TOF) analysis at two collision energies (30.4 and 33.6 kJ mol(-1)), (b) low temperature kinetics experiments ranging from 298 K down to 23 K, and (c) electronic structure calculations of stationary points and product energetics on the CH(4)S singlet potential energy surface. The rate coefficients for total loss of S((1)D) are found to be very large (ca. 2 × 10(-10) cm(3) molec(-1) s(-1)) down to very low temperatures indicating that the overall reaction is barrier-less. Similar measurements are also performed for S((1)D) + C(2)H(2), and also for this system the rate coefficients are found to be very large (ca. 3 × 10(-10) cm(3) molec(-1) s(-1)) down to very low temperatures. From laboratory angular and TOF distributions at different product masses for the reaction S((1)D) + CH(4), it is found that the only open reaction channel at the investigated collision energies is that leading to SH + CH(3). The product angular, T(θ), and translational energy, P(E'(T)), distributions in the center-of-mass frame are derived. The reaction dynamics are discussed in terms of two different micromechanisms: a dominant long-lived complex mechanism at small and intermediate impact parameters with a strongly polarized T(θ), and a direct pickup-type (stripping) mechanism occurring at large impact parameters with a strongly forward peaked T(θ). Interpretation of the experimental results on the S((1)D) + CH(4) reaction kinetics and dynamics is assisted by high-level theoretical calculations on the CH(4)S singlet potential energy surface. The dynamics of the SH + CH(3) forming channel are compared with those of the corresponding channel (leading to OH + CH(3)) in the related O((1)D) + CH(4) reaction, previously investigated in crossed-beams in other laboratories at comparable collision energies. The possible astrophysical relevance of S((1)D) reactions with hydrocarbons, especially in the chemistry of cometary comae, is discussed.

Low temperature kinetics: the association of OH radicals with O2.

We report the first measurements of rate constants for the reaction in which OH radicals associate with O(2) to form HO(3). Our recent measurements (Science, 2010, 328, 1258) have shown that the HO-O(2) bond dissociation energy is only (12.3 ± 0.3) kJ mol(-1). Consequently, above ca. 90 K under attainable experimental conditions, the rate of the reverse dissociation of HO(3) becomes comparable to, and then greater than, the rate of the forward association reaction. We have used the CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme) method to access low temperatures and have explored the kinetics of OH + O(2) + M → HO(3) + M in two series of experiments. At temperatures between 55.9 and 79.2 K, the OH radicals, created by pulsed laser photolysis of H(2)O(2) and observed by laser-induced fluorescence, decayed by pseudo-first-order kinetics to effectively zero concentration at longer times. The third-order rate constants derived from these experiments fit the expression: k(3rd)(o) (T) = (4.2 ± 1.9) × 10(-34) (T/298 K)(-(3.5 ± 0.3)) cm(6) molecule(-2) s(-1). At temperatures between 87.4 and 99.8 K, rate constants for the association reaction were determined allowing for the significant occurrence of the reverse dissociation reaction. The values of the derived rate constants are consistent with those obtained in the lower temperature range, though the errors are larger. The experimental values of k(3rd)(o) (T) are compared with (a) those for other association reactions involving species of similar complexity, and (b) values of k(3rd)(o) (T) estimated according to both the energy transfer (ET) and the radical-complex (RC) mechanisms. We conclude that the RC mechanism probably makes the major contribution to the association of OH + O(2) at the low temperatures of our experiments.

The thermodynamics of the elusive HO3 radical.

The role of HO3 as a temporary reservoir of atmospheric OH radicals remains an open question largely because of the considerable uncertainty in the value of the dissociation energy of the HO-O2 bond (D0) or, equivalently, the standard enthalpy of formation of HO3 (Delta(f)H;{\overline{);\circ }}$$). Using a supersonic flow apparatus, we have observed by means of laser-induced fluorescence the decay of OH radicals in the presence of O2 at temperatures between 55.7 and 110.8 kelvin (K). Between 87.4 and 99.8 K, the OH concentration approached a nonzero value at long times, allowing equilibrium constants for the reaction with O2 to be calculated. Using expressions for the equilibrium constant from classical and statistical thermodynamics, and values of partition functions and standard entropies calculated from spectroscopic data, we derived values of D0 = (12.3 +/- 0.3) kilojoules per mole and Delta(f)H;{\overline{);\circ }}$$ (298 K) = (19.3 +/- 0.5) kilojoules per mole. The atmospheric implications of HO3 formation are therefore very slight.

Low temperature rate coefficients for reactions of the butadiynyl radical, C4H, with various hydrocarbons. Part II: reactions with alkenes (ethylene, propene, 1-butene), dienes (allene, 1,3-butadiene) and alkynes (acetylene, propyne and 1-butyne).

The kinetics of the reactions of the linear butadiynyl radical, C4H (CCCCH), with a variety of unsaturated hydrocarbons have been studied over the temperature range of 39-300 K using a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme, or reaction kinetics in uniform supersonic flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. The rate coefficients for all the reactions studied are found to all be in excess of 10(-10) cm(3) molecule(-1) s(-1) over the entire temperature range. They can be fitted with the following expressions (valid from 39 K to 300 K, with RMS deviations of the experimental points from the predicted values shown, to which should be added 10% possible systematic error) for reaction of C4H with alkenes: k(C2H4) = (1.95 +/- 0.17) x 10(-10) (T/298 K)(-0.40) exp(9.4 K/T) cm3 molecule(-1) s(-1); k(C3H6) = (3.25 +/- 0.12) x 10(-10) (T/298 K)(-0.84) exp(-48.9 K/T) cm3 molecule(-1) s(-1); k(1-C4H8) = (6.30 +/- 0.35) x 10(-10) (T/298 K)(-0.61) exp(-65.0 K/T) cm3 molecule(-1) s(-1), for reaction of C4H with dienes: k(C3H4) = (3.70 +/- 0.34) x 10(-10) (T/298 K)(-1.18) exp(-91.1 K/T) cm3 molecule(-1) s(-1); k(1,3-C4H6) = (5.37 +/- 0.30) x 10(-10) (T/298 K)(-1.25) exp(-116.8 K/T) cm3 molecule(-1) s(-1), and for reaction of C4H with alkynes: k(C2H2) = (1.82 +/- 0.19) x 10(-10) (T/298 K)(-1.06) exp(-65.9 K/T) cm3 molecule(-1) s(-1); k(C3H4) = (3.20 +/- 0.08) x 10(-10) (T/298 K)(-0.82) exp(-47.5 K/T) cm3 molecule(-1) s(-1); k(1-C4H6) = (3.48 +/- 0.14) x 10(-10) (T/298 K)(-0.65) exp(-58.4 K/T) cm3 molecule(-1) s(-1). Possible reaction mechanisms and product channels are discussed in detail for each of these reactions. Potential implications of these results for models of low temperature chemical environments, in particular cold interstellar clouds and star-forming regions, are considered.

Low temperature rate coefficients for reactions of the butadiynyl radical, C4H, with various hydrocarbons. Part I: reactions with alkanes (CH4, C2H6, C3H8, C4H10).

The kinetics of the reactions of the linear butadiynyl radical, C4H (CCCCH), with methane, ethane, propane and butane have been studied over the temperature range of 39-300 K using a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. The rate coefficients, except for the reaction with methane, show a negative temperature dependence and can be fitted with the following expressions over the temperature range of this study: k(C2H6) = 0.289 x 10(-10) (T/298 K)(-1.23) exp(-24.8 K/T) cm3 molecule(-1) s(-1); k(C3H8) = 1.06 x 10(-10) (T/298 K)(-1.36) exp(-56.9 K/T) cm3 molecule(-1) s(-1); k(C4H10) = 2.93 x 10(-10) (T/298 K)(-1.30) exp(-90.1 K/T) cm3 molecule(-1) s(-1). The rate coefficients for the reaction with methane were measured only at 200 K and 300 K yielding a positive temperature dependence: k(CH4) = 1.63 x 10(-11) exp(-610 K/T) cm3 molecule(-1) s(-1). Possible reaction mechanisms and product channels are discussed in detail for each of these reactions. Potential implications of these results for models of low temperature chemical environments, in particular cold interstellar clouds and planetary atmospheres such as that of Titan, are considered.

A chemical dynamics, kinetics, and theoretical study on the reaction of the cyano radical (CN; X(2)Sigma+) with phenylacetylene (C6H5CCH; X(1)A1).

The chemical reaction dynamics to form o-, m-, and p-cyanophenylacetylene via the neutral-neutral reaction of ground state cyano radicals with phenylacetylene and D(1)-phenylacetylene were investigated in crossed beam experiments; these studies were combined with kinetics measurements of the rate coefficients at temperatures of 123, 200, and 298 K and supplemented by electronic structure calculations. The data suggest that the reaction is initiated by a barrier-less addition of the electrophilic cyano radical to the o-, m-, or p-position of the aromatic ring. The eventually fragmented via atomic hydrogen elimination to form o-, m-, and p-cyanophenylacetylene via tight exit transition states with the hydrogen atom being ejected almost perpendicularly to the molecular plane of the rotating complex. The overall reaction to form o-, m-, and p-cyanophenylacetylene was found to be exoergic by 89 +/- 18 kJ mol(-1) in nice agreement with the calculations. The o-cyanophenylacetylene isomer is of particular relevance as a potential building block to the formation of nitrogen-substituted didehydronaphthalene molecules in analogy to didehydronaphthalene in Titan's aerosol layers--a pathway hitherto neglected by the planetary science modeling community.

Kinetics and dynamics of the S(1D2) + H2 → SH + H reaction at very low temperatures and collision energies.

We report combined studies on the prototypical S(1D2) + H2 insertion reaction. Kinetics and crossed-beam experiments are performed in experimental conditions approaching the cold energy regime, yielding absolute rate coefficients down to 5.8 K and relative integral cross sections to collision energies as low as 0.68 meV. They are supported by quantum calculations on a potential energy surface treating long-range interactions accurately. All results are consistent and the excitation function behavior is explained in terms of the cumulative contribution of various partial waves.

Experimental measurements of low temperature rate coefficients for neutral-neutral reactions of interest for atmospheric chemistry of Titan, Pluto and Triton: reactions of the CN radical.

The kinetics of the reactions of cyano radical, CN (X2sigma+) with three hydrocarbons, propane (CH3CH2CH3), propene (CH3CH=CH2) and 1-butyne (CH[triple band]CCH2CH3) have been studied over the temperature range of 23-298 K using a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. These reactions are of interest for the cold atmospheres of Titan, Pluto and Triton, as they might participate in the formation of nitrogen and carbon bearing molecules, including nitriles, that are thought to play an important role in the formation of hazes and biological molecules. All three reactions are rapid with rate coefficients in excess of 10(-10) cm3 molecule(-1) s(-1) at the lowest temperatures of this study and show behaviour characteristic of barrierless reactions. Temperature dependences, different for each reaction, are compared to those used in the most recent photochemical models of Titan's atmosphere.

Highly stereoselective synthesis of alpha-D-mannopyranosyl phosphosugars.

Alpha-mannopyranosyl phosphosugars are obtained in 61-90% yields from 4,6-O-benzylidene-protected mannosyl thioglycosides bearing ester functionality in the 3-O-position by coupling reactions with ammonium salts of phosphosugars on activation with 1-benzenesulfinyl piperidine, 2,4,6-tri-tert-butylpyrimidine, and trifluoromethanesulfonic anhydride. Due to the presence of the disarming ester group, only the formation of the alpha-isomer was observed.