Triplet Energy Transfer from Ruthenium Complexes to Chiral Eniminium Ions: Enantioselective Synthesis of Cyclobutanecarbaldehydes by [2+2] Photocycloaddition.

Chiral eniminium salts, prepared from α,ß-unsaturated aldehydes and a chiral proline derived secondary amine, underwent, upon irradiation with visible light, a ruthenium-catalyzed (2.5 mol %) intermolecular [2+2] photocycloaddition to olefins, which after hydrolysis led to chiral cyclobutanecarbaldehydes (17 examples, 49-74 % yield), with high diastereo- and enantioselectivities. Ru(bpz)3 (PF6 )2 was utilized as the ruthenium catalyst and laser flash photolysis studies show that the catalyst operates exclusively by triplet-energy transfer (sensitization). A catalytic system was devised with a chiral secondary amine co-catalyst. In the catalytic reactions, Ru(bpy)3 (PF6 )2 was employed, and laser flash photolysis experiments suggest it undergoes both electron and energy transfer. However, experimental evidence supports the hypothesis that energy transfer is the only productive quenching mechanism. Control experiments using Ir(ppy)3 showed no catalysis for the intermolecular [2+2] photocycloaddition of an eniminium ion.

Thermally Activated Transient Dipoles and Rotational Dynamics of Hydrogen-Bonded and Charge-Transferred Diazabicyclo [2.2.2]Octane Molecular Rotors.

We present here dielectric properties and rotational dynamics of cocrystals formed with either triphenylacetic acid (cocrystal I) or 9,10-triptycene dicarboxylic acid (cocrystal II), as hydrogen-bonding donors, and diazabicyclo[2.2.2]octane (DABCO), as a ditopic hydrogen-bond acceptor. While cocrystal I forms discrete 2:1 complexes with one nitrogen of DABCO hydrogen bonded and the other fully proton transferred, cocrystal II consists of 1:1 complexes forming infinite 1-D hydrogen-bonded chains capable of exhibiting a thermally activated response in the form of a broad asymmetric peak at ca. 298 K that extends from ca. 200 to 375 K in both the real and imaginary parts of its complex dielectric. The state of protonation in cocrystal II at 298 and 386 K was established by CPMAS 15N NMR, which showed signals typical of a neutral hydrogen-bonded complex. Taken together, these observations suggest a dielectric response that results from a small population of transient dipoles thermally generated when acidic protons are transiently transferred to either side of the DABCO base. A potential order-disorder transition further explored by taking advantage of the highly sensitive rotational dynamics of the DABCO group using line-shape analysis of solid-state spin echo 2H NMR and 1H NMR T1 spin-lattice relaxation showed no breaks in the Arrhenius plot or Kubo-Tomita 1H T1 fittings, indicating the absence of large structural changes. This was confirmed by variable-temperature single-crystal X-ray diffraction analysis, which showed a fairly symmetric hydrogen bond in cocrystal II at all temperatures, suggesting that both nitrogen atoms may be able to adopt a protonated state.

Transient Kinetics and Quantum Yield Studies of Nanocrystalline α-Phenyl-Substituted Ketones: Sorting Out Reactions from Singlet and Triplet Excited States.

Recent work has shown that diarylmethyl radicals generated by pulsed laser excitation in nanocrystalline (NC) suspensions of tetraarylacetones constitute a valuable probe for the detailed mechanistic analysis of the solid-state photodecarbonylation reaction. Using a combination of reaction quantum yields and laser flash photolysis in nanocrystalline suspensions of ketones with different substituents on one of the α-carbons, we are able to suggest with confidence that a significant fraction of the initial α-cleavage reaction takes place from the ketone singlet excited state, that the originally formed diarylmethyl-acyl radical pair loses CO in the crystal with time constants in the sub-nanosecond regime, and that the secondary bis(diarylmethyl) triplet radical pair has a lifetime limited by the rate of intersystem crossing of ca. 70 ns.

Evidence for Triplet Sensitization in the Visible-Light-Induced [2+2]†Photocycloaddition of Eniminium Ions.

Εniminium ions were prepared from the corresponding α,ß-unsaturated carbonyl compounds (enones and enals), and were found to be promoted to their respective triplet states by energy transfer. The photoexcited intermediates underwent intra- or intermolecular [2+2] photocycloaddition in good yields (50-78 %) upon irradiation at λ=433 nm or λ=457 nm. Iridium or ruthenium complexes with a sufficiently high triplet energy were identified as efficient catalysts (2.5 mol % catalyst loading) for the reaction. The intermolecular [2+2] photocycloaddition of an eniminium ion derived from a chiral secondary amine proceeded with high enantioselectivity (88 % ee).

Benzothiazole Amphiphiles Promote the Formation of Dendritic Spines in Primary Hippocampal Neurons.

The majority of excitatory synapses in the brain exist on dendritic spines. Accordingly, the regulation of dendritic spine density in the hippocampus is thought to play a central role in learning and memory. The development of novel methods to control spine density could, therefore, have important implications for treatment of a host of neurodegenerative and developmental cognitive disorders. Herein, we report the design and evaluation of a new class of benzothiazole amphiphiles that exhibit a dose-dependent response leading to an increase in dendritic spine density in primary hippocampal neurons. Cell exposure studies reveal that the increase in spine density can persist for days in the presence of these compounds, but returns to normal spine density levels within 24 h when the compounds are removed, demonstrating the capability to reversibly control spinogenic activity. Time-lapse imaging of dissociated hippocampal neuronal cultures shows that these compounds promote a net increase in spine density through the formation of new spines. Biochemical studies support that promotion of spine formation by these compounds is accompanied by Ras activation. These spinogenic molecules were also capable of inhibiting a suspected mechanism for dendritic spine loss induced by Alzheimer-related aggregated amyloid-ß peptides in primary neurons. Evaluation of this new group of spinogenic agents reveals that they also exhibit relatively low toxicity at concentrations displaying activity. Collectively, these results suggest that small molecules that promote spine formation could be potentially useful for ameliorating cognitive deficiencies associated with spine loss in neurodegenerative diseases such as Alzheimer disease, and may also find use as general cognitive enhancers.

Phosphorescence Control Mediated by Molecular Rotation and Aurophilic Interactions in Amphidynamic Crystals of 1,4-Bis[tri-(p-fluorophenyl)phosphane-gold(I)-ethynyl]benzene.

Here we present a structural design aimed at the control of phosphorescence emission as the result of changes in molecular rotation in a crystalline material. The proposed strategy includes the use of aurophilic interactions, both as a crystal engineering tool and as a sensitive emission probe, and the use of a dumbbell-shaped architecture intended to create a low packing density region that permits the rotation of a central phenylene. Molecular rotor 1, with a central 1,4-diethynylphenylene rotator linked to two gold(I) triphenylphosphane complexes, was prepared and its structure confirmed by single-crystal X-ray diffraction, which revealed chains mediated by dimeric aurophilic interactions. We showed that green-emitting crystals exhibit reversible luminescent color changes between 298 and 193 K, which correlate with changes in rotational motion determined by variable-temperature solid-state 2H NMR spin-echo experiments. Fast two-fold rotation with a frequency of ca. 4.00 MHz (τ = 0.25 µs) at 298 K becomes essentially static below 193 K as emission steadily changes from green to yellow in this temperature interval. A correlation between phosphorescence lifetimes and rotational frequencies is interpreted in terms of conformational changes arising from rotation of the central phenylene, which causes a change in electronic communication between the gold-linked rotors, as suggested by DFT studies. These results and control experiments with analogue 2, possessing a hindered tetramethylphenylene that is unable to rotate in the crystal, suggest that the molecular rotation can be a useful tool for controlling luminescence in the crystalline state.

Generation and Reactivity Studies of Diarylmethyl Radical Pairs in Crystalline Tetraarylacetones via Laser Flash Photolysis Using Nanocrystalline Suspensions.

The nanosecond electronic spectra and kinetics of the radical pairs from various crystalline tetraarylacetones were obtained using transmission laser flash photolysis methods by taking advantage of aqueous nanocrystalline suspensions in the presence of submicellar CTAB, which acts as a surface passivator. After showing that all tetraarylacetones react efficiently by a photodecarbonylation reaction in the crystalline state, we were able to detect the intermediate radical pairs within the ca. 8 ns laser pulse of our laser setup. We showed that the solid-state spectra of the radical pairs are very similar to those detected in solution, with λmax in the 330-360 nm range. Kinetics in the solid state was observed to be biexponential and impervious to the presence of oxygen or variations in laser power. A relatively short-lived component (0.3-1.7 µs) accounts for only 3-8% of the total decay with a longer-lived component having a time constant in the range of 40-90 µs depending on the nature of the substituents.

Triplet Sensitized Photodenitrogenation of Δ2-1,2,3-Triazolines To Form Aziridines in Solution and in the Crystalline State: Observation of the Triplet 1,3-Alkyl-aminyl Biradical.

Taking advantage of an operationally simple technique to perform transmission pump-probe spectroscopy in crystalline solids, based on the use nanocrystalline suspensions in water, we analyzed the intermediates in the photodenitrogenation of a Δ2-1,2,3-triazoline bearing a benzophenone group that served as an internal triplet sensitizer. Measurements carried out in acetonitrile solution revealed the formation of a transient with a λmax= 570 nm with a lifetime of 70 ns. Measurements in the solid state displayed an analogous blue-shifted transient with a λmax= 510 nm that first grows and then decays with time constants of 63 and 270 ns, respectively. Based on the comparison of the observed transient spectra with the one obtained from an independently generated aminyl radical, we assign it to the corresponding 1,3,-alkyl-aminyl biradical. We conclude that triplet state denitrogenation and the subsequent intersystem crossing-limited product formation are slower in the solid state than in solution.

Stereospecific photochemistry of Δ2-1,2,3-triazolines in solution and in the solid state: scope and mechanistic studies.

The stereospecific photochemistry of ten N-aryl-substituted cis- or trans-Δ2-1,2,3-triazolines to form the corresponding cis- or trans-aziridines was investigated both in solution and in the solid-state. We found that photochemical reactions in the solid state are more stereospecific than in solution for the 8 crystalline Δ2-1,2,3-triazolines. Additionally, triplet sensitization for some triazolines results in triplet biradicals, which provide the more thermodynamically favored trans-aziridine regardless of the starting triazoline stereochemistry. Product analyses as a function of temperature and solvent polarity suggest that the electronic excitation of the Δ2-1,2,3-triazolines results in the formation of a 1,3-biradical intermediate.

Photochemistry and Transmission Pump-Probe Spectroscopy of 2-Azidobiphenyls in Aqueous Nanocrystalline Suspensions: Simplified Kinetics in Crystalline Solids.

Aqueous nanocrystalline suspensions provide a simple and efficient medium for performing transmission spectroscopy measurements in the solid state. In this Letter we describe the use of laser flash photolysis methods to analyze the photochemistry of 2-azidobiphenyl and several aryl-substituted derivatives. We show that all the crystalline compounds analyzed in this study transform quantitatively into carbazole products via a crystal-to-crystal reconstructive phase transition. While the initial steps of the reaction cannot be followed within the time resolution of our instrument (ca. 8 ns), we detected the primary isocarbazole photoproducts and analyzed the kinetics of their formal 1,5-H shift reactions, which take place in time scales that range from a few nanoseconds to several microseconds. It is worth noting that the high reaction selectivity observed in the crystalline state translates into a clean and simple kinetic process compared to that in solution.

Benzothiazole Amphiphiles Ameliorate Amyloid ß-Related Cell Toxicity and Oxidative Stress.

Oxidative stress from the increase of reactive oxygen species in cells is a common part of the normal aging process and is accelerated in patients with Alzheimer's disease (AD). Herein, we report the evaluation of three benzothiazole amphiphiles (BAMs) that exhibit improved biocompatibility without loss of biological activity against amyloid-ß induced cell damage compared to a previously reported hexa(ethylene glycol) derivative of benzothiazole aniline (BTA-EG6). The reduced toxicity of these BAM agents compared to BTA-EG6 corresponded with their reduced propensity to induce membrane lysis. In addition, all of the new BAMs were capable of protecting differentiated SH-SY5Y neuroblastoma cells from toxicity and concomitant oxidative stress induced by AD-related aggregated Aß (1-42) peptides. Binding and microscopy studies support that these BAM agents target Aß and inhibit the interactions of catalase with Aß in cells, which, in turn, can account for an observed inhibition of Aß-induced increases in hydrogen peroxide in cells treated with these compounds. These results support that this family of benzothiazole amphiphiles may have therapeutic potential for treating cellular damage associated with AD and other Aß-related neurologic diseases.

Stereospecific Synthesis of Substituted Aziridines by a Crystal-to-Crystal Photodenitrogenation of Δ(2)-1,2,3-Triazolines.

Crystalline cis- or trans-Δ(2)-1,2,3-triazolines prepared by highly stereospecific and regioselective hydrogen bonding-catalyzed dipolar cycloaddition of activated cis- or trans-alkenes with aryl azides undergo a highly stereospecific photodenitrogenation to form the corresponding cis- or trans- azidirines in high chemical yields. While examples involving disubstituted and trisubstituted triazolines highlight steric challenges encountered in the dipolar cycloaddition reaction, the stereochemical control exerted by the crystalline lattice is enhanced by bulky substituents in the triazoline precursors to generate aziridines photochemically.