Triphenylamine Sensitized 8-Dimethylaminoquinoline: An Efficient Two-Photon Caging Group for Intracellular Delivery.

Triphenylamine-sensitized 8-dimethylaminoquinoline (TAQ) probes showed fair two-photon absorption and fragmentation cross sections in releasing kainate and GABA ligands. The water-soluble PEG and TEG-analogs allowed cell internalization and efficient light-gated liberation of the rhodamine reporter under UV and two-photon (NIR) irradiation conditions.

Photoinduced Electron Transfer (PET)-Mediated Fragmentation of Picolinium-Derived Redox Probes.

The photolysis of covalently linked N-alkyl picolinium phenylacetate-carbazole dyads was analyzed experimentally and by using density functional theory (DFT) and time dependent-DFT (TD-DFT) calculations. In contrast to earlier observations efficient one and two-photon fragmentations conditions were found for 15 c (δu =0.16 GM at 730 nm) opening the way for the design of a novel class of "caged" compounds.

Quinoline-Derived Two-Photon Sensitive Quadrupolar Probes.

Quadrupolar probes derived from 8-dimethylamino-quinoline (8-DMAQ) having a pegylated fluorene core were prepared and studied under "one-photon" (λ=365 nm) and "two-photon" (TP) (λ=730 nm) irradiation conditions. Compound 1 a was identified as the most efficient probe by UV activation that showed sequential release of acetic acid as a model. Although the probe showed high two-photon absorption it stayed inert under femtosecond irradiation conditions. Fast and selective photolysis was observed, however, by using picosecond irradiation conditions with a remarkably high TP uncaging cross-section (δu =2.3 GM).

Quinoline-derived two-photon sensitive quadrupolar probes.

The first quadrupolar 8-dimethylaminoquinoline-derived 6-(8-DMAQ-OAc)2 (1c) and 5-(8-DMAQ-OAc)2 (2c) photosensitive probes underwent photolysis under UV (365 nm) and NIR (730 nm two-photon (TP)) irradiation conditions, showing Qu = 9.3% and 6.6% quantum yields and δu = 0.07 GM and 0.40 GM uncaging cross-sections, respectively.

Red-shifted two-photon-sensitive phenanthridine photocages: synthesis and characterisation.

Herein we describe the rational design, synthesis and photophysical study of a novel class of phenanthridine-based, one- and two-photon sensitive, photoremovable protecting groups with absorption wavelengths extending beyond 400 nm. This design facilitated the development of scaffolds with enhanced uncaging quantum yield, paving the way for broader applications in controlled drug delivery and molecular manipulation.

From one-photon to two-photon probes: "caged" compounds, actuators, and photoswitches.

Molecular systems that can be remotely controlled by light are gaining increasing importance in cell biology, physiology, and neurosciences because of the spatial and temporal precision that is achievable with laser microscopy. Two-photon excitation has significant advantages deep in biological tissues, but raises problems in the design of "smart" probes compatible with cell physiology. This Review discusses the chemical challenges in generating suitable two-photon probes.

Synthesis and activation of an iron oxide immobilized drug-mimicking reporter under conventional and pulsed X-ray irradiation conditions.

An efficient nano-sized delivery system is presented here allowing the immobilized, picolinium-tethered organic ligand to be released by X-ray irradiation. A marked difference was observed in the fragmentation efficiency by using conventional Cs-137 vs. pulsed sources.

Quinoline-Derived Two-Photon-Sensitive Octupolar Probes.

A systematic study on quinoline-derived light sensitive probes, having third-order rotational symmetry is presented. The electronically linked octupolar structures show considerably improved linear and nonlinear photophysical properties under one- and two-photon irradiation conditions compared to the corresponding monomers. Photolysis of the three acetate derivatives shows strong structure dependency: whereas irradiation of the 6- and 7-aminoquinoline derivatives resulted in fast intramolecular cyclization and only trace amounts of fragmentation products, the 8-aminoquinoline derivative afforded clean and selective photolysis, with a sequential release of their acetate groups (δu[730]=0.67 GM).

Concise synthesis of the (+/-)-Nb-desmethyl-meso-chimonanthine.

The first total synthesis of the bis-pyrroloindoline alkaloid (+/-)-Nb-desmethyl-meso-chimonanthine, having a pseudo C2-symmetry, was realised in a seven-step convergent sequence without the use of protecting groups.

Photolysis-driven merging of microdroplets in microfluidic chambers.

Photolysis of microdroplets, stabilized by aminoquinoline-derived photosensitive surfactants composed of polyethyleneglycol/perfluorinated polyether (PEG/PFPE) diblock amphiphiles by using 355 nm ps pulsed laser light, resulted in rapid controlled coalescence of targeted microdroplets offering the prospect of a novel type of droplet merging with high stereospatial integrity for microfluidic systems.

Two-photon "caging" groups: effect of position isomery on the photorelease properties of aminoquinoline-derived photolabile protecting groups.

High two-photon photolysis cross sections and water solubility of probes are important to avoid toxicity in biomedical applications of photolysis. Systematic variation of the position of a carboxyl electron-withdrawing group (EWG) on photolysis of 8-dimethylaminoquinoline protecting groups identified the C5-substituted isomer as a privileged dipole. The 5-benzoyl-8-DMAQ substitution yields a caging group with an enhanced two-photon uncaging cross section (δu = 2.0 GM) and good water solubility (c ≤ 50 mM, pH 7.4).

In the golden age of organocatalysis.

The term "organocatalysis" describes the acceleration of chemical reactions through the addition of a substoichiometric quantity of an organic compound. The interest in this field has increased spectacularly in the last few years as result of both the novelty of the concept and, more importantly, the fact that the efficiency and selectivity of many organocatalytic reactions meet the standards of established organic reactions. Organocatalytic reactions are becoming powerful tools in the construction of complex molecular skeletons. The diverse examples show that in recent years organocatalysis has developed within organic chemistry into its own subdiscipline, whose "Golden Age" has already dawned.

Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts. dynamic kinetic resolution.

The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2-diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with high enantioselectivity. [reaction: see text]

Enantioselective Organocatalysis.

The last few years have witnessed a spectacular advancement in new catalytic methods based on metal-free organic molecules. In many cases, these small compounds give rise to extremely high enantioselectivities. Preparative advantages are notable: usually the reactions can be performed under an aerobic atmosphere with wet solvents. The catalysts are inexpensive and they are often more stable than enzymes or other bioorganic catalysts. Also, these small organic molecules can be anchored to a solid support and reused more conveniently than organometallic/bioorganic analogues, and show promising adaptability to high-throughput screening and process chemistry. Herein we focus on four different domains in which organocatalysis has made major advances: 1) The activation of the reaction based on the nucleophilic/electrophilic properties of the catalysts. This type of catalysis has much in common with conventional Lewis acid/base activation by metal complexes. 2) Transformations in which the organic catalyst forms a reactive intermediate: the chiral catalyst is consumed in the reaction and requires regeneration in a parallel catalytic cycle. 3) Phase-transfer reactions: The chiral catalyst forms a host-guest complex with the substrate and shuttles between the standard organic solvent and the second phase (i.e. a solid, aqueous, or fluorous phase in which the organic transformation takes place). 4) Molecular-cavity-accelerated asymmetric transformations: the catalyst can select between competing substrates, depending on size and structure criteria. The rate acceleration of a given reaction is similar to the Lewis acid/base activation and is the consequence of the simultaneous action of different polar functions. Herein it is shown that organocatalysis complements rather than competes with current methods. It offers something conceptually novel and opens new horizons in synthesis.

Recent Advances in the Conversion of Carbohydrate Furanosides and Pyranosides into Carbocycles.

Replacing the oxygen atom of the sugar ring with carbon is easy on paper, but it is more difficult to carry out this transformation and form five- and six-membered carbon rings (see scheme) in the flask. Nature has found a way to perform this tandem fragmentation/cyclization reaction in a stereospecific way at neutral pH values. Human creativity and good luck have uncovered synthetic strategies which can compete efficiently with nature.

Substitution effect on the one- and two-photon sensitivity of DMAQ "caging" groups.

The systematic SAR study of a "caging" group showed a strong influence of the position of the donor dimethylamino group on the efficiency of photolysis of the DMAQ (2-hydroxymethylene-(N,N-dimethylamino)quinoline) caged acetate under one-photon near-UV or two-photon near-IR excitation. Photorelease of l-glutamate by the most efficient 8-DMAQ derivative strongly and efficiently activated glutamate receptors, generating large, fast rising responses similar to those elicited by glutamate photoreleased from the widely used MNI-caged glutamate.

Free-radical approaches to stemoamide and analogues.

Two approaches allowing access to the tricyclic stemona backbone are presented. Both approaches rely on a free-radical cyclization reaction as the key step. In the formal synthesis of (+/-)-stemoamide, the construction of the A ring of the natural product was achieved via a 5-exo-trig radical cyclization with atom transfer. The two diastereoisomers issuing from this cyclization showed different reactivity while forming the seven-membered ring of the final product. In the second part of this study, a 7-exo-trig free radical cyclization was realized allowing access to the (+/-)-9,10-bis-epi-stemoamide. This reaction was highly stereoselective and allowed the control of three of the four contiguous stereocenters present in the molecule.

Hydrosilylation of terminal alkynes with alkylidene ruthenium complexes and silanes.

[reaction: see text] Ruthenium alkylidene complexes 1-3 mediate hydrosilylation of alkynes with silanes. When triethoxy- or triphenylsilanes are used as silylating agents, the reaction affords alpha-substituted vinylsilanes as major products.