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.

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.

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 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).

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).

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).

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.

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.

Rational design of a fluorescent NADPH derivative imaging constitutive nitric-oxide synthases upon two-photon excitation.

We report the structure-based design and synthesis of a unique NOS inhibitor, called nanoshutter NS1, with two-photon absorption properties. NS1 targets the NADPH site of NOS by a nucleotide moiety mimicking NADPH linked to a conjugated push-pull chromophore with nonlinear absorption properties. Because NS1 could not provide reducing equivalents to the protein and competed with NADPH binding, it efficiently inhibited NOS catalysis. NS1 became fluorescent once bound to NOS with an excellent signal-to-noise ratio because of two-photon excitation avoiding interference from the flavin-autofluorescence and because free NS1 was not fluorescent in aqueous solutions. NS1 fluorescence enhancement was selective for constitutive NOS in vitro, in particular for endothelial NOS (eNOS). Molecular dynamics simulations suggested that two variable residues among NOS isoforms induced differences in binding of NS1 and in local solvation around NS1 nitro group, consistent with changes of NS1 fluorescence yield. NS1 colocalized with eNOS in living human umbilical vein endothelial cells. Thus, NS1 constitutes a unique class of eNOS probe with two-photon excitation in the 800-950-nm range, with great perspectives for eNOS imaging in living tissues.

Diastereoselective functionalizations of enecarbamates derived from pipecolic acid towards 5-guanidinopipecolates as arginine mimetics.

Various substituents could be diastereoselectively introduced into the 5-position of pipecolic acid via electrophilic or free-radical-initiated addition to the carbon-carbon double bond of endocyclic enecarbamates derived from pipecolic acid. This study allowed the diastereoselective synthesis of both cis- and trans-5-guanidino pipecolates, which were designed as constrained arginine mimetics and whose potential inhibition of nitric oxide synthase (NOS) was evaluated with three NOS isoforms.