Shedding light on the mitochondrial matrix through a functional membrane transporter

The first fluorescent probes that are actively channeled into the mitochondrial matrix by a specific mitochondrial membrane transporter in living cells have been developed. The new functional probes (BCT) have a minimalist structural design based on the highly efficient and photostable BODIPY chromophore and carnitine as a biotargeting element. Both units are orthogonally bonded through the common boron atom, thus avoiding the use of complex polyatomic connectors. In contrast to known mitochondria-specific dyes, BCTs selectively label these organelles regardless of their transmembrane potential and in an enantioselective way. The obtained experimental evidence supports carnitine–acylcarnitine translocase (CACT) as the key transporter protein for BCTs, which behave therefore as acylcarnitine biomimetics. This simple structural design can be readily extended to other structurally diverse starting F-BODIPYs to obtain BCTs with varied emission wavelengths along the visible and NIR spectral regions and with multifunctional capabilities. BCTs are the first fluorescent derivatives of carnitine to be used in cell microscopy and stand as promising research tools to explore the role of the carnitine shuttle system in cancer and metabolic diseases. Extension of this approach to other small-molecule mitochondrial transporters is envisaged.

A BODIPY derivative of carnitine enters mitochondria regardless of their membrane potential and in an enantioselective way through a specific mitochondrial membrane transporter in living cells.     

Reversible Activation of Water by an Air- and Moisture-Stable Frustrated Rhodium Nitrogen Lewis Pair

[Cp*Rh(κ³N,N′,P- L )][SbF₆] (Cp*=C₅Me₅), bearing a guanidine-derived phosphano ligand L , behaves as a “dormant” frustrated Lewis pair and activates H₂ and H₂O in a reversible manner. When D₂O is employed, a facile H/D exchange at the Cp* ring takes place through sequential C(sp³)−H bond activation.     

Aminomethyl Transfer (Mannich) Reactions Between an O-Triethylsilylated Hemiaminal and Anilines,RnC6H5−nNH2 Leading to New Diamines,Triamines, Imines,or 1,3,5-Triazines Dependent upon Substituent R

The reactions of the Mannich reagent Et₃SiOCH₂NMe₂ ( 1 ) with a variety of anilines (mono-substituted RC₆H₄NH₂, R=H, 4-CN, 4-NO₂, 4-Ph, 4-Me, 4-MeO, 4-Me₂N; di-substituted R₂C₆H₃NH₂, R₂=3,5-(CH₃)₂, 3,5-(CF₃)₂; tri-substituted R₃C₆H₂NH₂, R₃=3,5-Me₂-4-Br and a “super bulky” aniline (Ar*NH₂) [Ar*=2,6-bis(diphenylmethyl)-4-tert-butylphenyl]) led to the formation of a range of products dependent upon the substituent. With electron-withdrawing substituents, previously unknown diamines, RC₆H₄NH(CH₂NMe₂) [R=CN ( 2 a ), NO₂ ( 2 b )] and R₂C₆H₃NH(CH₂NMe₂) [R₂=3,5-(CF₃)₂ ( 2 c) ] were formed. Further reaction of 2 a , b , c with 1 yielded the corresponding triamines RC₆H₄N(CH₂NMe₂)₂ (R=CN ( 3 a ), NO₂ ( 3 b ) and R₂C₆H₃N(CH₂NMe₂)₂, R₂=3,5-(CF₃)₂ ( 3 c ). The new polyamines were characterized by NMR spectroscopy, and for 2 a , 2 c _, and 3 c , by single crystal XRD. In the case of electron-donating groups, R=4-OMe, 4-NMe₂, 4-Me, 3,5-Me₂, 3,5-Me₂-4-Br, and for R=4-Ph, the reactions with 1 immediately led to the formation of the related 1,3,5-triazines, R=4-MeO ( 5 a ), 4-Me₂N ( 5 b ), 4-Me ( 5 c ), 3,5-Me₂ ( 5 d ), 3,5-Me₂-4-Br ( 5 e ), 4-Ph ( 5 f ), 4-Cl ( 5 g ). The “super bulky” aniline rapidly produced a single product, namely the corresponding imine Ar*N=CH₂ ( 4 ) which was also characterized by single crystal XRD. Imine 4 is both thermally and oxidatively stable. All reactions are very fast, thus based upon the presence of Si we are tempted to denote the reactions of 1 as examples of “Silick” chemistry.     

Janus Gold Nanostars–Mesoporous Silica Nanoparticles for NIR-Light-Triggered Drug Delivery

Janus gold nanostar–mesoporous silica nanoparticle ( AuNSt–MSNP ) nanodevices able to release an entrapped payload upon irradiation with near infrared (NIR) light were prepared and characterized. The AuNSt surface was functionalized with a thiolated photolabile molecule ( 5 ), whereas the mesoporous silica face was loaded with a model drug (doxorubicin) and capped with proton-responsive benzimidazole-β-cyclodextrin supramolecular gatekeepers ( N 1 ). Upon irradiation with NIR-light, the photolabile compound 5 photodissociated, resulting in the formation of succinic acid, which induced the opening of the gatekeeper and cargo delivery. In the overall mechanism, the gold surface acts as a photochemical transducer capable of transforming the NIR-light input into a chemical messenger (succinic acid) that opens the supramolecular nanovalve. The prepared hybrid nanoparticles were non-cytotoxic to HeLa cells, until they were irradiated with a NIR laser, which led to intracellular doxorubicin release and hyperthermia. This induced a remarkable reduction in HeLa cells viability.     

Emulsion Copolymerization of Vinyl Acetate and Vinyl Silanes: Kinetics and Development of Microstructure

The batch emulsion copolymerization of vinyl acetate with different vinyl silane functional monomers (vinyl trimethoxysilane [VTMS], vinyl triethoxysilane [VTES], and vinyl silanetriol [VSTO]) is studied. The nature of the silane strongly affects the development of the microstructure and crosslinking ability of the latexes. A combination of techniques (Soxhlet extraction, centrifugation, assymetric‐flow field flow fractionation AF4/MALS/RI) shows that the factor controlling the molar mass and crosslinking density is the degree of hydrolysis of the alkoxysilane, producing higher molar masses and degrees of crosslinking when the degree of hydrolysis is high. Thus, the copolymer containing VSTO produced a very crosslinked latex, the one with VTMS produced a latex with a low degree of crosslinking in the wet state that can yield high degrees of crosslinking upon drying, and the latex with VTES do not produce significant amounts of crosslinking neither before nor after drying.     

Synthesis,characterization, thermal and photophysical properties of novel strontium (II) phthalocyanine

Journal of Inclusion Phenomena and Macrocyclic Chemistry - Newly phthalocyanine derivative which carries 2,6-dimethoxyphenoxy bioactive groups as tetrakis from non-peripheral positions of the...     

Pore-Scale Level Set Simulations of Capillary-Controlled Displacement with Adaptive Mesh Refinement

Transport in Porous Media - Multiphase flow simulations on imaged porous rock structures require numerical methods that are accurate and robust when applied on complex geometries. A key element in...     

On the hyperbolic order

We define the hyperbolic order of any locally injective holomorphic function between arbitrary hyperbolic domains of the complex plane and study the relation between the hyperbolic order and the Schwarzian derivative for locally injective holomorphic functions from the unit disk into itself.