NIR multiphoton ablation of cancer cells, fluorescence quenching and cellular uptake of dansyl-glutathione-coated gold nanoparticles.

Theranostics based on two-photon excitation of therapeutics in the NIR region is an emerging and powerful tool in cancer therapy since this radiation deeply penetrates healthy biological tissues and produces selective cell death. Aggregates of gold nanoparticles coated with glutathione corona functionalized with the dansyl chromophore (a-DG-AuNPs) were synthesized and found efficient nanodevice for applications in photothermal therapy (PTT). Actually the nanoparticle aggregation enhances the quenching of radiative excitation and the consequent conversion into heat. The a-DG-AuNPs are readily internalized in Hep G2 where the chromophore acts as both antenna and transducer of the NIR radiation under two-photons excitation, determining efficient cell ablation via photothermal effect.

Phosphasalen group IV metal complexes: synthesis, characterization and ring opening polymerization of lactide.

We report the synthesis of a series of Zr and Ti complexes bearing phosphasalen which differs from salen by the incorporation of two P atoms in the ligand backbone. The reaction of phosphasalen proligands (1a-1c)H2 with Zr(CH2Ph)4 led to different products depending on the nature of the N,N-linker in the ligand. In the case of ethylene-linked phosphasalen, octahedral Zr complex 2a formed as a single stereoisomer in trans geometry. With the phenylene linker, it was shown by dynamic NMR spectroscopy that complex 2b exists as a mixture of trans and cis-ß isomers in solution, both enantiomers (Δ and Λ) of the cis-ß isomer being in fast equilibrium with respect to the NMR time-scale. The use of a propylene-linked phosphasalen proligand 1cH2 led to a mixture of complexes among which a binuclear Zr complex 2c bridged only by one phosphasalen ligand could be isolated and characterized. Addition of 2 equiv. of iPrOH to 2a and 2b afforded diisoproxy Zr complexes 3a and 3b as a mixture of trans and cis-ß isomers, the latter undergoing fast Δ/Λ isomerization in solution. Addition of B(C6F5)3 to 2a and 2b gave cationic monobenzyl Zr complexes 4a and 4b which have been further converted into cationic alkoxy Zr complexes 5a-b and 6a-b by alcoholysis with iPrOH and (S)-methyl-lactate, respectively. The reaction of the phosphasalen proligands with Ti(NMe2)4 proceeded diastereoselectively giving rise to Ti complexes 7a-c in octahedral geometry with cis-ß wrapping of the ligand. The complexes have been tested for the ROP of rac-lactide. The neutral phosphasalen Ti and Zr complexes showed only poor activity probably due to the encumbered and electron donating nature of the phosphasalen ligand. In contrast, the cationic Zr alkoxides 5a, 6a and 6b are effective initiators for the controlled and hetero-selective ROP of rac-lactide.

Cyclic(Alkyl)(Amino)Carbene (CAAC)-Supported Zn Alkyls: Synthesis, Structure and Reactivity in Hydrosilylation Catalysis.

The reactivity of ZnII dialkyl species ZnMe2 with a cyclic(alkyl)(amino)carbene, 1-[2,6-bis(1-methylethyl)phenyl]-3,3,5,5-tetramethyl-2-pyrrolidinylidene (CAAC, 1), was studied and extended to the preparation of robust CAAC-supported ZnII Lewis acidic organocations. CAAC adduct of ZnMe2 (2), formed from a 1:1 mixture of 1 and ZnMe2 , is unstable at room temperature and readily undergoes a CAAC carbene insertion into the Zn-Me bond to produce the ZnX2 -type species (CAAC-Me)ZnMe (3), a reactivity further supported by DFT calculations. Despite its limited stability, adduct 2 was cleanly ionized to robust two-coordinate (CAAC)ZnMe+ cation (5+ ) and derived into (CAAC)ZnC6 F5 + (7+ ), both isolated as B(C6 F5 )4 - salts, showing the ability of CAAC for the stabilization of reactive [ZnMe]+ and [ZnC6 F5 ]+ moieties. Due to the lability of the CAAC-ZnMe2 bond, the formation of bis(CAAC) adduct (CAAC)2 ZnMe+ cation (6+ ) was also observed and the corresponding salt [6][B(C6 F5 )4 ] was structurally characterized. As estimated from experimental and calculations data, cations 5+ and 7+ are highly Lewis acidic species and the stronger Lewis acid 7+ effectively mediates alkene, alkyne and CO2 hydrosilylation catalysis. All supporting data hints at Lewis acid type activation-functionalization processes. Despite a lower energy LUMO in 5+ and 7+ , their observed reactivity is comparable to those of N-heterocyclic carbene (NHC) analogues, in line with charge-controlled reactions for carbene-stabilized ZnII organocations.

Phenylene-Bridged OSSO-Type Titanium Complexes in the Polymerization of Ethylene and Propylene.

The dichloro titanium complexes (OSSO tBu)TiCl2 (1) and (OSSOCum)TiCl2 (2) bearing o-phenylene-bridged OSSO-type ligands [OSSO tBu-H = 6,6'-((1,2-phenylenebis(sulfanediyl))bis(methylene))bis(2,4-di-tert-butyphenol) and OSSOCum-H = 6,6'-((1,2-phenylenebis(sulfanediyl))bis(methylene))bis(2,4-bis(2-phenylpropan-2-yl)phenol)] were prepared and characterized. The X-ray structure of 1 revealed that Ti atom has an octahedral coordination geometry with an fac-fac wrapping of the [OSSO] ligand. In solution at 25 °C, 1 mainly retains the C 2 symmetric structure, whereas 2 shows an equilibrium between C 2- and C 1-symmetric stereoisomers. Activation of 2 with (Ph3C)[B(C6F5)4] led to a highly active catalytic system with an activity of 238 kgPE·molcat -1·bar-1·h-1; linear polyethylene with a T m of 122 °C and M w of 107 kDa were obtained under these conditions. Catalyst 1 displayed the moderate activity of 59 kgPE·molcat -1·bar-1·h-1. Gel permeation chromatography analysis revealed the formation of high-molecular-weight polyethylenes with very large distributions of the molecular weights, indicating a low control of the polymerization process, probably becaue of the presence of different active species in solution. Density functional theory investigation provides a rational for the relative high-molecular-weight polymers obtained with these complexes. The precatalyst 2 was also active in propylene polymerization producing atactic oligomers terminated with unsaturated end groups.

Brain insulin resistance impairs hippocampal synaptic plasticity and memory by increasing GluA1 palmitoylation through FoxO3a.

High-fat diet (HFD) and metabolic diseases cause detrimental effects on hippocampal synaptic plasticity, learning, and memory through molecular mechanisms still poorly understood. Here, we demonstrate that HFD increases palmitic acid deposition in the hippocampus and induces hippocampal insulin resistance leading to FoxO3a-mediated overexpression of the palmitoyltransferase zDHHC3. The excess of palmitic acid along with higher zDHHC3 levels causes hyper-palmitoylation of AMPA glutamate receptor subunit GluA1, hindering its activity-dependent trafficking to the plasma membrane. Accordingly, AMPAR current amplitudes and, more importantly, their potentiation underlying synaptic plasticity were inhibited, as well as hippocampal-dependent memory. Hippocampus-specific silencing of Zdhhc3 and, interestingly enough, intranasal injection of the palmitoyltransferase inhibitor, 2-bromopalmitate, counteract GluA1 hyper-palmitoylation and restore synaptic plasticity and memory in HFD mice. Our data reveal a key role of FoxO3a/Zdhhc3/GluA1 axis in the HFD-dependent impairment of cognitive function and identify a novel mechanism underlying the cross talk between metabolic and cognitive disorders.

Stereorigid OSSO-Type Group 4 Metal Complexes in the Ring-Opening Polymerization of rac-Lactide.

The synthesis and characterization of a series of group 4 metal complexes of general formula {OSSOX}M(OR)2 (X = R = tBu, M = Zr (1); X = cumyl, M = Zr, R = tBu (2); X = cumyl, M = Ti, R = iPr (4); X = cumyl, M = Hf, R = tBu (5)) and {OSSOX}2Zr (X = Cl (3)) supported by o-phenylene-bridged bis(phenolato) ligands (OSSOtBu-H = 6,6'-((1,2-phenylenebis(sulfanediyl))bis(methylene))bis(2,4-di-tert-butyphenol); OSSOCum-H = 6,6'-((1,2-phenylenebis(sulfanediyl))bis(methylene))bis(2,4-bis(2-phenylpropan-2-yl)phenol); OSSOCl-H = 6,6'-((1,2-phenylenebis(sulfanediyl))bis(methylene))bis(2,4-dichlorophenol)) are described herein. Complexes 1-5 were readily obtained by σ-bond metathesis reactions between the proligand and the appropriate homoleptic metal precursor. The reaction with OSSOCl yielded the bis-ligand complex{OSSOCl}2Zr (3) regardless of the OSSOCl-H/Zr(OtBu)4 molar ratio or experimental conditions. All complexes were characterized in solution using NMR spectroscopy and, in the case of 2, by single-crystal X-ray diffraction experiments. These complexes show a fac-fac ligand wrapping and a cis relationship between the other two monodentate ligands; zirconium and hafnium complexes 1-3 and 5 are configurationally stable, whereas titanium complex 4 is fluxional in solution at room temperature. The complexes tested in the ring-opening polymerization (ROP) of racemic-lactide showed, except in the case of 3, moderate rates and good levels of polymerization control. Upon addition of an exogenous alcohol (isopropyl alcohol or tert-butyl alcohol) efficient binary catalytic systems were achieved. Polymerizations were well-controlled, as testified by the linear growth of the molecular weight as polymerization proceeded, narrow polydispersity indices, and molecular weights close to those expected on the basis of added alcohol amounts. Experimental and theoretical evidence is provided that ROP reactions operate according to an activated monomer mechanism.