Spectroscopic and Crystallographic Characterization of the R3N+−C−H⋅⋅⋅X Interaction

As appreciation for nonclassical hydrogen bonds has progressively increased, so have efforts to characterize these interesting interactions. Whereas several kinds of C−H hydrogen bonds have been well-studied, much less is known about the R₃N⁺−C−H⋅⋅⋅X variety. Herein, we present crystallographic and spectroscopic evidence for the existence of these interactions, with special relevance to Selectfluor chemistry. Of particular note is the propensity for Lewis bases to engage in nonclassical hydrogen bonding over halogen bonding with the electrophilic F atom of Selectfluor. Further, the first examples of ¹H NMR experiments detailing R₃N⁺−C−H⋅⋅⋅X (X=O, N) hydrogen bonds are described.     

In silico optimization of merocyanine-spiropyran compounds as second-order nonlinear optical molecular switches

Time-dependent Hartree-Fock and M?ller-Plesset second-order calculations have been used to unravel the relationships between structure and first hyperpolarizability in spiropyran/merocyanine couples and therefore to design efficient second-order nonlinear optical switching compounds. Large first hyperpolarizabilities for the merocyanine form as well as large contrasts of first hyperpolarizability have been obtained when, on the same species, (i) substituents at R(1) and R(2) positions on the phenolate ring of the merocyanine form are strong acceptor and donor substituents, respectively, (ii) the ethylenic bridge is substituted by donor groups, (iii) the other aromatic part of the system is benzimidazolo rather than indolino or benzothiazolo, and (iv) strong donor substituents are placed on the benzimidazolo moiety.     

New picropodophyllin analogs via palladium-catalyzed allylic alkylation-Hiyama cross-coupling sequences

Unsaturated malonyl esters underwent Pd-catalyzed intramolecular allylic alkylation to give 4-vinyl-substituted gamma-lactones. In contrast to the formerly studied cyclization of malonamides, this reaction could be achieved only with a substrate incorporating a suitably positioned silicon moiety, which directs the ionization toward the desired eta(3)-allylpalladium complex. The resulting 4-[dimethyl-(2-thienyl)silylvinyl]lactone could be subsequently engaged into Hiyama couplings with various iodoarenes, to give the corresponding 4-(alpha-styryl)-gamma-lactones. The use of a specifically substituted iodoarene generated an advanced tetracyclic lactone intermediate incorporating rings A-D of lignans belonging to the podophyllotoxin family. Subsequent electrophilic aromatic substitution with a variety of electron-rich arenes afforded the target picropodophyllin analogs.     

Role of Cu-doping in CdTe thin films: Experiments and simulations

Due to its outstanding physical properties, CdTe is used to fabricate high efficiency solar cells. However, its high work function poses a challenge, and hence, to fabricate an efficient CdTe-based solar cell, Cu-doping may be useful. Here, we present the role of temperature-dependent Cu-doping in radio frequency sputter-deposited CdTe films and the related changes occurring in their optical, electrical, structural and microstructural properties. For instance, Cu-doping at different temperatures leads to an increase in the grain size and a reduction in the optical reflectance with increasing temperature. In addition, Kelvin probe force microscopy measurements reveal that the work function is found to be smaller corresponding to the annealing temperature of 473 K, whereas resistivity measurements show that it decreases with increasing temperature (the lowest value of resistivity is found to be 1.8 × 10⁻² Ω-cm). To understand the electronic structure of CdTe before and after Cu-doping, we have carried out first-principles density functional theory (DFT) simulation, which reveals a strong hybridization among Cu, Cd and Te atoms. This study paves the way to fabricate efficient Cu-doped CdTe-based solar cells.     

A Lock-and-Kill Anticancer Photoactivated Chemotherapy Agent†

Photosubstitutionally active ruthenium complexes show high potential as prodrugs for the photoactivated chemotherapy (PACT) treatment of tumors. One of the problems in PACT is that the localization of the ruthenium compound is hard to trace. Here, a ruthenium PACT prodrug, [Ru(3)(biq)(STF-31)](PF₆)₂ (where 3 = 3-(([2,2′:6′,2″-ter- pyridin]-4′-yloxy)propyl-4-(pyren-1-yl)butanoate) and biq = 2,2′-biquinoline), has been prepared, in which a pyrene tracker is attached via an ester bond. The proximity between the fluorophore and the ruthenium center leads to fluorescence quenching. Upon intracellular hydrolysis of the ester linkage, however, the fluorescence of the pyrene moiety is recovered, thus demonstrating prodrug cellular uptake. Further light irradiation of this molecule liberates by photosubstitution STF-31, a known cytotoxic nicotinamide phosphoribosyltransferase (NAMPT) inhibitor, as well as singlet oxygen via excitation of the free pyrene chromophore. The dark and light cytotoxicity of the prodrug, embedded in liposomes, as well as the appearance of blue emission upon uptake, were evaluated in A375 human skin melanoma cells. The cytotoxicity of the liposome-embedded prodrug was indeed increased by light irradiation. This work realizes an in vitro proof-of-concept of the lock-and-kill principle, which may ultimately be used to design strategies aimed at knowing where and when light irradiation should be realized in vivo.     

Interaction between water-soluble peptidic CdSe/ZnS nanocrystals and membranes: formation of hybrid vesicles and condensed lamellar phases

Due to their tunable optical properties and their well-defined nanometric size, core/shell nanocrystals (quantum dots, QDs) are extensively used for the design of biomarkers as well as for the preparation of nanostructured hybrid materials. It is thus of great interest to understand their interaction with soft lipidic membranes. Here we present the synthesis of water-soluble peptide CdSe/ZnS QDs and their interaction with the fluid lipidic membrane of vesicles. The use of short peptides results in the formation of small QDs presenting both high fluorescence quantum yield and high colloidal stability as well as a mean hydrodynamical diameter of 10 nm. Their interaction with oppositely charged vesicles of various surface charge and size results in the formation of hybrid giant or large unilamellar vesicles covered with a densely packed layer of QDs without any vesicle rupture, as demonstrated by fluorescence resonance energy transfer experiments, zetametry, and optical microscopy. The adhesion of nanocrystals onto the vesicle membrane appears to be sterically limited and induces the reversion of the surface charge of the vesicles. Therefore, their interaction with small unilamellar vesicles induces the formation of a well-defined lamellar hybrid condensed phase in which the QDs are densely packed in the plane of the layers, as shown by freeze-fracture electron microscopy and small-angle X-ray scattering. In this structure, strong undulations of the bilayer maximize the electrostatic interaction between the QDs and the bilayers, as previously observed in the case of DNA polyelectrolytes interacting with small vesicles.     

Redox‐Active‐Ligand‐Mediated Formation of an Acyclic Trinuclear Ruthenium Complex with Bridging Nitrido Ligands

Coordination of a redox‐active pyridine aminophenol ligand to Ru^II followed by aerobic oxidation generates two diamagnetic Ru^III species [ 1 a (cis) and 1 b (trans)] with ligand‐centered radicals. The reaction of 1 a / 1 b with excess NaN₃ under inert atmosphere resulted in the formation of a rare bis(nitrido)‐bridged trinuclear ruthenium complex with two nonlinear asymmetrical Ru‐N‐Ru fragments. The spontaneous reduction of the ligand centered radical in the parent 1 a / 1 b supports the oxidation of a nitride (N^3?) to half an equivalent of N₂. The trinuclear omplex is reactive toward TEMPO‐H, tin hydrides, thiols, and dihydrogen.     

UPLC-MS/MS detection of disaccharides derived from glycosaminoglycans as biomarkers of mucopolysaccharidoses

Mucopolysaccharidoses (MPSs) are a group of disorders resulting from primary defects in lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Depending on the specific enzyme defect, the catabolism of one or more GAGs is blocked leading to accumulation in tissues and biological fluids. GAG measurements are important for high-risk screening, diagnosis, monitoring treatment efficacy, and patient follow up. The dimethylmethylene blue (DMB) spectrophotometric method commonly used in most biochemical genetics laboratories relies on a non-specific total GAG analysis which has led to false positive results, and even false negative results (mainly for MPS III and IV patients). The main objective of our project was to devise and validate a reliable tandem mass spectrometry multiplex analysis for the urine quantitation of four GAGs (dermatan sulfate (DS), heparan sulfate (HS), keratan sulfate (KS), and chondroitin sulfate (CS)) for an eventual technological transfer to the clinic. The developed methodology is rapid (7 min) and our results showed good intraday and interday precision (RSDs ≤ 8.7%) and accuracy (Biases range: −12.0%–18.4%). Linearity was good (r² > 0.995) for DS, HS, CS, and KS calibration curves. In comparison with the DMB spectrophotometric method, this multiplex tandem mass spectrometry method allows GAG fractionation, thus a differentiation of MPS types, except for MPS I and II which are characterized by the same GAG profile. The devised method is a useful and reliable tool for diagnosis of MPS patients, as well as their monitoring and follow up, as shown by longitudinal studies.     

Positioning a Carbon–Fluorine Bond over the π Cloud of an Aromatic Ring: A Different Type of Arene Activation

It is known that the fluoro group has only a small effect on the rates of electrophilic aromatic substitutions. Imagine instead a carbon–fluorine (C?F) bond positioned tightly over the π cloud of an aryl ring—such an orthogonal, noncovalent arrangement could instead stabilize a positively charged arene intermediate or transition state, giving rise to novel electrophilic aromatic substitution chemistry. Herein, we report the synthesis and study of molecule 1 , containing a rigid C?F???Ar interaction that plays a prominent role in both its reaction chemistry and spectroscopy. For example, we established that the C?F???Ar interaction can bring about a >1500 fold increase in the relative rate of an aromatic nitration reaction, affording functionalization on the activated ring exclusively. Overall, these results establish fluoro as a through‐space directing/activating group that complements the traditional role of fluorine as a slightly deactivating aryl substituent in nitrations.