Cross‐Coupling of Organolithium with Ethers or Aryl Ammonium Salts by C−O or C−N Bond Cleavage

Various aryl‐, alkenyl‐, and/or alkyllithium species reacted smoothly with aryl and/or benzyl ethers with cleavage of the inert C?O bond to afford cross‐coupled products, catalyzed by commercially available [Ni(cod)₂] (cod=1,5‐cyclooctadiene) catalysts with N‐heterocyclic carbene (NHC) ligands. Furthermore, the coupling reaction between the aryllithium compounds and aryl ammonium salts proceeded under mild conditions with C?N bond cleavage in the presence of a [Pd(PPh₃)₂Cl₂] catalyst. These methods enable selective sequential functionalizations of arenes having both C?N and C?O bonds in one pot.     

Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Europium(III) DO3A as a Bimodal Imaging Probe

A new prototype consisting of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles decorated with europium(III) ions encapsulated in a DO3A organic scaffold was designed as a platform for further development of bimodal contrast agents for MRI and optical imaging. The USPIO nanoparticles act as negative MRI contrast agents, whereas the europium(III) ion is a luminophore that is suitable for use in optical imaging detection. The functionalized USPIO nanoparticles were characterized by TEM, DLS, XRD, FTIR, and TXRF analysis, and a full investigation of the relaxometric and optical properties was conducted. The typical luminescence emission of europium(III) was observed and the main red emission wavelength was found at 614 nm. The relaxometric study of these ultrasmall nanoparticles showed r₂ values of 114.8 mm ^?1_Fes^?1 at 60 MHz, which is nearly double the r₂ relaxivity of Sinerem^®.     

Enantioselective Sulfoxidation Catalyzed by a Bisguanidinium Diphosphatobisperoxotungstate Ion Pair

The first enantioselective tungstate‐catalyzed oxidation reaction is presented. High enantioselectivities were achieved for a variety of drug‐like phenyl and heterocyclic sulfides under mild conditions with H₂O₂, a cheap and environmentally friendly oxidant. Synthetic utility was demonstrated through the preparation of (S)‐Lansoprazole, a commercial proton‐pump inhibitor. The active ion‐pair catalyst was identified to be bisguanidinium diphosphatobisperoxotungstate using Raman spectroscopy and computational studies.     

Investigating the Photostability of Quantum Dots at the Single‐Molecule Level

Quantum dots (QDs) have shown great potential to provide spatial, temporal, and structural information for biological systems. However, blinking, photobleaching, and spectral blueshift are adverse effects on their practical applications in biomedical research. An investigation of the effects of six reducing agents including cysteine (Cys), 1,4‐dithiothreitol (DTT), ethyl gallate (EG), L ‐glutathione (GSH), mercaptoacetic acid (MAA), and thiourea (TU) on the photostability of single QDs was studied. Our experiments demonstrate that both DTT and EG effectively inhibit blinking, photobleaching, and spectral blueshift. GSH molecules block blinking and photobleaching of QDs. The other reagents, Cys, MAA, and TU, only have the ability to counteract blinking. Possible explanations are given on the basis of research evidence. The results suggest possibilities for significant improvements in QDs for biological applications by adjusting the environmental conditions.     

Noria: A Highly Xe‐Selective Nanoporous Organic Solid

Separation of xenon and krypton is of industrial and environmental concern; the existing technologies use cryogenic distillation. Thus, a cost‐effective, alternative technology for the separation of Xe and Kr and their capture from air is of significant importance. Herein, we report the selective Xe uptake in a crystalline porous organic oligomeric molecule, noria, and its structural analogue, PgC‐noria, under ambient conditions. The selectivity of noria towards Xe arises from its tailored pore size and small cavities, which allows a directed non‐bonding interaction of Xe atoms with a large number of carbon atoms of the noria molecular wheel in a confined space.     

Hydroxyl Radical Generation and DNA Nuclease Activity: A Mechanistic Study Based on a Surface‐Immobilized Copper Thioether Clip‐Phen Derivative

Coordination compounds of copper have been invoked as major actors in processes involving the reduction of molecular oxygen, mostly with the generation of radical species the assignment for which has, so far, not been fully addressed. In the present work, we have carried out studies in solution and on surfaces to gain insights into the nature of the radical oxygen species (ROS) generated by a copper(II) coordination compound containing a thioether clip‐phen derivative, 1,3‐bis(1,10‐phenanthrolin‐2‐yloxy)‐N‐(4‐(methylthio)benzylidene)propan‐2‐amine (2CP‐Bz‐SMe), enabling its adsorption/immobilization to gold surfaces. Whereas surface plasmon resonance (SPR) and electrochemistry of the adsorbed complex indicated the formation of a dimeric Cu^I intermediate containing molecular oxygen as a bridging ligand, scanning electrochemical microscopy (SECM) and nuclease assays pointed to the generation of a ROS species. Electron paramagnetic resonance (EPR) data reinforced such conclusions, indicating that radical production was dependent on the amount of oxygen and H₂O₂, thus pointing to a mechanism involving a Fenton‐like reaction that results in the production of OH^..     

Tetraphenylethene‐Based Conjugated Fluoranthene: A Potential Fluorescent Probe for Detection of Nitroaromatic Compounds

This study reports the synthesis and photophysical properties of a star‐shaped, novel, fluoranthene–tetraphenylethene (TFPE) conjugated luminogen, which exhibits aggregation‐induced blue‐shifted emission (AIBSE). The bulky fluoranthene units at the periphery prevent intramolecular rotation (IMR) of phenyl rings and induces a blueshift with enhanced emission. The AIBSE phenomenon was investigated by solvatochromic and temperature‐dependent emission studies. Nanoaggregates of TFPE, formed by varying the water/THF ratio, were investigated by SEM and TEM and correlated with optical properties. The TFPE conjugate was found to be a promising fluorescent probe towards the detection of nitroaromatic compounds (NACs), especially for 2,4,6‐trinitrophenol (PA) with high sensitivity and a high Stern–Volmer quenching constant. The study reveals that nanoaggregates of TFPE formed at 30 and 70 % water in THF showed unprecedented sensitivity with detection limits of 0.8 and 0.5 ppb, respectively. The nanoaggregates formed at water fractions of 30 and 70 % exhibit high Stern–Volmer constants (K_sv=79 998 and 51 120 m ^?1, respectively) towards PA. Fluorescence quenching is ascribed to photoinduced electron transfer between TFPE and NACs with a static quenching mechanism. Test strips coated with TFPE luminogen demonstrate fast and ultra‐low‐level detection of PA for real‐time field analysis.     

Structure-Based Design,Synthesis, and Biological Evaluation of Hsp90β-Selective Inhibitors

The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that are responsible for the folding and/or trafficking of ∼400 client proteins, many of which are directly associated with cancer progression. Consequently, inhibition of Hsp90 can exhibit similar activity as combination therapy as multiple signaling nodes can be targeted simultaneously. In fact, seventeen small-molecule inhibitors that bind the Hsp90 N-terminus entered clinical trials for the treatment of cancer, all of which exhibited pan-inhibitory activity against all four Hsp90 isoforms. Unfortunately, most demonstrated undesired effects alongside induction of the pro-survival heat shock response. As a result, isoform-selective inhibitors have been sought to overcome these detriments. Described herein is a structure-based approach to design Hsp90β-selective inhibitors along with preliminary SAR. In the end, compound 5 was shown to manifest ∼370-fold selectivity for Hsp90β versus Hsp90α, and induced the degradation of select Hsp90β-dependent clients. These data support the development of Hsp90β-selective inhibitors as a new paradigm to overcome the detriments associated with pan-inhibition of Hsp90.