Near-Infrared Aggregation-Induced Emission Luminogens for In Vivo Theranostics of Alzheimer's Disease

Optimized theranostic strategies for Alzheimer's disease (AD) remain almost absent from bench to clinic. Current probes and drugs attempting to prevent β-amyloid (Aβ) fibrosis encounter failures due to the blood–brain barrier (BBB) penetration challenge and blind intervention time window. Herein, we design a near-infrared (NIR) aggregation-induced emission (AIE) probe, DNTPH, via balanced hydrophobicity-hydrophilicity strategy. DNTPH binds selectively to Aβ fibrils with a high signal-to-noise ratio. In vivo imaging revealed its excellent BBB permeability and long-term tracking ability with high-performance AD diagnosis. Remarkably, DNTPH exhibits a strong inhibitory effect on Aβ fibrosis and promotes fibril disassembly, thereby attenuating Aβ-induced neurotoxicity. DNTPH treatment significantly reduced Aβ plaques and rescued learning deficits in AD mice. Thus, DNTPH serves as the first AIE in vivo theranostic agent for real-time NIR imaging of Aβ plaques and AD therapy simultaneously.     

Grafting and thermal stripping of organo-bimetallic clusters on AU surfaces: toward controlled CO/RU aggregates

The controlled stoichiometry of heterometallic carbonyl clusters make them attractive precursors for the stabilization of bare metal alloy clusters for magnetic applications. The mixed-metal molecular cluster [RuCo3(H)(CO)12] has been functionalized with the phosphane-thiol ligand Ph2PCH2CH2SH to allow subsequent anchoring on a gold surface. The resulting tetrahedral cluster [RuCo3(H)(CO)11(Ph2PCH2CH2SH)] (1) has been characterized by X-ray diffraction and the P-monodentate ligand is axially bound to a cobalt center and trans to the ruthenium cap. This synthesis also yielded the product of oxidative coupling, in which two SH groups were coupled intermolecularly to give a disulfide ligand that links two tetrahedral cluster units in [{RuCo3(H)(CO)11(Ph2PCH2CH2S)}2] (2). This cluster has also been characterized by X-ray diffractions studies. After deposition of 1 on a Au(111) surface by self-assembly, the carbonyl ligands were stripped off by thermal annealing in ultra-high vacuum (UHV) to form a metallic species. X-ray photoelectron spectroscopic measurements performed as a function of the annealing temperature show that the cobalt and ruthenium centers converge towards metallic character and that the stoichiometry of the alloy is retained during the annealing process. Preliminary X-ray absorption spectroscopy (XAS) synchrotron experiments indicate that clusters 1 and 2 behave similarly, which is consistent with the retention of their tetrahedral units on the gold surface after transformation of the thiol function or breaking of the disulfide bond to form Au--S bonds, respectively, has occurred.     

Label-free fluorescent probing of G-quadruplex formation and real-time monitoring of DNA folding by a quaternized tetraphenylethene salt with aggregation-induced emission characteristics

Biosensing processes such as molecular beacons require non-trivial effort to covalently label or mark biomolecules. We report here a label-free DNA assay system with a simple dye with aggregation-induced emission (AIE) characteristics as the fluorescent bioprobe. 1,1,2,2-Tetrakis[4-(2-bromoethoxy)phenyl]ethene is nonemissive in solution but becomes highly emissive when aggregated. This AIE effect is caused by restriction of intramolecular rotation, as verified by a large increase in the emission intensity by increasing viscosity and decreasing temperature of the aqueous buffer solution of 1,1,2,2-tetrakis[4-(2-triethylammonioethoxy)phenyl]ethene tetrabromide (TTAPE). When TTAPE is bound to a guanine-rich DNA strand (G1) via electrostatic attraction, its intramolecular rotation is restricted and its emission is turned on. When a competitive cation is added to the G1 solution, TTAPE is detached and its emission is turned off. TTAPE works as a sensitive poststaining agent for poly(acrylamide) gel electrophoresis (PAGE) visualization of G1. The dye is highly affinitive to a secondary structure of G1 called the G-quadruplex. The bathochromic shift involved in the G1 folding process allows spectral discrimination of the G-quadruplex from other DNA structures. The strong affinity of TTAPE dye to the G-quadruplex structure is associated with a geometric fit aided by the electrostatic attraction. The distinct AIE feature of TTAPE enables real-time monitoring of folding process of G1 in the absence of any pre-attached fluorogenic labels on the DNA strand. TTAPE can be used as a K+ ion biosensor because of its specificity to K+-induced and -stabilized quadruplex structure.     

Amine-catalyzed polycyclotrimerization of arylene bipropiolate: A metal-free and regioselective route to hyperbranched polymer

This paper presents a new synthetic route to hyperbranched polymer. An arylene bipropiolate monomer,dimethylmethylenebis(1,4-phenylene) bipropiolate,was prepared by a one-step esterification reaction of bisphenol A with propiolic acid. Polycyclotrimrtization of the monomer was effected by reflux in dimethylformamide(DMF),producing a soluble hyperbranched poly(aroxycarbonylphenylene) in a good yield. The polymer was perfectly branched with a degree of branching of 100%.     

Aggregation-enhanced emissions of intramolecular excimers in disubstituted polyacetylenes

Whereas chain aggregation commonly quenches light emission of conjugated polymers, we here report a phenomenon of aggregation-induced emission enhancement (AIEE): luminescence of polyacetylenes is dramatically boosted by aggregate formation. Upon photoexcitation, poly(1-phenyl-1-alkyne)s and poly(diphenylacetylene)s emit blue and green lights, respectively, in dilute THF solutions. The polymers become more emissive when their chains are induced to aggregate by adding water into their THF solutions. The polymer emissions are also enhanced by increasing concentration and decreasing temperature. Lifetime measurements reveal that the excited species of the polymers become longer-lived in the aggregates. Conformational simulations suggest that the polymer chains contain n=3 repeat units that facilitate the formation of intramolecular excimers. The AIEE effects of the polymers are rationalized to be caused by the restrictions of their intramolecular rotations by the aggregate formation.     

Sterol-containing tetraphenylethenes: synthesis,aggregation-induced emission,and organogel formation

Cholesterol- and stigmasterol-containing tetraphenylethenes (TPEs) (TPE-Chol and TPE-Stig) are facilely synthesized in satisfactory yields by Cu (I)-catalyzed click reaction of 1,2-bis(4-azidomethylphenyl)-1,2-diphenylethene and cholesteryl-4-ethylbenoate and sigmasteryl 11-(4-ethynylphenoxy)undecanoate, respectively. Whereas they are nonluminescent in solution, they become highly emissive when aggregated in the condensed phase. The molecules of TPE-Stig can self-assemble in methanol solution, generating organogels with gelation-induced emission characteristics.     

Exploring New Molecular Architectures for Anion Recognition: Synthesis and ATP Binding Properties of New Cyclam‐Based Ditopic Polyammonium Receptors.

Synthesis and characterization of three new polyamine receptors, composed of a cyclam unit (cyclam=1,4,8,11‐tetraazacyclotetradecane) linked by a 2,6‐dimethylpyridinyl spacer to the linear polyamines 1,4,8,11‐tetraazaundecane ( L1py ), 1,4,7‐triazaheptane ( L2py ), and to a quaternary ammonium group ( L3 py⁺ ), are reported. All receptors form highly charged polyammonium cations at neutral pH, suitable for anion recognition studies. ATP recognition was analyzed by using potentiometric, calorimetric, ¹H and ³¹P NMR measurements in aqueous solution. All receptors form 1:1 adducts with ATP in aqueous solution, stabilized by charge–charge and hydrogen‐bonding interactions between their ammonium groups and the anionic triphosphate chain of ATP. The binding ability of the three receptors for ATP increases in the order of L3 py⁺ < L2py < L1py . These adducts are stabilized by largely favourable entropic contributions, probably due to the large desolvation of the host and guest species upon complexation. The sequence observed for the binding affinity is explained in terms of the different ability of the three receptors to wrap around the phosphate chain of ATP.     

Electroneutrality in the Lekner–Sperb method

A slightly different derivation of the Lekner–Sperb method for partially periodic boundary conditions is given in this note. This derivation allows one to take explicitly into account the electroneutrality of systems and give the exact value of a constant that was determined numerically in the past.     

Chiral Poly(4‐ethynylbenzoyl‐L‐valine)‐Induced Helical Self‐Assembly of Alkynylplatinum(II) Terpyridyl Complexes with Tunable Electronic Absorption,Emission, and Circular Dichroism Changes

The aggregation and self‐assembly of square‐planar alkynylplatinum(II) complexes is induced by the use of a chiral polyacetylene with a helical conformation (see scheme). The chain helicity of the chiral polyacetylene under basic conditions has also been demonstrated to be enhanced by the presence of the positively charged platinum(II) complexes.

     

Manganese(III)-containing Wells-Dawson sandwich-type polyoxometalates: comparison with their manganese(II) counterparts

We present the synthesis and structural characterization, assessed by various techniques (FTIR, TGA, UV-vis, elemental analysis, single-crystal X-ray diffraction for three compounds, magnetic susceptibility, and electrochemistry) of five manganese-containing Wells-Dawson sandwich-type (WDST) complexes. The dimanganese(II)-containing complex, [Na(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](18-) (1), was obtained by reaction of MnCl(2) with 1 equiv of [As(2)W(15)O(56)](12-) in acetate medium (pH 4.7). Oxidation of 1 by Na(2)S(2)O(8) in aqueous solution led to the dimanganese(III) complex [Na(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](16-) (2), while its trimanganese(II) homologue, [Na(H(2)O)(2)Mn(II)(H(2)O)Mn(II)(2)(As(2)W(15)O(56))(2)](17-) (3), was obtained by addition of ca. 1 equiv of MnCl(2) to a solution of 1 in 1 M NaCl. The trimanganese(III) and tetramanganese(III) counterparts, [Mn(III)(H(2)O)Mn(III)(2)(As(2)W(15)O(56))(2)](15-) (4) and [Mn(III)(2)(H(2)O)(2)Mn(III)(2)(As(2)W(15)O(56))(2)](12-) (6), are, respectively, obtained by oxidation of aqueous solutions of 3 and [Mn(II)(2)(H(2)O)(2)Mn(II)(2)(As(2)W(15)O(56))(2)](16-) (5) by Na(2)S(2)O(8). Single-crystal X-ray analyses were carried out on 2, 3, and 4. BVS calculations and XPS confirmed that the oxidation state of Mn centers is +II for complexes 1, 3, and 5 and +III for 2, 4, and 6. A complete comparative electrochemical study was carried out on the six compounds cited above, and it was possible to observe the distinct redox steps Mn(IV/III) and Mn(III/II). Magnetization measurements, as a function of temperature, confirm the presence of antiferromagnetic interactions between the Mn ions in these compounds in all cases with the exception of compound 2.