K48-Linked Ubiquitination Contributes to Nicotine-Augmented Bone Marrow-Derived Dendritic-Cell-Mediated Adaptive Immunity.

K48-linked ubiquitination determining antigen degradation and the endosomal recruitments of p97 and Sec61 plays vital roles in dendritic cell (DC) cross-presentation. Our previous studies revealed that nicotine treatment increases bone marrow-derived dendritic cell (BM-DC) cross-presentation and promotes BM-DC-based cytotoxic T lymphocyte (CTL) priming. But the effect of nicotine on K48-linked ubiquitination and the mechanism of nicotine-increased BM-DC cross-presentation are still uncertain. In this study, we first demonstrated that ex vivo nicotine administration obviously increased K48-linked ubiquitination in BM-DC. Then, we found that K48-linked ubiquitination was essential for nicotine-augmented cross-presentation, BM-DC-based CTL priming, and thereby the superior cytolytic capacity of DC-activated CTL. Importantly, K48-linked ubiquitination was verified to be necessary for nicotine-augmented endosomal recruitments of p97 and Sec61. Importantly, mannose receptor (MR), which is an important antigenic receptor for cross-presentation, was exactly catalyzed with K48-linked ubiquitination by the treatment with nicotine. Thus, these data suggested that K48-linked ubiquitination contributes to the superior adaptive immunity of nicotine-administrated BM-DC. Regulating K48-linked ubiquitination might have therapeutic potential for DC-mediated immune therapy.

Synthesis and chelation study of a fluoroionophore and a glycopeptide based on an aza crown iminosugar structure.

Capitalizing on a recently reported iminosugar-based aza-crown (ISAC) accessed by a double Staudinger azaWittig coupling reaction, we have expanded the structural diversity of this new family of sweet cyclam analogs. Replacement of the two secondary amines linking the iminosugar units by two amide bonds obtained a cyclodimerization by with BOP and DIPEA led to a macrocycle that did not demonstrate efficient Zn2+ chelation unlike the parent ISAC. Introduction of two pyrene moieties on the secondary amines of the parent ISAC yielded a new fluoroionophore that selectively binds Hg2+ in methanol.

Aggregation-induced emission enhancement upon Al3+ complexation with a tetrasulfonated calix[4]bisazacrown fluorescent molecular sensor.

Aggregation-induced emission and aggregation-induced emission enhancement have attracted much attention due to their great potential in real-world applications. Up to now most of the reports are based on the restriction of free rotation of the luminogens in the aggregates. In the present work, we found that the dansyl fluorophore with typical intramolecular charge transfer characteristic also exhibited aggregation-induced emission enhancement, which was based on the change of micro-environmental polarity of the fluorophore. In the light of the phenomenon, a new water-soluble ligand bearing a tetrasulfonated calix[4]arene was constructed for ratiometric detection of Al(3+) based on an aggregation-induced emission enhancement mechanism. It displayed a distinct selectivity to Al(3+) among the tested cations in lutidine buffer solution (pH 6-7) with a detection limit of 1.8 µM. A reversible response was also demonstrated by the addition of EDTA or F(-).

Hg2+-promoted photoactivation of triazolyl rhodamine.

Hg(2+) was able to induce the ring-opening of glycosyl triazolyl rhodamines after 26 h incubation at room temperature in MeCN-DMSO (99 : 1). This reaction can be dramatically accelerated by irradiation at 313 nm, by reducing the response time to 2 min. Selectivity towards Hg(2+) has also been demonstrated, except for Cu(2+), other metal ions showed almost no influence on this photochromic process. Detailed mechanistic investigations indicated that a small amount of DMSO played an important role during the photochromic transformation, probably by stabilising the excited open form of the triazolyl rhodamine-Hg(2+) complex.

Isolable chiral aggregates of achiral π-conjugated carboxylic acids.

The induced aggregation of achiral building blocks by a chiral species to form chiral aggregates with memorized chirality has been observed for a number of systems. However, chiral memory in isolated aggregates of achiral building blocks remains rare. One possible reason for this discrepancy could be that not much is understood in terms of designing these chiral aggregates. Herein, we report a strategy for creating such isolable chiral aggregates from achiral building blocks that retain chiral memory after the facile physical removal of the chiral templates. This strategy was used for the isolation of chiral homoaggregates of neutral achiral π-conjugated carboxylic acids in pure aqueous solution. Under what we have termed an "interaction-substitution" mechanism, we generated chiral homoaggregates of a variety of π-conjugated carboxylic acids by using carboxymethyl cellulose (CMC) as a mediator in acidic aqueous solutions. These aggregates were subsequently isolated from the CMC templates whilst retaining their memorized supramolecular chirality. Circular dichroism (CD) spectra of the aggregates formed in the acidic CMC solution exhibited bisignated exciton-coupled signals of various signs and intensities that were maintained in the isolated pure homoaggregates of the achiral π-conjugated carboxylic acids. The memory of the supramolecular chirality in the isolated aggregates was ascribed to the substitution of COOH/COOH hydrogen-bonding interaction between the carboxylic acid groups within the aggregates for the hydrogen-bonding interactions between the COOH groups of the building blocks and the chiral templates. We expect that this "interaction-substitution" procedure will open up a new route to isolable pure chiral aggregates from achiral species.

Supramolecular aggregation/disaggregation-based molecular sensing: a review focused on investigations from China.

Supramolecular aggregation and disaggregation induced by external stimuli can impact the optical or electrical signals of the aggregates/constituting units (receptors). Therefore, manipulating supramolecular aggregation/disaggregation has recently been employed to construct novel and promising photoluminescence (PL)-based sensing and recognition systems. The sensing systems were capable of substantially enhancing the sensitivity, relying on cooperative interactions occurring in the assembly/disassembly processes (mostly operating in emission turned-on or emission-enhanced mode). This review focuses mainly on recent advances in the new emerging PL-based sensing platforms, based on manipulating the behaviours of supramolecular aggregation/disaggregation, including aggregation-induced emission (AIE), metallophilic interactions-related sensing (metallophilic interactions-induced aggregation/disaggregation), metal coordination polymers-related sensing, and other sensing systems involving supramolecular aggregation/disaggregation. In particular, those sensing systems developed by scientists in China are summarized and highlighted.

A ratiometric luminescent sensing of Ag+ ion via in situ formation of coordination polymers.

A ratiometric luminescent sensing of Ag(+) ion is developed via the Ag(I)-NCys coordination polymeric luminophore in situ formed in aqueous solution upon mixing Ag(+) ion with the designed fluorescent thiol ligand NCys.

Highly sensitive naked-eye and fluorescence "turn-on" detection of Cu(2+) using Fenton reaction assisted signal amplification.

Increase of pH induced by Cu(2+)-catalyzed Fenton reaction promoted ring-opening of triazole-linked fluorescein lactone, which enabled selective "turn-on" fluorescent detection of Cu(2+), along with ultralow naked-eye detection limit down to 200 nM.

Specific Hg(2+)-mediated perylene bisimide aggregation for highly sensitive detection of cysteine.

Hg(2+) was found to specifically induce the aggregation of perylene bisimide in a "thymine-Hg(2+)-thymine" binding motif and the resultant aggregates showed a highly selective and sensitive turn-on fluorescence response for cysteine, with a detection limit down to 9.6 nM.

Enhanced saccharide sensing based on simple phenylboronic acid receptor by coupling to Suzuki homocoupling reaction.

Substantially enhanced monosaccharide fluorescent sensing in aqueous solutions using a simple phenylboronic acid receptor is achieved by coupling the classic strategy based on saccharide-boronic acid interaction with catalytic Suzuki homocoupling reaction.

Molecular logic gates and switches based on 1,3,4-oxadiazoles triggered by metal ions.

Organic molecular devices for information processing applications are highly useful building blocks for constructing molecular-level machines. The development of "intelligent" molecules capable of performing logic operations would enable molecular-level devices and machines to be created. We designed a series of 2,5-diaryl-1,3,4-oxadiazoles bearing a 2-(para-substituted)phenyl and a 5-(o-pyridyl) group (substituent X=NMe(2), OEt, Me, H, and Cl; 1a-e) that form a bidentate chelating environment for metal ions. These compounds showed fluorescence response profiles varying in both emission intensity and wavelength toward the tested metal ions Ni(2+), Cu(2+), Zn(2+), Cd(2+), Hg(2+), and Pb(2+) and the responses were dependent on the substituent X, with those of 1d being the most substantial. The 1,3,4-oxadiazole O or N atom and pyridine N atom were identified as metal-chelating sites. The fluorescence responses of 1d upon metal chelation were employed for developing truth tables for OR, NOR, INHIBIT, and EnNOR logic gates as well as "ON-OFF-ON" and "OFF-ON-OFF" fluorescent switches in a single 1,3,4-oxadiazole molecular system.

N-(Acetamido)thiourea based simple neutral hydrogen-bonding receptors for anions.

N-(Acetamido)-N'-phenylthioureas (4-6) were found to be efficient anion receptors with higher anion affinity than their N-benzamido-N'-phenylthiourea counterparts (1 and 2). The N'-phenylthiourea moiety in 4-6 was shown to be the chromophore with an absorption maximum at ca. 270 nm. It was found that, in the presence of anions, the absorption at ca. 270 nm of 4-6 (except 5f) in acetonitrile (MeCN) was blue shifted and enhanced while a red-shifted shoulder appeared at ca. 295 nm, together with an isosbestic point at ca. 240 nm. The 1:1 anion binding constants of 4-6, for example at 10(6)-10(7) M(-1) order of magnitude for AcO(-) in MeCN, were found to be higher than those of 1 and 2, although the acidity of the thioureido -NH protons in 4-6 is lower than that in 1 and 2. (1)H NMR data indicates that the N-N single bond in 4-6 is twisted but less than that in 1 and 2. A conformation change at the N-N single bond of 4-6 was suggested to occur upon anion binding which leads to a planar hydrogen-bonding network in the anion binding complex in which a charge transfer takes place with the N-acyl moiety being the electron acceptor. Variations in the CD signals of a proline derivative 6 bearing a chiral center in the N-amido moiety provide direct evidence for this conformation change upon its binding with anions in MeCN. The amplified effect of substituent X at the N'-phenyl ring of 5 on the anion binding constant supports the conclusion of anion-binding switched charge transfer in the anion binding complex. (1)H NMR and absorption titrations for 5 indicated that the anion-receptor interaction was of a hydrogen-bonding nature until the N'-phenyl substituent X is as electron-withdrawing as m-CF(3) (5e). With X being the more electron-withdrawing p-NO(2) (5f), deprotonation of the thioureido -NH occurs in the presence of anion. Results reported here confirm that N-amidothioureas derived from both N-aliphatic and N-aromatic amides can in general be a family of efficient hydrogen-bonding receptors, with the aliphatic N-amido derivatives being more efficient. This provides a wider structural diversity for designing thiourea-based functional molecules such as anion receptors and organocatalysts. Preliminary experiments confirm that 6 could catalyse efficiently the reduction of nitrostyrene in CH(2)Cl(2) and MeCN.

Oxidative cyclization of N-acylhydrazones. Development of highly selective turn-on fluorescent chemodosimeters for Cu2+.

A series of N-acylhydrazones were synthesised and found to be "turn-on" fluorescent chemodosimeters for Cu(2+). Among the tested transition metal ions such as Cu(2+), Pb(2+), Zn(2+), Cd(2+), Hg(2+), and Ni(2+), a prominent fluorescence enhancement of up to 1000-fold was only observed for Cu(2+) in acetonitrile (CH(3)CN). This was indicated by an onset of unprecedented structured emission. Detailed experiments established that the highly Cu(2+) selective fluorescence enhancement resulted from an oxidative cyclization by Cu(2+)of the originally nonfluorescent N-acylhydrazones into highly fluorescent rigid 1,3,4-oxadiazoles, n-dope type blocks in optoelectronic materials. The chemodosimeters can be applied to sense Cu(2+) at nM levels in CH(3)CN and sub-microM levels in neutral aqueous environments, despite a slower response in the latter case. It is expected that these redox-based chemodosimeters might be of general applicability.