Enantiomer Recognition Based on Chirality Transfer from Chiral Amines to Ternary Dynamic Covalent Systems.

Enantiomer recognition is usually required in organic synthesis and materials and life sciences. This paper describes an enantiomer recognition method based on ternary dynamic covalent systems constructed via the complexation of chiral amines with a chiral boronate derived from 1,4-phenylenediboric acid and an L-DOPA-modified naphthalenediimide. The ternary systems aggregate into chiral assemblies driven by π-π interactions, and the chirality is transferred from the chiral amines to assemblies with high stereospecificity. Consequently, the enantiomer composition of chiral amines and the absolute configuration of the major enantiomer can be determined according to the sign of the Cotton effect of the ternary system by using circular dichroism (CD) spectroscopy. This method offers the advantage of using the long wavelength CD signals of the boronate at around 520 nm, thereby avoiding interference with those of the carbon skeleton. This ternary system provides a novel approach to the design of enantiomer recognition systems.

Oxidation-responsive G-quadruplex ligand for selective inhibition of the proliferation of tumour cells.

Tumour cells show a higher level of reactive oxygen species (ROS) than normal cells. On the basis of this difference, we designed an oxidation-responsive G-quadruplex proligand PDS-B by installing borolanylbenzyls on a well-known pyridostatin (PDS) ligand PDS-S to response high level ROS in tumour cells. The rapid oxidative degradation of the proligand to its active form PDS-S in the presence of H2O2 confirms the oxidation-responsive design. According to Förster resonance energy transfer (FRET) assays, circular dichroism (CD) spectra and confocal fluorescence imaging, PDS-B stabilizes telomeric G4 structures after oxidation with H2O2 or intracellular ROS. Apoptosis assays and cell cycle assays showed significant selectivity of PDS-B in inhibiting the proliferation of tumour cells over normal cells through responses to a high level of ROS in the formers. Further assays confirmed higher level of relative Caspase-3 activity in tumour cells than normal cells, consequently the enhanced apoptosis of the tumour cells induced by PDS-B. In summary, the results demonstrate a modification approach to solve the poor selectivity of the G4 ligand in tumour cells and cytotoxicity in normal cells.

Synergistic effect of naphthalenediimide and squaraine ligand targeting G-quadruplex DNA in cancer cells.

Targeting and stabilizing nonclassical DNA G-quadruplexes (G4s) with a ligand to inhibit cell proliferation is a very promising approach for cancer treatment. Here, we demonstrate that the combination of a naphthalenediimide (NDI) ligand and a squaraine ligand significantly improves the anticancer activity of either ligand alone. The NDI ligand binds the 5'-terminal of hybrid-type G4s and induces the topological conversion from a metastable hybrid to a stable parallel conformation, which allows the end-stacking of the squaraine ligand on the 3'-terminal of the resultant parallel-type G4 structure. Moreover, the NDI ligand promotes the diffusion of the squaraine ligand into the nucleus, and the synergistic effect of the two ligands improves the stability of G4s in cancer cells, blocks the cell cycle in the sub-G1 phase, and induces the DNA damage response. These findings will be helpful in the development of combinational ligands targeting DNA G4s with enhanced bioactivity toward the inhibition of cancer cell proliferation.

Chiral Naphthalenediimides with High-Efficiency Fluorescence and Circularly Polarized Luminescence in the Solid State for the Application in Organic Optoelectronics.

Naphthalenediimides (NDIs) have been extensively studied due to their tunable luminescent properties. However, generally, the monomers or aggregates of non-core substituted NDIs exhibit low fluorescence quantum yields (ΦFL <10 %) in the solid state, which limit their applications as light-emitting materials and render their chiral species unsuitable for circularly polarized luminescence (CPL). Herein, a series of non-core substituted chiral NDIs that exhibit high luminous efficiencies (ΦFL up to 56.8 % for racemate and 36.5 % for enantiomer) and a strong CPL behavior in the solid state is reported. These significant improvements are attributed to the unique molecular conformation of the chiral NDIs and the formation of distinctive discrete dimers. The structures of the NDIs were significantly simpler and more accessible than those of other NDIs. The findings evidence that non-core substituted NDIs can exhibit strong fluorescence in the solid state and provide a new pathway to improve photophysical properties of NDIs.

Correction: Unusual design strategy for a stable and soluble high-molecular-weight copper(I) arylacetylide polymer.

Correction for 'Unusual design strategy for a stable and soluble high-molecular-weight copper(I) arylacetylide polymer' by Li Jiang et al., Chem. Commun., 2021, 57, 12004-12007, DOI: 10.1039/D1CC05080J.

Self-assembly of chiral foldamers with alternating hydrophilic and hydrophobic side chains into acid-sensitive and solvent-exchangeable vesicular particles.

It is difficult for the same molecule to self-assemble into stable vesicular particles in water and aliphatic hydrocarbon (oil), respectively. Here we demonstrated that chiral oligo(methylene-p-phenyleneethynylene)s with alternating hydrophilic and hydrophobic side chains were able to self-assemble into vesicular particles independent of solvent polarity. These particles were well dispersed in aliphatic hydrocarbon, alcohol or water for at least one month at room temperature, and readily transferred from organic to aqueous phases via dialysis. They displayed a noticeable response to the acidity of the aqueous phase, and could be used as simple cargos for loading hydrophilic or hydrophobic molecules in aqueous cores, which were different from loading in polymersomes. The vesicular particles loaded with hydrophobic paclitaxel exhibited comparable anti-HeLa cell activity to free paclitaxel in vitro.

Unusual design strategy for a stable and soluble high-molecular-weight copper(I) arylacetylide polymer.

A long enough side chain, electron-withdrawing ester groups and a chloroform solvent in the polymerization can together relay solubility and/or stability to the copper(I) arylacetylide polymer.

A naphthyridine-indole ligand for selective stabilization of G-quadruplexes and conformational conversion of hybrid topology.

The development of ligands to stabilize G-quadruplexes (G4s) or induce G4s to transition from metastable topology to stable topology is a potential strategy for inhibiting cancer cell proliferation. In this study, a novel G-quadruplex (G4) ligand based on a naphthyridine scaffold with two indole pendants, L5-DA, is reported to convert hybrid to the parallel topology. Circular dichroism (CD) and fluorescence spectroscopies were used to investigate the interactions between L5-DA and G4s. The CD spectra revealed that the L5-DA induced the conformational conversion from hybrid topologies to parallel topologies with a melting temperature increase of more than 30 °C. According to Förster resonance energy transfer assays, the presence of excess duplex competitor had no effect on the ligand-induced stabilization of the hybrid topology, confirming the L5-DA's selectivity for G4s over ds26. With IC50 values of 4.3 µM, the ligand showed significant cytotoxicity against HeLa cells and effectively induced growth inhibition and apoptosis in HeLa cells. Immunofluorescence microscopy revealed an increase in BG4 foci in the presence of the L5-DA, confirming ligand-induced G4s stabilization in HeLa cells. According to these results, the combination of naphthyridine and indole scaffold was an effective design strategy for G4s stabilization and conformational conversion of metastable G4 topology for inhibiting cancer cell growth.

Hydrogen-bond-driven dimers of naphthyridine derivatives for selective identification of DNA G-quadruplexes.

G-quadruplex (GQ) ligands as potential anti-cancer drugs have received extensive attention. Large aromatic systems are usually considered in the design of the ligands to improve the binding with GQs, which are typically constructed by the combination of small modules with covalent bonds. In this study, we presented a non-covalent bond approach to construct GQ ligands with an extended planar structure. The ligands were stable dimers assembled through quadruplex intermolecular hydrogen bonds between two molecules of naphthyridine derivatives. Spectroscopic analyses showed that dimeric ligands could stabilize GQs with an increase of the melting temperature up to 12 °C and induced conformational conversion of hybrid GQs. Confocal fluorescence microscopy confirmed the enrichment of naphthyridine ligands in the nucleus. The ligands showed moderate cytotoxicity against HeLa cells with an IC50 value of 7.5 µg mL-1 and effectively induced growth inhibition and apoptosis in HeLa cells. These results confirmed the feasibility of the quick building of GQ ligands through intermolecular interactions of simple molecules that are easily obtained during synthesis, which is helpful for GQ ligand design and quick establishment of a ligand library through the self-assembly of easily available molecular components.

Self-assembly of chiral oligo(methylene-p-phenylene-ethynylene)s into vesicle-like particles independent of hydrophobicity/hydrophilicity of side chains and solvents.

It is difficult for the same molecule to form vesicular assemblies in water and alipatic hydrocarbon (oil), respectively. Here, we report that chiral oligo(methylene-p-phenyleneethynylene)s bearing hydrophobic or hydrophilic side chains can take extended conformations to self-assemble into vesicle-like particles in a hydrophobic or hydrophilic solvent system. The self-assembly processes are highly independent of molecular design and chemical environments. Based on the analyses of TEM, UV, CD and PXRD data, it is plausible to expect that the vesicular membranes could be stabilized together by π-π stacking interactions between foldamer backbones and collective van der Waals interactions between side chains.

Topological conversion of human telomeric G-quadruplexes from hybrid to parallel form induced by naphthalene diimide ligands.

G-quadruplexes (GQs) have become promising anti-cancer therapeutic targets, which are formed by the folding of a guanine-rich repeat DNA/RNA sequence at human telomeres or oncogene promoters. Polymorphism has been observed for the folding topologies of intramolecular GQs. Here we report the topological conversion of human telomeric GQ induced by naphthalene diimide (NDI) ligands in K+ solution. The ligands selectively induce metastable hybrid-type GQs to highly stable parallel-type GQ at physiological temperature (37 °C) in dilute aqueous solutions and under crowding conditions that mimic cellular bioenvironment. According to spectroscopic analyses, the topological conversion is speculated to undergo stepwise unfolding of hybrid-type GQ through intermediate states to parallel-type GQ. The results will prompt further studies on the designs of ligands with GQ conformation regulation functions and nanotechnological systems based on nucleic acids with dynamic regulation of GQ conformation.

Developing substrate-based small molecule fluorescent probes for super-resolution fluorescent imaging of various membrane transporters.

Super-resolution imaging technology has been a powerful tool for revealing fine biological structures and functions. Its high-quality imaging always needs highly accurate labeling. Here, by exploiting the high specificity and affinity of natural substrates to transporters, we developed one set of substrate-based small molecule fluorescent probes for labeling membrane transporters. A glucose-based probe (Glu-probe) and tyrosine-based probe (Tyr-probe) were synthesized as two examples. Confocal imaging showed that the Glu-probe could label glucose transporters on live cells by being stuck into the binding site. Compared with antibody-probe labeling, the labeling advantages of the Glu-probe were revealed. High specificity of the Glu-probe or Tyr-probe was examined by a colocalization experiment and glucose replacement or amino acid (AA) blocking. The synthetic probes were also tested on imaging HeLa cells to confirm their wide labeling application. Additionally, we found that membrane transporters were mostly in the clustered state on cellular membranes, changing their assembly pattern to regulate the transport effectiveness. These results suggest that the substrate-based probes can serve as valuable tools for investigating the spatial information of membrane transporters.

An Optically Active Polymer for Broad-Spectrum Enantiomeric Recognition of Chiral Acids.

Recognition of enantiomers of chiral acids by anion-π or lone pair-π interactions has not yet been investigated but is a significant and attractive challenge. This study reports an optically active polymer-based supramolecular system with capabilities of discriminating enantiomers of various chiral acids. The polymer featuring alternate π-acidic naphthalenediimides (NDIs) and methyl l-phenylalaninates in the backbone exhibits an unprecedented slow self-assembly process that is susceptible to perturbation by various chiral acids. Thus, the combination of anion-π or lone pair-π interactions and sensitivity of the polymeric self-assembly process to external chiral species endows the system with recognition capabilities. This is the first time that anion-π or lone pair-π interactions have been applied in the recognition of enantiomers of various chiral acids with a single system. The results shed light on new strategies for material design by integrating π-acidic aromatic systems and chiral building blocks to afford relevant advanced functions.

Sequence-Dependent Self-Assembly of Chiral Polyimides.

Sequence-defined chiral polyimides comprising identical asymmetric diamine monomers arranged in different directions along the main chain were designed and prepared. These new sequence-defined polymers exhibit sequence-dependent self-assembly behaviors and responses to ibuprofen enantiomers, as revealed by their chiroptical spectra and gelation properties. For the first time, the self-assembly of polymers and their interactions with guest molecules have been successfully controlled by means of the directional arrangement of the monomers in their polymer backbones.

Hexagonal Lyotropic Liquid Crystal from Simple "Abiotic" Foldamers.

The motivation of foldamer chemistry is to identify novel building blocks that have the potential to imitate natural species. Peptides and peptide mimetics can form stable helical conformations and further self-assemble into diverse aggregates in water, where it is difficult to isolate a single helix. In contrast, most "abiotic" foldamers may fold into helical structures in solution, but are difficult to assemble into tertiary ones. It remains a challenge to obtain "abiotic" species similar to peptides. In this paper, a novel foldamer scaffold, in which p-phenyleneethynylene units are linked by chiral carbon atoms, was designed and prepared. In very dilute solutions, these oligomers were random coils. The hexamer and octamers could form a hexagonal lyotropic liquid crystal (LC) in CH2Cl2 when the concentrations reached the critical values. The microscopic observations indicated that they could assemble into the nanofibers in the LC. Interestingly, after some LC phases were diluted at room temperature, the nanofibers could be preserved. The good stabilities of the assemblies are possibly attributed to a more compact backbone and more rigid side chains.

The determination of the absolute configuration of a chiral 2,3'-diindolylarylmethane by NMR spectroscopy.

We present the determination of the absolute configuration of a chiral 2,3'-diindolylarylmethane 1 by using the combination of NMR spectroscopic and circular dichroism techniques. The results would be useful for the future study of the effect of chirality on the biological activity of 2,3'-diindolylarylmethanes.

Supramolecular hydrogels derived from cyclic amino acids and their applications in the synthesis of Pt and Ir nanocrystals.

New simple hydrogelators containing the structural features of cyclic amino acids were investigated for water gelation through H-bonds from carboxylic acids and amino groups, showing for the first time the use of a single amino acid as a hydrogelator. The hydrogels were used for the synthesis of Pt and Ir nanoparticles, showing for the first time that a supramolecular hydrogel was used for the in situ formation of Pt and Ir nanocrystals.

Dehydrogenation and dehalogenation of amines in MALDI-TOF MS investigated by isotopic labeling.

Secondary and tertiary amines have been reported to form [M-H](+) that correspond to dehydrogenation in matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS). In this investigation, we studied the dehydrogenation of amines in MALDI-TOF MS by isotopic labeling. Aliphatic amines were labeled with deuterium on the methylene of an N-benzyl group, which resulted in the formation of [M-D](+) and [M-H](+) ions by dedeuteration and dehydrogenation, respectively. This method revealed the proton that was removed. The spectra of most tertiary amines with an N-benzyl group showed high-intensity [M-D](+) and [M-H](+) ion peaks, whereas those of secondary amines showed low-intensity ion peaks. Ratios between the peak intensities of [M-D](+) and [M-H](+) greater than 1 suggested chemoselective dehydrogenation at the N-benzyl groups. The presence of an electron donor group on the N-benzyl groups enhanced the selectivity. The dehalogenation of amines with an N-(4-halobenzyl) group was also observed alongside dehydrogenation. The amino ions from dehalogenation can undergo second dehydrogenation. These results provide the first direct evidence about the position at which dehydrogenation of an amine occurs and the first example of dehalogenation of haloaromatic compounds in MALDI-TOF MS. These results should be helpful in the structural identification and elucidation of synthetic and natural molecules.

In situ gel-to-crystal transition and synthesis of metal nanoparticles obtained by fluorination of a cyclic ß-aminoalcohol gelator.

A new fluorinated version of a cyclic ß-aminoalcohol gelator derived from 1,2,3,4-tetrahydroisoquinoline is presented. The gelator is able to gel various nonprotic solvents through OH⋅⋅⋅N hydrogen bonds and additional CH⋅⋅⋅F interactions due to the introduction of fluorine. A bimolecular lamellar structure is formed in the gel phase, which partly preserves the pattern of molecular organization in the single crystal. The racemate of the chiral gelator shows lower gelation ability than its enantiomer because of a higher tendency to form microcrystals, as shown by X-ray diffraction analysis. The influence of fluorination on the self-assembly of the gelator and the properties of the gel was investigated in comparison to the original fluorine-free gel system. The introduction of fluorine brings two new features. The first is good recognition of o-xylene by the gelator, which induces an in situ transition from gels of o-xylene and of an o-xylene/toluene mixture to identical single crystals with unique tubular architecture. The second is the enhanced stability of the toluene gel towards ions, including quaternary ammonium salts, which enables the preparation of a stable toluene gel in the presence of chloroaurate or chloroplatinate. The gel system can be used as a template for the synthesis of spherical gold nanoparticles with a diameter of 5 to 9 nm and wormlike platinum nanostructures with a diameter of 2 to 3 nm and a length of 5 to 12 nm. This is the first example of a synthesis of platinum nanoparticles in an organogel medium. Therefore, the appropriate introduction of a fluorine atom and corresponding nonbonding interactions into a known gelator to tune the properties and functions of a gel is a simple and effective tactic for design of a gel system with specific targets.

Donor-induced helical inversion of 1,1'-binaphthyl connecting with two molybdenum complexes.

An atropisomeric biaryl molecule with a given absolute configuration could present two opposite helical conformations through the rotation around C-C single bond. To the best of our knowledge, the biaryl system is the simplest helical inversion model apart from stereomutation between two enantiomers. Herein, we first report such true helical inversion phenomena of biaryl compounds. Two [Mo(VI)O(2)(L)]-type complexes, in which L is a tridentate dioxoanionic pyridine O,N,O-ligand, are coalesced on the 2,2',3,3'-positions of an (R)-1,1'-binaphthyl unit and an intramolecular dioxo bridge is formed by two Mo=O⋅⋅⋅Mo interactions. Exterior strong donors can coordinate to molybdenum to interrupt this dioxo bridge and inversions from negative to positive chirality are explicitly observed by circular dichroism spectroscopy, consistent with single-crystal X-ray diffraction analyses.