Chuanqi Zhao

Ionic liquids as precursors for highly luminescent, surface-different nitrogen-doped carbon dots used for label-free detection of Cu2+/Fe3+ and cell imaging

Carbon nanodots (C-Dots) have attracted much attention in recent years due to their low cost, ready scalability, excellent chemical stability, biocompatibility and multicolor luminescence. Here, we report a facile strategy for producing highly luminescent, surface-different nitrogen-doped carbon dots (C-Dots) by using different ionic liquids (ILs). Intriguingly, the surface-different C-Dots show different selectivity for Cu(2+) and Fe(3+). To the best of our knowledge, this is the first example which shows that ILs are excellent precursors for producing luminescent nanomaterial used for detection of different metal ions. The resultant nitrogen-doped C-Dots are highly photoluminescent and can be used for multicolor bioimaging. Most notable, by taking different ILs as precursors, we obtain surface-different C-Dots, which can be directly used for selective detection of Cu(2+) and Fe(3+) without any modification. These C-Dots based sensors exhibit high sensitivity and selectivity and the sensing process can be easily accomplished with one-step rapid operation. More importantly, compared with other method using QDs, organic dyes and organic solvent, this strategy is much more eco-friendly. This work may offer a new approach for developing low cost and sensitive C-Dots-based sensors for biological and environmental applications.

Insights into the biomedical effects of carboxylated single-wall carbon nanotubes on telomerase and telomeres

Both human telomeric G-rich and C-rich DNA have been considered as specific drug targets for cancer therapy. However, due to i-motif structure instability and lack of specific binding agents, it remains unclear whether stabilization of telomeric i-motif can inhibit telomerase activity. Single-walled carbon nanotubes (SWNTs) have been reported as the first ligand that can selectively stabilize human telomeric i-motif DNA. Here we report that SWNTs can inhibit telomerase activity through stabilization of i-motif structure. The persistence of i-motif and the concomitant G-quadruplex eventually leads to telomere uncapping and displaces telomere-binding proteins from telomere. The dysfunctional telomere triggers DNA damage response and elicits upregulation of p16 and p21 proteins. This is the first example that SWNTs can inhibit telomerase activity and interfere with the telomere functions in cancer cells. These results provide new insights into understanding the biomedical effects of SWNTs and the biological importance of i-motif DNA.

Targeting Human Telomeric Higher-Order DNA: Dimeric G-Quadruplex Units Serve as Preferred Binding Site

Long human telomeric fragments can form stable, higher-order G-quadruplex structures, recently identified in human cells, which are potential drug targets. However, there are very few examples of ligand binding to higher-order G-quadruplexes, and all the reported ligands are proposed to bind at the cleft between two G-quadruplexes. Here we report that zinc-finger-like chiral supramolecular complexes prefer binding to higher-order G-quadruplexes over a single G-quadruplex, with ∼200-fold higher selectivity. To our knowledge, this is the first example of a ligand that can distinguish higher-order G-quadruplexes from a single G-quadruplex with such high selectivity. Further studies indicate that the nanosized chiral complex would bind to two well-matched G-quadruplex units, instead of binding at the cleft between the two G-quadruplexes. These results provide new insights into the targeting of higher-order G-quadruplex ligands. Our work illustrates that dimeric G-quadruplex units can be ligand-preferred binding sites.

DNA Loop Sequence as the Determinant for Chiral Supramolecular Compound G-Quadruplex Selectivity

It is important to develop G-quadruplex binding agents that can discriminate between different quadruplexes. Recently we reported the first example that a chiral supramolecular complex can selectively stabilize human telomeric G-quadruplex among different G-quadruplex and duplex DNA, and the two enantiomers show different inhibition effect on telomerase activity. Here, we report that DNA loop sequence can be determinant for this chiral complex G-quadruplex selectivity. Adenine in the diagonal loop plays an important role in G-quadruplex hybrid structural transition, thus, it strongly influences the chiral complex induced DNA structural transition. The complexs preference for human telomeric DNA and its chiral selectivity prompted us to investigate whether the two enantiomers, M and P, can show different effects on cancer cells. The P enantiomers chiral selectivity has been demonstrated in cancer cells by telomere shortening, beta-galactosidase activity, and up-regulation of cyclin-dependent kinase inhibitors p16 and p21.

Chiral metallo-supramolecular complexes selectively induce human telomeric G-quadruplex formation under salt-deficient conditions.

Chiral molecular recognition of human telomeric DNA is important for rational drug design and developing structural probes of G-quadruplexes. Here we report that a chiral supramolecular complex can selectively induce human telomeric G-quadruplex formation and discriminate different G-quadruplex sequences under salt-deficient conditions studied by circular dichroism (CD), UV meltings, stopped-flow spectroscopy, fluorescence resonance energy transfer, enzyme cleavage, and gel electrophoresis. P-enantiomer induced G-quadruplex formation is fast and does not require a large excess of P enantiomer. More importantly, this chiral compound induces loop sequence-dependent G-quadruplex formation.

Design of Surface-Active Artificial Enzyme Particles to Stabilize Pickering Emulsions for High-Performance Biphasic Biocatalysis

Surface-active artificial enzymes (SAEs) are designed and constructed by a general and novel strategy. These SAEs can simultaneously stabilize Pickering emulsions and catalyze biphasic biotransformation with superior enzymatic stability and good re-usability; for example, for the interfacial conversion of hydrophobic p-nitrophenyl butyrate into yellow water-soluble p-nitrophenolate catalyzed by esterase-mimic SAE.

Individual Surface‐Engineered Microorganisms as Robust Pickering Interfacial Biocatalysts for Resistance‐Minimized Phase‐Transfer Bioconversion

A powerful strategy for long-term and diffusional-resistance-minimized whole-cell biocatalysis in biphasic systems is reported where individually encapsulated bacteria are employed as robust and recyclable Pickering interfacial biocatalysts. By individually immobilizing bacterial cells and optimizing the hydrophobic/hydrophilic balance of the encapsulating magnetic mineral shells, the encased bacteria became interfacially active and locate at the Pickering emulsion interfaces, leading to dramatically enhanced bioconversion performances by minimizing internal and external diffusional resistances. Moreover, in situ product separation and biocatalyst recovery was readily achieved using a remote magnetic field. Importantly, the mineral shell effectively protected the entire cell from long-term organic-solvent stress, as shown by the reusability of the biocatalysts for up to 30 cycles, while retaining high stereoselective catalytic activities, cell viabilities, and proliferative abilities.

Contrasting enantioselective DNA preference: chiral helical macrocyclic lanthanide complex binding to DNA

There is great interest in design and synthesis of small molecules which selectively target specific genes to inhibit biological functions in which particular DNA structures participate. Among these studies, chiral recognition has been received much attention because more evidences have shown that conversions of the chirality and diverse conformations of DNA are involved in a series of important life events. Here, we report that a pair of chiral helical macrocyclic lanthanide (III) complexes, (M)-Yb[LSSSSSS]3+ and (P)-Yb[LRRRRRR]3+, can enantioselectively bind to B-form DNA and show remarkably contrasting effects on GC-rich and AT-rich DNA. Neither of them can influence non-B-form DNA, nor quadruplex DNA stability. Our results clearly show that P-enantiomer stabilizes both poly(dG-dC)2 and poly(dA-dT)2 while M-enantiomer stabilizes poly(dA-dT)2, however, destabilizes poly(dG-dC)2. To our knowledge, this is the best example of chiral metal compounds with such contrasting preference on GC- and AT-DNA. Ligand selectively stabilizing or destabilizing DNA can interfere with protein–DNA interactions and potentially affect many crucial biological processes, such as DNA replication, transcription and repair. As such, bearing these unique capabilities, the chiral compounds reported here may shed light on the design of novel enantiomers targeting specific DNA with both sequence and conformation preference.

Metallosupramolecular complex targeting an α/β discordant stretch of amyloid β peptide

The accumulation of amyloid β-peptide (Aβ) is one of the pathological hallmarks of Alzheimers disease (AD). Developing Aβ amyloid inhibitors has received much attention. Most reported Aβ inhibitors are small organic molecules or peptides. Here we use a cell-based novel Aβ–enhanced cyan fluorescent protein (ECFP) fluorescent fusion inhibitor screen system, biochemical and biophysical approaches and in vivo studies to identify two zinc-finger-like triple-helical metallo-supramolecular cylinders, [Ni2L3]4+ and [Fe2L3]4+, that can strongly inhibit Alzheimers disease β-amyloid aggregation. Further studies indicate that the two metallo-supramolecular cylinders are specifically targeting the α/β-discordant stretch and reducing Aβ cytotoxicity. In vivo studies demonstrate that these complexes can ameliorate spatial memory deficits in a transgenic mouse model and decrease the insoluble Aβ level. This is the first demonstration that zinc-finger-like metallo-supramolecular cylinders can be Aβ aggregation inhibitors that specifically target an α/β-discordant stretch. Our work will prompt design and screening of metallo-supramolecular complexes as potential therapeutic agents for AD.

Enzymatic Manipulation of DNA‐Modified Gold Nanoparticles for Screening G‐Quadruplex Ligands and Evaluating Selectivities

Enzymatic manipulation of DNA on well-dispersed gold nanoparticles (AuNPs) offers an ideal system for high-throughput screening of G-quadruplex ligands and evaluation of their selectivity with respect to duplex and quadruplex DNA (see figure). This work has implications for the future use of nanoparticle-based technologies in the discovery of potential cancer therapeutic agents.