Hydration Changes for DNA Intercalation Reactions

The hydration changes that accompany the DNA binding of five intercalators (ethidium, propidium, proflavine, daunomycin, and 7-aminoactinomycin D) were measured by the osmotic stress method with use of the osmolytes betaine, sucrose, and triethylene glycol. Water uptake was found to accompany complex formation for all intercalators except ethidium. The difference in the number of bound water molecules between the complex and the free reactants (Δnw) was different for each intercalator. The values found for Δnw were the following:  propidium, +6; daunomycin, +18; proflavine, +30; and 7-aminoactinomycin D, +32. For ethidium binding to DNA a value of Δnw = +0.25(±0.3) was found, indicating that within experimental error no water was released or taken up upon complex formation. Intercalation association constants measured in D2O were found to increase relative to values measured in H2O for all compounds except ethidium. A positive correlation between the ratio of binding constants (KD2O/KH2O) and Δnw was found. These combined studies identify water as an important thermodynamic participant in the formation of certain intercalation complexes

Natural DNA-Modified Graphene/Pd Nanoparticles as Highly Active Catalyst for Formic Acid Electro-Oxidation and for the Suzuki Reaction

Natural DNA has been considered as a building block for developing novel functional materials. It is abundant, renewable, and biodegradable and has a well-defined structure and conformation with many unique features, which are difficult to find in other polymers. Herein, calf thymus DNA modified graphene/Pd nanoparticle (DNA-G-Pd) hybrid materials are constructed for the first time using DNA as a mediator, and the prepared DNA-G-Pd hybrid shows high catalytic activity for fuel cell formic acid electro-oxidation and for organic Suzuki reaction. The main advantages of using DNA are not only because the aromatic nucleobases in DNA can interact through π–π stacking with graphene basal surface but also because they can chelate Pd via dative bonding in such defined sites along the DNA lattice. Our results indicate that isolated, homogeneous, and ultrafine spherical Pd nanoparticles are densely in situ decorated on DNA-modified graphene surfaces with high stability and dispersibility. The prepared DNA-G-Pd hybrid has much greater activity and durability for formic acid electro-oxidation than the commercial Pd/C catalyst and polyvinylpyrrolidone-mediated graphene/Pd nanoparticle (PVP-G-Pd) hybrid used for direct formic acid fuel cells (DFAFCs). Besides, the DNA-G-Pd hybrid can also be an efficient and recyclable catalyst for the organic Suzuki reaction in aqueous solution under aerobic conditions without any preactivation. Since DNA can chelate various transition metal cations, this proof-of-concept protocol provides the possibility for the tailored design of other novel catalytic materials based on graphene with full exploitation of their properties

G‑Quadruplexes Form Ultrastable Parallel Structures in Deep Eutectic Solvent

G-quadruplex DNA is highly polymorphic. Its conformation transition is involved in a series of important life events. These controllable diverse structures also make G-quadruplex DNA a promising candidate as catalyst, biosensor, and DNA-based architecture. So far, G-quadruplex DNA-based applications are restricted done in aqueous media. Since many chemical reactions and devices are required to be performed under strictly anhydrous conditions, even at high temperature, it is challenging and meaningful to conduct G-quadruplex DNA in water-free medium. In this report, we systemically studied 10 representative G-quadruplexes in anhydrous room-temperature deep eutectic solvents (DESs). The results indicate that intramolecular, intermolecular, and even higher-order G-quadruplex structures can be formed in DES. Intriguingly, in DES, parallel structure becomes the G-quadruplex DNA preferred conformation. More importantly, compared to aqueous media, G-quadruplex has ultrastability in DES and, surprisingly, some G-quadruplex DNA can survive even beyond 110 °C. Our work would shed light on the applications of G-quadruplex DNA to chemical reactions and DNA-based devices performed in an anhydrous environment, even at high temperature

Biophysical Studies on the Full-Length Human Cyclin A₂: Protein Stability and Folding/Unfolding Thermodynamics

Human cyclin A2 participates in cell cycle regulation, DNA replication, and transcription. Its overexpression has been implicated in the development and progression of a variety of human cancers. However, cyclin A2 or its truncated form is very unstable in the absence of binding partner, which makes it difficult to get a deep insight of structural basis of the interactions. Therefore, biophysical studies of the full-length human cyclin A2 would provide important information regarding protein stability and folding/unfolding process. To the best of our knowledge, these have not been reported. In this report, we found that cyclin A2 stability depended on pH, salt concentration, and denaturant concentration, and low concentration denaturant increased cyclin A2 stability studied by UV melting, fluorescence spectroscopy, limited proteolysis, and circular dichroism. The therrmal unfolding/folding process could be described by Lumry−Eyring model: N ↔ I → D, followed by decreasing α-helix content and forming intermolecular antiparallel pleated β-sheet structures in the aggregate. Our results are of importance for studying the interactions between cyclin A2 and therapeutic agents, such as small molecules or peptides, because cyclin A2 is very unstable in the absence of its biological associated kinases

“Plug and Play” Logic Gates Based on Fluorescence Switching Regulated by Self-Assembly of Nucleotide and Lanthanide Ions

Molecular logic gates in response to chemical, biological, or optical input signals at a molecular level have received much interest over the past decade. Herein, we construct “plug and play” logic systems based on the fluorescence switching of guest molecules confined in coordination polymer nanoparticles generated from nucleotide and lanthanide ions. In the system, the addition of new modules directly enables new logic functions. PASS 0, YES, PASS 1, NOT, IMP, OR, and AND gates are successfully constructed in sequence. Moreover, different logic gates (AND, INH, and IMP) can be constructed using different guest molecules and the same input combinations. The work will be beneficial to the future logic design and expand the applications of coordination polymers

Near-Infrared Upconversion Controls Photocaged Cell Adhesion

Dynamic control of cell-surface interactions with near-infrared (NIR) light is particularly attractive for regeneration medicine and cell-based therapy. Herein we successfully achieve NIR-controlled cell adhesion with upconversion nanoparticles (UCNPs) based programmable substrate. The UCNPs can harvest the biocompatible NIR light and convert it into local UV light, which results in cleavage of the photocaged linkers and on-demand release of adhesive cells. The strategy also enables the feasibility of deep-tissue photocontrol of cell adhesion on substrate. Our work may open a new avenue for design of UCNP-based cell scaffolds to dynamically manipulate cell–matrix and cell–cell interactions

Polyoxometalate-based Rewritable Paper

Polyoxometalate-based Rewritable Pape

A Simple, Universal Colorimetric Assay for Endonuclease/Methyltransferase Activity and Inhibition Based on an Enzyme-Responsive Nanoparticle System

An enzyme responsive nanoparticle system that uses a DNA−gold nanoparticle (AuNP) assembly as the substrate has been developed for the simple, sensitive, and universal monitoring of restriction endonucleases in real time. This new assay takes advantage of the palindromic recognition sequence of the restriction nucleases and the unique optical properties of AuNPs and is simpler than the procedure previously described by by Xu et al. (Angew. Chem. Int. Ed. Engl. 2007, 46, 3468−3470). Because it involves only one type of ssDNA modified AuNPs, this assay can be directed toward most of the endonucleases by simply changing the recognition sequence found within the linker DNA. In addition, the endonuclease activity could be quantitatively analyzed by the value of the reciprocal of hydrolysis half time (t1/2−1). Furthermore, our new design could also be applied to the assay of methyltransferase activity since the methylation of DNA inhibits its cleavage by the corresponding restriction endonuclease, and thus, this new methodology can be easily adapted to high-throughput screening of methyltransferase inhibitors

Enzyme Mimicry for Combating Bacteria and Biofilms

ConspectusBacterial infection continues to be a growing global health problem with the most widely accepted treatment paradigms restricted to antibiotics. However, antibiotics overuse and misuse have triggered increased multidrug resistance, frustrating the therapeutic outcomes and leading to higher mortalities. Even worse, the tendency of bacteria to form biofilms on living and nonliving surfaces further increases the difficulty in confronting bacteria because the extracellular matrix can act as a robust barrier to prevent the penetration of antibiotics and resist environmental stress. As a result, the inability to completely eliminate bacteria and biofilms often leads to persistent infection, implant failure, and device damage. Therefore, it is of paramount importance to develop alternative antimicrobial agents while avoiding the generation of bacterial resistance. Taking lessons from natural enzymes for destroying cellular structural integrity or interfering with metabolisms such as proliferation, quorum sensing, and programmed death, the construction of artificial enzymes to mimic the enzyme functions will provide unprecedented opportunities for combating bacteria. Moreover, compared to natural enzymes, artificial enzymes possess much higher stability against stringent conditions, easier tunable catalytic activity, and large-scale production for practical use.In this Account, we will focus on our recent progress in the design and synthesis of artificial enzymes as a new generation of “antibiotics”, which have been demonstrated as promising applications in planktonic bacteria inactivation, wound/lung disinfection, as well as biofilm inhibition and dispersion. First, we will introduce direct utilization of the intrinsic catalytic activities of artificial enzymes without dangerous chemical auxiliaries for killing bacteria under mild conditions. Second, to avoid the toxicity caused by overdose of H₂O₂ in conventional disinfections, we leveraged artificial enzymes with peroxidase-mimic activities to catalyze the generation of hydroxyl radicals at low H₂O₂ levels while achieving efficient antibacterial outcomes. Importantly, the feasibility of these artificial enzymes was further demonstrated in vivo by mitigating mice wound and lung disinfection. Third, by combining artificial enzymes with stimuli-responsive materials, smart on-demand therapeutic modalities were constructed for thwarting bacteria in a controllable manner. For instance, a photoswitchable “Band-Aid”-like hydrogel doped with artificial enzymes was developed for efficiently killing bacteria without compromising mammal cell proliferation, which was promising for accelerating wound healing. Lastly, regarding the key roles that extracellular DNAs (eDNAs) play in maintaining biofilm integrity, we further designed a multinuclear metal complex-based DNase-mimetic artificial enzyme toward cleaving the eDNA for inhibiting biofilm formation and dispersing the established biofilms. We expect that our rational designs would boost the development of artificial enzymes with different formulations as novel antibacterial agents for clinical and industrial applications

Luminescent Rare-Earth Complex Covalently Modified Single-Walled Carbon Nanotubes: Design, Synthesis, and DNA Sequence-Dependent Red Luminescence Enhancement

A novel luminescent Eu3+-complex functionalized single-walled carbon nanotube (SWNT) was constructed by covalent linkage through a diaminotriethylene glycol linker. TGA, FT-IR, and SEM demonstrated successful attachment of the Eu3+-complex onto the SWNT surface. Spectroscopic methods showed that the SWNT-Eu3+ complex is highly luminescent and DNA can further enhance the red luminescence, and the enhancement depends on DNA sequence and form. The order of the enhancement follows: AT alternative dsDNA > nonalternative AT dsDNA > GC dsDNA > ssDNA dA > ssDNA dT > ssDNA (GT)20