Polyoxometalate-Guanosine Monophosphate Hydrogels with Haloperoxidase-like Activity for Antibacterial Performance.

Haloperoxidases represent an important class of enzymes that nature adopts as a defense mechanism to combat the colonial buildup of microorganisms on surfaces, commonly known as biofouling. Subsequently, there has been tremendous focus on the development of artificial haloperoxidase mimics that can catalyze the oxidation of X- (halide ion) in the presence of H2O2 to form HOX. The natural intermediate HOX disrupts the bacterial quorum sensing, thus preventing biofilm formation. Herein, we report a simple method for the formation of supramolecular hydrogels through the self-assembly of Keggin-structured polyoxometalates, phosphotungstic acid, and silicotungstic acid with the small biomolecule guanosine monophosphate (GMP) in an aqueous medium. The polyoxometalate-GMP hydrogels that contained highly entangled nanofibers were mechanically robust and showed thixotropic properties. The gelation of the polyoxometalates with GMP not only rendered manifold enhancement in biocompatibility but also the fibril network in the hydrogel provided high water wettability and the polyoxometalates acted as an efficient haloperoxidase mimic to trigger oxidative iodination, as demonstrated by a haloperoxidase assay. The antifouling activity of the phosphotungstic acid-GMP hydrogel was demonstrated against both Gram-positive and Gram-negative bacteria, which showed enhanced antibacterial performance of the hydrogel as compared to the polyoxometalate alone. We envision that the polyoxometalate-GMP hydrogels may facilitate mechanically robust coatings in a simple pathway that can be useful for antifouling applications.

Cobalt-Adenosine Monophosphate Supramolecular Hydrogel with pH-Responsive Multi-Nanozymatic Activity.

Self-assembled metal-ion cross-linked multifunctional hydrogels are gaining a lot of attention in the fields of biomedical and biocatalysis. Herein, we report a heat-triggered metallogel that was spontaneously formed by the self-assembly of adenosine 5'-monophosphate (AMP) and cobalt chloride, accompanied by a color transition depicting an octahedral to tetrahedral transition at high temperature. The hydrogel shows excellent stability in a wide pH window from 1 to 12. The metallogel is being exploited as a multienzyme mimic, exhibiting pH-responsive catalase and peroxidase activity. Whereas catalase mimicking activity was demonstrated by the hydrogel under neutral and basic conditions, it shows peroxidase mimicking activity in an acidic medium. The multifunctionality of the synthesized metallogel was further demonstrated by phenoxazinone synthase-like activities. Owing to its catalase-mimicking activity, the metallogel could effectively reduce the oxidative stress produced in cells due to excess hydrogen peroxide by degrading H2O2 to O2 and H2O under physiological conditions. The biocompatible metallogel could prevent cell apoptosis by scavenging reactive oxygen species. A green and simple synthetic strategy utilizing commonly available biomolecules makes this metallogel highly attractive for catalytic and biomedical applications.

Photoinduced Enhanced Decomposition of TBHP: A Convenient and Greener Pathway for Aqueous Domino Synthesis of Quinazolinones and Quinoxalines.

Catalyst-free photoinduced processes in aqueous medium represent significant advancement toward development of green and sustainable pathways in organic synthesis. tert-Butyl hydroperoxide (TBHP) is a widely used oxidant in organic reactions, where the decomposition of TBHP into its radicals by metal catalysts or other reagents is a key factor for efficient catalytic outcome. Herein, we report a simple and environmentally friendly visible light-promoted synthetic pathway for the synthesis of N-heterocyclic moieties, such as quinazolinones and quinoxalines, in the presence of TBHP as an oxidizing agent in aqueous medium that requires no catalysts/photocatalysts. The enhanced rate of decomposition to generate free radicals from TBHP upon visible light irradiation is the driving force for the domino reaction.

Cationic Organic Nanoaggregates as AIE Luminogens for Wash-Free Imaging of Bacteria and Broad-Spectrum Antimicrobial Application.

The increase in the use of bactericides is a matter of grave concern and a serious threat to human health. The present situation demands rapid and efficient detection and elimination of antibiotic-resistant microbes. Herein, we report the synthesis of a simple C3-symmetric molecular system (TGP) with an intrinsic positive charge through a single-step Schiff base condensation. In a water-dimethyl sulfoxide (DMSO) solvent mixture (80:20 v/v), TGP molecules self-aggregate to form spherical nanoparticles with a positively charged surface that displays efficient fluorescence owing to the aggregation-induced emission (AIE) phenomenon. Both Gram-positive and Gram-negative bacteria could be effectively detected through "turn-off" fluorescence spectroscopy as the electrostatic interaction of the resultant nanoaggregates with the negatively charged bacterial surface induced quenching of fluorescence of the nanoparticles. The fluorescence analysis and steady-state lifetime studies of TGP nanoparticles suggest that a nonradiative decay through photoinduced electron transfer from the nanoparticles to the bacterial surface leads to effective fluorescence quenching. Further, the TGP nanoaggregates demonstrate potent antimicrobial activity against microbes such as multidrug-resistant bacteria and fungi at a concentration as low as 74 µg/mL. A combination of factors including ionic surface characteristics of the nanoparticles for strong electrostatic binding on the bacterial surface followed by possible photoinduced electron transfer from the nanoaggregates to the bacterial membrane and enhanced oxidative stress in the membrane resulting from reactive oxygen species (ROS) generation is found accountable for the high antimicrobial activity of the TGP nanoparticles. The effective disruption of membrane integrity in both Gram-positive and Gram-negative bacteria upon interaction with the nanoaggregates can be observed from field emission scanning electron microscopy (FESEM) studies. The development of simple pathways for the molecular design of multifunctional broad-spectrum antimicrobial systems for rapid and real-time detection, wash-free imaging, and eradication of drug-resistant microbes might be crucial to combat pathogenic agents.

Counter Anion-Directed Growth of Iron Oxide Nanorods in a Polyol Medium with Efficient Peroxidase-Mimicking Activity for Degradation of Dyes in Contaminated Water.

Development of nanozymes, which are nanomaterials with intrinsic enzymatic properties, has emerged as an appealing alternative to the natural enzymes with tremendous application potential from the chemical industry to biomedicine. The self-assembled growth of micrometer-sized oxide materials with controlled nonspherical shapes can be an important tool for enhancing activity as artificial enzymes, as the formation of these superstructures often results in high surface area with favorable impact on catalytic activity. Herein, the growth of rod-shaped Fe3O4 microstructures via a one-pot microwave-based method and using a water-poly(ethylene glycol) mixture as a solvent is reported, without the involvement of external shape-directing agents. The precursor metal salt played a key role in the size, shape, and phase selective evolution of iron oxide micro/nanomaterials. Whereas self-assembled microrod superstructures were obtained using Fe(NO3)3 as the metal salt precursor, use of FeCl3 or Fe-acetate as precursors afforded hollow Fe2O3 microparticles and Fe3O4 nanoparticles, respectively. A graphitic layer was deposited on the Fe3O4 surface, imparting a negative surface charge as a result of a high-temperature treatment of poly(ethylene glycol). The rod-shaped Fe3O4 microcrystals show efficient peroxidase-mimicking activity toward 3,3,5,5'-tetramethylbenzidine and pyrogallol as peroxidase substrates with a Michaelis-Menten rate constant (K m) value of 0.05 and 0.52 mM, respectively. The proficient enzyme mimicking behavior of these magnetic superstructures was further explored for the degradation of organic dyes that includes rhodamine B, methylene blue, and methyl orange with a rate constant (k) of 0.038, 0.011, and 0.007 min-1 respectively, using H2O2. This fast and simple method could help to develop a new pathway for differently shaped oxide nanoparticles in a sustainable and economical manner that can be harnessed as nanozymes for industrial as well as biological applications.

Biocompatible Fe3+ and Ca2+ Dual Cross-Linked G-Quadruplex Hydrogels as Effective Drug Delivery System for pH-Responsive Sustained Zero-Order Release of Doxorubicin.

The ultimate aim in developing controlled drug delivery systems is to derive formulations to achieve drug release at a constant rate over a long duration. The drug release profile that follows zero-order kinetics is crucial for reduction in the drug administration frequency, reduced cytotoxicity, and improved convenience and compliance of patients. Designed drug delivery systems for achieving zero-order release are often complex, expensive, and difficult to manufacture. Herein, we demonstrate that a supramolecular hydrogel formed through the self-assembly of guanosine monophosphate (GMP) into highly ordered G-quadruplex structure and cross-linked through Fe3+ and Ca2+ ions exhibits potential for the pH-responsive controlled zero-order drug release of doxorubicin, a model chemotherapeutic drug. The fibril formation is initiated by the self-assembly of GMP into a quadruplex complex, which is cross-linked through the complexation of the phosphate groups with Fe(III) ions, resulting in a spontaneous hydrogel formation. The Ca2+ ions facilitate the improvement in the mechanical integrity of the fibril network in the Fe-GMP hydrogel via cross-linking of sugar moieties. The hydrogel showed a high loading capacity for drug molecules and a pH-responsive sustained zero-order drug release over several days owing to the lowered degradability of the cross-linked hydrogel in acidic buffer stimulant. In vitro drug-release studies further established a controlled pH-triggered drug release profile. The Ca2+ cross-linking of the Fe-GMP hydrogel also resulted in significant enhancement in the biocompatibility of the drug delivery system. The fabrication of biocompatible, low-cost, and efficient Ca2+ cross-linked metal-organic hydrogels may present promising applications in biological fields.

Cd(ii)-nucleobase supramolecular metallo-hydrogels for in situ growth of color tunable CdS quantum dots.

The integration of nanoscale materials into unconventional environments such as gels is a magnificent strategy towards development of engineered hybrid functional systems. Herein, the in situ formation of CdS quantum dots integrated into a metallogel formed through the coordination of Cd2+ with two pyrimidine nucleobases is reported. Thymine and uracil formed spontaneous hydrogels with nanofibrous morphology through coordinative interaction with Cd2+ ions at alkaline pH. Introduction of Na2S resulted in generation of CdS quantum dots within the hydrogels with tunable emission properties from blue to white to yellow. The quenching of emission of white light system was exploited for the sensing of Fe3+ and Cu2+ ions. Such a color tunable quantum dot incorporated metallogel system will find applications in energy harvesting and sensing.

One-Pot Magnetic Iron Oxide-Carbon Nanodot Composite-Catalyzed Cyclooxidative Aqueous Tandem Synthesis of Quinazolinones in the Presence of tert-Butyl Hydroperoxide.

The development of synthetic protocols for biologically important molecules using biocompatible catalysts in aqueous medium holds the key in green and sustainable chemistry. Herein, a magnetically recoverable iron oxide-carbon dot nanocomposite has been demonstrated as an effective catalyst for cyclooxidative tandem synthesis of quinazolinones in aqueous medium using alcohols as starting materials. Fluorescent carbon dots, the newest entrant in the nanocarbon family, were used as the stabilizing agent for the iron oxide nanoparticles, and a continuous layer of carbon dots decorates the iron oxide nanoparticle surface as observed by transmission electron microscopy. The fluorescence studies demonstrated the effective electron transfer from carbon dots to the iron oxide nanoparticles resulting in complete quenching of emission owing to carbon dots, once it binds with iron oxide nanoparticles. The nanocatalyst showed high activity with significant reusability for the syntheses of quinazolinones in the presence of tert-butyl hydroperoxide (TBHP) in an aqueous medium. Controlled experiments revealed the synergistic effect of carbon dots in enhancing the catalytic activity of iron oxide, as they might influence the decomposition of TBHP into radicals owing to their peroxidase activity. These radicals stabilized over the nanoparticle surface are known to have increased lifetime compared to solution-based radicals. These surface-stabilized radicals then could catalyze the tandem reaction resulting in the formation of the quinazolinone derivatives in high yields.

Carbon Dots as Nanodispersants for Multiwalled Carbon Nanotubes: Reduced Cytotoxicity and Metal Nanoparticle Functionalization.

The colloidal stabilization of multiwalled carbon nanotubes (MWCNTs) in an aqueous medium through noncovalent interactions has potential benefits toward the practical use of this one-dimensional carbonaceous material for biomedical applications. Here, we report that fluorescent carbon nanodots can efficiently function as dispersing agents in the preparation of stable aqueous suspensions of CNTs at significant concentrations (0.5 mg/mL). The amphiphilic nature of carbon dots with a hydrophobic graphitic core could effectively interact with the CNT surface, whereas hydrophilic oxygenated functionalization on the C-dot surface provided excellent water dispersibility. The resultant CNT-C-dot composite showed significantly reduced cytotoxicity compared to that of unmodified or protein-coated CNTs, as demonstrated by cell viability and proliferation assays. Furthermore, the reducing capability of C-dots could be envisaged toward the formation of a catalytically active metal nanoparticle-CNT-C-dot composite without the addition of any external reducing or stabilizing agents that showed excellent catalytic activity toward the reduction of p-nitrophenol in the presence of NaBH4. Overall, the present work establishes C-dots as an efficient stabilizer for aqueous dispersions of CNTs, leading to an all-carbon nanocomposite that can be useful for different practical applications.

Probing Carbocatalytic Activity of Carbon Nanodots for the Synthesis of Biologically Active Dihydro/Spiro/Glyco Quinazolinones and Aza-Michael Adducts.

Herein, we report the fluorescent carbon dots as an effective and recyclable carbocatalyst for the generation of carbon-heteroatom bond leading to quinazolinone derivatives and aza-Michael adducts under mild reaction conditions. The results establish this nanoscale form of carbon as an alternative carbocatalyst for important acid catalyzed organic transformations. The mild surface acidity of carbon dots imparted by -COOH functionality could effectively catalyze the formation of synthetically challenging spiro/glycoquinazolinones under the present reaction conditions.

Carbon nanodots as ligand exchange probes in Au@C-dot nanobeacons for fluorescent turn-on detection of biothiols.

Au nanoparticle-carbon dot core-shell (Au@C-dot) nanocomposite was synthesized in aqueous medium at room temperature using the carbon dots as reducing agents themselves. The carbon nanodots also function as an effective stabilizer by forming a thin layer surrounding Au nanoparticles (Au NPs) similar to self-assembled monolayers. Ligand exchange with thiol containing biomolecules resulted in the release of carbon dots from the Au NP surface leading to an enhancement of fluorescence. Simultaneously the agglomeration of Au NPs stimulated by the interaction of biothiols led to changes in the surface plasmon properties of Au NPs. A detailed spectroscopic investigation revealed a combination of static and dynamic quenching being involved in the process. Thus, the Au nanoparticle-carbon dot composite could be used as a dual colorimetric and fluorometric sensor for biothiols ranging from amino acids, peptides, proteins, enzymes etc. with a detection limit of 50 nM.

Enzymes as bionanoreactors: glucose oxidase for the synthesis of catalytic Au nanoparticles and Au nanoparticle-polyaniline nanocomposites.

The use of biomaterials such as enzymes for the synthesis of functional materials is important because such biologically guided processes can significantly reduce energy consumption in manufacturing processes. Glucose oxidase (GOx) has been exploited as a reducing as well as a stabilising agent for the green chemical synthesis of Au nanoparticles at pH 7.0 under ambient conditions. The synthesized Au nanoparticle-GOx composite was found to act as a highly-effective catalyst towards the reduction of p-nitrophenol to p-aminophenol in the presence of NaBH4. The catalytic activity of GOx was largely inhibited after its participation in the reduction of metal salt to form nanoparticles. A detailed mechanistic investigation was carried out using fluorescence spectroscopy, Fourier transform infra-red (FTIR) spectroscopy and circular dichroism (CD) to gain insights into the conformational changes in the enzyme structure. The catalytic activity of GOx towards the oxidation of glucose was taken advantage of to form a Au nanoparticle-polyaniline (Au NP-PANI) composite at room temperature. The production of the green emeraldine salt form of polyaniline (PANI) was extremely low in case of Au nanoparticle-GOx composite, where GOx was involved as a reducing agent. However, H2O2 generated during the catalytic reaction of GOx acted as a simultaneous reducing and oxidizing agent, leading to the formation of an Au NP-PANI core-shell composite in a controlled fashion.

Biogenic growth of alloys and core-shell nanostructures using urease as a nanoreactor at ambient conditions.

Biomineralization is an extremely efficient biologically guided process towards the advancement of nano-bio integrated materials. As a prime module of the natural world, enzymes are expected to play a major role in biogenic growth of inorganic nanostructures. Although there have been developments in designing enzyme-responsive nanoparticle systems or generation of inorganic nanostructures in an enzyme-stimulated environment, reports regarding action of enzymes as reducing agents themselves for the growth of inorganic nanoparticles still remains elusive. Here we present a mechanistic investigation towards the synthesis of metal and metallic alloy nanoparticles using a commonly investigated enzyme, Jack bean urease (JBU), as a reducing as well as stabilizing agent under physiological conditions. The catalytic functionality of urease was taken advantage of towards the development of metal-ZnO core-shell nanocomposites, making urease an ideal bionanoreactor for synthesizing higher order nanostructures such as alloys and core- shell under ambient conditions.

Carbon dot reduced palladium nanoparticles as active catalysts for carbon-carbon bond formation.

Carbon dots were used as a reducing agent for the synthesis of Pd nanoparticles coated with ultrathin carbon dot shells of ca. 4 nm. The resulting composite nanoparticles showed high catalytic activity for the Heck and Suzuki coupling reactions.