Chemically fueled dynamic switching between assembly-encoded emissions.

Self-assembly provides access to non-covalently synthesized supramolecular materials with distinct properties from a single building block. However, dynamic switching between functional states still remains challenging, but holds enormous potential in material chemistry to design smart materials. Herein, we demonstrate a chemical fuel-mediated strategy to dynamically switch between two distinctly emissive aggregates, originating from the self-assembly of a naphthalimide-appended peptide building block. A molecularly dissolved building block shows very weak blue emission, whereas, in the assembled state (Agg-1), it shows cyan emission through π stacking-mediated excimer emission. The addition of a chemical fuel, ethyl-3-(3-(dimethylamino)propyl)carbodiimide (EDC), converts the terminal aspartic acid present in the building block to an intra-molecularly cyclized anhydride in situ forming a second aggregated state, Agg-2, by changing the molecular packing, thereby transforming the emission to strong blue. Interestingly, the anhydride gets hydrolyzed gradually to reform Agg-1 and the initial cyan emission is restored. The kinetic stability of the strong blue emissive aggregate, Agg-2, can be regulated by the added concentration of the chemical fuel. Moreover, we expand the scope of this system within an agarose gel matrix, which allows us to gain spatiotemporal control over the properties, thereby producing a self-erasable writing system where the chemical fuel acts as the ink.

Formation of Catalytic Hotspots in ATP-Templated Assemblies.

The self-assembly of surfactant-based structures that rely for their formation on the combination of a thermodynamically controlled and a dissipative pathway is described. Adenosine triphosphate (ATP) acts as a high-affinity template and triggers assembly formation at low surfactant concentrations. The presence of these assemblies creates the conditions for the activation of a dissipative self-assembly process by a weak-affinity substrate. The substrate-induced recruitment of additional surfactants leads to the spontaneous formation of catalytic hotspots in the ATP-stabilized assemblies that cleave the substrate. As a result of the two self-assembly processes, catalysis can be observed at a surfactant concentration at which low catalytic activity is observed in the absence of ATP.

Boosting the photocatalytic performance of Bi2Fe4O9 through formation of Z-scheme heterostructure with In2S3: Applications towards water decontamination.

Design of biocompatible nano-heterostructure photocatalyst with broad UV-visible spectrum response and strong redox ability is a promising approach with potential application in micropollutant degradation and pathogen deactivation from aqueous sources. Herein, we have reported the facile fabrication of In2S3/Bi2Fe4O9 (ISxBFO) binary heterostructure by hydrothermally depositing In2S3 nanoparticles (20-40 nm) over Bi2Fe4O9 nanocuboids/nanoplates prepared by combustion synthesis route. In depth characterization study revealed broad spectrum UV-Vis absorption, large interfacial contact, improved charge carrier separation and mobility and a longer excited state life time (4.7 ns) for the ISxBFO heterostructure materials. The integration of In2S3 with Bi2Fe4O9 strongly boosts the optoelectrical and photocatalytic property of pristine Bi2Fe4O9. The ISxBFO heterostructure material exhibited enhanced photocatalytic efficiency for aqueous phase degradation of sulfamethoxazole antibiotics (kapp = 0.06 min-1) and phenyl urea herbicides (kapp = 0.028 min-1) with reaction rates 3-8 times higher than the pure BFO component. The MTT assay experiments confirmed non-cytotoxic nature of treated sulfamethoxazole and diuron solutions. The composite materials also displayed convincing antibacterial behavior towards toxigenic Vibrio cholerae pathogen. Haemagglutination assay study revealed excellent biocompatibility of the binary composite up to 200 mg L-1. Radical trapping study suggested expeditious generation of •OH and •O2- radicals over the ISxBFO surface which is nearly 3.8 and 2.3 times higher than pure BFO and In2S3 respectively. The occurrence of a direct Z-scheme mechanism is inferred from radical trapping and XPS study which accounted for the improved photocatalytic activity and strong radical generation property of the ISxBFO heterostructure material.

Pythiosis in a patient with Acute Myeloid Leukemia: Diagnosis and clinical course.

Pythiosis, caused by Pythium insidiosum (a fungal-like stramenipila, a group of eukaryotes away from the true fungi). Pythium insidiosum causes rare human and animal infections. Transmission from animals to human is yet to be reported. Wet soil and plants near watery environments are the source of infection. We report here a fatal case of human pythiosis in a 9-year old child with acute myeloid leukemia. Organism was identified by DNA sequencing.

Progressive Local Accumulation of Self-Assembled Nanoreactors in a Hydrogel Matrix through Repetitive Injections of ATP.

Cellular functions are regulated with high spatial control through the local activation of chemical processes in a complex inhomogeneous matrix. The development of synthetic macroscopic systems with a similar capacity allows fundamental studies aimed at understanding the relationship between local molecular events and the emergence of functional properties at the macroscopic level. Here, we show that a kinetically stable inhomogeneous hydrogel matrix is spontaneously formed upon the local injection of ATP. Locally, ATP templates the self-assembly of amphiphiles into large nanoreactors with a much lower diffusion rate compared to unassembled amphiphiles. The local depletion of unassembled amphiphiles near the injection point installs a concentration gradient along which unassembled amphiphiles diffuse from the surroundings to the center. This allows for a progressive local accumulation of self-assembled nanoreactors in the matrix upon repetitive cycles of ATP injection separated by time intervals during which diffusion of unassembled amphiphiles takes place. Contrary to the homogeneous matrix containing the same components, in the inhomogeneous matrix the local upregulation of a chemical reaction occurs. Depending on the way the same amount of injected ATP is administered to the hydrogel matrix different macroscopic distributions of nanoreactors are obtained, which affect the location in the matrix where the chemical reaction is upregulated.

Chemically Fueled Self-Assembly in Biology and Chemistry.

Life is a non-equilibrium state of matter maintained at the expense of energy. Nature uses predominantly chemical energy stored in thermodynamically activated, but kinetically stable, molecules. These high-energy molecules are exploited for the synthesis of other biomolecules, for the activation of biological machinery such as pumps and motors, and for the maintenance of structural order. Knowledge of how chemical energy is transferred to biochemical processes is essential for the development of artificial systems with life-like processes. Here, we discuss how chemical energy can be used to control the structural organization of organic molecules. Four different strategies have been identified according to a distinguishable physical-organic basis. For each class, one example from biology and one from chemistry are discussed in detail to illustrate the practical implementation of each concept and the distinct opportunities they offer. Specific attention is paid to the discussion of chemically fueled non-equilibrium self-assembly. We discuss the meaning of non-equilibrium self-assembly, its kinetic origin, and strategies to develop synthetic non-equilibrium systems.

Time-gated fluorescence signalling under dissipative conditions.

Precise control over specific functions in the time domain is ubiquitous in biological systems. Here, we demonstrate time-gated fluorescence signalling under dissipative conditions exploiting an ATP-fueled self-assembly process. A temporal ATP-concentration gradient allows the system to pass through three states, among which only the intermediate state generates a fluorescent signal from a hydrophobic dye entrapped in the assemblies. The system can be reactivated by adding a new batch of ATP. The results indicate a strategy to rationally programme the temporal emergence of functions in complex chemical systems.

Fatty acid based transient nanostructures for temporal regulation of artificial peroxidase activity.

Natural systems access transient high energy self-assembled structures for temporal regulation of different biological functions through dissipative processes. Compartmentalization within self-assembled structures is used by living systems to organize vital biochemical reactions that define cellular metabolism. Herein, we demonstrate a simple fatty acid based system where a redox active base (dimethylaminomethyl ferrocene, Fc-NMe2 ) acts as a countercation to access unique hexagonal compartments resulting in the formation of a self-supporting gel. An oxidizing environment helps in the dissipation of energy by converting Fc-NMe2 to oxidized waste and the gel autonomously undergoes transition to a sol. Hence, the system requires the addition of the fuel Fc-NMe2 to access the temporal gel state. Notably, these transient compartments were able to temporally upregulate and downregulate hemin-catalyzed oxidation reactions mimicking peroxidase, a ubiquitous enzyme in extant biology. An order of magnitude variation in k cat values was observed with time and the chemical reaction persists as long as the gel state was present.

Designed Negative Feedback from Transiently Formed Catalytic Nanostructures.

Highly dynamic and complex systems of microtubules undergo a substrate-induced change of conformation that leads to polymerization. Owing to the augmented catalytic potential at the polymerized state, rapid hydrolysis of the substrate is observed, leading to catastrophe, thus realizing the out-of-equilibrium state. A simple synthetic mimic of these dynamic natural systems is presented, where similar substrate induced conformational change is observed and a transient helical morphology is accessed. Further, augmented catalytic potential of these helical nanostructures leads to rapid hydrolysis of the substrate providing negative feedback on the stability of the nanostructures and realization of an out-of-equilibrium state. This simple system, made from amino acid functionalized lipids, demonstrates a substrate-induced self-assembled state, where the fuel-to-waste conversion leads to the temporal presence of helical nanostructures.

Chemically Fueled Dissipative Self-Assembly that Exploits Cooperative Catalysis.

In living systems, dissipative processes are driven by the endergonic hydrolysis of chemical fuels such as nucleoside triphosphates. Now, through a simple model system, a transient self-assembled state is realized by utilizing the catalytic effect of histidine on the formation and breaking of ester bonds. First, histidine facilitates the ester bond formation, which then rapidly co-assembles to form a self-supporting gel. An out-of-equilibrium state is realized owing to the cooperative catalysis by the proximal histidines in the assembled state, driving the second pathway and resulting in disassembly to sol. Cooperative effects that use the dual role of imidazoles as nucleophile and as proton donor is utilized to achieve transient assemblies. This simple system mimics the structural journey seen in microtubule formation where the substrate GTP facilitates the non-covalent assembly and triggers a cooperative catalytic process, leading to substrate hydrolysis and subsequent disassembly.

l-Phenylalanine-Tethered, Naphthalene Diimide-Based, Aggregation-Induced, Green-Emitting Organic Nanoparticles.

The present article delineates the formation of green fluorescent organic nanoparticle through supramolecular aggregation of naphthalene diimide (NDI)-based, carboxybenzyl-protected, l-phenylalanine-appended bola-amphiphile, NDI-1. The amphiphilic molecule is soluble in DMSO, and, with gradual addition of water within the DMSO solution, the amphiphile starts to self-assemble via H-type aggregation to form spherical nanoparticles. These self-assembly of NDI-1 in the presence of a high amount of water exhibited aggregation-induced emission (AIE) through excimer formation. Notably, in the presence of 99% water content, the amphiphile forms spherical aggregated nanoparticles as confirmed from microscopic investigations and dynamic light scattering study. Interestingly, the emission maxima of molecularly dissolved NDI-1 (weak blue fluorescence) red-shifted upon aggregation with increase in water concentration and led to the formation of green-emitting fluorescent organic nanoparticles (FONPs) at 99% water content. These green-emitting FONPs were utilized in cell imaging as well as for efficient transportation of anticancer drug curcumin inside mammalian cells.

An Integrin-Targeting RGDK-Tagged Nanocarrier: Anticancer Efficacy of Loaded Curcumin.

Herein we report the design and development of α5 ß1 integrin-specific noncovalent RGDK-lipopeptide-functionalized single-walled carbon nanotubes (SWNTs) that selectively deliver the anticancer drug curcumin to tumor cells. RGDK tetrapeptide-tagged amphiphiles were synthesized that efficiently disperse SWNTs with a suspension stability index of >80 % in cell culture media. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)- and lactate dehydrogenase (LDH)-based cell viability assays in tumor (B16F10 melanoma) and noncancerous (NIH3T3 mouse fibroblast) cells revealed the non-cytotoxic nature of these RGDK-lipopeptide-SWNT conjugates. Cellular uptake experiments with monoclonal antibodies against αv ß3 , αv ß5 , and α5 ß1 integrins showed that these SWNT nanovectors deliver their cargo (Cy3-labeled oligonucleotides, Cy3-oligo) to B16F10 cells selectively via α5 ß1 integrin. Notably, the nanovectors failed to deliver the Cy3-oligo to NIH3T3 cells. The RGDK-SWNT is capable of delivering the anticancer drug curcumin to B16F10 cells more efficiently than NIH3T3 cells, leading to selective killing of B16F10 cells. Results of Annexin V binding based flow cytometry experiments are consistent with selective killing of tumor cells through the late apoptotic pathway. Biodistribution studies in melanoma (B16F10)-bearing C57BL/6J mice showed tumor-selective accumulation of curcumin intravenously administered via RGDK-lipopeptide-SWNT nanovectors.

Fluorescent Indicator Displacement Assay: Ultrasensitive Detection of Glutathione and Selective Cancer Cell Imaging.

This Research Article reports the development of nanohybrid comprising of anionic carbon dots (ACD) protected gold nanoparticle (GNP). ACD directly cap GNP through its anionic surface functionalization leading to the formation of stable aqueous GNP dispersion. This newly developed ACD-GNP nanohybrid has been thoroughly characterized by different spectroscopic and microscopic techniques. This nanohybrid is successfully employed toward the selective sensing of glutathione (GSH). The mechanism of GSH sensing by this nanosensor is based on the GSH triggered displacement of fluorescent indicator ACD from the GNP surface. Upon capping GNP, intrinsic fluorescence of ACD gets quenched. Addition of GSH displaces the fluorescent indicator ACD from GNP surface and restores the fluorescence signal of ACD. This nanosensor exhibits very high selectivity as well as sensitivity toward glutathione over the other biothiols and can detect as low as 6 nM of GSH. More importantly, selective imaging of the cancer cells over the noncancerous cells was achieved by this ACD-GNP hybrid implying its potential applications in biosensing, as well as in cancer diagnosis.

Hydrophobically Tailored Carbon Dots toward Modulating Microstructure of Reverse Micelle and Amplification of Lipase Catalytic Response.

This article delineates the modulation of microstructure of cationic reverse micelle utilizing hydrophobically modified carbon dots (CDs) with varying surface functionalizations. Citric acid was used as the source of the carbon core, and Na-salt of glycine, glycine, Na-salt of 11-aminoundecanoic acid, 11-aminoundecanoic acid, and n-hexadecylamine were used for the surface fabrication of CDs to produce CD 1s, CD 1a, CD 2s, CD 2a, and CD 3, respectively. All these CDs having dimension of 5-7 nm were characterized by spectroscopic and microscopic techniques. The hydrodynamic diameter of cetyltrimethylammonium bromide (CTAB) reverse micelle (CTAB/isooctane/n-hexanol/water) at z ([cosurfactant]/[surfactant]) = 6.4 and W0 ([water]/[surfactant]) = 44 is around 15-20 nm. Interestingly, the size of the water-in-oil (w/o) microemulsions dramatically increased up to 120-200 nm upon doping hydrophobic surface functionalized CD 2a and CD 3. This is possibly due to change in the micellar exchange dynamics and reorganization of the micellar aggregates via hydrophobic interaction between surfactant (CTAB) tail and hydrophobic surface modifier of the carbon dots. However, no alteration in the size of reverse micelles was noted in the presence of carbon dots CD 1s, CD 1a, and CD 2s. Spectroscopic and microscopic investigations confirmed that the hydrophobic CD 2a and CD 3 were localized at the interface of reverse micelles whereas CD 1s, CD 1a, and CD 2s were possibly located in the water pool (away from interface). The activity of Chromobacterium viscosum lipase encapsulated within CD 3 and CD 2a doped significantly large CTAB reverse micelles showed remarkable improvement (3.7-fold and 3.4-fold) in its catalytic response. However, hydrophilic carbon dots CD 1s and CD 2s as well as moderately hydrophobic CD 1a had no significant effect on the microstructure of reverse micelles as well as on the lipase activity.

Probing enzyme location in water-in-oil microemulsion using enzyme-carbon dot conjugates.

This article delineates the formation and characterization of different enzyme-carbon dot conjugates in aqueous medium (pH = 7.0). We used soybean peroxidase (SBP), Chromobacterium viscosum (CV) lipase, trypsin, and cytochrome c (cyt c) for the formation of conjugate either with cationic carbon dot (CCD) or anionic carbon dot (ACD) depending on the overall charge of the protein at pH 7.0. These nanobioconjugates were used to probe the location of enzymes in water-in-oil (w/o) microemulsion. The size of the synthesized water-soluble carbon dots were of 2-3 nm with distinctive emission property. The formation of enzyme/protein-carbon dot conjugates in aqueous buffer was confirmed via fluorescence spectroscopy and zeta potential measurement, and the structural alteration of enzyme/protein was monitored by circular dichroism spectroscopy. Biocatalytic activities of protein/enzymes in conjugation with carbon dots were found to be decreased in aqueous phosphate buffer (pH 7.0, 25 mM). Interestingly, the catalytic activity of the nanobioconjugates of SBP, CV lipase, and cyt c did not reduce in cetyltrimethylammonium bromide (CTAB)-based reverse micelle. It indicates different localization of carbon dots and the enzymes inside the reverse micelle. The hydrophilic carbon dots always preferred to be located in the water pool of reverse micelle, and thus, enzyme must be located away from the water pool, which is the interface. However, in case of trypsin-carbon dot conjugate, the enzyme activity notably decreased in reverse micelle in the presence of carbon dot in a similar way that was observed in water. This implies that trypsin and carbon dots both must be located at the same place, which is the water pool of reverse micelle. Carbon dot induced deactivation was not observed for those enzymes which stay away from the water pool and localized at the interfacial domain while deactivation is observed for those enzymes which reside at the water pool. Thus, the location of enzymes in the microdomain of w/o microemulsion can be predicted by comparing the activity profile of enzyme-carbon dot conjugate in water and w/o microemulsion.

Water-in-oil microemulsion doped with gold nanoparticle decorated single walled carbon nanotube: scaffold for enhancing lipase activity.

The present work reports the development of water-in-oil (w/o) microemulsion doped with newly designed nanocomposite comprising of gold nanoparticle (GNP) decorated single walled carbon nanotube (SWNT). This nanocomposite included cationic reverse micelle was used to boost the catalytic activity of a surface-active enzyme, Chromobacterium viscosum lipase (CV lipase). SWNT was non-covalently dispersed using cetyltrimethylammonium bromide (CTAB), cetylalaninetrimethylammonium chloride (CATAC) while GNP was synthesized by reduction of HAuCl4 with reducing/stabilizing agent trisodium citrate. Counterion exchange between cationic SWNT dispersing agent and anionic capping agent of GNP led to the formation of GNP decorated SWNT (SWNT-GNP) nanocomposite. This newly developed SWNT-GNP included CTAB reverse micelle was characterized by several microscopic and spectroscopic techniques. Interfacially located SWNT-GNP included w/o microemulsion (confirmed from biphasic and fluorescence experiment) was used as a proficient host for enhancing the catalytic activity of lipase. Lipase activity within this self-assembled soft nanocomposite improved up to 3.9-fold (second order rate constant, k2=1694±16 cm(3) g(-1) s(-1)) compared to standard CTAB reverse micelle (k2=433±7 cm(3) g(-1) s(-1)). In case of cetyltripropyl ammonium bromide (CTPAB) based reverse micelle, the observed lipase activity improved to k2=2036±11 cm(3) g(-1) s(-1) in the presence of SWNT-GNP composite. Notably, this catalytic activity of lipase within SWNT-GNP included reverse micelle was till date the highest activity found in any w/o microemulsion. The attainment of flexibility in enzyme conformation at the augmented interface was verified using circular dichroism (CD) spectroscopy.

Label-free fluorimetric detection of histone using quaternized carbon dot-DNA nanobiohybrid.

A fluorimetric histone sensing technique is developed using quaternized carbon dot-DNA nanobiohybrid. The method is simple, specific, and can detect a minimum of 0.2 ng mL(-1) histone.

Graphene oxide in cetyltrimethylammonium bromide (CTAB) reverse micelle: a befitting soft nanocomposite for improving efficiency of surface-active enzymes.

Herein, we report the successful inclusion of 2D allotrope of carbon, graphene oxide (GO) in cetyltrimethylammonium bromide (CTAB)/isooctane/n-hexanol/water reverse micelle without compromising the stability of water-in-oil (w/o) microemulsion. This newly developed self-assembled nanocomposites act as proficient host for surface-active enzymes, lipase, horseradish peroxidase (HRP), and soybean peroxidase (SBP). Lipase activity within GO-doped CTAB reverse micelles remarkably improved by 3.8-fold compared to that was observed in only CTAB reverse micelle (second-order rate constant, k2=433±7 cm3 g(-1) s(-1)). In case of GO-doped CTAB reverse micelle, the observed enzyme activity (k2=1653±11 cm3 g(-1) s(-1)) is till date the highest ever activity of lipase in CTAB w/o microemulsions. In case of HRP and SBP, the catalytic efficiency maximally increased up to 2.6-fold and 2.3-fold, respectively. Electrostatic attraction between cationic head group of CTAB and anionic surface of GO as well as intrinsic amphiphilic character of GO possibly resulted in the confinement of this 2D nanosheet at the interface of reverse micelles. Integration of GO at the interface augmented the interfacial space in vicinity of surface-active enzyme. This enlarged interface might have accommodated higher amount of substrate and lipase with flexibility in its conformation resulting in marked improvement in the enzyme activity. Interfacial localization of GO was established by fluorescence spectroscopy. In addition, change in secondary structure of lipase in presence of 2D carbon allotrope was substantiated by circular dichroism spectroscopy.