Dinesh Jagadeesan

Intrinsically Fluorescent Carbon Nanospheres as a Nuclear Targeting Vector: Delivery of Membrane-Impermeable Molecule to Modulate Gene Expression In Vivo

In this report, we demonstrate glucose-derived carbon nanospheres to be an emerging class of intracellular carriers. The surfaces of these spheres are highly functionalized and do not need any further modification. Besides, the intrinsic fluorescence property of carbon nanospheres helps in tracking their cellular localization without any additional fluorescent tags. The spheres are found to target the nucleus of the mammalian cells, causing no toxicity. Interestingly, the in vivo experiments show that these nanospheres have an important ability to cross the blood-brain barrier and localize in the brain besides getting localized in the liver and the spleen. There is also evidence to show that they are continuously being removed from these tissues over time. Furthermore, these nanospheres were used as a carrier for the membrane-impermeable molecule CTPB (N-(4-chloro-3-trifluoromethylphenyl)-2-ethoxybenzamide), the only known small-molecule activator of histone acetyltransferase (HAT) p300. Biochemical analyses such as Western blotting, immunohistochemistry, and gene expression analysis show the induction of the hyperacetylation of histone acetyltransferase (HAT) p300 (autoacetylation) as well as histones both in vitro and in vivo and the activation of HAT-dependent transcription upon CTPB delivery. These results establish an alternative path for the activation of gene expression mediated by the induction of HAT activity instead of histone deacetylase (HDAC) inhibition.

Microbubbles loaded with nanoparticles: a route to multiple imaging modalities.

We report a single-step approach to producing small and stable bubbles functionalized with nanoparticles. The strategy includes the following events occurring in sequence: (i) a microfluidic generation of bubbles from a mixture of CO(2) and a minute amount of gases with low solubility in water, in an aqueous solution of a protein, a polysaccharide, and anionic nanoparticles; (ii) rapid dissolution of CO(2) leading to the shrinkage of bubbles and an increase in acidity of the medium in the vicinity of the bubbles; and (iii) co-deposition of the biopolymers and nanoparticles at the bubble-liquid interface. The proposed approach yielded microbubbles with a narrow size distribution, long-term stability, and multiple functions originating from the attachment of metal oxide, metal, or semiconductor nanoparticles onto the bubble surface. We show the potential applications of these bubbles in ultrasound and magnetic resonance imaging.

pH-Sensitive breathing of clay within the polyelectrolyte matrix.

Stimuli-responsive organic-inorganic hybrid spheres were synthesized by coating the colloidal polystyrene spheres with polyelectrolyte-protected aminoclay, Mg phyllo(organo)silicate layers in a layer-by-layer method. The clay layers are sandwiched between the polyelectrolyte layers. The aminoclay swells in water due to protonation of amino groups, and the degree of swelling depends on the pH of the medium. As a result, the hybrid spheres undergo a size change up to 60% as the pH is changed from 9 to 4. The stimuli-responsive property of the hybrid spheres was used for the release of ibuprofen and eosin at different pH.

Synthesis, structure and properties of homogeneous BC4N nanotubes

BCN nanotube brushes have been obtained by the high temperature reaction of amorphous carbon nanotube (a-CNT) brushes with a mixture of boric acid and urea. The a-CNT brushes themselves were obtained by the pyrolysis of glucose in a polycarbonate membrane. The BCN nanotubes have been characterized by EELS, XPS, electron microscopy, Raman spectroscopy and other techniques. The composition of these nanotubes is found to be BC4N. The nanotubes, which are stable up to 900 °C, are insulating and nonmagnetic. They exhibit a selective uptake of CO2 up to 23.5 wt%. In order to understand the structure and properties, we have carried out first-principles density functional theory based calculations on (6,0), (6,6) and (8,0) nanotubes with the composition BC4N. While (8,0) BC4N nanotubes exhibit a semiconducting gap, the (6,0) BC4N nanotube remains metallic if ordered BN bonds are present in all the six-membered rings. The (6,6) BC4N nanotubes, however, exhibit a small semiconducting gap unlike the carbon nanotubes. The most stable structure is predicted to be the one where BN3 and NB3 units connected by a B–N bond are present in the graphite matrix, the structure with ordered B–N bonds in the six-membered rings of graphite being less stable. In the former structure, (6,0) nanotubes also exhibit a gap. The calculations predict BC4N nanotubes to be overall nonmagnetic, as is indeed observed.

Microfluidic Study of Fast Gas–Liquid Reactions

We present a new concept for studies of the kinetics of fast gas-liquid reactions. The strategy relies on the microfluidic generation of highly monodisperse gas bubbles in the liquid reaction medium and subsequent analysis of time-dependent changes in bubble dimensions. Using reactions of CO(2) with secondary amines as an exemplary system, we demonstrate that the method enables rapid determination of reaction rate constant and conversion, and comparison of various binding agents. The proposed approach addresses two challenges in studies of gas-liquid reactions: a mass-transfer limitation and a poorly defined gas-liquid interface. The proposed strategy offers new possibilities in studies of the fundamental aspects of rapid multiphase reactions, and can be combined with throughput optimization of reaction conditions.

Microgels for the Encapsulation and Stimulus-Responsive Release of Molecules with Distinct Polarities

A microfluidic strategy for the encapsulation and stimulus-responsive release of molecules with distinct polarities from the interior of microgels is reported. The approach relies on (i) the generation of a primary O/W emulsion by the ultrasonication method, (ii) MF emulsification of the primary emulsion, and (iii) photopolymerization of the monomer present in the aqueous phase of the droplets, thereby transforming them into microgels. Non-polar molecules are dissolved in oil droplets embedded in the microgels. Polar molecules are physically associated with the hydrogel network. Upon heating, the microgels contract and release polar and non-polar cargo molecules. The approach paves the way for stimuli-responsive vehicles for multiple drug delivery.

Functionalized carbon nanomaterials derived from carbohydrates.

A tremendous growth in the field of carbon nanomaterials has led to the emergence of carbon nanotubes, fullerenes, mesoporous carbon and more recently graphene. Some of these materials have found applications in electronics, sensors, catalysis, drug delivery, composites, and so forth. The high temperatures and hydrocarbon precursors involved in their synthesis usually yield highly inert graphitic surfaces. As some of the applications require functionalization of their inert graphitic surface with groups like -COOH, -OH, and -NH(2), treatment of these materials in oxidizing agents and concentrated acids become inevitable. More recent works have involved using precursors like carbohydrates to produce carbon nanostructures rich in functional groups in a single-step under hydrothermal conditions. These carbon nanostructures have already found many applications in composites, drug delivery, materials synthesis, and Li ion batteries. The review aims to highlight some of the recent developments in the application of carbohydrate derived carbon nanostructures and also provide an outlook of their future prospects.

Observation of Pore‐Switching Behavior in Porous Layered Carbon through a Mesoscale Order–Disorder Transformation

Structural flexibility in biomacromolecules is a well-known phenomenon in nature. For example, enzymes efficiently change their tertiary structures, the channels and cavities in which are reversibly modified to accommodate a guest molecule. The high specificity of enzymes in biologically important reactions is primarily attributed to their ability to change their structures in response to external stimuli. Taking a cue from nature, researchers are now looking for ways to make structurally flexible porous materials, as such materials could find wide-ranging application in catalysis, separation, sensors, fuel cells, and gas storage owing to their unique properties and functions. Recently, metal–organic frameworks (MOFs) were shown to modify their framework structure in response to chemical or physical stimuli. 6] However, such a rearrangement of structure is not possible in rigid inorganic porous solids, such as zeolites, activated charcoal, and mesoporous silica. Considering their industrial significance, structural flexibility in these porous materials would be very advantageous for the size-selective separation of molecules or switching between different properties of the material itself. Herein, we report the first observation of a reversible, mesoscale order–disorder transformation of a porous layered carbon (PLC) as a response to an applied mechanical force. The PLC containing crystallographically oriented graphene nanocrystallites on its layers was synthesized by graphitizing glucose within an aminoclay template. Although clay galleries have been used previously to make structurally rigid, porous carbon materials containing nanographene domains, these materials failed to show any mesoscale, long-range order replicating the stacked clay layer structure. 8] On the other hand, carbon materials obtained by using mesoporous silica as the template are often amorphous and exhibit ordered but rigid pores replicating the template. In contrast to these rigid carbon materials, the PLC that we obtained showed a flexible pore size associated with a mesoscale order–disorder transformation, which we exploited for the size-selective separation (sorption) of dye molecules. We used an aminoclay template to make layered carbon. 12] Aminoclay is an organophyllosilicate of approximate composition R8Si8Mg6O16(OH)4 (in which R = CH2CH2NH2) consisting of octahedrally coordinated MgO/ OH sheets (brucite) overlaid on both sides with a tetrahedrally coordinated aminopropyl-functionalized silicate network. Since the amine groups get protonated in water, the clay layers can readily be exfoliated owing to charge repulsion between the layers. 14] The exfoliated clay in water consists of a single layer or bundles containing a few layers (nanobundles). The dispersed layers can be restacked by the addition of ethanol (appearance of a white precipitate). In the present study, we first mixed a solution of glucose with a transparent aminoclay dispersion and then induced the stacking of clay layers/nanobundles by adding ethanol (see Scheme S1 in the Supporting Information). During the precipitation, glucose molecules get trapped in between the layers as well as in the space between the nanobundles. Thermogravimetric analysis (TGA) of the resulting composite after the excess glucose had been washed out with ethanol showed nearly 60% weight loss, mainly as a result of the removal of glucose (results not shown). Carbonization of the composite and subsequent etching of the clay, followed by filtration, left porous layered carbon (PLC). The absence of Si and Mg peaks in the energy-dispersive X-ray spectrum of the resulting PLC confirmed the complete removal of the clay template (see Figure S1 in the Supporting Information). The powder X-ray diffraction pattern of the resulting PLC is shown in Figure 1a. The low-angle diffraction peak at 2q = 1.278 corresponding to a basal distance of 6 nm confirms the existence of mesostructural order in the carbon after the removal of the clay. Considering that the basal distance of the clay–glucose composite is 2.5 nm (and that this peak is lost on carbonization), it is unlikely that the individual clay layers would have acted as the template to generate this large d spacing of 6 nm. The PLC with a large d spacing (6 nm) therefore originates from the carbonization of glucose mostly trapped between the clay nanobundles, which are 2–3 layers thick, during the precipitation. The broad peak at 2q = 258 (the characteristic d002 graphitic peak in the higher-angle XRD pattern) indicates that the PLC is composed of nano[*] K. K. R. Datta, Dr. D. Jagadeesan, C. Kulkarni, A. Kamath, Prof. M. Eswaramoorthy Chemistry and Physics of Materials Unit and DST Unit on Nanoscience, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Jakkur P.O., Bangalore 560064 (India) Fax: (+ 91)80-2208-2766 E-mail: eswar@jncasr.ac.in Homepage: http://www.jncasr.ac.in/eswar/

Investigations of the Conversion of Inorganic Carbonates to Methane

Inorganic carbonates, which occur abundantly on earth, constitute an inexpensive natural source of carbon. Therefore, the direct conversion of these carbonates into methane is of considerable importance. Thermal decomposition of transition metal carbonates with the composition MCa(CO(3))(2) (where M=Co, Ni, or Fe, and M/Ca is 1:1) and M(1)M(2)Ca(CO(3))(3) (where M(1)M(2)=CoNi, NiFe, or FeCo, and M(1)/M(2)/Ca is 1:1:2) shows that the reduced transition metals in combination with metal oxide nanoparticles (e.g., Co/CoO/CaO) act as catalysts for the conversion of CO(2) (produced from the carbonates) into methane. The favorable decomposition conditions include heating at 550 degrees C in an H(2) atmosphere for 5-6 h. These catalysts are found to be excellent for the methanation of CaCO(3), exhibiting high efficiency in the utilization of H(2) with 100 % conversion and 100 % selectivity. The best catalyst for conversion of CaCO(3) into CH(4) is Co/CoO/CaO. There are also indications that similar catalysts based on Fe may yield higher hydrocarbons.

ATP driven clathrin dependent entry of carbon nanospheres prefer cells with glucose receptors

BackgroundIntrinsically fluorescent glucose derived carbon nanospheres (CSP) efficiently enter mammalian cells and also cross the blood brain barrier (BBB). However, the mechanistic details of CSP entry inside mammalian cells and its specificity are not known.ResultsIn this report, the biochemical and cellular mechanism of CSP entry into the living cell have been investigated. By employing confocal imaging we show that CSP entry into the mammalian cells is an ATP-dependent clathrin mediated endocytosis process. Zeta potential studies suggest that it has a strong preference for cells which possess high levels of glucose transporters such as the glial cells, thereby enabling it to target individual organs/tissues such as the brain with increased specificity.ConclusionThe endocytosis of Glucose derived CSP into mammalian cells is an ATP dependent process mediated by clathrin coated pits. CSPs utilize the surface functional groups to target cells containing glucose transporters on its membrane thereby implicating a potential application for specific targeting of the brain or cancer cells.