Anti-microbial Nanohybrids Based on Naturally Derived Citric Acid Intercalated Layered Double Hydroxides

Currently, there is an increased demand for advanced food packages, which can significantly increase the shelf life of food items. In the current context, it is envisaged that nanotechnology has the potential to address stability, toxicity, shelf-life, and low-cost issues of antimicrobials associated with the packaging industry. Antimicrobial nanocomposite systems are believed to be more efficient than their microscale counterparts due to the high surface area to volume ratio and quantum mechanical involvement in deciding their properties. As a result of high surface area, they are able to attach more copies of microbial molecules and cells, thus reducing the quantity of material required while significantly improving their activity. This study focuses on the development of slow-release antimicrobial material based on natural citrate (α-hydroxycitrate) intercalated layered double hydroxide (LDH) nanohybrid. Natural citrate ions available in Citrus aurantifolia (lime) were extracted by a simple chemical method and intercalated into Mg-Al-Layered Double Hydroxide following a one-step co-precipitation method. Successful intercalation of the citrate ion was confirmed by powder X-ray diffraction (PXRD) and Fourier transform infrared (FTIR) spectroscopic analysis. Release kinetics of resulted nanohybrid was studied and compared using different release kinetic models. Antimicrobial properties of this novel nanohybrid were confirmed against two common food pathogens, Colletotrichum gloeosporioides and Saccharomyces cerevisiae, and the results were compared against sodium benzoate, which is the commonly used commercial antimicrobial agent in the food industry. Successful intercalation of natural citrate ions into LDH and its activity against the tested microbes show the potential of using it as a slow-release nanohybrid material in many food-related applications. Keywords: Layered Double Hydroxide, α-Hydroxycitrate, Natural, Safe, Lime Extract, Slow Release, Antimicrobia

Urea-Hydroxyapatite Nanohybrids for Slow Release of Nitrogen.

While slow release of chemicals has been widely applied for drug delivery, little work has been done on using this general nanotechnology-based principle for delivering nutrients to crops. In developing countries, the cost of fertilizers can be significant and is often the limiting factor for food supply. Thus, it is important to develop technologies that minimize the cost of fertilizers through efficient and targeted delivery. Urea is a rich source of nitrogen and therefore a commonly used fertilizer. We focus our work on the synthesis of environmentally benign nanoparticles carrying urea as the crop nutrient that can be released in a programmed manner for use as a nanofertilizer. In this study, the high solubility of urea molecules has been reduced by incorporating it into a matrix of hydroxyapatite nanoparticles. Hydroxyapatite nanoparticles have been selected due to their excellent biocompatibility while acting as a rich phosphorus source. In addition, the high surface area offered by nanoparticles allows binding of a large amount of urea molecules. The method reported here is simple and scalable, allowing the synthesis of a urea-modified hydroxyapatite nanohybrid as fertilizer having a ratio of urea to hydroxyapatite of 6:1 by weight. Specifically, a nanohybrid suspension was synthesized by $\textit{in situ}$ coating of hydroxyapatite with urea at the nanoscale. In addition to the stabilization imparted due to the high surface area to volume ratio of the nanoparticles, supplementary stabilization leading to high loading of urea was provided by flash drying the suspension to obtain a solid nanohybrid. This nanohybrid with a nitrogen weight of 40% provides a platform for its slow release. Its potential application in agriculture to maintain yield and reduce the amount of urea used is demonstrated.Authors thank Hayleys Agro Ltd., Sri Lanka for initiating this research programme at SLINTEC and Nagarjuna Fertilizer and Chemical Ltd (NFCL), India for providing further support. Authors acknowledge Mr Sunanda Gunesekara of SLINTEC for assistance with scaling up the production process to enable the field trials. ARK acknowledges the financial support received from ICTPELETTRA Users Program, Trieste, Italy to conduct photoemission experiments at Materials Science beam line (MSB) and ELETTRA SRS on HA and urea coated HA samples. ARK further acknowledges Dr. R.G. Acres of MSB beam line for his extensive support to conduct photoemission experiments. We acknowledge the Department of Agriculture and Rice Research and Development Institute of Sri Lanka, in particular Dr Priyantha Weerasinghe, Mr D Sirisena and Dr Amitha Benthota for the assistance in carrying out pot and farmers filed trials. NFCL and Central Salt & Marine Chemicals Research Institute, Gujarat, India for TEM and BET analysis

Urea-Hydroxyapatite Nanohybrids for Slow Release of Nitrogen

While slow release of chemicals has been widely applied for drug delivery, little work has been done on using this general nanotechnology-based principle for delivering nutrients to crops. In developing countries, the cost of fertilizers can be significant and is often the limiting factor for food supply. Thus, it is important to develop technologies that minimize the cost of fertilizers through efficient and targeted delivery. Urea is a rich source of nitrogen and therefore a commonly used fertilizer. We focus our work on the synthesis of environmentally benign nanoparticles carrying urea as the crop nutrient that can be released in a programmed manner for use as a nanofertilizer. In this study, the high solubility of urea molecules has been reduced by incorporating it into a matrix of hydroxyapatite nanoparticles. Hydroxyapatite nanoparticles have been selected due to their excellent biocompatibility while acting as a rich phosphorus source. In addition, the high surface area offered by nanoparticles allows binding of a large amount of urea molecules. The method reported here is simple and scalable, allowing the synthesis of a urea-modified hydroxyapatite nanohybrid as fertilizer having a ratio of urea to hydroxyapatite of 6:1 by weight. Specifically, a nanohybrid suspension was synthesized by $\textit{in situ}$ coating of hydroxyapatite with urea at the nanoscale. In addition to the stabilization imparted due to the high surface area to volume ratio of the nanoparticles, supplementary stabilization leading to high loading of urea was provided by flash drying the suspension to obtain a solid nanohybrid. This nanohybrid with a nitrogen weight of 40% provides a platform for its slow release. Its potential application in agriculture to maintain yield and reduce the amount of urea used is demonstrated.Authors thank Hayleys Agro Ltd., Sri Lanka for initiating this research programme at SLINTEC and Nagarjuna Fertilizer and Chemical Ltd (NFCL), India for providing further support. Authors acknowledge Mr Sunanda Gunesekara of SLINTEC for assistance with scaling up the production process to enable the field trials. ARK acknowledges the financial support received from ICTPELETTRA Users Program, Trieste, Italy to conduct photoemission experiments at Materials Science beam line (MSB) and ELETTRA SRS on HA and urea coated HA samples. ARK further acknowledges Dr. R.G. Acres of MSB beam line for his extensive support to conduct photoemission experiments. We acknowledge the Department of Agriculture and Rice Research and Development Institute of Sri Lanka, in particular Dr Priyantha Weerasinghe, Mr D Sirisena and Dr Amitha Benthota for the assistance in carrying out pot and farmers filed trials. NFCL and Central Salt & Marine Chemicals Research Institute, Gujarat, India for TEM and BET analysis

[C+NC+CC] REACTION-ENABLED CONSTRUCTION OF A PYRROLIDINE FRAGMENT LIBRARY AND ASYMMETRIC SYNTHESIS OF THE CORE ERGOT SUBUNIT, LYSERGIC ACID

The pyrrolidine ring is an important structural motif found in bioactive molecules, natural products, and drugs. Consequently, the asymmetric synthesis of pyrrolidine-containing targets has been the focus of intense research. However, current pyrrolidine synthesis strategies have been largely limited to stable imine precursors derived from non-enolizable (usually aromatic) aldehydes. To address these limitations Garner’s lab introduced the asymmetric [C+NC+CC] coupling reaction which assembles highly functionalized pyrrolidines in a controlled and predictable fashion. Generally, any type of aldehyde, enolizable, non-enolizable, alkyl, or aromatic, can be introduced to the reaction as the “C” component. Fragment-based drug discovery (FBDD) is a frontline technique established to find high-quality small molecule leads and drug candidates. Pyrrolidine is one of the highly focused scaffolds in FBDD and appropriately substituted and functionalized pyrrolidines provide good coverage of functional vector space for fragment optimization. In a collaborative effort with AbbVie Inc., I was able to synthesize a homochiral 5-heteroaromatic-substituted pyrrolidine fragment drug library using the asymmetric [C+NC+CC] coupling reaction. From the standing point of physicochemical properties, the synthesized library fits at the upper acceptable range for fragments, and from the 3D profile calculated using shape-based descriptors (normalized principal moments of inertia and plane of best fit) they were found to sit well within 3D space proving the versatility of our chemistry in fragment synthesis.Lysergic acid is a pharmacologically important and structurally intriguing molecule obtained by the hydrolysis of ergot alkaloids. Lysergic acid processes a unique tetracyclic ergoline skeleton containing a tetrahydropyridine and a [C, D]-fused indole, an interesting but rather challenging target for synthetic chemists. Herein, utilizing the [C+NC+CC] coupling reaction we were able to complete the total formal synthesis of (+)-lysergic acid in 20 steps starting from commercially available 4-bromoindole. During the quest we were able to directly construct the C and the (pre) D rings, stereoselectively in a single operation. This challenging synthesis featured the first example of the intermolecular asymmetric [C+NC+CC] coupling reaction and a novel application of the Cossy-Charette ring expansion

EMUNE: a bulk transfer service architecture for multi-interfaced mobile devices

Today's mobile devices increasingly contain multiple radios, enabling users on the move to take advantage of a heterogeneous wireless network environment. In addition, many bandwidth intensive services, such as podcasts or software updates are highly delay tolerant and memory in mobile devices is effectively unlimited. To take advantage of these technology trends, we propose EMUNE, a new transfer service architecture. EMUNE supports opportunistic bulk transfers in high bandwidth networks with intermittent availability. In addition, EMUNE can also satisfy a minimum data transfer rate, and dynamically adapt to application requirements and user preferences for quality and monetary/power costs.Our proposed architecture consists of an API, a prediction engine, a scheduling engine and a transport service. The API specifies what the transfer service offers, and how the service can be used by the applications. The prediction engine infers future network availability and their characteristics such as the available bandwidth for a time duration ahead. The scheduling engine takes the output of the prediction engine as well as the power and monetary costs of networks, application requirements and user preferences into account. It then determines which interface to use, when and for how long for all outstanding data transfer requests within that duration. The transport service accordingly executes the inferred data transfer schedule by assigning applications' data flows to the corresponding access networks. The architecture repeats this process for successive time durations, as long as there is data available to be transferred. In addition to presenting EMUNE, we provide a thorough evaluation of the architecture and its components using data of many real users, to show the effectiveness of EMUNE in improving the utilization of multiple network interfaces of mobile devices in a heterogeneous networking environment