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News Article | March 27, 2016
Site: www.techtimes.com

Methane is one of the major climate change contributors that is 24 times more potent than carbon dioxide as a greenhouse gas. Researchers discover methane's new potential as a chemical building block that they can use to make more complex molecules such as the ones used in pharmaceuticals. This new method provides a way to optimize methane's properties without releasing the damaging greenhouse gasses. According to University of Pennsylvania's Daniel Mindiola, developing new ways to use this abundant gas besides burning it as fuel creates a new approach towards methane use. "Our method will hopefully provide inspiration to move away from burning our resources and instead using them more as a carbon building block to prepare more valuable materials," added Mindiola, the study's senior author and the University's Presidential Professor in the Department of Chemistry in the School of Arts & Sciences. The study is set for publication in the journal Science. Methane is made up or a carbon atom linked to four hydrogen atoms. When methane is burned, the four bonds are destroyed. This results in the production of greenhouse gasses. The researchers theorized that if only one of two of the hydrogen bonds are efficiently broken down, it could be possible to link the carbon atoms from two or more molecules of methane to produce bigger hydrocarbons. In the study, Mindiola and team used the borylation method to selectively manipulate the carbon-hydrogen bonds. This process is when a hydrocarbon reacts with a compound that contains boron. A metal is used to catalyze the reaction. This replaces a hydrocarbon's carbon-hydrogen bond with a carbon-boron bond. Later on, the replacement bond can be coaxed to bond the carbon to any chemical groups. The borylation process was created over 10 years ago by Professor Milton R. Smith III from Michigan State University but this is the first time it was utilized using methane. The researchers tried this approach at the University's High Throughput Screening Center, which enables the researchers to test reactions under high-pressure conditions. Here, the team was able to work with methane in its gas state and used iridium as the metal catalyst. "It turns out methane is not as inert as one would have expected. We were able to borylate it using off-the-shelf reagents, which is very convenient," said Mindiola. "I think this work is going to inspire a lot of chemistry and get people thinking about methane in a different way." The new study completed a separate paper which will be published in the same Science journal issue, spearheaded by Melanie Sanford from the University of Michigan.


News Article | March 24, 2016
Site: phys.org

With a new method, a research team led by chemists at the University of Pennsylvania has demonstrated the potential to use methane not as a fossil fuel but as a versatile chemical building block with which to make more complex molecules, such as pharmaceuticals and other value-added substances. The reaction also offers a way of taking advantage of the properties of methane without releasing greenhouse gases. "Finding ways to use methane besides burning it as a fuel constitutes a practical approach to using this abundant gas," said Daniel Mindiola, senior author on the paper and a Presidential Professor in Penn's Department of Chemistry in the School of Arts & Sciences. "Our method will hopefully provide inspiration to move away from burning our resources and instead using them more as a carbon building block to prepare more valuable materials." The study will be published in Science. Mindiola collaborated on the work with Kyle Smith, a graduate student in Mindiola's lab and the paper's lead author; Simon Berritt, director of Penn's High Throughput Screening Center based in the Department of Chemistry; Mariano González-Moreiras, a visiting scholar; Seihwan Ahn and Mu-Hyun Baik of Korea's Advanced Institute of Science and Technology; and Milton R. Smith III, a professor at Michigan State University who, together with Rob Maleczka, first discovered the chemical reaction known as carbon-hydrogen borylation upon which the current work builds. Methane is comprised of a carbon atom bonded to four hydrogen atoms. When it is burned, all four of the carbon-hydrogen bonds are broken, resulting in the production of carbon dioxide and water, both of which are greenhouse gases. "If only one or two hydrogen bonds could be broken efficiently, then it might be possible to connect carbon atoms from two or more methane molecules to make larger hydrocarbons," said Michigan State's Smith. "For example, gasoline is a mixture of hydrocarbons containing between four and 12 carbon atoms. The polyethylene used to make garbage bags and milk jugs is composed of millions of carbon atoms." Selectively controlling the carbon-hydrogen bonds has been difficult, however. Chemists have therefore considered methane relatively inert unless burned. In addition, because methane is a gas at ambient temperatures and pressures, it is not the easiest chemical to manipulate. But Mindiola had a brainstorm: what if he tried a borylation reaction using methane while varying pressure conditions? Carbon-hydrogen borylation is a process developed by Smith and colleagues in which a hydrocarbon reacts with a boron-containing compound, catalyzed by a metal. The reaction results in the replacement of a carbon-hydrogen bond on the hydrocarbon with a carbon-boron bond. This bond can then later be easily swapped to bond the carbon to any number of other chemical groups. Though borylation was discovered more than a decade ago, no one had tried it using methane, the simplest of hydrocarbons. The researchers decided to attempt this. Taking advantage of known conditions reported in the literature for other substrates, they determined the right combination of compounds and catalysts that might work, then used a computational approach to evaluate different conditions and reagents that might improve the reaction's efficiency. Finally, they used Penn's High Throughput Screening Center, one of only a handful of such facilities in the country, which allows for the testing of 96 different reactions at once, to identify the most efficient conditions for the reaction. The Penn facility is unique in that it allows for reactions to be done under high-pressure conditions, which permitted the team to use methane in a gaseous state as opposed to working under ambient conditions. The most favorable reaction, conducted under relatively mild conditions of 150 degrees Celsius and 500 pound per square inch of methane, using the metal iridium as a catalyst, resulted in yields as high as 52 percent borylated methane with high selectivity for the carbon-hydrogen borylation of one C-H bond as opposed to multiple bonds. "It turns out methane is not as inert as one would have expected," Mindiola said. "We were able to borylate it using off-the-shelf reagents, which is very convenient." The team is currently evaluating other reagents to do a similar reaction. For example, they are trying to find alternative catalysts because iridium, though commercially available, is relatively rare and expensive. Cobalt may offer a promising alternative. They are also testing silicon compounds as an alternative to those containing the rarer boron. Methane is currently so abundant that the petrochemical industry burns approximately $50 million of methane each year in gas flares, in part due to a lack of storage capacity. And while some methane is used for steam reforming, a process that forms carbon monoxide and hydrogen that can be used in fuel cells or to make ammonia for fertilizers, the researchers believe the borylation reaction can offer a meaningful alternative use for methane. "I think this work is going to inspire a lot of chemistry and get people thinking about methane in a different way," Mindiola said. "That doesn't mean that the natural gas industry is going to borylate all the methane they're extracting—there is a lot out there and boron is rare—but it's another valuable option." Mindiola noted that this work complements another paper, published in the same issue of Science, led by the University of Michigan's Melanie Sanford. That report identifies a way to perform borylation of methane's carbon-hydrogen bonds selectively, borylating either one or two bonds, and to expand this method to the second most abundant hydrocarbon, ethane. Implementing both reactions could make it more feasible for methane to be used by the pharmaceutical industry as well as many others to craft designer molecules with a plethora of uses. Explore further: Cheap metals can be used to make products from petroleum


Nebane N.M.,High Throughput Screening Center | Coric T.,University of Alabama at Birmingham | McKellip S.,High Throughput Screening Center | Woods L.,High Throughput Screening Center | And 4 more authors.
Journal of Laboratory Automation | Year: 2016

The development of acoustic droplet ejection (ADE) technology has resulted in many positive changes associated with the operations in a high-throughput screening (HTS) laboratory. Originally, this liquid transfer technology was used to simply transfer DMSO solutions of primarily compounds. With the introduction of Labcyte’s Echo 555, which has aqueous dispense capability, the application of this technology has been expanded beyond its original use. This includes the transfer of many biological reagents solubilized in aqueous buffers, including siRNAs. The Echo 555 is ideal for siRNA dispensing because it is accurate at low volumes and a step-down dilution is not necessary. The potential for liquid carryover and cross-contamination is eliminated, as no tips are needed. Herein, we describe the siRNA screening platform at Southern Research’s HTS Center using the ADE technology. With this technology, an siRNA library can be dispensed weeks or even months in advance of the assay itself. The protocol has been optimized to achieve assay parameters comparable to small-molecule screening parameters, and exceeding the norm reported for genomewide siRNA screens. © 2015, © 2015 Society for Laboratory Automation and Screening.


PubMed | High Throughput Screening Center and University of Alabama at Birmingham
Type: Journal Article | Journal: Journal of laboratory automation | Year: 2016

The development of acoustic droplet ejection (ADE) technology has resulted in many positive changes associated with the operations in a high-throughput screening (HTS) laboratory. Originally, this liquid transfer technology was used to simply transfer DMSO solutions of primarily compounds. With the introduction of Labcytes Echo 555, which has aqueous dispense capability, the application of this technology has been expanded beyond its original use. This includes the transfer of many biological reagents solubilized in aqueous buffers, including siRNAs. The Echo 555 is ideal for siRNA dispensing because it is accurate at low volumes and a step-down dilution is not necessary. The potential for liquid carryover and cross-contamination is eliminated, as no tips are needed. Herein, we describe the siRNA screening platform at Southern Researchs HTS Center using the ADE technology. With this technology, an siRNA library can be dispensed weeks or even months in advance of the assay itself. The protocol has been optimized to achieve assay parameters comparable to small-molecule screening parameters, and exceeding the norm reported for genomewide siRNA screens.


Rasmussen L.,High Throughput Screening Center | Tigabu B.,University of Texas Medical Branch | White E.L.,High Throughput Screening Center | Bostwick R.,High Throughput Screening Center | And 7 more authors.
Assay and Drug Development Technologies | Year: 2015

High-throughput screening (HTS) has been integrated into the drug discovery process, and multiple assay formats have been widely used in many different disease areas but with limited focus on infectious agents. In recent years, there has been an increase in the number of HTS campaigns using infectious wild-type pathogens rather than surrogates or biochemical pathogen-derived targets. Concurrently, enhanced emerging pathogen surveillance and increased human mobility have resulted in an increase in the emergence and dissemination of infectious human pathogens with serious public health, economic, and social implications at global levels. Adapting the HTS drug discovery process to biocontainment laboratories to develop new drugs for these previously uncharacterized and highly pathogenic agents is now feasible, but HTS at higher biosafety levels (BSL) presents a number of unique challenges. HTS has been conducted with multiple bacterial and viral pathogens at both BSL-2 and BSL-3, and pilot screens have recently been extended to BSL-4 environments for both Nipah and Ebola viruses. These recent successful efforts demonstrate that HTS can be safely conducted at the highest levels of biological containment. This review outlines the specific issues that must be considered in the execution of an HTS drug discovery program for high-containment pathogens. We present an overview of the requirements for HTS in high-level biocontainment laboratories. © Copyright 2015, Mary Ann Liebert, Inc. 2015.

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