PROMOTING EFFICIENT GAS DEPENDENT FLOW REACTIONS



Uniqsis Ltd has announced a new Gas Addition Module for its FlowSyn continuous flow reactor range. The new module enables fast, controllable pre-saturation of liquid reagents with a wide range of gases thereby promoting efficient gas-dependent reactions in flow, such as carbonylation, hydrogenation, ozonolysis and direct synthesis of carboxylic acids.
Mixing gas and liquids in a controllable and reliable manner has always posed a particular challenge for flow chemists, in particular the prevention of undissolved gas bubbles which have an adverse effect on the control of pressure and residence time in flow chemistry. The novel pressurised tube-in-tube design of the Gas Addition Module overcomes this problem by ensuring continuous interaction between the gas and liquid at every point along its length.
The tube-in-tube design is based on semi-permeable membrane technology, whereby the semi-permeable inner tube containing the liquid (typically a solvent) is bathed by a stream of pressurised gas, which is enclosed within a thick-walled impermeable outer tube. The pressurised gas is able to cross the semi-permeable membrane of the inner tube and dissolve into the liquid carried within. However, because of the semi-permeable nature of the inner tube material, the liquid is unable to cross in the opposite direction.
The Gas Addition Module is compatible with a wide range of reactive gases (e.g. CO, CO₂, H₂, ethene, ethyne, SO₂) and organic solvents (e.g. THF, Acetonitrile, Methanol, Propanol). Capable of generating a continuous gas-saturated solvent stream in typically less than 10 seconds, it enables flow chemists to carry out a wide variety of applications with minimum effort, including heterogeneous and homogeneous gas-liquid reactions such as hydrogenation, ozonolysis, carbonylation, and direct synthesis of carboxylic acids.
A particularly convenient feature of the Uniqsis Gas Addition Module is the availability of an optional Portable Gas Reservoir. This handy space-saving device is easy and safe to charge with gas from a larger reservoir and obviates the need to bring bulky pressurised gas cylinders into the immediate experimental area. The Gas Addition Module can be added in-line to any FlowSyn system and other continuous flow reactors to provide a solvent feed stream pre-saturated with gas, although it can also be used as a reactor in its own right.

For further information about the Gas Addition Module please contact Uniqsis now on +44-845-864-7747 or info@uniqsis.com.
Uniqsis specialises in the design of meso-scale continuous flow chemistry systems for a wide range of applications in chemical and pharmaceutical research. The company’s aim is to make flow chemistry easily accessible to both novices and experienced users.

UNIQSIS - FLOW METHODOLOGY FOR HIGHLY REPRODUCIBLE BROMINATION REACTIONS



Uniqsis has announced an application note that describes a continuous flow methodology for electrophilic bromination that offers excellent control of both temperature and mixing using a proprietary mixer chip, leading to a highly reproducible outcome.
Electrophilic bromination is a useful reaction in organic synthesis. However, when molecular bromine is used as the electrophile, under acidic conditions, it can be difficult to control both the exothermic addition and to prevent subsequent bis-bromination of the desired monobrominated product.
In application note 21** - the authors demonstrate that using a static mixer chip on a FlowSyn flow chemistry system to control both mixing and temperature - bromination becomes a titration and the reaction can be performed rapidly under elevated temperatures. The bromination could be performed in a coil reactor however the short reaction time of 30 seconds at 70°C makes it better suited to implementation in a chip. The authors suggest how the chip based bromination methodology could be straightforwardly scaled to 28g / hour by connecting a 5 ml HT-PTFE coil reactor in line with the mixer chip and increasing the flow rate to 13.2 ml/min.
The Uniqsis FlowSyn™ is a compact integrated continuous flow reactor system designed for easy, safe and efficient operation. The FlowSyn™ range includes models for performing single or multiple homogeneous or heterogeneous reactions, either manually or automatically. The range of chemistries that can be explored with Uniqsis’ integrated and modular flow chemistry systems grows ever wider and is exemplified by the growing number of applications published both in the academic press and in Uniqsis’ own application notes. Typical examples of flow chemistry applications include hydrogenation, nitration, bromination, metalation, molecular rearrangements and synthesis of compounds suchas dihyropyridine, indole, pyrazole, quinolinone and benzimidazole.
To find out more about using the FlowSyn Continuous Flow Chemistry System for bromination reactions please visit www.uniqsis.com/fcApplications.aspx#22 or contact Uniqsis now on +44-845-864-7747 / info@uniqsis.com.
www.uniqsis.com/fcApplications.aspx#22

NOVEL DISCOVERY PAVES THE WAY TO IMPROVE WASTE DEGRADATION AND LASER-ASSISTED ETCHING OF MATERIALS
A team of researchers from the National University of Singapore (NUS) led by Professor Loh Kian Ping, Head of the Department of Chemistry at the NUS Faculty of Science, has successfully altered the properties of water, making it corrosive enough to etch diamonds. This was achieved by attaching a layer of graphene on diamond and heated to high temperatures. Water molecules trapped between them become highly corrosive, as opposed to normal water. This novel discovery, reported for the first time, has wide-ranging industrial applications, from environmentally-friendly degradation of organic wastes to laser-assisted etching of semiconductor or dielectric films.
The findings were published online in Nature Communications on 5 March 2013 with Ms Candy Lim Yi Xuan, a Ph.D. candidate at the NUS Graduate School for Integrative Sciences and Engineering as the first author.

When Diamond Meets Graphene
While diamond is known to be a material with superlative physical qualities, little is known about how it interfaces with graphene, a one-atom thick substance composed of pure carbon.
A team of scientists from NUS, Bruker Singapore and Hasselt University Wetenschapspark in Belgium, sought to explore what happens when a layer of graphene, behaving like a soft membrane, is attached on diamond, which is also composed of carbon. To encourage bonding between the two rather dissimilar carbon forms, the researchers heated them to high temperatures.
At elevated temperatures, the team noted a restructuring of the interface and chemical bonding between graphene and diamond. As graphene is an impermeable material, water trapped between the diamond and graphene cannot escape. At a temperature that is above 400 degree Celsius, the trapped water transforms into a distinct supercritical phase, with different behaviours compared to normal water.
Said Professor Loh, who is also a Principal Investigator with the Graphene Research Centre at NUS, "We show for the first time that graphene can trap water on diamond, and the system behaves like a 'pressure cooker' when heated. Even more surprising, we found that such superheated water can corrode diamond. This has never been reported."

Industrial Applications and New Insights
Due to its transparent nature, the graphene bubble-on-diamond platform provides a novel way of studying the behaviours of liquids at high pressures and high temperature conditions, which is traditionally difficult.
"The applications from our experiment are immense. In the industry, supercritical water can be used for the degradation of organic waste in an environmentally friendly manner. Our work can is also applicable to the laser-assisted etching of semiconductor or dielectric films, where the graphene membrane can be used to trap liquids," Prof Loh elaborated.
To further their research, Prof Loh and his team will study the supercritical behaviours of other fluids at high temperatures, and strive to derive a wider range of industrial applications.
www.nus.edu.sg

BIOLOGICAL ROBOTS COULD AID DRUG SCREENING OR CHEMICAL ANALYSIS
The cardiac cells of rats have been used to propel biological machines that could one day be employed in drug screening or chemical analysis. The so-called ‘bio-bots’ developed at Illinois University are said to represent an advance in synthetic biology and demonstrate the team’s ability to forward-engineer functional machines using only hydrogel, heart cells and a 3D printer. The team claims that, with an altered design, the bio-bots could be customised for specific applications in medicine, energy or the environment. The research team, led by Prof Rashid Bashir, published its results in the journal Scientific Reports. ‘The idea is that, by being able to design with biological structures, we can harness the power of cells and nature to address challenges facing society,’ said Bashir, an Abel Bliss professor of engineering at Illinois. ‘As engineers, we’ve always built things with hard materials; materials that are very predictable. Yet there are a lot of applications where nature solves a problem in such an elegant way. Can we replicate some of that if we can understand how to put things together with cells?’ Resembling a tiny springboard, each bio-bot has one long, thin leg resting on a supporting leg. The thin leg is covered with rat cardiac cells. When the heart cells beat, the long leg pulses, propelling the bio-bot forward. The team uses a 3D printing method common in rapid prototyping to make the main body of the bio-bot from hydrogel — a soft, gelatin-like polymer. This approach allowed the researchers to explore various conformations and adjust their design for maximum speed. The ease of quickly altering design also will allow them to build and test other configurations for further potential applications. Bashir envisions the bio-bot being used for drug screening or chemical analysis, since its motion can indicate how the cells are responding to the environment. By integrating cells that respond to certain stimuli, such as chemical gradients, the bio-bot could be used as sensors.‘ Our goal is to see if we can get this thing to move towards chemical gradients, so we could eventually design something that can look for a specific toxin and then try to neutralise it,’ he said. ?’Now you can think about a sensor that’s moving and constantly sampling and doing something useful, in medicine and the environment. The applications could be many, depending on what cell types we use and where we want to go with it.’ Next, the team will work to enhance control and function, such as integrating neurons to direct motion or cells that respond to light. The researchers are also working on creating robots of different shapes and with different numbers of legs and robots that could climb slopes or steps. ‘The idea here is that you can do it by forward engineering,’ said Bashir, who is the director of the Micro and Nanotechnology Laboratory. ‘We have the design rules to make these millimetre-scale shapes and different physical architectures, which hasn’t been done with this level of control. What we want to do now is add more functionality to it.’ Graduate student Vincent Chan, first author of the paper, said: ‘I think we are just beginning to scratch the surface in this regard. That is what’s so exciting about this technology — to be able to exploit some of nature’s unique capabilities and utilise it for other beneficial purposes or functions.’
www.theengineer.co.uk

RADIOACTIVE BACTERIA ATTACK CANCER



Two dangerous things together might make a medicine for one of the hardest cancers to treat. In a mouse model of pancreatic cancer, researchers have shown that bacteria can deliver deadly radiation to tumours — exploiting the immune suppression that normally makes the disease so intractable.
Fewer than one in 25 people diagnosed with pancreatic cancer are alive five years later. Chemotherapy, surgery and radiotherapy are generally ineffective, mainly because the disease has often spread to other organs even before it is detected.
The work, which is described in the Proceedings of the National Academy of Sciences1, began when Ekaterina Dadachova of the Albert Einstein College of Medicine in New York thought of combining two ways to fight cancer. She studies how radioactive isotopes can be used as anti-cancer weapons, and her colleague Claudia Gravekamp has been looking at whether weakened bacteria can be used to carry compounds that provoke a patient’s white blood cells into attacking the cancer. “I thought maybe we could combine the power of radiation with the power of live bacteria,” Dadachova says.
Sometimes found in food, the bacterium Listeria monocytogenes can cause severe infection, but is usually wiped out by the immune system. Exploiting the fact that cancer cells tend to suppress the immune reaction to avoid being destroyed, the two researchers and their collaborators decided to coat Listeria with radioactive antibodies and injected the bacterium into mice with pancreatic cancer that had spread to multiple sites. After several doses, the mice that had received the radioactive bacteria had 90% fewer metastases compared with mice that had received saline or radiation alone. “That was the first time we'd seen such a big effect,” says Gravekamp.
The immune system rapidly clears Listeria from healthy tissue, says Gravekamp, but tumour cells suppress the immune system and allow Listeria to remain. That means that tumour cells will receive continuous exposure but normal cells will be spared, she says.

Unexplained effects
But Elizabeth Jaffee, an oncologist at Johns Hopkins University in Baltimore, Maryland, who has used non-radioactive Listeria in human trials for advanced cancers, including pancreatic cancer, says that some of the observations in the paper are hard to explain, particularly how weakened Listeria gets into metastases and why it's ineffective against the primary tumour.
Other researchers worry that healthy organs may receive excessive amounts of radiation. James Abbruzzese, an oncologist at the University of Texas MD Anderson Cancer Center in Houston, says that the levels of radiation reported in the liver and other organs were disturbingly high, and that he would have liked clearer data that the radiation is being delivered specifically to tumours.
Estimating dose levels between animals and humans is not always straightforward, but Dadachova counters that, according to her calculations, the radiation levels are below what is considered the safety threshold for humans, and that patients with pancreatic cancer tend to be less prone to radiation sickness because they have not usually received chemotherapy beforehand.
Joseph Herman, a radiation oncologist at Johns Hopkins, says that he would have liked to have seen results for other tumour types. And although the study found no signs of tissue damage one week after high-dose treatment of radioactive Listeria, Herman thinks that the effects of radiation might take longer to show up.
Still, Herman says, the approach might present an option where few exist. “The benefit is that it's a way of killing cancer cells in a cancer where therapy has not been very effective,” he says. “It's exciting, but it needs to be further validated.”
Listeria bacteria carrying the compound rhenium-188 (red) can deliver sustained doses of radiation to pancreatic-cancer cells.
www.nature.com

UW SPINOFF IMPEL NEUROPHARMA PASSES KEY NOSE-TO-BRAIN CLINICAL TRIAL
Seattle-based Impel Neuropharma has been working for five years to show it can quickly deliver drugs through the nose, directly to the brain, for the treatment of central nervous system disorders. The animal data so far has been encouraging, but now the company has got key confirmation that it can do its thing in human beings.
Impel, a University of Washington spinoff, is announcing today that it has gotten those positive results from a study of seven patients, which was supported by one of its pharmaceutical collaborators. Full details are being saved for a peer-reviewed publication, but Impel chief scientist John Hoekman says that the company’s nose-to-brain drug delivery device was able to propel a small peptide molecule deep into the upper nasal passages and to the brain stem at an “order of magnitude” greater concentration than a conventional nasal spray.
The study enrolled research subjects at the Lovelace Respiratory Research Institute in Albuquerque, NM, Hoekman says. Researchers used an off-the-shelf peptide (not an actual drug candidate), attached to a radioactive tracer molecule, and used noninvasive SPECT imaging technology to confirm that the drug was getting delivered to the brain. Volunteers in the study were able to self-administer the compound through the nose, and researchers saw it get delivered to the destination within 10 to 20 minutes, Hoekman says.
“This is a pretty seminal study for us,” says Impel CEO Michael Hite. “The impact to the field of nose-to-brain delivery in general is going to be pretty significant.”
The idea at Impel, which I first wrote about for Xconomy in August 2008, is to noninvasively get drugs deep into the anatomy of the skull, where nasal sprays can’t go. Most nasal sprays don’t propel drugs anywhere close to the upper nasal passage—the only place in the body where primary neurons are possibly accessible to the outside environment. Impel’s device delivers a pressurized, rotational flow of aerosol to reach those neurons.
This kind of technology could be valuable for a number of different patient groups with central nervous system disorders. The body’s blood-brain barrier stops many drugs from getting where they need to go in the brain. Oral pills that are effective for central nervous system disorders, like, say, Parkinson’s disease, take some time to be absorbed thoroughly into the blood, and they can cause side effects when absorbed throughout the body. A nose-to-brain delivery device could, in theory, get an effective pain reliever to work more quickly for patients in need of something fast, and do it safely by minimizing the amount that gets absorbed into the bloodstream. It also could be convenient for patients, especially when compared with injectable treatment options.
Impel has gotten this far on about $1.5 million in investment from friends, family, and angel investors, plus about $3.5 million in grants from the National Institutes of Health, Department of Defense, and the state of Washington’s Life Sciences Discovery Fund. The company has struck a series of small research collaborations with seven pharmaceutical and medical device manufacturers that are developing central nervous system drugs, Hite says.
Of course, Impel isn’t the only group seeking to effectively deliver biologics through the nose and to the brain. UW researcher Suzanne Craft made headlines a couple years ago when she led a study which suggested that insulin—a well-known peptide used for treating diabetes—might be an effective option for treating Alzheimer’s disease when delivered through a nasal spray.
The next step at Impel will be to show biotech and pharma partners the data at the Biotechnology Industry Organization convention in Chicago, Hite says. The goal will be to strike a bigger type of drug/device development collaboration, which would involve an active drug candidate at a pharma company that is being tested in a typical early-stage clinical trial to assess safety, absorption, and drug distribution through tissues, Hite says.
Impel believes its device can work with a variety of biologic drugs—peptides and larger protein molecules. The company’s animal trials have suggested it can deliver a wide variety of biologics in different shapes and sizes, Hoekman says.
www.xconomy.com

WATERS CORPORATION. ST. JOHN’S RESEARCH INSTITUTE HONORED BY WATERS CENTER OF INNOVATION PROGRAM
Structural Proteomics Laboratory Directed by Prof. Dr. Amit Kumar Mandal Recognized for Global Disease Research. At a ceremony at St. John’s Research Institute (Bangalore, India) Waters announced the selection of the St. John’s Research Institute for its Centers of Innovation Program for research in the field of structural proteomics. It is the first institution in India to receive the designation of a Waters® Center of Innovation.
Under the direction of Prof. Dr. Amit Kumar Mandal, a Professor of Molecular Medicine and Clinical Proteomics, St. John’s has earned a reputation for its research in blood disorders and other diseases that disproportionately affect disadvantaged populations. 
Prof. Mandal’s relationship with Waters began when he first began using a combination of a nanoACQUITY UPLC^® System and a Waters SYNAPT^® HDMS Mass Spectrometer equipped with an electrospray ionization source, a MALDI source, and an option for doing hydrogen deuterium exchange mass spectrometry (HDXMS). 
Waters became one of the first analytical instrument industry companies to establish a direct presence in India in 1988. Now with headquarters in Bangalore and satellite offices in six cities throughout the country, Waters supports its many customers directly with training, applications development and service support.
www.waters.com

HOVIONE ANNOUNCES A CO-PROMOTION AND COLLABORATION AGREEMENT WITH LIGAND FOR CAPTISOL^®
Hovione today announced a co-promotion and collaboration agreement with Ligand to provide Hovione’s customers efficient access to Captisol^® technology. Captisol, a chemically modified cyclodextrin, is proven to improve the solubility and stability of drugs and is currently used in six marketed products. Hovione offers innovative particle engineering technologies to improve the solubility of modern drugs.  The agreement allows Hovione to use Captisol technology in its solubilization programs, which include amorphous solid dispersions, crystal design and size reduction and control of particle size.  By adding this new technology, it increases the likelihood of solving the molecule’s bioavailability challenges.
http://www.hovione.com