CHEMICAL INFORMATION

Green chemistry has ecological, financial benefits for Pfizer

2012-02-13T23:09:00.000-08:00

When people hear the word "green" these days, they automatically think "environmentally friendly." But among chemists at Pfizer Inc. in Groton, the word also denotes efficiency, which equals a different type of "green" - money.

And Pfizer's local laboratories have been saving the company plenty of money - millions of dollars, most likely, though the company won't provide specific figures - over the past few years through a relatively new idea called green chemistry. Scientists in Groton are constantly reviewing and revising the chemical processes that go into the manufacture of top-selling medicines such as the cholesterol blockbuster Lipitor and pain reliever Lyrica, making sure new drugs are produced in the most efficient manner possible.

"Pfizer is a leader in both the research and implementation of green-chemistry and green-engineering practices," said S. Stewart Slater, a professor of chemical engineering at Rowan University in Glassboro, N.J.

By going green - which local scientists spearheaded at Pfizer a decade ago, though the chemistry principles date to the early 1990s - the making of pharmaceuticals is being done in a less wasteful, safer and more benign manner.

"By being green chemists, I think we provide a particular benefit to the environment," said John Wong, senior research fellow at Pfizer's Groton labs and leader of the eight-member Green Chemistry Team there. "When you use enzymes to do chemistry, they are not toxic and certainly environmentally friendly."

In the pharmaceutical industry, green chemistry often means the replacement of organic solvents with enzymes, commonly referred to as "nature's catalysts" and naturally occurring in all living organisms. Companies try to implement green chemistry ideas right from the start, because changing drug formulations after a product is out requires additional human testing for safety and effectiveness.

Eric Watters, environmental manager of the Groton facility and a team member, said the use of green-chemistry methods doesn't have a big impact on the local air and water because the pharmaceutical giant no longer has extensive manufacturing facilities here. It's at the company's drug-making plants worldwide that the use of green chemistry is most noticeable on the environment, he said.

The environmental impact is felt most profoundly with reductions in the amount of carbon dioxide released into the atmosphere. Efficiencies and cost savings come largely from reduced use of raw materials and significant cuts in energy use.

To give an example, Wong pointed to a new process for manufacturing Lyrica developed by his team in Groton that reduced carbon-dioxide emissions by 43 percent using one of Pfizer's measurement tools. The company expects a further reduction in emissions of 20 percent as it continues to refine the method through the end of next year, he said.

Avoiding chemical waste

"The pharmaceutical sector has embraced green chemistry most enthusiastically, perhaps because it has the most to gain," according to an article last month in Nature News. "Pharmaceutical plants typically generate 25 to 100 kilograms of waste per kilogram of product, a ratio known as the environmental factor, or 'E-factor.' So there is plenty of room to increase efficiency - and cut costs."

The company expects that green-chemistry processes used to reimagine the production of Lyrica will, over a 13-year period, avoid about 200,000 metric tons of organic chemical waste. Pfizer scientist Peter Dunn, who in 2006 became the pharmaceutical industry's first full-time green chemistry leader, has said the rejiggering of three product lines alone saved the company the cost of 500,000 metric tons of chemicals.

According to Pfizer spokeswoman Sperry Mylott, the company's drugs currently in late-stage development use 24 percent less solvent per kilogram than the most advanced compounds it was testing a few years ago, "thus achieving one of Groton's chemical R&D team's environmental goals two years ahead of schedule."

Chemists do small-scale experiments in Groton before trying out their ideas on a bigger stage with Pfizer's manufacturing partners, said local team leader Wong. The idea is to be as "atom economical" as possible, he added, meaning that less material used up front leads to less waste in the end.

"The company is quite good at implementing process improvements," he said.

Although the pharmaceutical industry in general did not embrace the principles of green chemistry right away - chemical companies faced with outcries after the Love Canal fiasco and the Bhopal disaster had a greater incentive - it now is more motivated, as drug discovery has waned and cost-cutting is getting more attention.

As far back as 1998, Pfizer scientists in Sandwich, England, had worked to improve efficiencies in the manufacture of Viagra, which at that point produced 105 kilograms of waste for every kilogram of product. Pfizer eventually reduced the E-factor to 8, meaning the production of Viagra became more than 90 percent more efficient.

"Ultimately, it's all economics that drives it," said Connecticut College chemistry chair Marc Zimmer. "You can't just let waste go down the drain anymore. You have to dispose of it, and that means you have to pay for it."

Improving production methods of antidepressant Zoloft as well as Viagra and Lyrica have won Pfizer major green chemistry awards. The 2002 Zoloft green chemistry project, conducted at the Groton labs, won the U.S. Environmental Protection Agency's Presidential Green Chemistry Award.

Early stage development

The local labs also have their own internal awards, and winners may designate the prize to an educational institution. In the past year, the prize went to Pfizer scientist Jamison Tuttle, who designated that the $5,000 award be given to his former Connecticut College professor Timo Ovaska, who in turn plans to use it for research stipends for summer students.

"Green chemistry is still in an early stage," Ovaska said, "but it's definitely having more and more of an impact."

Wong said Pfizer doesn't force green chemistry on anyone, but there is a constant effort to educate employees in the science. He added that chemists have been quick to embrace the concept and are always brainstorming and experimenting with new ideas for making pharmaceutical production less costly and easier on the environment.

"It's part of our day-to-day activities," he said.

Everyday Chemistry

2012-02-02T04:20:00.000-08:00

Chemists help make products safer, develop new drugs, and catch criminals, among many other things. Chemistry permeates everything we do,everyday.

Future Cities: The right choices on transportation can shrink your own personal carbon footprint

A study published in the American Chemical Society’s journal, Environmental Science & Technology, offers new insights into how people can shrink their own personal carbon footprints by selecting specific modes of transportation. It provides a comparison of how different means of transportation impact global warming.

Source: Global Challenges/Chemistry Solutions

Our Sustainable Future: A “green grid” for delivering solar and wind-based electricity

After years of neglect, scientists and policy makers are focusing more attention on developing technologies needed to make the so-called “green grid” possible. That’s the much-needed future electrical grid, an interconnected network for delivering solar and wind-based electricity from suppliers to consumers.

Source: Global Challenges/Chemistry Solutions

Molecular robot can be programmed to follow instructions

Scientists have developed a programmable “molecular robot” — a sub-microscopic molecular machine made of synthetic DNA that moves between track locations separated by 6nm.

Source: PressPacs

'Super sand' for better purification of drinking water

Scientists have developed a way to transform ordinary sand — a mainstay filter material used to purify drinking water throughout the world — into a “super sand” with five times the filtering capacity of regular sand.

Source: PressPacs

Our Sustainable Future: Green cars made from pineapples and bananas

Scientists in Brazil have developed a more effective way to use fibers from pineapples, bananas and other plants in a new generation of automotive plastics that are stronger, lighter, and more eco-friendly than plastics now in use.

Source: Global Challenges/Chemistry Solutions

Visual Elements Periodic Table

2012-02-02T04:11:00.000-08:00

No chemistry textbook, classroom, auditorium, or research laboratory is complete without a copy of the periodic table of the elements. Since the earliest days of chemistry, attempts have been made to arrange the known elements in ways that revealed similarities between them. However, it required the genius of Mendeleev in 1869 to see that arranging elements into patterns was not enough; he realized that there was a natural plan in which each element has its allotted place. This applied not only to the known elements, but also left room for elements that were undiscovered at that time. More than 700 versions of the periodic table were produced in the century after Mendeleev. The table shown here was drawn by Murray Robertson based on scientific data provided by chemist John Emsley. In the interactive version available online, one may click on an element to provide chemical data and other relevant information. More information about the history and logical arrangement of the periodic table is available at http://www.chemsoc.org/viselements.

Synthesis of Pleocarpenone

2012-02-02T03:41:00.000-08:00

An extraordinary synthesis of this simple-looking guaiane natural product (along with it’s exo-methylene analogue, pleocarpenene), Marc Snapper has once again used deft control of pericyclic reactions to produce some extremely odd looking intermediates in this synthesis. As regular readers will know, I tend to use a disconnection-based retrosynthesis to explain the synthetic plan, but as you can see, Snapper’s approach makes this a little tricky!

From this retro, it’s clear that the double ring-expansion (is that the correct term?) is key to this synthesis, but that 3,4,4,5 ring system looks just a little strained to me, and to my eyes, it’s construction is far from trivial. However, Snapper used some incredibly funky iron chemistry to build those cyclobutanes, performing a photochemical cyclisation to build the first ring (a cyclobutadiene), and then inserting iron to stabilise it. Functionalisation of the exocyclic ester using fairly standard chemistry (and a oxidation/CBS reduction sequence to introduce asymmetry) left them with a free alkene, which they were able to add to the freed butadiene in one step. This generated the second four-member, along with the cyclopentane, in good yield, and with an reasonable excess of the preferred diastereoisomer.

The final elaboration to produce the rearrangement substrate was cyclopropanation of the butene ring; I thought that this might be a tricky step, but it really didn’t faze them at all:

Copper catalysed elimination of the diazo group left the carbene, which added very efficiently to the butene, generating that amazing 3,4,4,5 ring system, and after oxidation and treatment with methyl grignard, the target substrate. A bit of (somewhat less than gentle) thermal persuasion then snapped those strained rings open, inverted the stereocentre at C1, completed the carbocyclic skeleton. More mundane chemistry was then applied over a couple of steps, completing the synthesis of the target, and my favourite paper of 2007 so far.

Total Synthesis of Bryostatin 16

2012-02-02T03:35:00.000-08:00

Ah, back in to Nature for another nibble at organic synthesis for the biologists, and some slightly-odd looking structures. It took me rather a while to get used to COOMe rather than CO₂Me… However, one thing guaranteed with chemistry in Nature is quality, and it certainly shows in Trost’s latest work.

The target is one he’s been working on for quite a while, but with good reason, as it’s quite a tasty number. To quote the paper, they speak of ‘exceptional biological activity’ and back this up with references to use of bryostatins in the clinic. However (and isn’t this always the stickler…) it’s not exactly bountiful in abundance – apparently only 18 grammes were isolated from 14 tonnes!! That’s quite a column…

Anyway, on with the synthesis – and the starting point, as usual, is assembly of the fragments. One of those was already discussed in a previous Trost paper on this molecule (last year), but a different, and shorter synthesis is used here. One step I found particularly interesting was a propargylation of an aldehyde using chemistry developed by Teck-Peng Loh a few years back. Interesting brew of reagents, but it’s a neat way to build this homo-propagylic alcohol. However, the result is still racemic, so an oxidation and CBS reduction was used to induce an enantiomeric excess.

For the coupling of this fragment with a (somewhat) related partner, Trost used his own funky ruthenium chemistry. In this case, the situation is complicated by the highly functionalised nature of the partners; ligation of the metal to the olefins in both SMs or the product is the reason given for the lowish yield. However, the starting materials were easily isolated, resubmitted and a decent amount brought through.

Transformation of the vinyl silane into a vinyl bromide was done with a bit of NBS – not a reaction I’d thought of as being so high yielding (98%) or selective in such a substrate. Next up was a rather sweet series of acid-mediated reactions in one pot, selectively removing the TBS group and performing a neat transesterification/ketalisation. Really, a very neat way to put in that ketal.

The vinyl bromide was carbonylated rather nicely using fairly traditional reagents to get a decent yield (83%). More traumatic to my eye was the required selective saponification of the beta-hydroxyl methyl ester. I’d probably be thinking about ways to use that hydroxyl to differentiate the esters, but no way would I have fell upon the reagent used by Trost. A bit of trimethyl tin hydroxide, and tickle with the bunsen did the job amazingly well, which Trost suggests is down to the lewis acidity of the reagent. This allowed it to be directed by the hydroxyl, and deliver the impressive selectivity. I’m again impressed with the robustness of the substrate, though – heating under (admittedly mildly) Lewis acidic conditions…

Last is a seriously impressive run of reactions – firstly, a palladium mediated coupling of the diyne, using Trost’s chemistry again. The selectivity, again, is hugely impressive, though as with most macrocyclisations, dilution was key to keeping the reactivity intramolecular. Quite an impressive example of a new means for macrocyclisation, though (even if the yield is only moderate). More impressive was the fact that they were now perfectly set up for the final cyclisation. After attempting this with a few different gold catalysts (a regioselectivity problem was apparent), they struck gold with the reagents shown (I should write the Angewandte captions…).

After that, all that remained was pivalation and deprotection; again done with apparent ease, rounding off an incredible synthesis, using impressive methodology in exactly the right way.

Total Synthesis Of Asteriscunolide D

2012-02-02T03:24:00.000-08:00

Medium rings are a beguiling feature found in a host of natural products, owing to their behavioural oddities. While the properties and synthesis of smaller rings (three to six atoms in size) are well known, and that of true macrocycles can at least be estimated, each medium ring has its own personality. Without the predictable rigidity of the smaller rings, or the freedom of a macrocycle, rings of 7-14 atoms can behave very strangely, and can often be reluctant in their making.

Asteriscunolide D is one such beast, containing an 11-membered triene ring at its heart - typical of the humulene class of natural products. This family is popular in biological circles, owing to members' activity against a variety of cancer cell lines. However, synthesis of the humulene ring system is awkward - one cited example using a Horner-Wadsworth-Emmons olefination achieves a barely detectable 3% yield. All this gives Barry Trost and his team at Stanford University in California, US, more than enough reason to attempt its synthesis, and showcase their use of thionium ions as 'super-carbonyls' - equivalents of that endlessly useful functional group, but with a little more activity.

The team began its synthetic efforts with a typical carbonyl reaction: aldol addition of isobutyraldehyde to formaldehyde. The product formed a dimer, which was cracked under warming in preparation for a Horner-Wadsworth-Emmons olefination, building the required enone with ease (figure 1). The next move was to introduce asymmetry using a neat catalyst-controlled alkylation, after oxidising the neopentyl alcohol to an aldehyde. The catalyst in question is the rather large (S,S)-ProPhenol, which - as its name suggests - contains a phenol group flanked by a pair of proline derivatives. Using this, in conjunction with dimethyl zinc, directed enantioselective addition of methyl propiolate to the aldehyde, generating the desired secondary alcohol in excellent yield and stereochemical control.

The purpose of installing the acetylene functionality was to form the butenolide ring, something the team accomplished in only one step. Treating the acetylene with allyl alcohol and a ruthenium catalyst prompted direct alkyne-alkene coupling, completing the lactone and leaving a pendant aldehyde as a useful functional handle (figure 2).

The team immediately converted this aldehyde into a thioacetal, followed by forming a trimethylsilyl (TMS) enol ether from the enone. This slightly strange mixture of functional groups is actually their intended substrate for their postulated 'super-carbonyl' aldol equivalent. All that was required was a little encouragement from dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF). This prompted formation of a phenyl sulfonium intermediate, similar in character to a carbonyl group but much more reactive. Reaction with the TMS enol ether was prompt, generating a useful yield of the 11-membered ring under very mild conditions (figure 3).

Shunning protection

Usefully, the product contained a phenyl sulfane group, which could be eliminated to provide the final alkene present in the natural product. Although this might sound simple, the mechanism for elimination is highly substrate dependant - and when the substrate is a medium ring, a bit of luck as well as forethought is required. Oxidative elimination (commonly used in conjuction with phenylselenium groups) resulted in the undesired beta,gamma-unsaturated ketone. However, alkylative thioether elimination gave the desired E-olefin, completing their synthesis in only eight steps. What's more impressive is that their route is entirely protecting group free - while the TMS group is normally considered a protecting group, it is more of an activator in this case.

Manufacturing the Carbon Nanotube Market

2012-02-02T03:18:00.000-08:00

Bayer MaterialScience has opened a new carbon nanotube (CNT) production facility at Laufenburg on the German-Swiss border, doubling its production capacity to 60 tonnes per year.

The plant, which began operating in September, is just the latest evidence that chemical companies both large and small are betting on a bright commercial future for the versatile tubes.

'We see a big future in carbon nanotubes and we believe that it's an area of innovation and growth,' said Martin Schmid, head of Bayer MaterialScience's global CNT operations. 'All being well, we will build another plant that will give us a total new capacity of over 200 tonnes of nanotubes by the end of 2009.' Even further in the future, Bayer MaterialScience plans to build an industrial-scale production plant with an annual capacity of 3000 tonnes.

Other chemical companies are also getting in on the act. French chemical giant Arkema, for example, opened a CNT pilot plant in south-west France in January 2006 with an annual production capacity of 10 tonnes. Smaller businesses are also getting involved, whether they are well-established chemical companies such as Thomas Swan in the UK, or new start-ups such as Nanocyl in Belgium, which has a production capacity of

40 tonnes a year.

The attraction of CNTs is that they are lightweight yet strong, and have high thermal and electrical conductivities. Yet despite more than 40 per cent annual growth in the CNT market, its long-term future is still uncertain. 'If the cost and price of carbon nanotubes decrease over the next few years then this will open up new opportunities for the product,' predicted Schmid. 'But if we stay at today's price level then it's probably not going to happen.' And for costs and prices to come down, companies need to find cheaper ways to manufacture CNTs.

Smaller, faster cheaper

Practically every manufacturer currently uses catalytic chemical vapour deposition (CVD) to make their tubes. This involves growing the CNTs by passing a carbon-based gas, such as methane or ethylene, over metal particles that catalyse CNT growth, although each company has developed its own proprietary version of the process.

Improved manufacturing and large-scale production have already caused the price of CVD-produced CNTs to fall substantially, from around $200 per gram in 1999 to under $50 per gram today. Although there are other methods for producing CNTs, such as arc discharge and laser ablation, they don't produce CNTs in such large quantities as CVD. So most existing manufacturers are concentrating on developing more efficient versions of CVD, as well as gaining more control over the types of tubes they make.

There are two basic types of CNT: single-walled (SWNTs), which comprise a one-atom thick sheet of graphite rolled into a tube; and multi-walled (MWNTs), consisting of numerous SWNTs nested inside each other like Russian dolls.

Most manufacturers concentrate on producing MWNTs, which are easier to produce with CVD but see wide variations in length, width and number of walls. This doesn't matter for now, because CNTs are usually added in bulk to strengthen polymers in products such as vehicle chassis and sports goods. But more advanced uses of CNTs will require specific types of SWNT. 'An area that is growing very rapidly and is very exciting is advanced electronics,' said Harry Swan, managing director of Thomas Swan, and great-grandson of the company's founder. Indeed, SWNT-based electronic circuits are being touted as one way to continue shrinking the computer chip.

Thomas Swan is already producing SWNTs using CVD, but they cost much more than MWNTs (around $200 a gram). A number of US companies, including Idaho Space Materials and Nanotailor, have obtained a licence to exploit a novel SWNT production process developed by a researcher at Nasa's Goddard Space Flight Center in Maryland. This uses a helium arc welding process to vapourise an amorphous carbon rod, with carbon nanotubes forming as the vapour is deposited onto a water-cooled carbon cathode.

'Single-walled technology just hasn't taken off because of the cost,' commented Nanotailor president Ramon Perales. 'If we can get the cost down, we can be a step ahead and make higher-quality nanotechnology affordable.'

Chicken and egg

But electronic applications still face a major hurdle: the precise arrangement of carbon bonds in SWNTs determines whether they are metallic or semi-conducting, and all the current synthesis methods produce a mixture of the two. Although a number of methods have been developed for separating them, such as centrifuging SWNTs in a density gradient or attaching diazonium salts and then separating them by electrophoresis, none have yet left the laboratory.

Surrey NanoSystems, a company spun out from the University of Surrey in late 2006, is helping to address that with its range of CNT generators, which grow tubes at the relatively low temperatures necessary for semiconductor fabrication processes. According to Guan Yow Chen, the company's chief scientist, the devices allow scientists to fine-tune every aspect of CNT production, from catalyst generation to final material processing, and are primarily used as research tools.

If cutting-edge research can open up paths to commercialisation - in applications such as computer chips, sensors and display units - it's likely that a booming market could drive improvements in production to deliver lower costs. To that end, Bayer MaterialScience recently announced that it is looking to set up strategic business and research collaborations to develop novel applications for its CNTs. 'It's going to be a bit of a "chicken and egg" situation,' predicted Swan. 'You'll have to make sure the market place is there before scaling up, but in some instances you have to scale up to make the market.'

Smart drug delivery via thermo-triggered squirting

2012-02-02T03:14:00.000-08:00

Chinese researchers have developed a method for delivering nanoparticles to a specific site of action using temperature-triggered squirting.

Nanoparticles are becoming more widespread for disease diagnosis and therapy but protecting them from degradation and delivering them to target tissue is still a challenge. Some promising drug delivery systems exhibit low physical and chemical stabilities causing them to leak or deliver the nanoparticles too early. Now Liang-Yin Chu and colleagues, from Sichuan University, have developed hydrogel capsules that protect the nanoparticles, and release them only in response to a change in temperature.

Chu encapsulated the nanoparticles in a water/oil emulsion inside a NIPAM-based hydrogel. Heating the capsules above a critical temperature triggers rapid shrinkage, which increases the internal pressure. Because the hydrogels have a low mechanical strength, the capsule violently ruptures, squirting the nanoparticles out. Chu says the inspiration for these nanoparticles bombs came from plants, such as the squirting cucumber (ecballium elaterium), that eject their seeds into the air by sudden contraction of their walls.

The key to the site-specific delivery is the use of a remote trigger (temperature) to tune exactly when and where the capsules rupture. This allows the release of the drug at exactly the right time and place. Crucially, Chu has been able to tune the temperature at which this squirting happens to above body temperature, so the capsules can be used in the body. Local thermotherapy at the target site, using microwave, ultrasound or infrared irradiation could be used to trigger the nanoparticle release.

Chu is keen to stress that the force at which the nanoparticles are ejected is also important, 'some biological tissues present diffusion obstacles for nanoparticles and/or their surrounding media are quite viscous, and so higher initial momentum for the nanoparticle delivery is required,' he explains.

The team now plan to reduce the size of the capsules so they can be used in the body. Zhibing Hu, an expert in the development of hydrogel materials for drug delivery saw great potential in the system, saying that 'in principle, the same technology can also be applied to controlled drug release once the nanoparticles are replaced by a specific drug.'

The World's Strongest Fibres

2012-02-02T03:10:00.000-08:00

The toughest polymer yarn of all time has been made by mixing a polymer with sheets of reduced graphene oxide (RGOF) and carbon nanotubes (CNTs) during spinning. The yarns are much cheaper than those using CNTs as the only additive, producing fibres that can be sewn like threads and coiled into springs.

One of the most common ways to strengthen polymeric fibres is to mix them with additives like CNTs during wet spinning. The composite materials formed have superior toughness to the neat polymers. One type of fibre made using poly(vinyl alcohol) (PVA) and CNTs has a toughness of up to 870J/g, which is far stronger than spider silk (165J/g) and the synthetic para-aramid Kevlar (78J/g) used in body armour.

More recent studies have replaced CNTs with flakes of RGOF, which has a two-dimensional structure like graphene. The resultant PVA composites were not as strong as those with CNTs but were cheaper to make due to the lower cost of RGOFs.

Now, Seon Jeong Kim, at Hanyang University, Korea, and colleagues have taken things a step further by mimicking the structure of spider silk and adding a combination of functionalised CNTs (strands) and RGOFs (sheets) to the polymer. 'In nature, spider silk is very strong and flexible, and it is composed of two types of proteins: sheet type (beta sheet nanocrystals, 2D structure) and strand type (beta strands, 1D structure),' Kim says. 'Their combination is very important for enhancing the toughness of the spider silk.'

A solution of single-wall CNTs and wrinkled RGOFs was injected into an aqueous solution of PVA as it was being spun and the fibres were treated with methanol to increase the crystallinity of the material to create robust fibres. Scanning electron microscopy showed that the RGOFs and CNTs form an interconnecting network during spinning, which is helped by the wrinkled nature of the RGOF sheets that keep them well dispersed inside the polymer.

Different proportions of CNTs and RGOFs were tried out but the best combination was a 1:1 ratio which produced a high degree of spontaneous alignment of the CNTs and RGOFs along the fibre direction. The CNT bundles also attached themselves to the edges and surfaces of the RGOF sheets. This alignment led to toughness values up to 970J/g, which are greater than those reported so far for any material.

The yarns can be twisted without breaking or sewn like thread. They can also be coiled into spring shapes which are fixed by heating and return to their coil shape after complete elongation or compression. 'We think that our tough fibres can be applied soon for specialised applications like bulletproof vests,' Kim says. 'Our fabrication process is quite simple and suitable for industry. We used cheap and mass produced graphene oxide to replace some of the more expensive single-walled CNT.'

CNTs cost $25,000-90,000/kg (£15,700-56,800) but industrial grade graphene oxide costs just $450/kg. This could be reduced further by replacing the remaining single wall nanotubes with multi-wall CNTs, which are even cheaper, although their effectiveness has yet to be tested.

Water Repellent Polymer Slows Down Drug Delivery

2012-02-02T03:04:00.000-08:00

In looking for potential uses for highly water-repellent, superhydrophobic materials, scientists have mainly focused on obvious applications such as water-proof clothing and self-cleaning surfaces. But now US scientists have a new idea: using them to deliver drugs.

It turns out that superhydrophobic materials are very good at slowly releasing drugs over extended periods of time, from weeks to months. This is because the water-repellent properties of these materials arise from their rough, rippled surfaces, which trap air between the ripples. This trapped air prevents liquids such as water from penetrating the ripples, forcing it to remain perched on top as intact droplets.

Mark Grinstaff, professor of chemistry at Boston University, realised this trapped air could also be used to control the rate of drug release. The idea is that the trapped air prevents any drug loaded onto the superhydrophobic material from escaping, until the material is immersed in a liquid such as blood. Then, as the liquid slowly soaks into the material, it gradually displaces the air and releases the drug. More hydrophobic materials, which trap the air more securely, will release the drug over longer periods of time.

To demonstrate the potential of this technique, Grinstaff and his colleagues employed electrospinning, which uses an electrical charge to draw fibres from a liquid, to create hydrophobic meshes, just 300um thick, from polycaprolactone (PCL). By altering the concentration of a hydrophobic dopant - poly(glycerol monostearate-co--caprolactone) - they could control the hydrophobicity of the mesh and load it with a drug by adding it to the electrospinning solution.

Using an anticancer drug, Grinstaff tested the drug delivery ability of these meshes in both salt water and blood serum. In salt water, PCL lacking any hydrophobic dopant released its drug load after around 15 days, whereas PCL with 10% by weight of dopant took 70 days to release its load. PCL with 30% by weight of dopant only released 10% of its drug load after nine weeks. When exposed to cancer cells in blood serum, PCL lacking any dopant stopped killing cancer cells after 25 days, whereas PCL with 10% by weight of dopant was still killing tumour cells after 65 days.

Grinstaff is now assessing the efficacy of these meshes in mice and trying them with other drugs. 'There are several unmet clinical needs where this time frame of delivery would be important,' Grinstaff tells Chemistry World. 'Pain management after lung surgery and prevention of lung tumour recurrence after surgical resection.'

This is not the first time that superhydrophobic materials have been used for drug delivery, says Nicola Tirelli, professor of polymers and biomaterials at the University of Manchester, UK, but it is the first time that air has been used to control drug release. 'The key point is the use of air for modulating the release of the drug,' he says.

Pesticides Linked to Vitamin D Deficiency

2012-02-02T03:00:00.000-08:00

Pesticides could be suppressing people's vitamin D levels, leading to deficiency and disease, say scientists. The warning follows the discovery that adults with high serum concentrations of organochlorine pesticides such as DDT have lower vitamin D levels.

Exposure to lose doses of organochlorine pesticides has been previously linked to common diseases like type 2 diabetes, metabolic syndrome and cardiovascular disease. Vitamin D deficiency has similarly been associated with a rise in chronic diseases, but the two have been studied separately by researchers in different fields. 'The known associations between vitamin D deficiency and various diseases can be at least partly be explained by the common exposure to organochlorine pesticides,' says senior author Duk-Hee Lee of Kyungpook National University in Korea.

The US-Korean research team studied 1275 adults in the US aged 20 years or older and checked their blood for seven organochlorine pesticides. DDT and beta-hexachlorocyclohexane levels in study volunteers showed significant associations with lower serum concentrations of a vitamin D pre-hormone, 25-hydroxyvitamin D, which is the standard way to assess vitamin D levels in the body. The study sheds no light on how pesticides might influence vitamin D levels, though.

Organochlorine pesticides were banned in the US decades ago, but are still detectable in people because they resist biodegradation in the environment, are lipophilic and accumulate in fat tissues. The World Health Organization still recommends the use of DDT to control mosquitoes in malarial regions and, while there is a global moratorium on spraying it on crops, illegal use in some countries is suspected.

Levels of these chemicals are far lower than they were in the 1960s and 1970s, but Lee believes that they may still be significant because they act as endocrine disruptors. 'One characteristic of endocrine disruptors is that they show their possible harmful effects at levels lower than those which we currently think are safe,' Lee says. 'As chemicals like organochlorine pesticides travel a long distance through a variety of ways, humans can be exposed to these kinds of chemicals even though the country where they live does not use them anymore.'

'We have known for many years that DDT causes egg shell thinning,' says David Carpenter, director of the institute for health and environment at the University of Albany, New York. 'Since egg shell thickness is regulated by vitamin D, this study shows that the same suppression of vitamin D occurs in humans.' Carpenter says he is concerned about the push to bring DDT back into use as a potent pesticide against mosquitoes and other insects. 'It is very important to communicate how harmful DDT is to humans, not just mosquitoes.'

The Sweet Scent of Success

2012-02-02T02:54:00.000-08:00

Emma Davies pokes her nose into some of the world's most celebrated perfume molecules

In Short

Nature provides a wide variety of fragrant molecules, from fruity floral notes to deer musks
Fragrance chemists have created an array of new aromas by modifying the structure of natural scents
Developing a cost effective synthetic route is a key hurdle before an aroma can be incorporated into a perfume
Demand for new fragrances from today's consumers is unprecedented, fuelling the search for new aromas

Philip Kraft designs molecules which elicit strong and immediate emotions in people. He creates new fragrances for Givaudan, a Swiss flavour and fragrance company, and some of his molecules play star roles in best-selling perfumes. He has the unusual skill that when he smells a compound, he can almost visualise its chemical structure. His work is driven by an obsession to create new molecules that will move people.

Kraft was drawn to fragrances and science at a very young age. As a 12-year-old with a desire to understand the science of teenage hormones, he bought a biochemistry textbook from his local university bookshop in Hamburg, Germany. A year later, his questions still unanswered, Kraft returned to buy a chemistry textbook. The shop assistant was most amused and gave him a test subscription to a chemistry journal - Liebigs Annalen der Chemie . Kraft was captivated by an article by Peter Weyerstahl, a fragrance chemist who had modified the odour of rose oxide. 'He had sent fragrance compounds to a company for evaluation so I wrote to that company and they sent me some materials, which I even used to give courses at school.'

Almost three decades on, Kraft is still entranced by fragrance molecules. He creates patent-protected 'captive ingredients' for Givaudan to hold in its fragrance arsenal. The chemistry is challenging: 'It's tough work and despite all the molecular design tools, you still have to be lucky,' he says.

Scent search

Fragrance researchers search high and low for chemical inspiration. Givaudan, for example, runs its much-publicised ScentTrek missions to remote parts of the world to capture new smells.

The easily accessible fragrance ingredients were identified a long time ago, explains Koenraad Vanhessche, director of product and process research at Firmenich, another Swiss flavour and fragrance company. 'What is now happening is that we are looking at trace compounds - a lot of these have low thresholds or are relatively unstable.'

But much of the work is done by altering existing molecules, or by searching for commercially viable synthetic routes for known compounds. Kraft likes to follow a 'hardcore design approach,' twisting, tweaking, and trimming existing molecules to modify odour and its intensity. 'When I smell an odour I can almost see the shape of the molecule. You look at the molecule, make a hypothesis as to why it smells like it does, and then test this hypothesis by modifying the molecule and seeing if you get the odour you desire,' he explains. 'Often I make a molecule just to see how it smells.'

Kraft and his team frequently work on paper, sketching out molecular variations using ball and stick models. They also use olfactophore models, which show the molecular features that are key to a given odour, such as hydrophobic groups, and H-bond donors and acceptors. 'You can play with conformational elements that drive a certain molecular shape - for example you can introduce structural elements that cause a molecule to fold itself into a horseshoe shape and thus smell musky,' explains Kraft. Adding rigidity to molecules often gives more defined odour notes, he adds. 'Or you can make the molecule more flexible to add new by-notes - you can cut some parts to make it lighter and more diffusive while conserving its overall shape.'

But his team sometimes takes the more traditional approach to creating captive ingredients. 'You can have chemical inspiration - you take known odour compounds and submit them to a specific series of reactions to see how the odour is modified. If you like something then you can follow up a certain aspect,' says Kraft. Fragments of known fragrance molecules can also be incorporated.

Any new fragrance molecules created in the lab are assessed by perfumers. 'Sometimes it can be that a few love your molecule, while some hate it. If you love a certain molecule it can be frustrating if you see that other people don't like it,' says Kraft. Firmenich employs 67 perfumers. 'We have one very special person who is a chemist and also an excellent perfumer. He gets the feedback from his colleagues on what consumers want and interprets the information in olfactory tonalities,' explains Toni Gautier, corporate vice-president of R&D at Firmenich.

When the perfumers take a liking to a new molecule, it's often not long before new fragrances bearing the signature compound hit the high street. Looking back at perfume trends, it is clear when chemical breakthroughs have taken place in the industry, says Gautier.

Chart toppers

To make a fine fragrance, new molecules are mixed with old favourites. But which fragrance compounds are most valued by industry - a kind of fragrance top 10? It's a difficult question to answer. Gautier has no doubt about the value of Hedione (methyl dihydrojasmonate), used in almost all fine fragrances and Firmenich's top seller in terms of volume. The compound was discovered at Firmenichin the early 1960s as an analogue of methyl jasmonate, a key component of jasmine oil. Said to give a warm floral-jasmine note, Hedione has been used in perfumes for over 40 years, first starring in Dior's Eau Sauvage in 1966.

Alpha (top) and beta damascone are fruity components of rose oil

'The synthesis of Hedione gives four stereoisomers,' explains Gautier. 'Only one of them truly contributes to the odour - (+)-cis-methyl dihydrojasmonate - while the others are thought to modulate other fragrances. Over the years we've been able to synthesise new versions of Hedione which have a much higher quantity of the right isomer.'

Gautier also has a soft spot for the rose ketones: damascenone, and alpha and beta damascone. Firmenich is famed for their discovery and synthesis in the 1960s during a quest to identify the characteristic smell of Bulgarian rose oil. But batch purity problems meant that damascenone was not released commercially until 1982. Then came alpha-damascone (rose-apple note) and beta-damascone (blackcurrant-plum note). The rose ketones broke new ground in the 1980s, giving female perfumes such as Dior's Poison their unusual and distinctive fragrance. Today, beta-damascenone and beta-damascone remain two of the most important fragrance ingredients.

Chemists are forever improving on the rose ketones, which are still trendsetters. One of Kraft's recent and 'very successful' captives is Pomarose, a 'cut-open' seco-damascone. Pomarose introduced the dried-fruit character of Poison to the male market and had its debut in DKNY's male fragrance Be delicious Men . 'It has a very specific note of cooked apple, rose, and dried plums. It's very diffusive so it gives a lot of bloom to a fragrance,' enthuses Kraft. Givaudan's process development team had to try 19 different synthesis routes before it managed to produce Pomarose. 'Initially we thought we couldn't produce it. It was a crazy idea that originated from a 1 per cent impurity for which different structures were proposed based on the NMR spectrum. After we had discovered the correct structure we synthesised the "wrong proposal" for fun but it turned out to be so powerful,' recalls Kraft. Interestingly, it wasn't the impurity itself that became Pomarose, but one of the alternative structures.

Pomarose was recently used in high concentrations in Unforgivable man by Sean Jean - also known as US rapper P Diddy - who is said to have been quite taken with the compound's champagne-like qualities.

Another essential - and once controversial - group of flavour compounds is the macrocyclic musks, which are extremely important to the industry, says Gautier. Musks once had a bad name, in the days when they were derived from the musk pods of the Asian musk deer. These days, musk odourants are all synthetic. 'Replacing the musk ingredients caused something of a stir but the industry is probably better off now because it has biodegradable ingredients with no environmental effects,' says John Leffingwell of flavour and fragrance consultants Leffingwell and associates.

Musks belong to several classes that are structurally very different. Those synthesised by the industry are generally nitro musks, polycyclic musks and macrocyclic musks. Gautier would like to add Helvetolide, a linear musk discovered by Firmenich in 1990, to the 'most-valued' list. Helvetolide had a totally different structure to existing musk compounds and its discovery opened up a whole new domain of musk chemistry, says Gautier. Together with macrocyclic musks, Helvetolide is key to 'white musk' compounds, said to be reminiscent of freshly ironed linen. These are currently very fashionable, says Kraft.

Out of the woods

Woody fragrances such as Iso E Super, a compound known as a 'floraliser' and used in most new fine fragrances, also rate highly, says Gautier. Some people smell a cedarwood note in Iso E Super, while others perceive it to be musky. The male fragrance Fahrenheit (Dior, 1988) is 25 per cent Iso E Super while Perles de lalique (Lalique, 2007) is 80 per cent Iso E Super. The commercial Iso E Super owes its woody smell to a 5 per cent impurity which has an odour threshold about 100 000 times lower than that of the main product.

In 1999, Kraft's team at Givaudan isolated this impurity by epoxidation of a commercial Iso E Super and proposed a structure based on NMR spectra. The team came up with a way to synthesise the compound but it was not commercially viable and the structure turned out to be too complex for an alternative synthetic procedure. But out of several synthesised analogues, one had an almost equal odour threshold and smelled even better. What is more, its industrial synthesis is straightforward and it has become a big hit - used by Givaudan as the captive material Georgywood.

However, on strictly cash terms, the most valuable fragrances are the natural products. For example, East Indian sandalwood oil is one of the most precious and expensive perfumery raw materials.

Beta-santalol is the main olfactory constituent of sandalwood oil. It wasn't until 1990 that beta-santalol could be prepared in the lab - this took an 11-step reaction that was unsuitable for industrial scale-up. The best sandalwood oil substitutes are derivatives of alpha-campholenic aldehyde, prepared from inexpensive alpha-pinene, most of which is a byproduct of the paper industry.

'The components in sandalwood oil are not easy to make,' acknowledges Gautier. 'But what Firmenich has done is screened all around that kind of structure to try to find woody notes. We have a lot of substitutes so that perfumers can create something close to sandalwood without needing sandalwood oil.' Kraft agrees that there are 'excellent synthetic substitutes' out there. For example, the campholenic aldehyde derivatives typically have a good sandalwood smell. 'The other olfactory parts of natural sandalwood oil - such as the smokey, cedar-like aspects - can easily be added using, for example, cedarwood oil,' says Kraft.

Sandalwood was initially quite cheap (Guerlain's Samsara contained 25 per cent sandalwood) but overharvesting has led to Indian sandalwood trees being listed on the World Conservation Union's threatened species red list.

'There's still a good market for sandalwood oil and the price has gone, in the past six or seven years, from $1000 [£680] per kg to over $2000,' says Leffingwell. One Australian firm, TFS Corporation, has taken the initiative and planted over 1700 hectares of the endangered Indian sandalwood (Santalum album ) in plantations in Western Australia.

After sandalwood comes the hippy favourite - patchouli oil. Its fragrance comes largely from patchoulol. 'It's a truly unique ingredient that is ideal for perfumes. But it is a molecule that we have not been able to make cost-effectively by synthesis. So this is one of the holy grails of organic synthesis - to find a route to make patchoulol,' says Gautier.

Firmenich works with farmers to cultivate research crops, one of which is patchouli, grown in Indonesia. 'It is of extreme importance to the industry that we are able to improve any way of making this product - be it by organic synthesis or plant cultivation, improvement of the strains, and extraction from the plant,' says Gautier.

Finally, there's nootkatone, a key ingredient in grapefruit, and much valued for today's light and fruity perfumes. This, says Leffingwell, is a very expensive chemical that can currently only be synthesised from a byproduct from the citrus industry, which is in short supply. Only one of its isomers has the grapefruit odour ((+)-(4R,4aS,6R )-nootkatone)). The other, (-)-(4S,4aR,6S )-nootkatone, is very weak, with almost no grapefruit character.

Perfume challenge

The perfume industry is also facing new challenges from regulators, particularly from the EU, which is limiting the use of possible allergenic compounds in perfumes. Current legislation means that fine fragrance producers have to declare on packaging if a perfume contains any of a list of 26 'allergens'. Leffingwell thinks that there's a risk that before long fragrance producers won't even be able to use orange oil and lemon oil (these contain limonene, which at high concentrations can cause a skin reaction). 'It's ridiculous. If you took all these things away from the perfumer they'd have real difficulty making nice fragrances,' he says.

But the industry is reacting in a positive way. 'Our clients would prefer not to have allergens on the label so in a lot of cases we are now generating fragrances that don't have the compounds in them,' says Gautier.

'It is a bit more difficult when clients want you to take these molecules out of existing perfumes without having any change. We do have replacers but they are not exactly equivalent. To have the same organoleptic, physical and economic properties is a challenge.'

There is also the issue of biodegradability. Fragrance chemists have to be careful to keep the molecular building blocks for fragrances relatively inert. 'We try to avoid reactions in the perfume. Most of the compounds are carbonyl compounds. If the pH is neutral you don't get aldol reactions so we don't use a lot of acids in fragrances

except a few for honey notes,' says Kraft.

A few years ago, the perfume industry ran into problems because its molecules were too inert and didn't biodegrade, recalls Kraft. 'Now we're going back to make them biodegradable. It's a challenge to make them stable enough that they don't decompose in the perfume itself.'

Fickle fragrance

The demand for new fragrance compounds is driven by today's consumers, who are always on the lookout for something different. Unlike 30 years ago, the life of a perfume today is relatively short. 'In many cases now a fragrance will be very popular for a year or two, then the consumers move on,' explains Lefingwell.

Since 2000, over 5000 new perfumes have been introduced, says Michael Edwards, who compiles the book Fragrances of the world , commonly described as the perfume bible. He thinks that customers are confused. 'Why do all fragrances smell alike?' he asks. 'The problem is that product managers want as broad an audience as possible. If you go for broad appeal it's very hard to come up with a fragrance that has got guts and signature.' He thinks that the industry doesn't need to search perpetually for new compounds. 'We're not using the great materials that we already have imaginatively enough. Look at Iso E Super, first used in 1975 and now becoming a star in its own right. It's really a case of imagination over raw materials.'

From what I've seen, it's imagination that leads to new materials. And there's no stopping the fragrance chemist in the addictive search for the next 'hit' and the ensuing public reaction. Asking them to stop what they're doing would be like asking the Rolling Stones to stop performing. 'Perfumery can be very gratifying because, as with music, you create a real effect - you can create sensuous moments for people,' says Kraft. 'My mother doesn't understand any chemistry but with a smelling strip containing one of my molecules she can feel the chemistry of the molecule.'

How Green is your Detergent?

2012-02-02T02:47:00.000-08:00

Fragranced household products, even those labelled as 'green', can emit large numbers of hazardous chemicals that aren't listed on their labels, US researchers have confirmed. The research raises questions about the risks associated with these products and regulating the claims on their labels.

A team led by Anne Steinemann at the University of Washington in Seattle, US, used gas chromatography to analyse the volatile organic compounds (VOCs) released from 25 of the top-selling US products such as detergents, hand sanitisers and air fresheners, and found that they emit many hazardous compounds.

Among the most toxic of these were carcinogens such as acetaldehyde, formaldehyde, 1,4-dioxane and dichloromethane. According to Steinemann, the US Environmental Protection Agency states that there is no safe threshold for exposure to these chemicals. Other hazardous compounds found included methanol, cumene, hexane and chloromethane.

Under US regulations, companies are not required to disclose ingredients in a fragrance mixture. There is also no regulation over the use of terms such as 'green', 'organic', 'non-toxic' or 'natural'. These claims appeared on 19 of the 25 tested products' packaging or advertising, but the team found that they emitted toxic compounds as much as 'non-green' products did.

'No one really knows the definitions of these words,' says Ian Colbeck, an air quality specialist from the University of Essex, UK. 'I think it would help if the manufacturers agreed, in some way, to use these terms based on certain conditions.'

Colbeck is concerned by the lack of exposure studies on human beings. But Steinemann responds that, 'even if we had done exposure analysis, we cannot say based on that whether these products are safe. There are so many factors involved in the ultimate effects on health.'

Research into the toxicity of these products is challenging because the same air freshener may cause an asthma attack in one person, but a seizure in someone else, and have no apparent effect on another person, says Steinemann. The analysis is made more difficult as 'it may not be that a single VOC causes one effect and another VOC causes a different effect, but it may be that it is a mixture of VOCs that cause the harmful effect.'

However, Colbeck remains skeptical, 'I don't think that householders should be particularly concerned about these products,' he says. 'But it would be interesting to study the occupational hazards of these compounds in people who work, for example, at launderettes.'

Steinemann reiterates the gravity of the situation and urges researchers to investigate further and raise these questions to the regulatory authorities, 'Some people are known to react to much lower concentrations of these chemicals than we can even detect.'

Surfactants Stop Microbubbles Popping for a Year

2012-02-02T02:39:00.000-08:00

Tiny bubbles of air can last for over a year if they are covered in elastic shields of surfactant, US scientists have found. A long-lasting dispersion of bubbles this small, they suggest, might improve the properties of foams, paints, contrast agents for ultrasound imaging, and aerated foods such as ice cream.

Scientists at Unilever observed in the 1990s that they could whip up stable micrometre-sized bubbles of air whose surfaces had nanoscale facets - looking like a golf ball with convex dimples. 'We could make the bubbles incredibly small and much more stable than they'd ever been, but we didn't understand why it worked,' says retired Unilever physical chemist Rodney Bee.

Now Bee and other Unilever researchers have collaborated with Howard Stone and colleagues from Harvard University, Massachusetts, to show how some surfactants can form nanoscale features on a bubble's surface, and keep it intact for over a year.

Surfactants - used in detergent to keep particles of oil and grease from clumping together - have often been used to stabilise gas bubbles. They line up at a bubble's surface, relieving the surface tension that would otherwise cause it to shrink and dissolve. Keeping bubbles less than a micrometre across intact for a long time is more difficult, although researchers have stabilised microbubbles for a few months by filling them with poorly soluble gases such as nitrogen or perfluorocarbons, and by surrounding them with lipid structures or nanoparticles.

Emilie Dressaire, part of the Harvard team and lead author of the study, played with a few surfactants and solutions before hitting on a mixture of mono- and diesters of sucrose stearate in glucose and water. The ingredients are mixed at 70°C, and a kitchen mixer whips in air to create a foam as the mixture cools to room temperature.

As surfactants crystallise out of the viscous syrup, they latch onto the small bubbles as they are forming. The bubbles inevitably start to shrink, but their shells are elastic: the tails of the attached surfactant molecules bend and their heads clash together, building up stress that counteracts the shrinking. Stone's team showed they could tune the sizes of the nanoscale interfaces that form by changing the chemical nature of the surfactants.

Stone says that now the principles are understood, the team are looking at possible applications. He suggests that tiny bubbles might improve adhesives or change the light-scattering properties of paints. Bee says microbubbles can change the fracture properties of foamed construction materials, and are also used as contrast agents to improve ultrasound images. 'The current system might work for changing the taste or appearance of ice cream but we would have to use different surfactants and solutions for other applications,' says Dressaire.

'Studying the stability for a year is unusual: I don't think anybody has followed microbubble stability for that long,' comments Marjorie Longo, who has worked on stabilising small bubbles at the University of California, Davis. Other chemists were not sure that the effect would be useful - or exactly how new it was. David Needham, a materials scientist at Duke University, North Carolina, says he's shown how slightly larger gas bubbles (20 micrometres) can be stabilised by surfactants. 'The field has also moved on substantially by using nanoparticles to stabilise bubbles,' adds Bernie Binks, a physical chemist at the University of Hull, UK. Still, Stone is enthusiastic about the beauty of the team's structures. 'The surface of a gas bubble, less than a micrometre across and with these fifty nanometre polygon patterns - it's stunning.'

The World's First Magnetic Soap

2012-02-02T02:32:00.000-08:00

Researchers have created a liquid surfactant that can be moved by a magnet. The discovery opens the way to soaps and detergents which could be directed to a specific point or removed from a mixture by applying an external magnetic field.

Surfactants, which are ubiquitous in society in the form of everything from detergents and emulsifiers to wetting agents, consist of molecules containing a water-soluble anionic 'head' joined to a water-insoluble cationic 'tail'. The molecules then spontaneously aggregate into particles known as vesicles or micelles.

The research team, led by Julian Eastoe at the University of Bristol in the UK, took conventional surfactants and mixed them with an iron salt, resulting in the exchange of the original anion with the iron-containing ion. The resulting ionic liquid surfactant was shown to be able to respond to a magnetic field. Vertically suspended droplets could be deviated by a small magnet and, more spectacularly, surfactant covered by a less dense organic solvent could be pulled through the upper layer of the solvent by a magnet, overcoming both gravity and the surface tension effects at the interface of the two liquids (see video).

To understand the cause of the magnetic effects, the team probed the surfactant using small angle neutron scattering, carried out at the Institut Laue-Langevin neutron source in Grenoble, France.

'This told us that there was internal organisation in the liquid, that there were clusters present,' says Eastoe. These clusters consist of micelles around 10nm across, in which the iron is aggregated in the central core. 'Isolated ions are not of themselves magnetic,' he explains. 'There needs to be a connection between the units. The proximity of the iron in the aggregates provides this communication between the iron-containing parts of the molecule.'

Eastoe says the team is now looking to develop more responsive and sensitive magnetic surfactants. 'What we have done is a proof of principle,' he says. 'We want to know if we can modify and improve chemicals so that they can perform different tricks and different tasks. We have shown that magnetic soaps and surfactants are a reality. It opens the way to being able to tell such solutions where to go, to target them or direct them to specific areas.'

Peter Griffiths, who researches surfactant chemistry at Cardiff University in the UK, is impressed by the study. 'Surfactants are some of the most versatile molecules known to us - indeed they are encountered in huge quantities by us all everyday - because of their ability to alter the properties of surfaces and interfaces,' he says. 'Eastoe has shown another remarkable feature of these fascinating molecules, where magnetic fields may be used to tune the behaviour of the surfactant at the air-water interface, indeed overcoming the effects of gravity it would seem. This study opens the door for a range of new application for surfactants that could lead to more efficient and greener chemical process.'

Water-Based Metathesis

2012-02-02T02:27:00.000-08:00

Polish chemists have demonstrated the unprecedented catalytic efficiency of olefin metathesis reactions in a water solution.

Karol Grela and his colleagues from the Polish Academy of Sciences, Warsaw University and Warsaw University of Technology studied the performance of commercially available olefin metathesis catalysts in water. Grela explained 'Water is an ideal "green" replacement for conventional organic solvents because of its low cost and lack of organic vapours.'

Initial work found that ultrasonication of water-insoluble reactants floating on water formed an emulsion, in which smooth catalytic metathesis took place in up to quantitative yields after addition of water-insoluble, commercially available catalysts. Next, Grela's team extended their experiments in water to more challenging cross-metathesis reactions with electron-deficient substrates. Grela: 'This transformation is extremely rare in aqueous conditions, usually leading to poor conversions and low selectivities.'

Grela's team revealed that cross metathesis of electron-poor substrates was also possible in water, proceeding with very good yields and selectivities. 'To our knowledge, such reactions represent the first successful example of the high-yielding aqueous cross metathesis between an alkene and an electron-deficient partner,' he said. 'We speculate that under such conditions the sensitive ruthenium intermediates are "protected" inside the water-insoluble organic droplets, thus allowing higher turnovers.'

Jason Eames, a synthetic organic chemist at the University of Hull, UK, was impressed. 'Aqueous olefin metathesis has significant environmental and process advantages,' he said. 'Much attention has been focused previously on the use of water-soluble metathesis reagents, but Grela has now demonstrated that water insoluble metathesis reagents can be used successfully through simple sonification.' Further studies leading to improve the ultrasound conditions for metathesis applications are currently underway in Grela's laboratory.

A simple way to join an Olefin to an Arene

2012-02-02T02:21:00.000-08:00

Chemists in the US have developed a simple and effective way to carry out a key class of reaction in organic synthesis - the bolting an olefin to an aromatic ring.

Olefination of arenes is challenging because there are a number of positions on the aromatic ring to which the olefin can attach. One widely used technique to dictate the point of attack is the palladium-catalysed Mizoroki-Heck reaction, which requires the target carbon of the ring to be halogenated. This, however, is in itself often tricky, adding to the complexity of the procedure.

Now, Jin-Quan Yu and colleagues at the Scripps Research Institute in California have shown that a particular C-H bond can be targeted by a palladium catalyst without the need for prior halogenation.

To steer the catalyst to its target the researchers adopted a twin approach. Firstly, the presence of a carboxyl group adjacent to the target C-H on the ring results in a phenomenon called the complex-induced proximity effect, which pulls the catalyst towards the relevant bond. In cases where the two ortho positions are equivalent, this approach alone can result in good yields of the desired product.

Where the two ortho positions on the ring are different, however, as in multiply substituted arenes, the researchers found that modified amino acids can act as ligands to the Pd catalyst and can steer it towards one or other of the ortho carbons, as required. The ligands do this by differentiating between the subtle electronic or steric environments of the two ortho carbons. 'The COOH dictates the ortho position, the ligand then distinguishes between the two ortho positions when they are different in multi-substituted arenes,' Yu says.

Using this approach, Yu and his colleagues demonstrated the olefination of a range of complex molecules, including the drug ibuprofen and various analogous compounds. Yu points out that given the wide availability of carboxylated substrates, the reaction can be applied broadly. 'The substrates represent a major class of synthetically useful compounds abundantly available off the shelf,' he says.

Matthew Gaunt, an expert in synthetic organic chemistry at the University of Cambridge in the UK believes that the technique could find 'broad utility in the synthesis of complex aromatic molecules.' 'Particularly noteworthy is the use of amino acid-derived ligands to enhance reactivity and control the selectivity of C-H olefination between sterically and electronically similar ortho positions,' Gaunt adds. 'This selectivity has rarely been achieved before.'

New Method for Aromatic Coupling

2012-02-02T02:15:00.000-08:00

Chemists in Switzerland have developed a way to couple aromatic rings through the Friedel-Crafts mechanism - something many people would have believed impossible. Furthermore, the method involves activating the highly stable bond between an aromatic carbon and a fluorine. So far the method only works for aromatic sites in the same molecule, but the team believes that the underlying concept could allow for couplings between discrete molecules.

The Friedel-Crafts reaction enables alkyl or acyl groups to be attached to an aromatic ring via the generation of a carbocation that attacks the ring's electron-rich pi clouds. Coupling two aromatic rings in this way has been problematic because of the instability of the phenyl cation. Instead, aromatic coupling - a hugely important reaction in the fine chemical and pharmaceutical industries - is usually carried out via palladium catalysts.

Now, Jay Siegel's team at the University of Zurich has shown that an aryl halide can be coaxed to participate as an electophile in Friedel-Crafts reactions. The precursor molecule for the reaction is a polyaromatic containing a strong C-F bond. However, the bond between silicon and fluorine is even stronger.
The researchers showed that when the C-F bond is exposed to a silyl cation - R₃Si⁺ - the fluorine hops off the ring to join with the silicon. This would leave an aryl cation, were it not captured by its neighbouring ring, thus coupling the two rings. The proton that is released is then reacts with a silane to regenerate the silyl cation and repeat the cycle.

Siegel says that the technique could be used to make finely tuned fragments of graphene - sheets of carbon one atom thick. Large numbers of fluorinated polyaromatic precursor molecules could be bolted together by conventional methods, then the new method used to knit-up the 'loose ends'. 'If you bring many molecules together you end up with effectively a tattered sail, says Siegel. 'We can knit this together to make a single contiguous sheet of very specific geometry.' Fluorine is useful in this context, rather than the other halogens, because it is much smaller and so more suited to a sterically congested environment where fine control over molecular geometries is being sought.

The team is now looking into the possibility of coupling aromatic sites from separate molecules. To carry out this reaction the various intermediate species need to survive long enough for the relevant collisions to occur. 'We have some ideas of how we might tackle this,' says Siegel.

Scott Denmark at the University of Illinois in the US, is impressed and describes the approach as 'ingenious', adding that 'the accomplishment is particularly remarkable because it engages the least reactive of all the aryl halides, namely aryl fluorides. This new transformation allows ready access to important polyarene structures and opens vistas for exploration of novel chemical reactivity.'

Trifluoromethylation Made Easy

2012-02-02T02:08:00.000-08:00

US researchers have discovered a simple, low-cost way to add fluorine atoms to heteroaromatic rings. Inserting fluorine into molecules that are drug candidates can give the compounds many improved properties, such as increased stability or improved interaction with target proteins.

Trifluoromethylation of heteroaromatic compounds is a key reaction in many organic syntheses, and is widely used in the development of new pharmaceuticals and agrochemicals. 'One procedure involves the gas CF₃I which is difficult to measure and medicinal chemists do not like using it,' says Phil Baran, of the Scripps Research Institute in California, who led the new research.

Another common method is to use anhydrous hydrogen fluoride as the fluorinating agent, explains Graham Sandford, who researches organofluorine chemistry at the University of Durham, UK. 'For discovery chemists, using anhydrous hydrogen fluoride is not very convenient to say the least and direct, efficient trifluoromethylation methods have long been sought.'

Baran's team set about searching for a simpler method for trifluoromethylation of heterocycles. The team tested scores of reagents in more than 500 reaction systems for the trifluoromethylation of a test compound, 4-t-butylpyridine. One reagent achieved the desired result: sodium trifluoromethanesulfinate, CF₃SO₂Na, a stable, inexpensive solid also known as Langlois reagent.

The CF₃ radical is generated through induced decomposition of the reagent. But, Baran says: 'The addition of the electron-deficient radical to electron-deficient heterocycles was counterintuitive and a surprise.' No metal catalyst was necessary. The radical attaches to the heterocycle at the most innately reactive C-H bonds on the substrate, and the point of attack is largely predictable. A degree of control can be exerted by choice of solvent, Baran says. The method works on complex heteroaromatic molecules and can tolerate the presence of multiple functional groups.

The new technique, in principle, should make it easier for pharmaceutical companies to modify and improve specific drug compounds of interest. 'It also means that these companies can expand the existing compound libraries they use for drug-discovery screening by making trifluoromethylated versions of these compounds quickly and easily,' says Baran.

'Medicinal chemistry exploration of pharmacophore space and ligand interactions benefits tremendously from methods that introduce substituents late in syntheses,' says Jotham Coe, a medicinal chemist at Pfizer. 'Such reactions are best when versatile and reliable enough to work in conjunction with variable substitution within target molecule classes. The Baran chemistry addresses these shortcomings economically, providing options never before available.'

The work represents 'a significant advance', Sandford says, 'especially since highly functional heterocycles and natural products may be trifluoromethylated regioselectively.'

Simple One Stop Shop for Difluoromethylation

2012-02-02T01:59:00.000-08:00

Inserting fluorine atoms directly and simply into various organic substrates including heteroaromatic rings is now possible thanks to a user-friendly and scaleable difluoromethylation process developed by US researchers. The find opens the way for adding difluoromethyl (CF₂H) groups to drugs and agrochemicals in order to enhance their properties.

Many new life science products, including drugs and agrichemicals, contain fluorine atoms or trifluoromethyl (CF₃) groups because the fluorine atom can increase the metabolic stability and efficiency of bioactive compounds. For example, the CF₃ group in prozac allows the drug to be transported across the blood-brain barrier. However, until now, CF₂H groups could only be added to bioactive compounds using complicated two-step or multi-step difluoromethylation processes.

'Medicinal chemists have told us for years exactly what they want and how they want to do it. We have listened,' says Phil Baran, who led the research at the Scripps Research Institute in La Jolla, California. 'This reaction installs a functional group that they sorely desire in a way that is amenable to parallel synthesis in an open flask and in water with simple, non-toxic reagents and a procedure that rivals the simplicity of preparing your morning coffee - add one solid reagent, one liquid reagent and stir.'

The team invented the solid reagent using difluoromethanesulfonyl chloride as a starting point and added various metal counterions until they identified zinc dialkylsulfinate salt (DFMS) (Zn(SO₂CF₂H)₂) - an easily prepared, air-stable white powder - as the optimum precursor for the CF₂H radical.

They then tested the reagent on a variety of organic substrates and successfully demonstrated the effective direct transfer of a CF₂H unit to heteroarenes, ,-unsaturated enones and aromatic thiols. 'There is no alternative for a chemist who wishes to directly install a difluoromethyl group in these kinds of spots on a molecule,' says Baran

'I think it's a nice way of making aromatics with CF₂H groups attached and I know that a lot of pharmaceutical companies are looking at systems like that,' says Graham Sandford, who researches organofluorine chemistry at the University of Durham, UK. 'You don't get fluorinated molecules from nature, so you have to put the fluorine atom in there and that's a difficult thing - that's why new methodology that is simple and scaleable like Baran's process are always very valuable,' he adds.

'I think a reaction can always be made more practical and higher yielding, but in the meantime Sigma-Aldrich has commercialised this reagent and it is already being employed at a few pharma companies,' Baran adds.

Free Chemical Databases Info

2012-01-19T22:06:00.000-08:00

The listed websites provide information about chemicals (physical and chemical characteristics, structure, MSDS and more). You can search for compounds by registry number, CAS number, molecular formula, chemical name or synonyms in different languages as well as by physical and chemical characteristics and combinations of those data. You can now search for chemicals and molecular information directly using the below form. Search compound by: CAS registry number, molecular formula, chemical name, part of name or synonyms.

Biomolecule Binding Database
The BindingDB is a public, web-accessible database of measured binding affinities for biomolecules, genetically or chemically modified biomolecules, and synthetic compounds.
http://www.bindingdb.org/bind/index.jsp

ChEBI
Chemical Entities of Biological Interest (ChEBI) is a freely available dictionary of molecular entities focused on "small" chemical substances. ChEBI draws its information from two main sources: Integrated Relational Enzyme Database of the EBI and the Kyoto Encyclopedia of Genes and Genomes.
http://www.ebi.ac.uk/chebi/

ChemACX
ChemACX is a comprehensive online catalog containing current product information from 405 leading chemical supplier catalogs such as Sigma Aldrich, Fisher Scientific, Acros, Alfa Aesar, Lancaster, Novabiochem and TCI America. ChemACX provides rapid ordering information for over 352,300 unique chemical compounds, over 733,100 products, and is updated bi-annually.
http://chemacx.cambridgesoft.com/

Chemazone - Organic Chemicals for R&D
Are you looking for organic chemicals for research and development and cannot find them commercially available anywhere? The Chemazone website contains more than 2,000,000 readily available synthetic organic compounds.
http://www.chemazone.com

ChemBank
Chembank is a freely available collection of data about small molecules and resources for studying their properties, especially relating chemistry to biology, and a suite of informatics tools and databases aimed at promoting the development and use of chemical genetics by scientists worldwide. Chembank currently has a database of about 2000 compounds, with SMILES strings, chemical structures and biological activity. Soon other files will be downloadable.
http://chembank.broad.harvard.edu

ChemExper Chemical Directory
The ChemExper Chemical Directory displays information about chemicals (physical and chemical characteristics, structure, MSDS and more.) on the Internet in order to create a world-wide database. It is free to consult and easily accessible over the Internet on any computer using a web browser. The ChemExper Chemical Directory contains for now over 200,000 different chemicals, 10,000 MSDS and over 10,000 IR spectra.
http://www.chemexper.com

ChemFinder
CambridgeSoft maintains ChemFinder, a remarkably efficient Internet search engine, which searches for information on specific compounds by name, formula, CAS registry number, and molecular weight.
http://www.chemfinder.com

Chemical Abstracts Service
CAS is the producer of Chemical Abstracts, SciFinder, SciFinder Scholar, and also operates STN International and the web based STN Easy online searching services which provide access to chemical and scientific information from databases covering topics such as chemistry, engineering, patents, medicine regulatory data and business. CAS databases provide access to over 25 million documents, 26 million chemical substances and 56 million sequences.
http://www.cas.org

Chemical Catalog by Exchemistry
An online catalog of chemicals searchable by Chemical Name, Product Number, CAS Registry Number and Molecular Formula. Chemical custom synthesis of compounds that cannot be found in the major catalogues (Sigma-Aldrich, Acros Organics, etc) is also available.
http://www.exchemistry.com/chemicals-catalog.html

Chemical Structure Lookup Service
Look up whether a structure occurs in any of tens of different databases, both public and commercial. Currently loaded pointers to: over 39 million entries from more than 80 databases, representing more than 27 million unique chemical structures.
http://cactus.nci.nih.gov/lookup/

Chemicals for R&D
The R&D Chemicals is a free service that allows to find a chemical by its molecular formula, IUPAC name, smiles, common name, CAS number, catalog number, substructure or physical characteristics as well as chemical suppliers.
Examples of a textual query: Extrasynthese, Jrd Fluorochemicals, Frinton Laboratories.
http://www.rdchemicals.com

ChemIDplus
ChemIDplus provides access to structure and nomenclature information for the identification of chemical substances cited in NLM (National Library of Medicine) databases. The database contains over 380,000 chemical records, of which over 263,000 include chemical structures. ChemIDplus Lite is available for Name and RN searching without the need for plugins or applets.
http://chem.sis.nlm.nih.gov/chemidplus

Chemsink
ChemSink is a chemical reaction database. It is a place for anyone interested in chemical synthesis to come and discuss their successes and failures with specific chemical reactions. The chemsink database is free to download, alter, and use.
http://www.chemsink.com/

ChemSpider - Database of Chemical Structures
ChemSpider is a chemistry search engine. It has been built with the intention of aggregating and indexing chemical structures and their associated information into a single searchable repository and making it available to everybody, at no charge. ChemSpider is a value-added offering since many properties have been added to each of the chemical structures within the database - structure identifiers such as SMILES, InChI, IUPAC and Index Names as well as many physicochemical properties.
http://www.chemspider.com

ChemSub Online
ChemSub Online is a free web-based database which allows you to retreive information for over 237,000 chemical substances of which 138,000 include chemical structures.
http://chemsub.online.fr/

Common Chemistry
This database contains the CAS Registry Number, chemical names (both formal and common), molecular formulas, and structures or sequences for 7800 chemicals of widespread general public interest. These substances are of global commercial use or importance and have been cited 1,000 or more times in the CAS databases.
http://www.commonchemistry.org

CrossFire Beilstein
The CrossFire Beilstein database is the world's largest compilation of chemical facts. As the cornerstone database to organic chemistry, the CrossFire Beilstein database is essential for generating new leads, planning synthetic routes (including starting materials and intermediates), determining bioactivity and physical properties and ascertaining the environmental fates of compounds. With the second update in 2006, the 10 millionth reactions in CrossFire Beilstein have been released. Passing this important milestone emphasizes the enduring and increasing value of the database as the essential first step in chemical discovery.
http://www.beilstein.com

eMolecules
eMolecules is the world's free open-access chemistry search engine. eMolecules' mission is to discover, curate and index all of the public chemical information in the world, and make it available to the public. eMolecules distinguishes itself by extremely fast searches, an appealing presentation of results, and high-quality chemical drawings.
http://www.emolecules.com

HDAC Inhibitors Database
A small database contains information about molecules or drugs that block HDACs. Histone deacetylase inhibitors are emerging as a new class of potential anticancer agents.
http://www.hdacis.com

MSD Ligand Chemistry
This is a database of the small molecules, ligands and monomers which may appear in molecules that are classified in the larger Protein Data Bank database. This resource forms a part of the Macromolecular Structure Database at the European Bioinformatics Institute. The database is searchable by atom energy types, molecular classification, via a JME structure editor, and other properties.
http://www.ebi.ac.uk/msd-srv/msdchem/cgi-bin/cgi.pl

Sigma Aldrich
Online version of the well-known Sigma-Aldrich chemical catalog. Includes CAS registry numbers and a variety of physical and chemical properties of chemicals manufactured by Sigma-Aldrich. Free registration is required to access additional features such as MSDS and NMR and IR spectra.
http://www.sigmaaldrich.com

SpresiWeb
SpresiWeb a new dimension of integrating scientific databases. The search can be carried out for molecules, reactions and references. SpresiWeb combines a large chemical database with lots of links to additional information sources. SpresiWeb contains over 5,0 million compounds, 3,7 million reactions, 600.000 references and 164.000 patents.
http://www.spresi.com

The PubChem Project
PubChem provides information on the biological activities of small molecules. It is a component of NIH's Molecular Libraries Roadmap Initiative. PubChem includes substance information, compound structures, and bioactivity data in three primary databases, PCSubstance, PCCompound, and PCBioAssay, respectively. PCSubstance contains more than 10 million records. PCCompound contains more than 5 million unique structures. PCBioAssay contains more than 200 bioassays. Each bioassay contains a various number of data points.
http://pubchem.ncbi.nlm.nih.gov

TOXNET
Chemical information (nomenclature, identification, structures), references to literature on biochemical, physiological, pharmacological, and toxicological effects of drugs and other chemicals, developmental and reproductive toxicology, and environmental teratology.
http://toxnet.nlm.nih.gov/

WebReactions
WebReactions is a unique reaction search system offering direct retrieval of reaction precedents through the internet. The system is easy to learn and use and is extremely fast in locating matches for reaction queries from the database.
http://www.webreactions.net/

ZINC - a Free Database for Virtual Screening
ZINC a free database of over 2.7 million commercially-available compounds for virtual screening in ready-to-dock, 3D format. ZINC contains multiple representations of molecules, since molecules that are not in the biologically relevant protonation state, tautomeric, stereo- or regio-isomeric form in the virtual library often fail to dock and score well.
http://blaster.docking.org/zinc/

Free Chemical Encyclopedias Info

2012-01-19T21:57:00.000-08:00

Chemical encyclopedias summarize and filter the chemistry literature to provide you with pertinent information. They provide detailed information on most chemical topics. Chemical encyclopedias are excellent places to start.

Encyclopedia 4U - Chemistry
A very detailed encyclopedia covering all aspects of chemistry that would be used in freshman level chemistry classes.
http://www.encyclopedia4u.com/c/chemistry.html

Encyclopedia of Chemistry
Growing encyclopedia with articles on chemical reactions, experimental chemistry, quantum chemistry, inorganic and organic chemistry.
http://scienceworld.wolfram.com/chemistry/

Kirk-Othmer Encyclopedia of Chemical Technology
Highly regarded source of information in applied chemistry and chemical technology. About half the articles focus on industrially important chemical substances or materials, their properties, manufacture, and industrial and economic significance. Other articles cover chemical processes and engineering principles, current research, and emerging technologies; environmental, safety, and health topics; and selected chemistry fundamentals.
http://www3.interscience.wiley.com/cgi-bin/mrwhome/104554789/HOME

Little Encyclopedia of Mass Spectrometry
The Little Encyclopedia of Mass Spectrometry was developed by the Mass Spectrometry Group of the University of Heidelberg, and is intended to serve as a fast source of basic knowledge of mass spectrometry. Explanations are given in a tutorial-like form aided by diagrams and links to the selected topic areas are provided for further explanation.
http://www.rzuser.uni-heidelberg.de/~bl5/encyclopedia.html

Free Chemical Literature Info

2012-01-19T21:49:00.000-08:00

In the course of chemical projects you often need to search a variety of chemical literature sources for physical data, reactions, syntheses, techniques or concepts. The following resources contain information relating to all areas of chemistry. Some of the home pages contain links to other potential resources.

Analytical Biochemistry
Methods in the Biological Sciences, emphasizes methods in the biological and biochemical sciences. The journal publishes the results of original research as well as reviews of methods.
http://www.elsevier.com/wps/find/journaldescription.cws_home/622781/description?navopenmenu=-2

Analytical Chemistry
Analytical Chemistry Chemistry is a peer-reviewed research journal that explores the latest concepts in analytical measurements and the best new ways to increase accuracy, selectivity, sensitivity, and reproducibility. Coverage includes the latest peer-reviewed research and significant applications in bioanalysis, electrochemistry, mass spectrometry, microscale systems, environmental analysis, separations, and spectroscopy.
http://pubs.acs.org/journals/ancham/

Beilstein Journal of Organic Chemistry
Beilstein Journal of Organic Chemistry offers organic chemists a unique opportunity to publish their research rapidly in an Open Access medium that is freely available online to researchers worldwide. In doing so it not only offers authors uniquely wide visibility and high impact, but it also ensures that their work is part of the permanent, publicly available archive of science. Open Access does not compromise the high quality of the articles published. All manuscripts submitted to the journal are subject to rigorous peer review.
http://bjoc.beilstein-journals.org/

Chemical Reviews
Chemical Reviews is one of the most highly regarded and highest ranked journals covering the general topic of chemistry. The mission of Chemical Reviews is to provide comprehensive, authoritative, critical, and readable reviews of important recent research in organic, inorganic, physical, analytical, theoretical, and biological chemistry.
http://pubs.acs.org/journals/chreay/

ChemPort
The ChemPort Connection is a free service that provides scientists and information professionals with links to full-text electronic documents from a large and growing group of chemistry publishers, subscription agents, patent offices, and patent document services.
http://www.chemport.org

ChemRefer
ChemRefer is a search engine that is designed to allow students, academics, chemical and pharmaceutical companies quick access to chemistry literature which is available on the internet. ChemRefer only finds literature that is full text and freely available (from many different sources).
http://www.chemrefer.com

Combinatorial Chemistry & High Throughput Screening
Combinatorial Chemistry & High Throughput Screening publishes full length original research articles describing various topics in combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries) and/or high throughput screening (e.g. developmental, practical or theoretical). The journal should be of value to individuals engaged in the process of drug discovery and development, in the settings of industry, academia, or government.
http://www.bentham.org/cchts/

Combinatorial Chemistry - an Online Journal
Combinatorial Chemistry - an Online Journal, is a unique WWW only publication, featuring papers accepted for publication in: Tetrahedron, Tetrahedron Letters, Tetrahedron: Asymmetry, Bioorganic& Medicinal Chemistry, Bioorganic & Medicinal Chemistry Letters, Carbohydrate Research, and other relevant Elsevier journals. In addition it will feature links to articles from other publications.
http://www.elsevier.com/locate/issn/14643383

Directory of Open Access Journals
The aim of the Directory of Open Access Journals is to increase the visibility and ease of use of open access scientific and scholarly journals thereby promoting their increased usage and impact. Section devoted to chemistry.
http://www.doaj.org/ljbs?cpid=60

Free Full-Text Journals in Chemistry
Directory of free full-text journals in chemistry, biochemistry, and related subjects. Includes two part: permanently available chemical journals and trial (temporarily) available chemical journals.
http://www.abc.chemistry.bsu.by/current/

Heterocycles Web Edition
Since its inception in 1973 Heterocycles has provided a platform for the rapid exchange of research in the areas of organic, pharmaceutical, analytical, and medicinal chemistry of heterocyclic compounds in addition to communications, papers, reviews, a special section of the journal presents newly-discovered natural products whose structure has recently been established.
http://www.heterocycles.jp/index.php

Journal of Combinatorial Chemistry
The Journal of Combinatorial Chemistry publishes studies that facilitate the synthesis of chemical libraries, as well as their subsequent characterization and screening for properties of interest. It is a must-read interdisciplinary journal that opens up channels of information for synthetic organic chemists, medicinal and analytical chemists, pharmaceutical scientists, biotechnologists, computational chemists, material scientists, and agrochemists.
http://pubs.acs.org/journals/jcchff/index.html

Journal of Fluorine Chemistry
The Journal of Fluorine Chemistry contains original papers and short communications describing both pure and applied research on the chemistry and applications of fluorine, and of compounds where fluorine exercises significant effects. The Journal of Fluorine Chemistry covers inorganic, organic, organometallic and physical chemistry and also includes papers on biochemistry and environmental industrial chemistry. Preparative and physico-chemical investigations as well as theoretical, structural and mechanistic aspects are covered.
http://www.elsevier.com/wps/find/journaldescription.cws_home/504088/description?navopenmenu=-2

Journal of Medicinal Chemistry
The Journal of Medicinal Chemistry publishes original research on the correlation of molecular structure to biological activity with a focus on the relationships of chemistry to biological activity. This includes design and synthesis of novel biologically active compounds, molecular modifications designed to target drugs to specific tissues, the role of metabolism in drug actions, application of NMR and X-ray crystallography to investigate molecular recognition at receptors, molecular modeling studies that furnish fresh insight into the design of novel agents, and molecular biology studies to study the interaction of ligands and receptors.
http://pubs.acs.org/journals/jmcmar/

Journal of Organic Chemistry
The Journal of Organic Chemistry (JOC) welcomes original contributions of fundamental research in all branches of the theory and practice of organic and bioorganic chemistry. JOC features full articles and notes, invited topical mini-reviews, as well as invited contributions from all the recipients of the annual national ACS awards in the field of organic chemistry.
http://pubs.acs.org/journals/joceah/

Journal of the American Chemical Society
The Journal of the American Chemical Society publishes articles, communications to the Editor, book reviews, and computer software reviews. This periodical is devoted to the publication of research papers in all fields of chemistry and publishes approximately 13,000 pages of new chemistry a year. Published weekly, JACS provides research essential to the field of chemistry.
http://pubs.acs.org/journals/jacsat/

Nucleic Acids Research
Nucleic Acids Research publishes the results of leading edge research into chemical, biochemical and biological aspects of nucleic acids and proteins involved in nucleic acid metabolism and/or interactions. It enables the rapid publication of papers under the following categories: chemistry, computational biology, genomics, molecular biology, nucleic acid enzymes, RNA and structural biology.
http://nar.oxfordjournals.org

Organic Process Research & Development
Organic Process Research & Development reports work in the broad field of process chemistry encompassing aspects of organic chemistry, catalysis, analytical chemistry, and chemical engineering. There is special focus on the development and optimization of chemical reactions and processes and their transfer to a larger scale, via large laboratory and pilot plant operations, for manufacturers.
http://pubs.acs.org/journals/oprdfk/

Organometallics
Organometallics records progress in one of the most active fields for organometallic, inorganic, organic and materials chemists. Articles, communications, mini-reviews, and notes detail the synthesis, structure, bonding, chemical reactivity and reaction mechanisms, and applications of organometallic and organometalloidal compounds. Applications coverage includes organic and polymer synthesis, catalytic processes, and synthetic aspects of materials science and solid-state chemistry.
http://pubs.acs.org/journals/orgnd7/

Tetrahedron
Tetrahedron publishes experimental and theoretical research results of outstanding significance and timeliness in the field of organic chemistry and its application to related disciplines especially bio-organic chemistry. Areas covered by the journal include the many facets of organic synthesis, organic reactions, natural products chemistry, studies of reaction mechanism and various aspects of spectroscopy.
http://www.elsevier.com/wps/find/journaldescription.cws_home/942/description

Tetrahedron Letters
Tetrahedron Letters provides maximum dissemination of outstanding developments in organic chemistry. The journal is published weekly and covers developments in techniques, structures, methods and conclusions in experimental and theoretical organic chemistry. Rapid publication of timely and significant research results enables researchers from all over the world to transmit quickly their new contributions to large, international audiences.
http://www.elsevier.com/wps/find/journaldescription.cws_home/233/description

Free Materials Safety Data Sheets (MSDS) Info

2012-01-19T21:34:00.000-08:00

Materials Safety Data Sheets (MSDS) contain basic safety information on the storage, handling and use of chemicals. Manufacturers are required to provide them on request for any chemical products they sell. There are a number of Internet sites which provide electronic collections of MSDS's for quick reference.

Alfa Aesar
Freely accessible material safety data sheet archive - searchable by CAS number, MDL number and product name. Sheets are in a OSHA and ANSI formats as PDF files.
http://www.alfa.com

Internet Resources for MSDS
Where to find Material Safety Data Sheets on the Internet. Over 100 free resources for Material Safety Data Sheets (MSDS) sites on the WWW and much more.
http://www.ilpi.com/msds/index.html

MSDS online
Free registration to search and view a limited number of OSHA, DOT, ANSI and WHIMIS compliant sheets in PDF format. 10,000+ new/updated sheets are added each month. The site also offers a 30-day free trial of an integrated (web/software) MSDS management solution.
http://www.msdsonline.com

MSDS Solutions
Free access to more than 2.5 Million MSDSs available online. Free trial, but allows only 5 free downloads. Registration/login is required to view the sheets which are available in a variety of MSDS formats (OSHA, ANSI, WHMIS) and file formats (HTML, PDF, text). 200,000 available in French. MSDS download "blocks" available on a fee basis.
http://www.msds.com

MSDS Xchange
MSDSXchange is the largest and most comprehensive reference collection of chemical manufacturer and distributor listings available on the web. In addition to this extensive collection, there are over 1 million manufacturer's original material safety data sheets (MSDS) available for meeting compliance with OSHA's Hazardous Communication Standard, Canada's WHMIS, the EPA, DOT and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO).
http://www.msdsxchange.com

MSDSSEARCH
The First Place to Look for an MSDS, MSDSSEARCH is the most comprehensive single address for free information related to the document known as a Material Safety Data Sheet (MSDS), providing access to over 2,500,000 MSDSs, 6000 links directly to manufacturers, plus links to databases, software vendors, and government sources and organizations.
http://www.msdssearch.com

Science Stuff
Science Stuff is a reliable MSDS resource supplying free, up-to-date MSDSs to the public. MSDS for science supplies, education, researches and others. Enter the CAS number to retrieve a MSDS directly or browse the catalog A-Z listing, select an item and click on "MSDS information". Nicely compact OSHA-compliant sheets in HTML format.
http://www.sciencestuff.com/msds/

SIRI MSDS Index
This site from Vermont Safety Resources on the Internet contains a searchable collection of MSDS from a variety of chemical manufacturers. It also includes a large collection of links to other Web MSDS sites.
http://hazard.com/msds/

See also: Synthesis - starting points for locating melting point, boiling point, density.