Spotlights

Chemists forge green path to alkylated amines

Posted on 2017-12-12

Chemists use alkylated amines to build plastics, pharmaceuticals, and more. Unfortunately, making these important building blocks on a large scale is energy intensive and relies on nonrenewable feedstocks. Now a team of researchers report a green approach to synthesizing the molecules.
Tao Yan, Ben L. Feringa, and Katalin Barta of the University of Groningen, describe an environmentally-friendly catalytic process that uses alcohols to add alkyl groups to amino acids harvested from microbes (Sci. Adv. 2017, DOI: 10.1126/sciadv.aao6494). The method retains the chirality of the amino acids and releases water as its only waste product.
Calling the research “nothing short of revolutionary,” Paul T. Anastas, the director of Yale University’s Center for Green Chemistry & Green Engineering, says the approach could mean a cheaper, cleaner way to make these industrially crucial building blocks.
Making alkylated amines is so energy intensive because it requires the Haber-Bosch process, which converts atmospheric nitrogen to ammonia at around 500°C. To add alkyl substituents to ammonia, chemists use molecules derived from fossil fuels and reactions that often generate as much waste as they do useful products.
Yan, Feringa—who shared the 2016 Nobel Prize in Chemistry—and Barta instead let nature do the hard work of reducing nitrogen: They isolated amino acids from bacteria. As for adding alkyl substituents to these amino acids, ethanol, isopropanol, and other simple alcohols act as both solvents and reactants. The chemists initially used a ruthenium catalyst, but also demonstrated the reaction with a catalyst containing iron, a more abundant metal.
In either case, the catalyst borrows a hydrogen atom from the alcohol and produces a carbonyl intermediate that then reacts with the amino acid, shedding a water molecule. The resulting imine intermediate then takes a hydrogen back from the catalyst, producing an alkylated amine.
The researchers demonstrated their method by synthesizing a surfactant from glycine and 1-dodecanol using an iron catalyst. Feringa says they believe the technique has broad potential beyond surfactants. The chemists have filed for a patent on the method and are looking for partners to explore adapting it for industrial uses.
Anastas thinks the approach could revolutionize industrial synthesis by providing useful starting materials at very low costs both economically and environmentally. “This shows, once again, that green chemistry is just simply better chemistry,” he says.

graphical abstract

https://cen.acs.org/articles/95/web/2017/12/Chemists-forge-green-path-alkylated.html

 

Drug delivery with the flip of a light switch

Posted on 2017-12-04

nature research highlights

A common medication has been converted into the first antibiotic to employ visible light as an on–off switch.

A drug that can be easily turned on and off could provide targeted treatment, and the ability to deactivate antibiotics could help to battle drug resistance. But previous efforts to develop light-sensitive antibiotics produced compounds controlled by ultraviolet (UV) light, which kills healthy cells.

Wiktor Szymański and Ben Feringa of the University of Groningen in the Netherlands and their colleagues wanted to make an antibiotic that could be activated by visible light, which is more benign. The researchers took the core structure of an antibiotic called trimethoprim and added chemical groups that act as ‘photoswitches’ at various positions; this initially created a compound responsive to UV light and active against the pathogen Escherichia coli.

When the team added chlorine to the photoswitch, the resulting antibiotic could be switched on with red light, making it eight times more potent against bacteria when on than off.

graphical abstract

https://www.nature.com/articles/d41586-017-07428-w

 

Microwaves reveal detailed structure of molecular motor

Posted on 2017-08-08

Study paves the way to investigate nano-machines in action

A team of scientists has used microwaves to unravel the exact structure of a tiny molecular motor. The nano-machine consists of just a single molecule, made up of 27 carbon and 20 hydrogen atoms (C27H20). Like a macroscopic motor it has a stator and a rotor, connected by an axle. The analysis reveals just how the individual parts of the motor are constructed and arranged with respect to each other. The team led by DESY Leading Scientist Melanie Schnell reports the results in the journal Angewandte Chemie International Edition. DOI: 10.1002/anie.201704221

The artificial molecular motor was synthesized by the team of Dutch Nobel laureate Ben Feringa from the University of Groningen who is a co-author of the paper. Feringa was awarded the 2016 Nobel Prize in Chemistry together with Jean-Pierre Sauvage from the University of Strasbourg and Sir Fraser Stoddart from the Northwestern University in the US for the design and synthesis of molecular machines.

“The functional performance of such nano-machines clearly emerges from their unique structural properties,” the authors write in their study. “To better understand and optimise molecular machinery it is important to know their detailed structure and how this structure changes during key mechanical steps, preferably under conditions in which the system is not perturbed by external influences.”

The rotary motor investigated here holds great promise for quite a few applications, as first author Sérgio Domingos from DESY and the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) explains: “Chemists are all abuzz about this molecule and try to connect it with a range of other molecules.” When activated by light, the nano-machine operates through consecutive photochemical and thermal steps, completing a half turn. A second trigger then forces the motor into completing a full turn, returning to its starting position.

Such an activation by light is ideal as it provides a non-invasive and highly localized means to remotely activate the motor,” says Domingos. “It could be used, for instance, as an efficient motor function that can be integrated with a drug, establishing control over its action and release it at a precisely targeted spot in the body: the light-activated drugs of the future. But also applications like light-activated catalysis and transmission of motion at the molecular level to the macroscopic world come to mind. For such applications it is important to understand the motor molecule’s exact structure and how it works in detail.”

The atomic make-up of the motor molecule had been investigated before with X-rays. For the X-ray analysis the molecules had to be grown into crystals first. The crystals then diffract the X-rays in a characteristic way, and from the resulting diffraction pattern the arrangement of atoms can be calculated. “In contrast, we investigated free floating, isolated molecules in a gas,” explains Schnell, who works at the Center for Free-Electron Laser Science (CFEL), a cooperation between DESY, the University of Hamburg and the Max Planck Society. “This way we can see the molecule as it is, free from any external influences like solvents or bindings.”

In order to determine their structure, the free-floating molecules had to be exposed to a resonant microwave field. “We used an electromagnetic field to orient the molecules all in the same direction in a coherent way and then recorded their relaxation when the field is switched off,” explains Schnell, who also leads a research group at MPSD and is a professor for physical chemistry at the University of Kiel. “This reveals the so-called rotational constants of the molecule, which in turn give us accurate information about its structural arrangement.”

This analysis of this so-called microwave spectroscopy is not straightforward. In the case of the motor molecule, the scientists had to match more than 200 lines of the spectrum and compare their numbers with simulations from quantum chemistry calculations. “Regarding the number of atoms, the molecular motor currently is the largest molecule whose structure has been solved with microwave spectroscopy,” explains Schnell.

In order to float the molecules in the microwave chamber, they had to be heated to 180 degrees Celsius before being cooled down rapidly to minus 271 degrees. “Heating made some of the motors fall apart, breaking at the axle,” reports Domingos. “This way we could see the rotor and the stator independently of each other, confirming their structures. This also provides us with some hint about the mechanism via which it falls apart.”

The final analysis indicates some small deviations from the structure determined with X-rays, where the molecules are interacting with each other in a crystal. “This shows that the structure of the motor is unmistakably affected by its environment,” says Domingos. Even more importantly, the microwave technique opens the possibility to study the dynamics of the motor molecule. “Now that we can see the molecule like it really is, we want to catch it in action,” underlines Domingos. The rotor goes through an intermediate state that lasts about three minutes – long enough to be investigated with microwave spectroscopy. The researchers are already planning such investigations from which they hope to learn in detail how the molecular motor works.

This work has been performed at DESY and the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, with strong involvement from the Universities of Amsterdam and Groningen in the Netherlands. The Hamburg Centre for Ultrafast Imaging and the Alexander von Humboldt Foundation supported this work.

graphical abstract

http://www.epsnews.eu/2017/08/microwaves-reveal-detailed-structure-of-molecular-motor/

 

Molecular motor turns rotor

Posted on 2017-06-10

Gearing up to make even more complex molecular machines, chemists at the University of Groningen have created a molecular motor coupled to a rotor. The motor turns the attached rotor such that the two components’ motions are synchronized, just like that of machines we encounter in everyday life (Science 2017, DOI: 10.1126/science.aam8808).
“This is fundamental research about how to control motion at the molecular level and how then to use it to synchronize motion and amplify motion,” says Ben L. Feringa, who led the Groningen team.
In a commentary that accompanies the paper, University of Bologna chemists and molecular machine makers Massimo Baroncini and Alberto Credi note that the motor-rotor combo “takes an important step forward toward more complex mechanical functions with artificial nanoscale devices.”

The unidirectional motor consists of a fluor­enyl unit attached to an indanyl group via a double bond. The system’s naphthyl rotor is covalently attached to the indanyl half of the motor. When illuminated, the motor’s double bond isomerizes, setting the system into motion. As the motor turns, the naphthyl rotor paddle slides alongside the fluorenyl unit so that the rotor is always facing the motor with the same side—a feat the group accomplished with a complex stereochemical design. Both nuclear magnetic resonance and circular dichroism spectroscopy confirmed this synchronized motion.
It was a delicate balance to achieve the desired movement, Feringa notes. “We had to induce motion, we had to couple motion, and we had to prevent free rotation of the rotor; otherwise we could not have synchronized rotation,” he says.
Next, Feringa’s group would like to create machines that can amplify the molecular machines’ motion to larger movements or transmit motion over longer distances.

graphical abstract
 

Gearing up molecular rotary motors

Posted on 2017-06-02

Macroscopic motors rely on gears to keep components in synchrony. Štacko et al. demonstrate an analogous type of coupled motion at the molecular scale. They constructed a molecular scaffold in which light absorption drives the rotation of upper and lower fragments around a connecting double bond. At the same time, steric constraints modulate the motion of a third component that is tethered to the top of the rotor, so that it continuously exposes the same face to the bottom. The design paves the way toward more complex synchronized motion in an assembly of molecular machines.

graphical abstract

10.1126/science.aan4353

 

Light responsive molecular motor winds up helicates

Posted on 2016-11-16

Molecular switch enables non-invasive control of chirality

Researchers in the Netherlands have used a light-sensitive molecular motor to control the chirality of a double-stranded ‘helicate’. The motor mimics the way that nature employs certain enzymes to unwind helical structures such as DNA.

Helicates are polymetallic complexes in which two organic ligands weave around metal centres and each other to form a double helix – similar to the structure famously observed in DNA. They were first discovered in 1987 by Jean-Marie Lehn, who shared a Nobel prize that same year with Donald Cram and Charles Pederson for pioneering work in the field of supramolecular chemistry.

Almost 30 years since the original research on helicates, a team of scientists led by another Nobel laureate, Ben Feringa of Groningen University, has adapted Lehn’s system to make a new type of molecular machine.

The team can dictate the direction two ligands weave around each other in dinuclear copper complexes, by capping the system with a molecular motor – one of the nanoscale machines that saw Feringa awarded with the 2016 Nobel prize, alongside Fraser Stoddart and Jean-Pierre Sauvage. ‘The idea was to use our molecular motor as a multi-state switch,’ explains Feringa. ‘Because it goes through a rotary cycle, we can address different states which have different chirality.’

The rotor is attached to the ends of two oligobipyridine ligands, which eventually form the strands of the helix. When copper is added, the system self-assembles into a helical structure in a favoured chiral configuration. When this system is treated with light and heat, the motor rotates, causing the helix to unravel and eventually reform as the opposite enantiomer. The chirality of helical molecular systems, including certain antibiotics and catalysts, is often crucial to the way that they carry out their biological or chemical functions.

Markus Albrecht, a supramolecular chemist at RWTH Aachen University, Germany, praises the ‘unique example of stereochemical switching of helicates’, adding that the research could pave the way for new ‘systems for control of chemical reactivity, molecular recognition and even with special mechanical properties’.

Bert Meijer, who also works on supramolecular systems at Eindhoven University of Technology, Netherlands, is similarly impressed with the new rotary motor scaffold. Describing the work as ‘a beautiful illustration of why the 2016 Nobel prize in chemistry was given for the design and synthesis of molecular machines’, he adds that ‘in every new contribution of the [Feringa] group, they come closer to mimicking natural molecular machines with very innovative and original designs’.

Looking to the future, Feringa says that the system could be used for the design of new selective catalysts. ‘Metal complexes that have a certain chirality can act as chiral catalysts,’ he says. ‘By using an external stimulus we might be able to change the configuration of the catalyst and as a result the outcome of the product.’

D Zhao et al, Nat. Chem., 2016, DOI: 10.1038/nchem.2668

graphical abstract

https://www.chemistryworld.com/news/light-responsive-molecular-motor-winds-up-helicates/1017698.article

 

Nanomotors change up a gear with metal turbocharge

Posted on 2016-10-19

Metal complexation can speed up molecular motor 32 times

‘We’ve come up with a way to switch gears in nanocars,’ says Sander Wezenberg, a postdoc at the University of Groningen in the Netherlands. Wezenberg is talking about a molecular motor made in Nobel prize winner Ben Feringa’s group that can now be shifted into top gear on demand. By adding a metal to the motor it can be accelerated up to 32 times its normal speed and is the first time dynamic control over the speed of rotation of a molecular motor has ever been demonstrated.

The motor has the classic shape of Feringa’s ‘windmills’, known as overcrowded alkene rotary motors. These windmills are not activated by wind, but light. A few months ago, the team designed a new type of motor sensitive to visible light. To do so, they incorporated two coordinating nitrogen atoms in its lower half and then attached a ruthenium complex to them. ‘We were surprised to see the motor was not only activated by visible light, but also rotated much faster. It was serendipity,’ says Wezenberg. ‘Then we thought about controlling this metal complexation and making it reversible, like a switch.’

Researchers found that certain metals, like zinc, palladium and platinum, could act as regulators. When they coordinate to the windmill, they induce a structural change that increases the rotational speed. ‘Platinum gives us the highest speed,’ says Wezenberg. ‘We can remove the metal adding competing ligands, and then turn the switch back on adding metal again.’ This gives chemists a level of control that was unprecedented in molecular machines. Being able to tune the speed of the motors opens a wide range of opportunities. ‘These motors can be used to power small devices or tiny robots. We envision molecular machines with higher levels of complexity,’ comments Wezenberg.

Steve Goldup, who researches interlocked molecules and molecular machines at the University of Southampton, says ‘this is a real breakthrough. Until now, different speeds could only be achieved designing different motors from scratch. Now, they can tweak the speed without changing the chemical structure of the motor.’ Goldup ponders the possibilities of this discovery. ‘Perhaps we could modify the speed by changing the ligands around the metal, or modifying its oxidation state. In the latter case, the speed of the nanomotor could then be adjusted simply by applying a voltage to the system.’

Goldup also finds fascinating how ‘Feringa makes it look really easy to achieve, when it’s actually really complicated. The simplicity of the solution belies the difficulty of the problem.’

BY FERNANDO GOMOLLÓN-BEL

References

A Faulkner et al, J. Am. Chem. Soc., 2016, DOI: 10.1021/jacs.6b06467

graphical abstract

https://www.chemistryworld.com/news/nanomotors-change-up-a-gear-with-metal-turbocharge/1017570.article

 

No turning back for motorized molecules

Posted on 2016-06-13

It is not easy to design a synthetic molecular motor. As was pointed out nearly 20 years ago, molecular motors are characterized by movement that must be more than random Brownian motion. Our group recently published a unidirectional molecular motor incorporating a rotating axle.

Collins, B. S. L., Kistemaker, J. C. M., Otten, E.& Feringa, B. L. Nature Chem. http://dx.doi.org/10.1038/nchem.2543 (2016).

For more details about the highlight, please see

Nature 534, 187–188 (09 June 2016)

graphical abstract

http://www.nature.com/nature/journal/v534/n7606/full/534187a.html

 

Molecular machines-where have they come from and where are they headed?

Posted on 2016-03-17

Victoria Richards is a science writer based in Cambridge, UK. She recently investigated the world of artificial molecular machines – where have they come from and where are they headed?

For a detailed report, see
http://www.rsc.org/chemistryworld/2016/02/molecular-machines-rotaxanes-macrocycles-nano-walkers

graphical abstract

http://www.rsc.org/chemistryworld/2016/02/molecular-machines-rotaxanes-macrocycles-nano-walkers

 

Molecular machines-where have they come from and where are they headed?

Posted on 2016-03-17

Victoria Richards is a science writer based in Cambridge, UK. She recently investigated the world of artificial molecular machines – where have they come from and where are they headed?

For a detailed report, see
http://www.rsc.org/chemistryworld/2016/02/molecular-machines-rotaxanes-macrocycles-nano-walkers

graphical abstract

http://www.rsc.org/chemistryworld/2016/02/molecular-machines-rotaxanes-macrocycles-nano-walkers

 

Third generation motor highlighted by Foresight Institute

Posted on 2015-11-16

Biological molecular motors are amazing nanomachines that make all life possible, but even smaller artificial molecular motors based upon organic chemistry instead of biological polymers continue to become more complex and better controlled. A hat tip to Nanowerk for reprinting this news release from the University of Groningen in The Netherlands “New molecular motor mimics two wheels on an axle“:

University of Groningen scientists led by Professor of Organic Chemistry Ben Feringa have designed a new type of molecular motor. In contrast to previous designs, this molecule is symmetrical. It comprises two parts, which are connected by a central ‘axle’ and rotate in opposite directions, just like the wheels of a car. The results, which were published … in the journal Nature Chemistry (Nature Chemistry 7, 2015, 890), would be ideal for nano transport systems.


It may sound odd, but from the perspective of the driver, the wheels on the left and right hand side of a car turn in opposite directions. When a car drives forward, the left front wheel turns clockwise and the right front wheel anti-clockwise. This is also the basic design of a new type of molecular motor from the lab of Ben Feringa, the creator of the first light-driven molecular motor back in 1999.

‘If you want a molecular motor to be of any use, you need to be able to control the rotary motion’, says Feringa. Up to now, this was done by using what are known as chiral molecules. These consist of two mirror-image parts, like a left and right hand, which are connected at a central point. ‘These motor molecules are therefore asymmetrical, and this difference between the two halves dictates the way it turns’, Feringa explains.

In Nature Chemistry, Feringa’s group presents the first symmetrical motor molecule with controlled rotary motion. Feringa: ‘This symmetrical motor, which is light-driven just like our other molecular motors, has two rotation axles and two rotating parts.’ The axles are attached to a central part, which is also symmetrical, with the exception of one carbon atom. This atom has two different chemical groups attached to it, which force the rotating parts to turn in opposite directions, as seen from the central part.

Just like a car, this means that the two ‘wheels’ make the molecule move in one direction. ‘This discovery has fantastic implications for realizing autonomous motion on the nanoscale, such as transport over a nano road in a predetermined direction’, Feringa explains. ‘We are now working in our lab to make this type of nano transport a reality.’

The progress over the past decade with many different types of artificial molecular machines has been encouraging. This research is a good example of progress in a sustained development effort.

—James Lewis

graphical abstract

http://www.foresight.org/nanodot/?p=6856

 

Moleculaire motor met twee wielen op één as

Posted on 21-10-2015

Groningse chemici hebben een nieuw type moleculaire motor ontworpen. Het bestaat uit twee groepen, verbonden via een centrale ‘as’ die in een tegenovergestelde richting draaien, net als de wielen van een auto. Het resultaat lijkt ideaal voor een nanotransportsysteem.

door René Fransen

graphical abstract

http://www.kennislink.nl/publicaties/moleculaire-motor-met-twee-wielen-op-een-as

 

The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps

Posted on 2015-09-07

Inspired by biology, chemists have created a cornucopia of molecular parts that act as switches, motors and ratchets. Now it is time to do something useful with them.

for more details, see
http://www.nature.com/news/the-tiniest-lego-a-tale-of-nanoscale-motors-rotors-switches-and-pumps-1.18262

by Mark Peplow,
Nature 2015, 525, 18–21

graphical abstract

http://www.nature.com/news/the-tiniest-lego-a-tale-of-nanoscale-motors-rotors-switches-and-pumps-1.18262

 

Enatioselective Allylic Alkylation of Ortho-Substituted Cinnamyl Bromides

Posted on 23-06-2013

Highlights on
Synfacts 2015; 11(7): 0729-0730

Enantioselective Allylic Alkylation of Ortho-Substituted Cinnamyl Bromides

Mark Lautens, Thomas Johnson

Significance

The asymmetric allylic alkylation (AAA) reaction is a powerful method for the formation of carbon–carbon bonds in high enantioselectivity. In the realm of copper catalysis, this reaction is known with allylic bromides and Grignard reagents, among other nucleophiles. However, the reaction with ortho-substituted cinnamyl bromides suffers from lower enantioselectivity. These ortho-substituted molecules can be used as precursors to heterocycles. Herein, the authors report a highly enantioselective AAA with ortho-substituted cinnamyl bromides.

Comment

Different ortho-substituents were ­tolerated on the substrate, and products were formed in high enantioselectivity. With EtMgBr, an inverse addition protocol was employed to maximize branched to linear selectivity and/or ee. The use of non-primary alkyl Grignard reagents is not reported.

van der Molen NC, Tiemersma-Wegman TD, Fañanas-Mastral M, Feringa BL.
Regio- and Enantioselective Copper-Catalyzed Allylic Alkylation of Ortho-Substituted Cinnamyl Bromides with Grignard Reagents.

J. Org. Chem. 2015; 80: 4981-4981


graphical abstract
 

Chemical Talking with Living Systems - Molecular Switches Steer Quorum Sensing in Bacteria

Posted on 23-06-2015

Most biological processes are controlled by changes on the molecular level. Therefore, treatment of diseases with small molecules has been highly successful in the past decades. However, controlling the pharmacokinetics of such a chemical compound is difficult, as their action cannot be turned on and off. In recent years molecular switches, which are able to change
their structure by an external stimulus, have been promoted to be able to steer the effect of a molecule after it has been administrated to biological systems. For more details, see: ChemBioChem 10.1002/cbic.201500276

10.1002/cbic.201500276

 

Drugs on demand

Posted on 2015-03-05

By designing photoswitchable groups into drug molecules, they can be turned on and off, at the flick of a light switch. A feature article in Chemistry & Industry about our work on phtopharmacology, reported by Rachel Brazil. (DOI: 10.1002/cind.792_10.x)

graphical abstract
 

Molecular mixers

Posted on 6 October 2014

"Scientists engineer light-driven molecular motors to create a stir." - News item by Chemical & Engineering News' Matt Davenport

graphical abstract

http://cen.acs.org/articles/92/i40/Molecular-Mixers.html

 

Molecular motors aim to pass water

Posted on 24 February 2014

Article in Chemistry World puts the spotlight on research by the Feringa group into manipulating and moving water with molecular motors.

graphical abstract

http://www.rsc.org/chemistryworld/2014/02/molecular-motors-aim-pass-water-light-driven-motion-hydrophobicity

 

Singlet Oxygen Produced at the Flip of a Switch

Posted on 22 January 2014

JACS Spotlight on the paper by Christine Herman.

http://pubs.acs.org/doi/full/10.1021/ja5003586