The mechanism of the most commonly used antimalarial drugs unveiled

For centuries, quinoline has been an effective compound in antimalarial drugs, although no one knew its mode of action in vivo.

Today, a team led by the Weizmann Institute has discovered its mechanism in infected red blood cells in near-native conditions, by using the ESRF, Alba Synchrotron and BESSY. They publish their results in PNAS.

Malaria remains one of the biggest killers in low-income countries. Estimates of the number of deaths each year range from 450,000 to 720,000, with the majority of deaths happening in Africa. In the last two decades, the malaria parasite has evolved into drug-resistant strains. “Recently, the increasing geographical spread of the species, as well as resistant strains has concerned the scientific community, and in order to improve antimalarial drugs we need to know how they work precisely”, explains Sergey Kapishnikov, from the University of Copenhagen, in Denmark, and the Weizmann Institute, in Israel, and leader of the study.

Plasmodium parasite, when infecting a human, invades a red blood cell, where it ingests hemoglobin to grow and multiply. Hemoglobin releases then iron-containing heme molecules, which are toxic to the parasite. However, these molecules crystallise into hemozoin, a disposal product formed from the digestion of blood by the parasite that makes the molecules inert. For the parasite to survive, the rate at which the heme molecules are liberated must be slower or the same as the rate of hemozoin crystallization. Otherwise there would be an accumulation of the toxic heme within the parasite.

>Read more on the ESRF website

Image (taken from BESSY II article): The image shows details such as the vacuole of the parasites (colored in blue and green) inside an infected blood cell.
Credit:
S. Kapishnikov

Two other institutes, BESSY II at HZB and ALBA Synchrotron, have participated in this research. Please find here their published articles:

> X-ray microscopy at BESSY II reveal how antimalaria-drugs might work

> The mechanism of the most commonly used antimlalarial drugs in near- native conditions unveiled

Dynamic pattern of skyrmions observed

Tiny magnetic vortices known as skyrmions form in certain magnetic materials, such as Cu2OSeO3.

These skyrmions can be controlled by low-level electrical currents – which could facilitate more energy-efficient data processing. Now a team has succeeded in developing a new technique at the VEKMAG station of BESSY II for precisely measuring these vortices and observing their three different predicted characteristic oscillation modes (Eigen modes).

Cu2OSeO3 is a material with unusual magnetic properties. Magnetic spin vortices known as skyrmions are formed within a certain temperature range when in the presence of a small external magnetic field. Currently, moderately low temperatures of around 60 Kelvin (-213 degrees Celsius) are required to stabilise their phase, but it appears possible to shift this temperature range to room temperature. The exciting thing about skyrmions is that they can be set in motion and controlled very easily, thus offering new opportunities to reduce the energy required for data processing.

>Read more on the BESSY II at HZB website

Image: The illustration demonstrates skyrmions in one of their Eigen modes (clockwise).
Credit: Yotta Kippe/HZB

New sample holder for protein crystallography

An HZB research team has developed a novel sample holder that considerably facilitates the preparation of protein crystals for structural analysis.

A short video by the team shows how proteins in solution can be crystallised directly onto the new sample holders themselves, then analysed using the MX beamlines at BESSY II. A patent has already been granted and a manufacturer found. Proteins are huge molecules that often have complex three-dimensional structure and morphology that can include side chains, folds, and twists. This three-dimensional shape is often the determining factor of their function in organisms. It is therefore important to understand the structure of proteins both for fundamental research in biology and for the development of new drugs. To accomplish this, proteins are first precipitated from solution as tiny crystals, then analysed using facilities such as the MX beamlines at BESSY II in order to generate a computer image of the macromolecular structure from the data.

>Read more on the BESSY II at HZB website

Image: Up to three indivudal drops may be placed onto the sample holder.
Credit: HZB

World record in tomography: watching how metal foam forms

An international research team at the Swiss Light Source (SLS) has set a new tomography world record using a rotary sample table developed at the HZB.

With 208 three-dimensional tomographic X-ray images per second, they were able to document the dynamic processes involved in the foaming of liquid aluminium. The method is presented in the journal Nature Communications.
The precision rotary sample table designed at the HZB rotates around its axis at several hundred revolutions per second with extreme precision. The HZB team headed Dr. Francisco García-Moreno combined the rotary sample table with high-resolution optics and achieved a world record of over 25 tomographic images per second using the BESSY II EDDI beamline in 2018.

>Read more on the Bessy II at HZB wesbite

Image: The precision rotary sample table designed at the HZB turns around its axis at several hundred revolutions per second with extreme precision.
Credit: © HZB

“Invisible ink” on antique Nile papyrus revealed by multiple methods

Researchers from the Egyptian Museum and Papyrus Collection, Berlin universities and Helmholtz-Zentrum Berlin studied a small piece of papyrus that was excavated on the island of Elephantine on the River Nile a little over 100 years ago.

The team used serval methods including non-destructive techniques at BESSY II. The researchers’ work, reported in the Journal of Cultural Heritage, blazes a trail for further analyses of the papyrus collection in Berlin.

The first thing that catches an archaeologist’s eye on the small piece of papyrus from Elephantine Island on the Nile is the apparently blank patch. Researchers from the Egyptian Museum, Berlin universities and Helmholtz-Zentrum Berlin have now used the synchrotron radiation from BESSY II to unveil its secret. This pushes the door wide open for analysing the giant Berlin papyrus collection and many more.

>Read more on the BESSY II at HZB website

Illustration: A team of researchers examined an ancient papyrus with a supposed empty spot. With the help of several methods, they discovered which signs once stood in this place and which ink was used.
Credit: © HZB

Alternative material investigated for superconducting radio-frequency cavity resonators

In modern synchrotron sources and free-electron lasers, superconducting radio-frequency cavity resonators are able to supply electron bunches with extremely high energy. These resonators are currently constructed of pure niobium. Now an international collaboration has investigated the potential advantages a niobium-tin coating might offer in comparison to pure niobium.
At present, niobium is the material of choice for constructing superconducting radio-frequency cavity resonators. These will be used in projects at the HZBsuch as bERLinPro and BESSY-VSR, but also for free-electron lasers such as the XFEL and LCLS-II. However, a coating of niobium-tin (Nb3Sn) could lead to considerable improvements.

Coatings may save money and energy

Superconducting radio-frequency cavity resonators made of niobium must be operated at 2 Kelvin (-271 degrees Celsius), which requires expensive and complicated cryogenic engineering. In contrast, a coating of Nb3Sn might make it possible to operate resonators at 4 Kelvin instead of 2 Kelvin and possibly withstand higher electromagnetic fields without the superconductivity collapsing. In the future, this could save millions of euros in construction and electricity costs for large accelerators, as the cost of cooling would be substantially lower.

> Read more on the HZB website

Image: The photomontage shows a sample of solid, pure niobium before coating (left), and coated with a thin layer of Nb3Sn (right). Copyright: HZB

Helmholtz-Zentrum Berlin has new scientific management

As of 1 June 2019, Prof. Dr. Bernd Rech and Prof. Dr. Jan Lüning are the new scientific directors of Helmholtz-Zentrum Berlin für Materialien und Energie. Bernd Rech is responsible for the “Energy and Information” department and Jan Lüning heads the “Matter” department. Thus the HZB Supervisory Board has appointed two internationally recognised experts at the top of HZB.
For the first two years, Bernd Rech will be the spokesman of the scientific direction of HZB. Then he will hand the role of spokesman over to Jan Lüning. The two scientific directors have been appointed for a period of five years. In November 2018, the HZB Supervisory Board made Bernd Rech and Jan Lüning the provisional scientific directors until final contracts could be negotiated. These have now been finalised, making their appointment permanent as of 1 June 2019.

>Read more on the HZB website

Image: Prof. Dr. Jan Lüning (l.) and Prof. Dr. Bernd Rech (r.) have been appointed as scientific directors of HZB since June 1, 2019.
Credit: HZB/P. Dera

“Molecular scissors” for plastic waste

A research team from the University of Greifswald and Helmholtz-Zentrum-Berlin (HZB) has solved the molecular structure of the important enzyme MHETase at BESSY II.

MHETase was discovered in bacteria and together with a second enzyme – PETase – is able to break down the widely used plastic PET into its basic building blocks. This 3D structure already allowed the researchers to produce a MHETase variant with optimized activity in order to use it, together with PETase, for a sustainable recycling of PET. The results have been published in the research journal Nature Communications.

Plastics are excellent materials: extremely versatile and almost eternally durable. But this is also exactly the problem, because after only about 100 years of producing plastics, plastic particles are now found everywhere – in groundwater, in the oceans, in the air, and in the food chain. Around 50 million tonnes of the industrially important polymer PET are produced every year. Just a tiny fraction of plastics is currently recycled at all by expensive and energy-consuming processes which yield either downgraded products or depend in turn on adding ‘fresh’ crude oil.

>Read more on the BESSY II at HZB website

Image: At the MX-Beamlines at BESSY II, Gottfried Palm, Gert Weber and Manfred Weiss could solve the 3D structure of MHETase.
Credit: F. K./HZB

Godehard Wüstefeld receives the Horst Klein Research Prize

The physicist Dr. Godehard Wüstefeld was awarded the Horst Klein Research Prize at the annual conference of the German Physical Society.

The award recognizes his outstanding scientific achievements in accelerator physics in the development of BESSY II and BESSY VSR.
Over the last thirty years, Dr. Godehard Wüstefeld has made decisive contributions to the further development of storage-ring-based synchrotron radiation sources. Thanks to its innovative concepts, the performance and application areas of storage rings have been consistently expanded. Wüstefeld participated in the development of BESSY II and the Metrology Light Source and implemented several innovations there.

>Read more on the BESSY II at Helmholtz-Zentrum Berlin website

Image: Dr. Godehard Wüstefeld was awarded the Horst Klein Research Prize.
Credit: DPG

Water is more homogeneous than expected

In order to explain the known anomalies in water, some researchers assume that water consists of a mixture of two phases even under ambient conditions.

However, new X-ray spectroscopic analyses at BESSY II, ESRF and Swiss Light Source show that this is not the case. At room temperature and normal pressure, the water molecules form a fluctuating network with an average of 1.74 ± 2.1% donor and acceptor hydrogen bridge bonds per molecule each, allowing tetrahedral coordination between close neighbours.
Water at ambient conditions is the matrix of life and chemistry and behaves anomalously in many of its properties. Since Wilhelm Conrad Röntgen, two distinct separate phases have been argued to coexist in liquid water, competing with the other view of a single-phase liquid in a fluctuating hydrogen bonding network – the continuous distribution model. Over time, X-ray spectroscopic methods have repeatedly been interpreted in support of Röntgen’s postulate.

>Read more on the BESSY II at HZB website

Image: Water molecules are excited with X-ray light (blue). From the emitted light (purple) information on H-bonds can be obtained.
Credit: T. Splettstoesser/HZB

Superferromagnetism with electric-field induced strain

Data storage in today’s magnetic media is very energy consuming. Combination of novel materials and the coupling between their properties could reduce the energy needed to control magnetic memories thus contributing to a smaller carbon footprint of the IT sector. Now an international team led by HZB has observed at the HZB lightsource BESSY II a new phenomenon in iron nanograins: whereas normally the magnetic moments of the iron grains are disordered with respect each other at room temperature, this can be changed by applying an electric field: This field induces locally a strain on the system leading to the formation of a so-called superferromagnetic ordered state.
Switching magnetic domains in magnetic memories requires normally magnetic fields which are generated by electrical currents, hence requiring large amounts of electrical power. Now, teams from France, Spain and Germany have demonstrated the feasibility of another approach at the nanoscale: “We can induce magnetic order on a small region of our sample by employing a small electric field instead of using magnetic fields”, Dr. Sergio Valencia, HZB, points out.

>Read more on the Bessy II at HZB website

Image: The cones represents the magnetization of the nanoparticles. In the absence of electric field (strain-free state) the size and separation between particles leads to a random orientation of their magnetization, known as superparamagnetism
Credit: HZB

Photocathodes with high quantum efficiency at bERLinPro

A team at the HZB has improved the manufacturing process of photocathodes and can now provide photocathodes with high quantum efficiency for bERLinPro.

Teams from the accelerator physics and the SRF groups at HZB are developing a superconducting linear accelerator featuring energy recovery (Energy Recovery Linac) as part of the bERLinPro project. It accelerates an intense electron beam that can then be used for various applications – such as generating brilliant synchrotron radiation. After use, the electron bunches are directed back to the superconducting linear accelerator, where they release almost all their remaining energy. This energy is then available for accelerating new electron bunches.

Electron source: photocathode

A crucial component of the design is the electron source. Electrons are generated by illuminating a photocathode with a green laser beam. The quantum efficiency, as it is referred to, indicates how many electrons the photocathode material emits when illuminated at a certain laser wavelength and power. Bialkali antimonides exhibit particularly high quantum efficiency in the region of visible light. However, thin films of these materials are highly reactive and therefore very sensitive, so they only work at ultra-high vacuum.

>Read more on the Bessy II at HZB website

Image: Photocathode after its production in the preparatory system.
Credit: J. Kühn/HZB

HZB builds undulator for SESAME in Jordan

The Helmholtz-Zentrum Berlin is building an APPLE II undulator for the SESAME synchrotron light source in Jordan. The undulator will be used at the Helmholtz SESAME beamline (HESEB) that will be set up there by five Helmholtz Centres. The Helmholtz Association is investing 3.5 million euros in this project coordinated by DESY.
SESAME stands for “Synchrotron Light for Experimental Science and Applications in the Middle East” and provides brilliant X-ray light for research purposes. The third-generation synchrotron radiation source became operational in 2017. Egypt, Iran, Israel, Jordan, Pakistan, the Palestinian Authority, Turkey, and Cyprus are cooperating on this unique project to provide scientists from the Middle East with access to one of the most versatile tools for research.

New beamline for soft x-rays

Thus far, SESAME has four beamlines and will now receive a fifth meant to generate “soft” X-ray light in the energy range between 70 eV and 1800 eV. This X-ray light is particularly suitable for investigating surfaces and interfaces of various materials, for observing certain chemical and electronic processes, and for non-destructive analysis of cultural artefacts. The new beamline will be constructed as the Helmholtz SESAME Beamline (HESEB) by the Helmholtz Centres DESY (coordinating Centre), Forschungszentrum Jülich, Helmholtz-Zentrum Dresden-Rossendorf (HZDR), Helmholtz-Zentrum Berlin (HZB) as well as the Karlsruhe Institute of Technology (KIT).

>Read more on the Bessy II at HZB website

Image: The APPLE II UE56 double undulator generates brilliant light with variable polarization.
Credit: HZB

Transition metal complexes: mixed works better

A team at BESSY II has investigated how various iron-complex compounds process energy from incident light. They were able to show why certain compounds have the potential to convert light into electrical energy. 

The results are important for the development of organic solar cells. The study has now been published in the journal PCCP, and its illustration selected for the cover.
Transition-metal complexes – that is a cumbersome word for a class of molecules with important properties: An element from the group of transition metals sits in the centre. The outer electrons of the transition-metal atom are located in cloverleaf-like extended d-orbitals that can be easily influenced by external excitation. Some transition-metal complexes act as catalysts to accelerate certain chemical reactions, and others can even convert sunlight into electricity. The well-known dye solar cell developed by Michael Graetzel (EPFL) in the 1990s is based on a ruthenium complex.

Why not Iron?
However, it has not yet been possible to replace the rare and expensive transition metal ruthenium with a less expensive element, such as iron. This is astonishing, because the same number of electrons is found on extended outer d-orbitals of iron. However, excitation with light from the visible region does not release long-lived charge carriers in most of the iron complex compounds investigated so far.

>Read more on the Bessy II at HZB website

Image: The illustration shows a molecule with an iron atom at its centre, bound to 4 CN groups and a bipyridine molecule. The highest occupied iron orbital is shown as a green-red cloud. As soon as a cyan group is present, the outer iron orbitals are observed to delocalize so that electrons are also densely present around the nitrogen atoms.
Credit: T. Splettstoesser/HZB

Graphene on the way to superconductivity

Scientists at HZB have found evidence that double layers of graphene have a property that may let them conduct current completely without resistance. They probed the bandstructure at BESSY II with extremely high resolution ARPES and could identify a flat area at a surprising location.

Carbon atoms have diverse possibilities to form bonds. Pure carbon can therefore occur in many forms, as diamond, graphite, as nanotubes, football molecules or as a honeycomb-net with hexagonal meshes, graphene. This exotic, strictly two-dimensional material conducts electricity excellently, but is not a superconductor. But perhaps this can be changed.

A complicated option for superconductivity
In April 2018, a group at MIT, USA, showed that it is possible to generate a form of superconductivity in a system of two layers of graphene under very specific conditions: To do this, the two hexagonal nets must be twisted against each other by exactly the magic angle of 1.1°. Under this condition a flat band forms in the electronic structure. The preparation of samples from two layers of graphene with such an exactly adjusted twist is complex, and not suitable for mass production. Nevertheless, the study has attracted a lot of attention among experts.

>Read more on the BESSY II at HZB website

Image: The data show that In the case of the two-layer graphene, a flat part of bandstructure only 200 milli-electron volts below the Fermi energy. Credit: HZB

Blue phosphorus – mapped and measured for the first time

For the first time an HZB team was able to examine samples of blue phosphorus at BESSY II and confirm via mapping of their electronic band structure that this is actually this exotic phosphorus modification.

Blue phosphorus is an interesting candidate for new optoelectronic devices. The results have been published in Nano Letters.
The element phosphorus can exist in  various allotropes and changes its properties with each new form. So far, red, violet, white and black phosphorus have been known. While some phosphorus compounds are essential for life, white phosphorus is poisonous and inflammable and black phosphorus – on the contrary – particularly robust. Now, another allotrope has been identified: In 2014, a team from Michigan State University, USA, performed model calculations to predict that “blue phosphorus” should be also stable. In this form, the phosphorus atoms arrange in a honeycomb structure similar to graphene, however, not completely flat but regularly “buckled”. Model calculations showed that blue phosphorus is not a narrow gap semiconductor like black phosphorus in the bulk but possesses the properties of a semiconductor with a rather large band gap of 2 electron volts. This large gap, which is seven times larger than in bulk black phosphorus, is important for optoelectronic applications.

>Read more on the BESSY II at HZB website

Image: https://pubs.acs.org/doi/10.1021/acs.nanolett.8b01305