Dr. Jeffery Huang Zhifeng, associate professor in the Department of Physics at HKBU, has developed a novel approach to manipulating the chirality of drug molecules.
Hong Kong Baptist University
Scientists from Hong Kong Baptist University (HKBU) have developed a novel technique that can produce pure therapeutic drugs without the associated side effects.
The approach, which uses a nanostructure fabrication device, can manipulate the chirality of drug molecules by controlling the direction a substrate is rotated within the device, thus eliminating the possible side effects that can arise when people take drugs containing molecules with the incorrect chirality.
Published in the scientific journal Nature Chemistry, the research findings pave the way towards the mass production of purer, cheaper, and safer drugs that can be made in a scalable and more environmentally-friendly way.
Control of molecular chirality improves drug safety
Many chemical molecules have two configurations, or chiral versions, that are mirror images of each other. While sharing the same molecular formula, the two chiral versions have different arrangements of their constituent atoms in space. The two versions of the molecules are characterized by left-handed and right-handed chiral configurations like human hands. Molecules with “left-handed” and “right-handed” chirality can have totally different biochemical effects.
More than half of the therapeutic drugs are made up of equal amounts of left-handed and right-handed chiral molecules, commonly known as “racemates;” one can cure specific diseases, but the other may have adverse effects. Separating and producing molecules with only the chiral arrangement (known as a single enantiomer) responsible for the therapeutic effects can help to produce drugs with improved safety and efficacy.
Macro-scale control of molecular chirality
In general, molecules have an extremely small size ranging from one-millionth to one hundred-thousandth of the diameter of a human hair. It is therefore extremely challenging to selectively produce one of the two chiral molecule versions using “macro-scale” control (i.e. the dimensional scale that can be seen using the naked eye and operated by hand). To produce single-enantiomer drugs, chemists have overwhelmingly used molecules called “chiral ligands” to effectively control the molecular chirality of drugs in the laboratory or industry at the molecular scale, a process called asymmetric synthesis. However, the existing technologies for producing single-enantiomer drugs are composed of complicated procedures, which are expensive and environmentally-unfriendly.
Dr. Jeffery Huang Zhifeng, associate professor in the Department of Physics at HKBU, and his research team devised a novel approach to manipulating molecular chirality through macro-scale control in collaboration with Sichuan University, Guangxi Medical University and the Southern University of Science and Technology. It involves mediating the manipulation with helical metal nanostructures (i.e. metal nanohelices) that are in the shape of a helical spring, and they have a characteristic size of one-thousandth of the diameter of a human hair.
Direction of rotation determines molecular chirality
The research team fabricated the metal nanohelices using a nanofabrication technique called glancing angle deposition (GLAD). Silver and copper were deposited onto a supporting substrate that was rotated clockwise and counterclockwise to fabricate the right-handed and left-handed metal nanohelices, respectively.
The research team then used ultraviolet light to induce a chemical reaction. This caused 2-anthracenecarboxylic acid (AC) molecules adsorbing on the metal nanohelices to undergo the chemical reaction and form chiral molecular products, which are similar to some chiral drugs. When AC was attached to the surface of the right-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced “right-handed” chiral molecular products. By the same token, when AC was adsorbed on the surface of the left-handed metal nanohelices and exposed to ultraviolet light, it preferentially produced “left-handed” chiral molecular products. In other words, the chirality of the molecular product can be reliably determined by the chirality of the metal nanohelices, which is controlled by the direction of substrate rotation.
The research demonstrates that controlling the direction of substrate rotation at a macroscopic level can conveniently manipulate molecular chirality. This is an unprecedented application of the macro-scale method (through the control of the rotation direction of a 4-inch substrate holder) to manipulate chirality at the molecular-scale (chiral molecular products in the range of one-billionth of a meter).
Green approach to reducing drug side effects
“Our success in manipulating molecular chirality through macroscopic engineering allows the convenient synthesis of drugs in single-enantiomer forms with only left- or right-handedness. Hence, it will help get rid of the adverse, sometimes fatal, side effects of many therapeutic drugs,” said Huang.
The use of chiral ligands in the conventional method of asymmetric synthesis is inevitable, and it may cause pollution to enter the environment. In contrast, in this novel approach the metal nanohelices can be used repeatedly to produce single-enantiomer drugs without the use of chiral ligands. As a result, it paves the way towards the mass production of affordable therapeutic drugs that are made in a scalable manner with recyclable materials.
TEL AVIV, Israel (AP) — A rare Bronze-Era jar accidentally smashed by a 4-year-old visiting a museum was back on display Wednesday after restoration experts were able to carefully piece the artifact back together.
Last month, a family from northern Israel was visiting the museum when their youngest son tipped over the jar, which smashed into pieces.
Alex Geller, the boy’s father, said his son — the youngest of three — is exceptionally curious, and that the moment he heard the crash, “please let that not be my child” was the first thought that raced through his head.
The jar has been on display at the Hecht Museum in Haifa for 35 years. It was one of the only containers of its size and from that period still complete when it was discovered.
The Bronze Age jar is one of many artifacts exhibited out in the open, part of the Hecht Museum’s vision of letting visitors explore history without glass barriers, said Inbal Rivlin, the director of the museum, which is associated with Haifa University in northern Israel.
It was likely used to hold wine or oil, and dates back to between 2200 and 1500 B.C.
Rivlin and the museum decided to turn the moment, which captured international attention, into a teaching moment, inviting the Geller family back for a special visit and hands-on activity to illustrate the restoration process.
Rivlin added that the incident provided a welcome distraction from the ongoing war in Gaza. “Well, he’s just a kid. So I think that somehow it touches the heart of the people in Israel and around the world,“ said Rivlin.
Roee Shafir, a restoration expert at the museum, said the repairs would be fairly simple, as the pieces were from a single, complete jar. Archaeologists often face the more daunting task of sifting through piles of shards from multiple objects and trying to piece them together.
Experts used 3D technology, hi-resolution videos, and special glue to painstakingly reconstruct the large jar.
Less than two weeks after it broke, the jar went back on display at the museum. The gluing process left small hairline cracks, and a few pieces are missing, but the jar’s impressive size remains.
The only noticeable difference in the exhibit was a new sign reading “please don’t touch.”
VICTORIA – The British Columbia government is partnering with a bear welfare group to reduce the number of bears being euthanized in the province.
Nicholas Scapillati, executive director of Grizzly Bear Foundation, said Monday that it comes after months-long discussions with the province on how to protect bears, with the goal to give the animals a “better and second chance at life in the wild.”
Scapillati said what’s exciting about the project is that the government is open to working with outside experts and the public.
“So, they’ll be working through Indigenous knowledge and scientific understanding, bringing in the latest techniques and training expertise from leading experts,” he said in an interview.
B.C. government data show conservation officers destroyed 603 black bears and 23 grizzly bears in 2023, while 154 black bears were killed by officers in the first six months of this year.
Scapillati said the group will publish a report with recommendations by next spring, while an independent oversight committee will be set up to review all bear encounters with conservation officers to provide advice to the government.
Environment Minister George Heyman said in a statement that they are looking for new ways to ensure conservation officers “have the trust of the communities they serve,” and the panel will make recommendations to enhance officer training and improve policies.
Lesley Fox, with the wildlife protection group The Fur-Bearers, said they’ve been calling for such a committee for decades.
“This move demonstrates the government is listening,” said Fox. “I suspect, because of the impending election, their listening skills are potentially a little sharper than they normally are.”
Fox said the partnership came from “a place of long frustration” as provincial conservation officers kill more than 500 black bears every year on average, and the public is “no longer tolerating this kind of approach.”
“I think that the conservation officer service and the B.C. government are aware they need to change, and certainly the public has been asking for it,” said Fox.
Fox said there’s a lot of optimism about the new partnership, but, as with any government, there will likely be a lot of red tape to get through.
“I think speed is going to be important, whether or not the committee has the ability to make change and make change relatively quickly without having to study an issue to death, ” said Fox.
This report by The Canadian Press was first published Sept. 9, 2024.
The European Space Agency is fast-tracking a new mission called Ramses, which will fly to near-Earth asteroid 99942 Apophis and join the space rock in 2029 when it comes very close to our planet — closer even than the region where geosynchronous satellites sit.
Ramses is short for Rapid Apophis Mission for Space Safety and, as its name suggests, is the next phase in humanity’s efforts to learn more about near-Earth asteroids (NEOs) and how we might deflect them should one ever be discovered on a collision course with planet Earth.
In order to launch in time to rendezvous with Apophis in February 2029, scientists at the European Space Agency have been given permission to start planning Ramses even before the multinational space agency officially adopts the mission. The sanctioning and appropriation of funding for the Ramses mission will hopefully take place at ESA’s Ministerial Council meeting (involving representatives from each of ESA’s member states) in November of 2025. To arrive at Apophis in February 2029, launch would have to take place in April 2028, the agency says.
This is a big deal because large asteroids don’t come this close to Earth very often. It is thus scientifically precious that, on April 13, 2029, Apophis will pass within 19,794 miles (31,860 kilometers) of Earth. For comparison, geosynchronous orbit is 22,236 miles (35,786 km) above Earth’s surface. Such close fly-bys by asteroids hundreds of meters across (Apophis is about 1,230 feet, or 375 meters, across) only occur on average once every 5,000 to 10,000 years. Miss this one, and we’ve got a long time to wait for the next.
When Apophis was discovered in 2004, it was for a short time the most dangerous asteroid known, being classified as having the potential to impact with Earth possibly in 2029, 2036, or 2068. Should an asteroid of its size strike Earth, it could gouge out a crater several kilometers across and devastate a country with shock waves, flash heating and earth tremors. If it crashed down in the ocean, it could send a towering tsunami to devastate coastlines in multiple countries.
Over time, as our knowledge of Apophis’ orbit became more refined, however, the risk of impact greatly went down. Radar observations of the asteroid in March of 2021 reduced the uncertainty in Apophis’ orbit from hundreds of kilometers to just a few kilometers, finally removing any lingering worries about an impact — at least for the next 100 years. (Beyond 100 years, asteroid orbits can become too unpredictable to plot with any accuracy, but there’s currently no suggestion that an impact will occur after 100 years.) So, Earth is expected to be perfectly safe in 2029 when Apophis comes through. Still, scientists want to see how Apophis responds by coming so close to Earth and entering our planet’s gravitational field.
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“There is still so much we have yet to learn about asteroids but, until now, we have had to travel deep into the solar system to study them and perform experiments ourselves to interact with their surface,” said Patrick Michel, who is the Director of Research at CNRS at Observatoire de la Côte d’Azur in Nice, France, in a statement. “Nature is bringing one to us and conducting the experiment itself. All we need to do is watch as Apophis is stretched and squeezed by strong tidal forces that may trigger landslides and other disturbances and reveal new material from beneath the surface.”
The Goldstone radar’s imagery of asteroid 99942 Apophis as it made its closest approach to Earth, in March 2021. (Image credit: NASA/JPL–Caltech/NSF/AUI/GBO)
By arriving at Apophis before the asteroid’s close encounter with Earth, and sticking with it throughout the flyby and beyond, Ramses will be in prime position to conduct before-and-after surveys to see how Apophis reacts to Earth. By looking for disturbances Earth’s gravitational tidal forces trigger on the asteroid’s surface, Ramses will be able to learn about Apophis’ internal structure, density, porosity and composition, all of which are characteristics that we would need to first understand before considering how best to deflect a similar asteroid were one ever found to be on a collision course with our world.
Besides assisting in protecting Earth, learning about Apophis will give scientists further insights into how similar asteroids formed in the early solar system, and, in the process, how planets (including Earth) formed out of the same material.
One way we already know Earth will affect Apophis is by changing its orbit. Currently, Apophis is categorized as an Aten-type asteroid, which is what we call the class of near-Earth objects that have a shorter orbit around the sun than Earth does. Apophis currently gets as far as 0.92 astronomical units (137.6 million km, or 85.5 million miles) from the sun. However, our planet will give Apophis a gravitational nudge that will enlarge its orbit to 1.1 astronomical units (164.6 million km, or 102 million miles), such that its orbital period becomes longer than Earth’s.
It will then be classed as an Apollo-type asteroid.
Ramses won’t be alone in tracking Apophis. NASA has repurposed their OSIRIS-REx mission, which returned a sample from another near-Earth asteroid, 101955 Bennu, in 2023. However, the spacecraft, renamed OSIRIS-APEX (Apophis Explorer), won’t arrive at the asteroid until April 23, 2029, ten days after the close encounter with Earth. OSIRIS-APEX will initially perform a flyby of Apophis at a distance of about 2,500 miles (4,000 km) from the object, then return in June that year to settle into orbit around Apophis for an 18-month mission.
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Furthermore, the European Space Agency still plans on launching its Hera spacecraft in October 2024 to follow-up on the DART mission to the double asteroid Didymos and Dimorphos. DART impacted the latter in a test of kinetic impactor capabilities for potentially changing a hazardous asteroid’s orbit around our planet. Hera will survey the binary asteroid system and observe the crater made by DART’s sacrifice to gain a better understanding of Dimorphos’ structure and composition post-impact, so that we can place the results in context.
The more near-Earth asteroids like Dimorphos and Apophis that we study, the greater that context becomes. Perhaps, one day, the understanding that we have gained from these missions will indeed save our planet.
