Nav: Home

HKUST scientists develop novel method to monitor molecular aggregation

January 11, 2019

Chiral molecules are defined as molecules that are non-superimposable on their mirror image, much like that of left and right human hand bone structure. There are many examples of chiral molecules in nature, including proteins and deoxyribonucleic acid (DNA). The dynamic processes of these chiral molecules is highly significant to understanding their biological activity. Indeed, protein aggregation is associated with many pathological conditions, including Alzheimer's disease which is caused by the build-up of beta-amyloid fragments within the brain over time. Thus, it is important to understand and observe such (chiral) molecular aggregation and conformation over time.

Currently available options for analysing molecular conformation include electron microscopy and nuclear magnetic resonance (NMR) spectroscopy. Both methods require sample extraction under harsh conditions, a time-consuming process that can damage the molecular conformation of the sample. The second limitation to these methods is that the ultimate result will only provide the conformation of the compound at a specific point in time.

This new method involves aggregation-annihilation circular dichroism (AACD) effect and a well-studied chiral molecule called 1,1'-binapthyl derivatives (BN). It was observed that the CD signals of the BN were annihilated after BN aggregates were formed, likely due to the conformational change of the 1,1'-binapthyl group during the aggregation process.

In their work, four BN-based chiral molecules (P-1 to P-4 respectively) were synthesized through simple Suzuki coupling reactions. Polymers with the "open" BN units showed clear signs of aggregation-annihilated chiral dichroism (AACD). When the BN units were locked, the annihilation is restrained. The polymers were first dissolved in an organic solvent, tetrahydrofuran (THF). The second step involved adding water, a poor solvent for the polymers, was gradually added to the solution, which led to aggregate formation. CD spectra of the different polymers were taken at different water fractions and analysed. This methodology allowed researchers to analyse the molecular aggregation process in real time.

A molecular dynamics (MD) simulation of the polymers was performed in THF and water to further examine the relationship between CD annihilation and conformational change. This model indicated that open P-1 showed a broad distribution of dihedral angle ? but locked P-3 showed a narrow distribution. From solution to aggregate, the ? in open polymers (P-1 and P-2) becomes more negative and part of the conformers relax from cisoid to transoid. The ? in locked polymers (P-3 and P-4) increases slightly and cisoid conformation is preserved throughout the aggregation process.

"The combination of MD simulation and analysis on the change of CD couplet intensity and wavelength splitting during the aggregation process is thus an appealing method of in-situ and real-time monitoring of the conformational change," said HKUST's Prof. Ben-Zhong TANG, who led this research.

"This is a far cheaper, simpler method of monitoring conformational changes in chiral macromolecules means that we can apply this method to understanding many biological processes more easily," said Dr. Haoke ZHANG, a co-author of the paper.
-end-
Details of the methodology and their findings were published in the journal Nature Communications on November 23, 2018. (DOI: 10.1038/s41467-018-07299-3)

Hong Kong University of Science and Technology

Related Polymers Articles:

Fluorescent technique brings aging polymers to light
Modern society relies on polymers, such as polypropylene or polyethylene plastic, for a wide range of applications, from food containers to automobile parts to medical devices.
Polymers to the rescue! Saving cells from damaging ice
Research published in the Journal of the American Chemical Society by University of Utah chemists Pavithra Naullage and Valeria Molinero provides the foundation to design efficient polymers that can prevent the growth of ice that damages cells.
Mixing the unmixable -- a novel approach for efficiently fusing different polymers
Cross-linked polymers are structures where large molecular chains are linked together, allowing exceptional mechanical properties and chemical resistance to the final product.
Theoretical tubulanes inspire ultrahard polymers
Rice University engineers print 3D blocks based on theoretical tubulanes and find they're nearly as hard as diamond.
New synthesis method yields degradable polymers
MIT chemists have come up with a way to make certain drug-delivery polymers more readily degradable by adding a novel type of building block to the polymer backbone.
Bottom-up synthesis of crystalline 2D polymers
Scientists at TU Dresden and Ulm University have succeeded in synthesizing sheet-like 2D polymers by a bottom-up process for the first time.
Secret messages hidden in light-sensitive polymers
Scientists from the CNRS and Aix-Marseille Université have recently shown how valuable light-sensitive macromolecules are: when exposed to the right wavelength of light, they can be transformed so as to change, erase or decode the molecular message that they contain.
Successful application of machine learning in the discovery of new polymers
As a powerful example of how artificial intelligence (AI) can accelerate the discovery of new materials, scientists in Japan have designed and verified polymers with high thermal conductivity -- a property that would be the key to heat management, for example, in the fifth-generation (5G) mobile communication technologies.
How to capture waste heat energy with improved polymers
By one official estimate, American manufacturing, transportation, residential and commercial consumers use only about 40 percent of the energy they draw on, wasting 60 percent.
Researchers can now predict properties of disordered polymers
Thanks to a team of researchers from the University of Illinois at Urbana-Champaign and the University of Massachusetts Amherst, scientists are able to read patterns on long chains of molecules to understand and predict behavior of disordered strands of proteins and polymers.
More Polymers News and Polymers Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Clint Smith
The killing of George Floyd by a police officer has sparked massive protests nationwide. This hour, writer and scholar Clint Smith reflects on this moment, through conversation, letters, and poetry.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Nina
Producer Tracie Hunte stumbled into a duet between Nina Simone and the sounds of protest outside her apartment. Then she discovered a performance by Nina on April 7, 1968 - three days after the assassination of Dr. Martin Luther King Jr. Tracie talks about what Nina's music, born during another time when our country was facing questions that seemed to have no answer, meant then and why it still resonates today.  Listen to Nina's brother, Samuel Waymon, talk about that April 7th concert here.