The Key to Treating Pneumonia can be Found in Soil?

Posted on March 27, 2020 by | Leave a comment

Can it really be that simple? Can the answer really be in the ground beneath our feet?

Source: Soil Science Society of America

Discovery of a gene cluster commonly found in soil-dwelling bacteria may be the key to treating anaerobic bacterial infections such as appendicitis and pneumonia. Researchers Jason B. Hedges and Prof. Dr. Katherine S. Ryan from the University of British Columbia have isolated the antibiotic compound azomycin from a biosynthetic gene cluster found in the bacterium Streptomyces cattleya.

With this information they believe it can lead to engineering bacteria to produce a new line of antibiotics.

What is a gene cluster?

The term gene cluster is moreso semantics to describe a group of genes that share a common phenomenon.

Originally, azomycin was isolated from a similar bacterium Streptomyces eurocidicus back in 1953 and became the blueprint to synthetic nitroimidazoles. 

“Nitroimidazoles are one of the most effective ways to treat anaerobic bacterial infections”,[1] Hedges writes in his 2019 study. The most commonly used nitroimidazole, metronidazole, is an antibiotic used to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis.[2] It is also on the World Health Organization’s List of Essential Medicines, the safest and most effective medicines needed in a health system.[3]

Figure 1: Molecular Structure of Nitroimidazole. Source: Sigma Aldrich

Despite its use in antibiotics for over 60 years, the incidence of nitroimidazole resistance in anaerobes remains low, making it an essential component of the antibiotic arsenal. [1,4]

Since the isolation of azomycin back in 1953, synthesis of nitroimidazoles were limited to synthetic routes, most commonly involving reactions of an imidazole with nitric acid and sulfuric acid. 

Using bioinformatics, however, in 2019 Hedges and Ryan were able identify a biosynthetic gene cluster in the same bacterium that makes penicillin,[5] Streptomyces cattleya. They were able to find that this gene cluster containing azomycin is widely distributed among soil-dwelling actinobacteria and proteobacteria.

Because of this they theorize that azomycin and other nitroimidazoles may be important factors in ecology.

What are bioinformatics?

Bioinformatics is the science of collecting and analyzing complex biological data such as genetic codes. As an interdisciplinary field of science, bioinformatics combines biology, computer science, information engineering, mathematics and statistics to analyze and interpret the biological data

In addition to the isolation of azomycin in a gene cluster, Hedges and Ryan were able to perform in vitro analysis in order to understand the enzymatic steps that take the primary protein L-arginine to become azomycin. 

Source: Washington Post

Their work opens the door to biocatalytic methods to synthesize azomycin and other nitroimidazoles. They believe this discovery can “lead to the possibility of engineering bacteria to produce nitroaromatic compounds”.[1]

In other words, this may lead to stronger antibiotics immune to drug resistance.

References

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

The American Society of Health-System Pharmacists. Archived from the original on 6 September 2015. Retrieved 31 July 2015.

World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization

David I. Edwards, Nitroimidazole drugs-action and resistance mechanisms I. Mechanism of action, Journal of Antimicrobial Chemotherapy, Volume 31, Issue 1, January 1993, Pages 9–20, https://doi.org/10.1093/jac/31.1.9

Kahan, JS; Kahan, FM; Goegelman, R; Currie, SA; Jackson, M; Stapley, EO; Miller, TW; Miller, AK; Hendlin, D; Mochales, S; Hernandez, S; Woodruff, HB; Birnbaum, J (Jan 1979). “Thienamycin, a new beta-lactam antibiotic. I. Discovery, taxonomy, isolation and physical properties”. The Journal of Antibiotics. 32 (1): 1–12

-Adrian Emata

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Posted in Analytical Chemistry, Biological Chemistry, Chemistry News, Organic Chemistry, Popular Science

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Origin of the Coronavirus

Posted on March 24, 2020 by | Leave a comment

Recently, the outbreak of new coronavirus has seriously affected people’s lives in countries and even around the world. New coronaviruses can be transmitted through air and contact. Symptoms include fever, cough, and difficulty breathing. In order to completely solve this infectious disease, it is very important to find the primary case.

Source:https://www.heywood.org/education/covid19-coronavirus-updates

Initially, Chinese scientists believed that the source of the virus was the South China Seafood Market in Wuhan, China. When people eat wild animals that contain the virus, the non-pathogenic version of the virus jumps from animal hosts to humans and then evolves into the current pathogenic state in the population. For example, the RBD structure of some coronaviruses from pangolins, armadillo mammals found in Asia and Africa, is very similar to SARS-CoV-2. Coronavirus from pangolin may have been transmitted to humans either directly or through an intermediary host such as a civet or ferret.

Source:http://m.cyol.com/content/2020-03/05/content_18413469.htm

Most people in this epidemic believed that this new coronavirus should be derived from flying mammals such as bats. Many people also criticized them, and even many people targeted the bats directly, thinking that those who eat bats Caused the disease. However, this is actually questionable. Although it is possible that bats can directly infect humans, so far, most of the time, bats are not the direct source of infection but are adapted to spread to humans through the intermediate source of infection. This can be seen from the case report published in the top medical journal “The Lancet”.

Source:https://news.sky.com/story/how-did-coronavirus-start-scientists-tackle-the-conspiracy-theories-11959500

Researchers from institutions such as the Xishuangbanna Tropical Botanical Garden of the Chinese Academy of Sciences recently published a paper in the form of a preprint, saying that they analyzed the genomic data of 93 new coronavirus samples in 12 countries on four continents and found that they contained 58 haplotypes, which are related to the South China Seafood Market The associated patient sample haplotypes were H1 or its derivative types, while the more “older” haplotypes such as H3, H13, and H38 came from outside the South China seafood market, confirming that the new crown virus of the South China seafood market was transmitted from elsewhere In perspective.

Source:https://meaww.com/coronavirus-did-chinese-officials-downplay-extent-of-deadly-wuhan-outbreak-in-early-stages

Finding an “index case” is equivalent to finding a weapon that can cut the epidemic from the source. But in the long history of humans fighting the epidemic, few “index cases” have been found. On the one hand, the timeline of the index case and first case are not necessarily the same, which makes the process of tracing like a needle in a haystack. In addition, the chain of evidence tracking “index case” is difficult to finalize and will always be repeatedly overturned and readjusted.

To this day, the epidemic of AIDS, Ebola, SARS and so on has never clearly identified the “index case” in the strict sense. From the perspective of the development of the global epidemic, it is still of great significance to curb the development of the epidemic while researching and developing effective drugs and vaccines and controlling the development of the epidemic in a timely manner. However, the new Coronavirus may be the same as AIDS and SARS. There is no way to accurately find the first human it infected.     

Yicheng Zhu

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Posted in Biological Chemistry, Popular Science

The magical “Ta” catalyst for pseudoalkaloids

Posted on March 23, 2020 by | Leave a comment

If you are a coffee lover, you would probably know the naturally occurring substance, caffeine. But, were you aware that this substance is classified as a pseudoalkaloid?

Many pseudoalkaloids can often have biological activities like caffeine stimulates our nervous system. Ultimately, pseudoalkaloids can be used as building blocks to produce useful drugs.

In 2019, researchers at the University of British Columbia, led by Dr. Schafer, uncovered a new pathway to produce structurally simple terpenoid-alkaloids, which belong to pseudoalkaloids.

This study can be simply summarized as a reaction between a terpene and an amine with the help of a tantalum catalyst. But, let’s first explore key ingredients to deeply understand how the synthetic route works!

 

An organotantalum compound with a ureate salt
The researchers developed a catalytic reaction run by a metallic compound. Based on other known studies, they chose an organoctantalum compound to produce terpenoid-alkaloids. As like an engine is the heart of a car, the tantalum compound is an engine to drive reactions to the final products, terpenoid-alkaloids

The choice of a metallic compound is of course crucial. However, it is more important for the compound to have complete catalytic potential. How could a bare metallic compound become a complete catalyst? The answer is associating a metallic compound with a ligand such as organic molecules or salts, which can coordinate to a metal center. Of numerous possible candidates of ligands, the researchers found that a specific salt can improve the efficiency and selectivity of the bare organotantalum compound, thereby allowing it to have a complete catalytic ability.


Figure 1.The ureate salt that improved selectivity and efficiency of the organotantalum compound, Ta(CH2SiMe3)3Cl2. Of several ureate salts, the above salt was the most suitable for this study due to its solubility.

Terpenes and anilines
As the name of final products, terpenoid-alkaloids, reflects the use of terpenes, one of key ingredients is a terpene, a naturally occurring molecule. By limiting the scope of terpenes to enantiopure limonene and pinene, the types of anilines were varied and reacted with the terpenes

Now, here comes a question. What is the consequence of mixing these ingredients together?

 

Fascinating results
This study is fascinating not only for the reason that a catalytic amination of terpenes is unexplored, but also the final products are not chaotic mixtures.

What does it mean by a chaotic mixture? Some catalysts have potential to alter an intrinsic structure of a staring substance. For example, if a catalyst was able to influence the chiral center of (R)-limonene by changing its stereochemistry, a reaction batch would contain both (S) and (R)-limonenes. Consequently, the occurrence of two products is equally probable.

Also, unexplored magical ability of the tantalum catalyst in the study allows anilines to react with one specific spot of an alkene moiety in terpenes. This astonishing selectivity gives a rise to one major product.

           Figure 2.The reaction of an enantiopure limonene with six different anilines (left). The reaction of an enantiopure pinene with six different anilines (right). Both reactions result in high regio- and diastereoselectivity.

Reference
Dipucchio RC, Rosca SC, Athavan G, Schafer LL. Exploiting Natural Complexity: Synthetic Terpenoid‐Alkaloids by Regioselective and Diastereoselective Hydroaminoalkylation Catalysis. ChemCatChem. 2019;11(16):3871–6.

-Young Cho

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No Medicine to Cure

Posted on March 23, 2020 by | Leave a comment

Can you imagine the world without medicine?

Nowadays, more and more bacteria begin to show resistance against antibiotics. Azomycin, a type of antibiotics used to treat multi-drug resistance is found to be used more and more frequently. What if bacteria start to grow resistance against Azomycin? However, it is actually nailed fact, the only question is when. In order to solve this problem, in 2019, Dr. Jason Hedges and Dr. Katherine Ryan of the University of British Columbia engaged in finding a new way to synthesize the nitroimidazole, the main component of azomycin.

source:https://www.reactgroup.org/toolbox/understand/how-did-we-end-up-here/few-antibiotics-under-development/

The study of antibiotics can be traced back to the 19th century. For these two centuries, antibiotics saved countless lives from all kinds of diseases. However, antibiotics can not kill all the bacteria. Every time when one bacteria survived from the massacre of the antibiotic, they grow the resistance against the antibiotic. Then it split, split and split. Finally, the survived bacteria become countless bacteria that can not be defeated by the antibiotic again. Thus, more and more bacteria begin to survive from the war with antibiotics, and more and more antibiotics become useless. Herein, the race between the evolving of antibiotics and evolving of bacteria begins. 

So, let’s take a look at what did Dr. Jason Hedges and Dr. Katherine Ryan do and what did they find.

By doing a lot of research, Dr. Jason Hedges and Dr. Katherine Ryan found that the development of nitroimidazole can be dated back to 1953 when azomycin was first found. And they noticed that when strain Streptomyces eurocidicus was produced, L-arginine is converted to azomycin. Therefore, they came up with a plan to synthesis nitroimidazoles by linking L-arginine to azomycin via in vitro reconstitution. 

In vitro reconstitution process of nitroimidazole. Source: Hedges and Ryan, 2019

Through the experiment, Dr. Jason Hedges and Dr. Katherine Ryan successfully synthesized nitroimidazole via in vitro reconstitution. But unfortunately, no azomycin was produced via Streptomyces cattleya. 

Although the experiment is failed to synthesis azomycin through Streptomyces cattleya, it still provides a lot of valuable information for further researchers. It points a direction on the biocatalytic pathway of azomycin synthesis and set the stage for the discovery of new antibiotics.

Reference:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

 

Yicheng Zhu

 

 

 

 

 

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Posted in Biological Chemistry, Chemistry News, Organic Chemistry

Biosynthetic Pathway Found to Synthesize Anaerobic Antibiotics!

Posted on March 23, 2020 by | Leave a comment

Fig 1. Image of Azomycin. source

Scientists found the biosynthetic pathway to the Nitroimidazole Antibiotic Azomycin. A steppingstone towards the revolution of anaerobic bacterial infection treatments.

Scientists from the University of British Columbia found the biosynthetic pathway to the Nitroimidazole antibiotic Azomycin. The enzymatic mechanism from L-Arginine to Nitroimidazole has now been proved and present to the public. Their formal paper was published online on July 17th, 2019. Nitroimidazole is an essential component for the modern antibiotics, it is crucial to know its synthetic pathway for further pharmaceutical studies. The result of their study set the stage for further development of important anaerobic antibiotic Azomycin.

What is it? Why do we need to know about this?

Nitroimidazole is an essential antibiotic specifically to treat anaerobic bacterial infections. They are widely used to treat diseases such as Amoebiasis, Parasitic infections, skin infections, diarrhea and so on. The low redox potential of anaerobic bacteria cells allowed nitroimidazole to act as the electron sink and form the radical species. The resultant radical species would induce the bacteria cells’ death by damaging their DNA. Antibiotic is the most powerful “weapon” to fight against bacterial infections. However, according to the World Health Organization, there are more than 700000 people die every year due to antibiotic resistance. Despite the several decade’s usages of Nitroimidazole antibiotics, the drug resistance of it still remains low relatively. Thus, Nitroimidazole antibiotics are increasingly used to treat multi-drug resistant bacteria as well.

 

Previous research established that L-Arginine is converted to azomycin by 2-aminioimidazole. They determined that the intermediate of the reaction is 4-hydroxy-2-ketoarginine (2). Furthermore, they also observed the accumulation of pyruvate(3) side products and 2-aminoimidazole(5) from the intermediate(2). However, the actual enzymatic synthetic pathway has not been determined detailly yet. Jason and Katherine in the research group determined that PLP-dependent enzymes, RohP,RohR,RohQ and RohS plays esstential role in the catalytic pathway of the reaction. Researchers examined the in vitro activity of RohP, RohR, RohQ and RohS. They put in these enzymes separately and stepwise to different reactants. For example, in order to test whether RohR could catalyze a retro-aldol cleavage of 2 into 3 and guanidinoacetaldehyde (4), they added purified RohR instead of RohP. Then according to activity analysis and also the mass spectrum, the result shows that RohP yields a bigger portion of 2.

Fig 2. Reaction scheme from L-Arginine to Nitroimidazole. Source

Antibiotics are the most powerful “weapon” to kill bacteria in modern pharmaceutical studies. As early as in the 20th century, the observation of penicillin saved millions of people injured in the World War. Yet, the enormous benefits of antibiotics cause the consequences of drug-resistance. Azomycin, consider as a low-resistance antibiotic, it is crucial to understand its enzymatic reaction mechanism. Reaction mechanism allows scientist to have a more detail interpretation of the synthesis. It is crucial to find the catalytic cycle of the reaction, in order to allow scientists to develop and derive further study.

The study done by Jason and Katherine at the University of British Columbia provides the public with a steppingstone in future nitroimidazole anti-biotics study. Their study expanded people’s knowledge of the biosynthetic pathway to nitro-compounds. It also makes bacteria engineering to produce nitroaromatic compounds possible. This study will open the new door in enzymatic synthesis and biochemistry synthesis.

Cited article:

Hedges, J. B.; Ryan, K. S. In Vitro Reconstitution of the Biosynthetic Pathway to the Nitroimidazole Antibiotic Azomycin. Angewandte Chemie International Edition 2019, 58 (34), 11647–11651.

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A new technique that can cut gene of RNA virus?

Posted on March 23, 2020 by | Leave a comment

Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), referred  as gene magic scissors, is a kind of tool that scientists can find in the immune system of bacteria to edit genes in other organisms is undoubtedly a revolutionary technology, which has greatly improved the efficiency of gene editing work.

In recent years, CRISPR-based gene screening has successfully helped scientists identify genes that play a key role in sickle cell anemia, cancer immunotherapy, lung cancer metastasis, and many other diseases.

However, the scope of these gene screenings is limited, and they can only edit and target DNA. This brings many restrictions since in many regions of the human genome, DNA may not work as a target; for some other organisms, such as RNA viruses including coronaviruses and influenza viruses.

On March 16, an important paper was published in the journal Nature-Biotechnology, reporting a new CRISPR screening technology that can target RNA. In the paper, researchers describe an enzyme called Cas13 that can be used for CRISPR screening techniques that target RNA instead of DNA.

Cas13 traveling along RNA (Source)

Cas13 is a type VI CRISPR enzyme, which is a class of RNA targeting proteins with nuclease activity that have only been discovered in recent years. They can knock out target genes without altering the genome. This property makes Cas13 a promising therapeutic tool that can affect gene expression without permanently altering the genome sequence.

Using Cas13, the researchers obtained an optimized platform for large-scale parallel genetic screening of human cells at the RNA level. Using this gene screening platform, researchers can learn about RNA regulation from all aspects and the functions used to identify non-coding RNAs (RNA molecules that cannot encode proteins).By targeting thousands of different sites in human RNA transcripts, they have developed a machine learning-based predictive model that can quickly identify the most effective Cas13 guide RNA (gRNA).

For example, one of the findings is about which regions of gRNA are more important when identifying target RNAs. They used thousands of gRNAs containing one, two, and three single bases that didn’t match the bases of the target RNA, and identified a key “seed” region that guides and targets CRISPR Mismatches between them are extremely sensitive. This is a very useful discovery for gRNA design.

Since a typical human cell can express approximately 100,000 RNAs, accurate targeting of Cas13’s predetermined targets is critical for screening and therapeutic applications. The “seed” area not only deepens our understanding of Cas13 off-target, it can also be used to study next-generation biosensors to more accurately distinguish between close relative RNA species.

Recently, researchers also applied their gRNA prediction model to the raging coronavirus Sars-CoV-2. We know that COVID-19 is caused by this coronavirus that contains RNA instead of DNA genome. The researchers said that using this new model, they have identified the best gRNAs for future detection and treatment.

Overall, the new study increased the data points of mammalian cells in Cas13 by more than two orders of magnitude, which is of great significance for advancing genomics and precision medicine.

 

-Xinyue Yang

-Posted on Mar. 23, 2020

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The Revolutionary Progress in Radiopharmaceutical that Shocked the Whole World

Posted on March 23, 2020 by | Leave a comment

Cancer is a disease that killed 8.9 million people by 2016, and it is very hard to detect. For someone suffering cancer, they may want to detect it as early as possible so they can be treated. In the past, doctors have to take a patient’s tissue. With naked eyes, the doctor has to search for tiny cancer monsters in this tissue under a microscope, which is like searching a needle in an ocean. Even for highly-experienced doctors, this process is time-consuming and has a high chance of miss-detecting.

Cancer Deaths
(Source: Our World Data)

Now there are radioactive chemicals that can efficiently detect cancer cells. It works like this. There is a blue-colored chew-chew train in these chemicals called a positron, which collides with the red chew-chew train in your body called an electron. When they collide, they annihilate each other and make huge lightning like in a nuclear bomb. These lights are so strong that they can penetrate through your body and be captured by our detecting machine. So you might wonder, how do we know if there are cancer monsters then? Well, the cancer monsters can eat away light, so when the detecting machine receive light from areas of the patient’s body where cancer cell is present, the picture coming out would be much, much darker.

chew-chew trains colliding (source: google)

But here is another problem–––the radioactive chemicals are so dangerous that they can destroy your body, which is also why we make nuclear bombs out of them. Therefore scientists have found types of these chemicals that only explode for a few hours, on top of them is something called Germanium, it is not made in Germany, but you could memorize it that way. It’s not just normal Germanium, but a thin, thin Germanium that is a little lighter than the normal Germanium.
But the problem has not been solved. What if the Germanium jumps around your body and destroys everything? We need a claw that clamps onto this Germanium to transfer it into the patient’s body and hold it in the spot. There used to be many candidates, but they can only function at small ranges of pH outside your body. Now you must be confused; what exactly is pH? Well, think of a pool of sticky bubble gums. These gums are called H. When the pH is low, there are a lot of gums in the pool, so when the claw enters the pool, the gum will stick onto the claw, now the claw surface becomes soft, and the Germanium just slips away. Unfortunately, the human body is such a low pH pool. No claw has been able to hold the playful Germanium under every condition. Surprisingly, Dr. Ovrig just made this new big claw in his lab that would hold onto the Germanium. When they tested it in different pools, even one similar to the human body, the Germanium stayed happily inside the claw. If you are curious about the name of this claw, it’s called Ga(hox).

 

The researchers then brought this claw into practice. They used the claw and germanium combination on a mouse, and it easily detected cancer monsters in the heart within a short 1 minute. The monsters in the liver and bladder are also exposed after 1 hour. Now, patients no longer have to worry about the long period of cancer examination. Besides, this technique can detect even tiny amounts of cancer monsters. Therefore, even in the very early stage of cancer, the claw-germanium combo can detect cancer and allow treatment before the cancer monster goes rampart.

Reference

Wang, X.; De Guadalupe Jaraquemada-Peláez, M.; Cao, Y.; Pan, J.; Lin, K. S.; Patrick, B. O.; Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. Inorg. Chem. [Online] 2019, 58, 2275-2285. (Accessed: March 23, 2020).

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An Innovative Method to Optimize New Products

Posted on March 23, 2020 by | Leave a comment

Can you make anything you want? You might be able to, with a modified blueprint.

Following instructions step-by-step can can be challenging, especially if there are multiple pathways. A specialized method can be used to selectively hand-pick specific products.

A design is invented from existing functional methods to counteract the difficulties of multiple products. Dr. Schafer at the University of British Columbia implements a system to accurately isolate the desired product.

The study urges the importance of terpenoid-alkaloids, compounds used for their pharmacological properties, compared to individual terpenes and alkaloids. The problem lies in the mechanism of producing terpenoid-alkaloids.

Past studies show the use of catalysts, a tool that promotes reactions to occur, result in multiple products to be formed. To selectively form a single product, the catalyst must be optimized.

A tantalum-based, metal catalyst, precursor was used to test its reactivity to terpene substrates, and shows promising results. The terpenoid-alkaloid conversion rate for the Ta(CH2SiMe3)3Cl catalyst is higher than the other precursors, as seen in Figure 1.

Figure 1. (a) Addition of Ta-based precursors in 1-octene and limonene (b) Ta-based precursor with N,O-chelating ligands in 1-octene and limonene (Source: Schafer)

An addition of various chelating ligands, molecules that attach to metal ion centers, to the Ta catalyst further increased the conversion rate. Different ligands show varying rates.

The reaction to synthesize terpenoid-alkaloids is called hydroaminoalkylation. Alongside the most optimal catalyst system created, terpenoid-alkaloids are produced with various yields and conversion rates on terpene substrates.

The selectivity factor can be supported by using NMR spectroscopy, a method that can determine the structure of the product. A chiral high performance liquid chromatography (HPLC) is used to determine if the product present is oriented in only one form.

The data is analyzed to determine the best possible reaction mechanism to accurately produce the desired product. The isolation and purification process is simple because the reaction went through to form one product.

The study experiments with different substrates of similar structure to further confirm their suspicions. The specificity of the reaction is recorded, including exact amounts of chemicals used and the reaction parameters studied in.

The hydroaminoalkylation reaction is chemically altered to regulate the formation of one specific product of terpenoid-alkaloids. More research is required to investigate reactivities of different substrates in various conditions to determine an even more optimal mechanism.

The act of modifying concrete steps to selectively isolate a distinct product is proven to succeed. The end result can offer enhanced properties to be applied.

 

Reference

Dipucchio, R. C.; Rosca, S. C.; Athavan, G.; Schafer, L. L. Exploiting Natural Complexity: Synthetic Terpenoid‐Alkaloids by Regioselective and Diastereoselective Hydroaminoalkylation Catalysis. ChemCatChem 2019, 11 (16), 3871–3876.

-Wilson Wong

 

 

 

 

 

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68Ga and H2hox: A Dynamic Duo

Posted on March 23, 2020 by | Leave a comment

Not every molecule gets to find their best partner in life. Luckily, in 2019, Orvig and his team at the University of British Columbia made a perfect partner for Gallium-68 (68Ga) to improve the results of medical imaging.

Medical imaging encompasses tests such as X-rays and ultrasound, and these tests allow doctors to look inside of our bodies to determine if there are any problems, or to monitor any changes post-surgery. Therefore, it is important that the science and technique behind the imaging is advanced, and that the results can be obtained quickly and accurately.

WHAT IS 68Ga?

68Ga, is an imaging tracer used in positron emission tomography (PET) scan, which is a type of imaging test. With a relatively short half-life, 68Ga wants to perform to the best of its ability during the test, and it yearns for an efficient partner to help show activity within the tissues. However, current partners present limitations in terms of synthesis and performance.

H2hox: IS IT THE ONE? 

Therefore, researchers created a molecule named H2hox. Unlike previous candidates for 68Ga, H2hox was easily synthesized within two steps. The team saw how strongly attracted H2hox was to 68Ga, and that only mild conditions and low concentrations of H2hox were needed for the two to bind together.

Figure 1. The chemical structure of H2hox. Adapted from Wang et al. (2019).

Once bound, the team found that a highly stable metal complex, [68Ga(hox)]+, was formed within the pH range of 1 to 11. Furthermore, this complex only existed as a single species, and did not require further purification. Because these combined characteristics were impossible to achieve with previous partners, the researchers thought that H2hox could be the one for 68Ga.

TESTING THEIR TEAMWORK

To test how well this complex worked in real life, the researchers conducted a PET/computed tomography (CT) scan in mice. The group witnessed high stability of the metal complex in mice, and more importantly, they observed that the metal complex was rapidly excreted from the mice. 

Furthermore, because the fluorescence intensity of H2hox increased upon complexing with 68Ga, the team thought that the complex could be used to analyze intracellular distribution and stability studies.

Figure 2. The fluorescence intensity of H2hox increased by fourfold when it was part of the [Ga(hox)]+complex. Adapted from Wang et al. (2019).

THE FUTURE IS PROMISING

Since the researchers also observed a fast heart uptake of the complex in mice, they suggested that H2hox could form the basis for tracers in heart imaging. Additionally, the team proposed that this complex could benefit fluorescence-directed surgery.

With this many unprecedented advantages, we cannot wait to see what else this dynamic duo has to offer the world.

 

Story source

Wang, X.; Jaraquemada-Pelaez, M. d. G.; Cao, Y.; Pan, J.; Lin, K.-S.; Patrick, B.O., Orvig, C. H2hox: Dual-Channel Oxine-Derived Acyclic Chelating Ligand for 68Ga Radiopharmaceuticals. J. Am. Chem. Soc. 2019, 58, 2275-2285

-Athena Wang

 

 

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Promoting Chemical Literacy in the Public

Posted on March 23, 2020 by | Leave a comment

Responding to a need for scientific literacy in the public, researchers at the Samuel Neaman Institute examine ways to promote chemical literacy among different stakeholders.

The public increasingly encounters with real-life scientific and technological contexts, and scientific professional and chemical educators have realized the need for chemical literacy among the public to understand, and critically evaluate the scientific information they absorb. The University of British Columbia even offers a course, called CHEM 300, which teaches how to communicate scientific knowledge.

Broggan Textbook
(source: thriftbooks)

In an attempt to narrow the gap between the scientific and the non-scientific communities, researchers led by Zehavit Kohen conducted a comprehensive analysis of chemistry education methods most valued by different stakeholders.

The researchers identified four groups, K-12 students, teachers, scientists, and the educated public, from a sample population of 347. The survey divides into two sections, scientific literacy construction, and communication channel types.

According to the study, K-12 students valued cognitive and affective components twice more than scientists or educated adults. Besides, all stakeholders favored open discussions as their communication channel. Mass media dominates the scientific community besides open discussions. Whereas, students use mass media, be available to the public, and share of scientific materials indistinguishably.

Mass Media
(Source: flickr)

Investigating question posts on an ask-a-scientist-type website, the research further discovered that the public’s questions usually concern symbols over processes or systems. The type of information involved in these questions is mostly explanatory.

Data from Zehavit’s article

The results encourage students to gain chemical literacy in real-world contexts through analogies and symbols. The researchers also suggest that scientists should attempt other communication channels since interactive and affective activities on mass media are often challenging.

 

Reference

Zehavit, K.; Orit, H.; Yehudit J. D. How to promote chemical literacy? On-line question posing and communicating with scientists. Chem. Educ. Res. Pract., 2020, 21, 250

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