Category Archives: Inorganic Chemistry

H2hox and Gallium: A Dynamic Duo in Medical Imaging

Posted on April 5, 2020 by | Leave a comment

Not every molecule gets to find their best “partner” in life. Luckily in 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed a partner molecule for Gallium to work with in medical imaging. They also determined that their creation has superior stability and binding ability compared to similar molecules currently being used.

THE NEW MOLECULE IN TOWN

The partner molecule is a chelating ligand known as H2hox. Let’s break down its name piece-by-piece to get a better understanding of what it does.

A ligand is a molecule that binds onto a metal ion such as iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+ ).

The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

Image sources (left to right): Research Gate, Wang et al..

THE DUO GETS TO WORK

H2hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is used to diagnose health issues related to the processes occurring inside our cells, such as cancer.

The main function of H2hox in PET imaging is to bind to radioactive Gallium ions, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2hox worked together with its partner, Gallium, the researchers conducted a PET scan in mice. The group witnessed high stability of the dynamic duo within mice, and they observed that it was rapidly excreted from the mice, which is important for a decrease in side effects.

Furthermore, the ligand has a strong affinity to Gallium, such that only low amounts of ligand are needed to significantly bind to Gallium ions in just five minutes! As a result of the molecule’s advanced properties, H2hox surpasses any ligand currently used as a Gallium’s partner.

ALL IT TAKES IS 1 STEP

In the lab, H2hox is synthesized (made) in only one reaction and is easy to purify, unlike similar ligands which are synthesized over multiple labor- and resource- intensive steps. As a bonus, the chemicals used to make it are inexpensive and readily available.

To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is quite easy to do, while the latter is a lot harder and is more labour-intensive. Ease of manufacturing is a key feature because it determines the commercial success of the product.

THE FUTURE IS PROMISING

The combination of unprecedented properties and easy synthesis makes H2hox a launching-off point for the development of even better chelating ligands to improve the future of PET imaging. With H2hox being such an advantageous molecule for Gallium PET imaging, we cannot wait to see what else this dynamic duo has to offer the world.

Literature cited:

  1. 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

 

-Group 6 (Mark, Akash, Athena, Charles)

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A New and Advantageous Molecule for Diagnostic Nuclear Medicine

Posted on March 29, 2020 by | Leave a comment

You may be aware of the role physicists and doctors play in diagnostic nuclear medicine; however you may not know that chemists also play a significant role in this area of science! In 2019, Dr. Chris Orvig and his team at the University of British Columbia constructed an advantageous molecule for use in medical imaging whose purpose is to bind to radioactive Gallium (Ga) ions. They also determined that their molecule has superior properties to similar molecules currently being used.

WHAT IS IT?

The molecule that was created by Dr. Orvig’s team is simply known as H2Hox , a chelating ligand. Let’s break its name down piece-by-piece to get a better understanding of what it does.

A ligand is a type of molecule that can bind onto a metal ion, like iron (Fe3+) or copper (Cu2+). In the case of H2hox, the metal ion is Gallium (Ga3+) because it is widely used in medical imaging. The word chelating comes from the latin root word chela, which means claw. This is because chelating ligands have multiple points of attachment to a metal ion, similar to a crab’s claw, making them significantly stronger binders to metal ions.

Image sources (left to right): Research Gate, Wang et al..

HOW IS IT MADE?

H2Hox is easy to synthesize, avoiding a number of potentially challenging synthetic pathways typically associated with Ga chelating species. The initial starting materials were inexpensive and readily available. To put this into perspective, it’s like baking a box cake versus baking a cake from scratch. The former is simple and quite easy to do, while the latter is a lot harder and is a lot more intensive. Ease of synthesis is an important feature as it can affect the commercial applicability of the molecule.

WHAT DOES IT DO?

H2Hox is used in a form of medical imaging known as positron-emission tomography (PET). PET imaging is primarily used to diagnose health issues related to biochemical processes occurring inside our cells, such as cancer. The main function of H2Hox in PET imaging is to bind to the radioactive Gallium ion, which aids in producing an image of a desired area or tissue inside the body.

To test how well H2Hox worked, the researchers conducted a PET scan in mice. The group witnessed high stability of the combined ligand and ion in mice, and more importantly, they observed that it was rapidly excreted from the mice. Furthermore, the ligand has a strong affinity to Gallium, exhibiting significant radiolabeling capabilities (binding to Ga3+) in only five minutes with low amounts of ligand under room temperature. As a result of the molecule’s advanced properties, H2Hox surpasses any ligand currently used as a Gallium chelator.

THE FUTURE IS PROMISING

The combination of superior properties and easy synthesis makes H2Hox an effective and convenient molecule for Gallium PET imaging. H2Hox acts as a launching-off point for the development of even better chelating ligands to improve the quality and ease of PET imaging.

Literature cited:

1. 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

 

-Group 6 (Mark, Akash, Athena, Charles)

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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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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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Gold: Precious in a Different Way

Posted on March 17, 2020 by | 2 comments

Let’s face it, to most people gold is just an over-glorified rock with no real value; however, that’s not the case at all! Just this month, researchers from University College London have created a novel light-activated coating that kills infectious bacteria. The key ingredient? Gold.

upgrading with gold…

The invention of a bacteria-killing coating sounds ingenious; however, Hwang’s team was actually not the first to come up with this idea. Previous studies have already shown that coatings incorporating the chemical crystal violet can adequately kill bacteria. The problem was that the coating had to be light-activated by UV rays, which harm the skin by promoting skin cancer.

This was exactly the problem Hwang’s team looked to solve; to make a coating that did not require harmful wavelengths of light. They overcame this challenge by incorporating small clusters of gold into a polymer containing crystal violet. The result? Now this new coating could effectively eliminate bacteria upon activation with low intensity white light – the level of light found in offices.

Concentration of bacteria (CFU/mL) across three conditions after 6 hours exposure to low-intensity white light. Star indicates bacterial concentration is undetected. Sample size = 6 per treatment, error bars are standard deviation. Adapted from Hwang et al.’s data

The figure above perfectly illustrates their result. Statistical analyses show that bacterial concentration does not significantly differ between the violet crystal and control (no coating) condition. This indicates that low-intensity white light cannot activate the bacterial-killing function in the violet crystal coating. What’s interesting is that addition of gold with the violet crystal, reduces the bacterial concentration significantly to near zero values, indicating successful activation.

More than a novelty…

The results of Hwang’s study are truly impactful. It is well known that hospitals are a hotbed for infectious bacteria. In fact, 27% of surfaces in hospital rooms are contaminated with bacteria even after regular and thorough cleaning. As such, applying the coating on these surfaces will definitely reduce the chances of contracting a hospital-related disease. Who would have thought? Not only is gold more than just a hunk of rock, it can also save lives.

-Kenny Lin

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Revised:4 Elements Newly Found – the 7th Row of Periodic Table is Completed!

Posted on February 15, 2020 by | Leave a comment

Have you ever curious about the abundance of elements in this world?

Research groups in Japan, Russia, and the USA published their discovery of elements 113,115,117 and 118. On November the 28th of 2016, International Union of Pure and Applied Chemistry (IUPAC) has formally approved the name of these elements as Nihonium (Nh), Moscovium (Mc), Tennessine (Ts), and Oganesson (Og). These four elements completed the 7th row of the periodic table and acted as an important stepping stone toward “superstable-elements” which are going to be influential in the future studies. 

Element 113, Nihonium (Nh), which called “The first element found in Asia” was found by Riken Center of Accelerator-Based Science in Japan. Joint Institute of Nuclear Research discovered three other elements of Moscovium (Mc), Tennessine (Ts), and Oganesson (Og) credited to Russia and the United States. After five months of public review, IUPAC eventually added them to the 7th row of the periodic table.

These four elements were classified as “super-heavy” elements with more than 104 protons. They were synthesized by using particle accelerators to fuse one nucleus to the other. Further experiments proved the existence of these elements by reproducing the synthesis procedures. However, the life of these “man-made” elements seem to be too short for further discovery. “A particular difficulty in establishing these new elements is that they decay into unknown isotopes very fast.” Said Paul Karol, chair of the IUPAC’s joint working party. Nihonium has a half-life of 20 seconds, which was the longest among the newly found elements. Moscovium and Tennessine have an even shorter half-life, which is only 220 milliseconds and 78 milliseconds respectively. 

Example of Super-heavy element. source:Vanderbilt University

What is the purpose of discovering these elements since they disappear almost right after they are produced?

There are “islands of stabilities” which describe certain super-heavy elements that are very stable when they have a certain number of protons or electrons, even though they are huge. Scientists believe that the next island will be in the 8th row of the periodic table. “the alleged but highly probable ‘island of stability’ at or near element 120 or perhaps 126.” Said by Paul Karol. These “Island of Stabilities” can stay from minutes to years which will be meaningful to study their chemistry.  

Although the life of these newly found elements is way too short to have a practical use, they are the sign of getting closer to the “Island of Stability” of “super-stable” heavy elements. Those “super-stable” radioactive elements are worthy of studying and could have a lot of industrial applications. For example, they might be useful as a stockpile of nuclear energy to maintain national safety. The discovery of these elements gave hope to scientists and encourage them to further discover the ultimate limit of the periodic table. Hopefully, they will be able to discover some stable super-heavy elements that are influential and have significant practical uses soon. The study of new elements would eventually be the breakthrough point of modern chemistry!

–Vicky Gu

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A Bright and Sunny Future – Revised

Posted on February 15, 2020 by | Leave a comment

Dye-Sensitized Solar Cells (DSSCs) are efficient and with low manufacturing costs, they are an ideal solution to our need for sustainable energy. This paper published in October 2012 reviews the fundamentals of DSSCs.

A DSSC. Retrieved from: engadget

DSSCs utilize sunlight as its source of energy, which is converted into usuable energy. It contains a light sensitizer connected to a semiconductor that faciliates the excitation of electrons which are able to enter a series of redox reactions. The continuous cycle of electrons through the circuit generates energy which can be used in our daily lives, or for other practical uses within industries.

In a separate study published in October 2019, Huang et al. proposed to optimize the counter electrode (CE) from a Pt CE, to a 2D nanosheet composed of Co-Ni-Se. This turned out to be successful as the Co-Ni-Se complex catalyzes the reduction of the I3– electrolyte more effectively compared to the traditional Pt CE that is typically used. This increases the rate at which energy is generated and stored for industrial or personal use.

Schematic Diagram of a DSSC. Retrieved from: Gamry

How can this be applied to us in everyday life?

DSSCs can be installed on the roof of our houses to supply electricity during the day. This decreases our dependency on fossil fuels for energy, which are harmful to both terrestrial and marine life. It can also be used to generate energy and be stored within a battery pack for portable charging of cellular devices.

DSSCs on the Roofs of Buildings. – Retrieved from RedNewsWire

Why Should we Invest in DSSCs?

The U.S Energy Information Administration (EIA) projects that energy consumption will increase by approximately 28.6% between 2020 and 2050. This increases the demand for sustainable energy along with the depletion and harmful environmental effects of fossil fuels. Solar energy is an abundant and clean source of energy which makes photovoltaics such as DSSCs a desirable product. More money should be allocated for the research and development of DSSCs as they may be the solution to our energy crisis in the long term.

– Jackson Kuan

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Revised:4 Elements Newly Found – the 7th Row of Periodic Table is Completed!

Posted on February 14, 2020 by | Leave a comment

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Revised:4 Elements Newly Found – the 7th Row of Periodic Table is Completed!

Posted on February 14, 2020 by | Leave a comment

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