Author Archives: mark rubinchik

H2hox and Gallium: A Dynamic Duo in Medical Imaging

Posted on April 5, 2020 | 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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Posted in Biological Chemistry, Chemistry News, Inorganic Chemistry, Uncategorized

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A New and Advantageous Molecule for Diagnostic Nuclear Medicine

Posted on March 29, 2020 | 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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Orvig Group at UBC Creates Novel Molecule for Diagnostic Nuclear Medicine

Posted on March 22, 2020 | 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, Chris Orvig of the Medicinal Inorganic Chemistry Group at the University of British Columbia (UBC) created a new organic molecule for medical imaging. They also determined that their novel organic molecule has superior properties to similar molecules currently being used.

The molecule created by the inorganic chemistry group at UBC is simply known as H2hox, a hexadentate chelating ligand. What exactly does that mean? Let’s break it down piece-by-piece.

A ligand is a type of molecule that can bind onto a metal ion, like sodium (Na+) or calcium (Ca2+). In the case of H2hox, the metal ion it’s binding to is Gallium (Ga3+) because it is 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.

The word hexadentate comes from the latin root words hexa, which means six and dent, which means tooth. So a hexadentate chelating ligand has six attachment points, or teeth, that can grab onto a desired metal ion.

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

 

So why is H2hox used in medical imaging?

Molecules such as H2hox are used in a form of medical imaging known as Positron-emission tomography (PET). John Hopkins Medicine defines PET imaging as “using a scanning device (a machine with a large hole at its center) to detect photons (subatomic particles) emitted by a radionuclide in the organ or tissue being examined”.

PET imaging is primarily used to diagnose health issues related to biochemical processes occurring inside our cells, such as cancer. The radionuclide, or radioactive atom, of choice for H2hox is Gallium ions. Since ions alone cannot be used in imaging, due to their poor mobility through our cells and tissues, they are packaged together with small organic molecules, such as H2hox, before injection into human tissue.

So what makes H2hox better than the current available options?

H2hox is an advantageous ligand for Gallium PET medical imaging because…

  • It can be easily synthesized (made) through only 1 reaction step.
  • It has a strong affinity to Gallium, exhibiting significant radiolabeling (binding to Ga3+) in only 5 minutes with low amounts of ligand and under mild conditions (room temperature)
  • The combined ligand and ion have excellent stability in vitro (inside cells) and in vivo (inside a beaker).

These combined properties make H2hox an effective and convenient molecule for Gallium PET imaging. Furthermore, Orvig’s research will act as a launching-off point for the development of even better ligands to improve the quality and ease of PET imaging and diagnosis.

I hope this news article educated you about medicinal inorganic chemistry through describing its role in medical imaging.

 

Literature cited:

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.                                                                                          https://pubs.acs.org/doi/10.1021/acs.inorgchem.8b01208 (accessed                      March 22, 2020).

 

-Mark Rubinchik

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LEGO: Is it more than just a kids toy?

Posted on March 21, 2020 | 4 comments

With everyone staying at home due to recent events, a common struggle is finding ways to pass the time. You remember having a box of LEGO bricks lying around, but you think to yourself “Building with LEGO? Nah, that’s just a kid’s toy!”. However, LEGO bricks are more than just a construction toy, they are also a technological marvel both in manufacturing and function.

The LEGO group first patented their iconic LEGO brick design in 1958 in Billund, Denmark. Modern LEGO bricks are made of ABS plastic, a copolymer of acrylonitrile, 1,3-butadiene and styrene, which is formed into its distinct brick-like shape using the injection molding process.  The molds are designed to produce LEGO pieces accurate to up to five-thousandth of a millimeter (0.005 mm), which is around half the thickness of a human hair. This results in a piece defect rate of 0.0018%. In other words, the LEGO manufacturing process produces 18 defective pieces out of every 1 million total pieces produced.

Left to right: Structures of styrene, acrylonitrile and 1,3-butadiene, the main components that make up the plastic used to make LEGO bricks. Source: Sigma-Aldrich

LEGO bricks have become an iconic construction toy due to the endless building possibilities they present. LEGO bricks are connected together through round nubs on top of the brick, known as studs, to tube-based cavities on the bottom of the brick. For instance, six LEGO bricks that are two studs wide by four studs long, commonly referred to as a 2×4 brick, can be combined in 915,103,765 unique ways. This number was determined computationally by mathematics professor  Søren Eilers from the University of Copenhagen in 2005.

(Photo credit: Mark Rubinchik)

Although a LEGO brick may seem like a simple piece of plastic, there is a lot more to it than meets the eye. Next time you’re looking for something to do, why not pull out some LEGO and see how many combinations you can make!

-Mark Rubinchik

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Posted in Organic Chemistry, Uncategorized

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Where Fluke meets Fortune: How Chance Lead to Discovering Novel Green Chemistry Reactions

Posted on February 29, 2020 | Leave a comment

Dr. Petri Turhanen from the University of Eastern Finland discovered that Dowex, a cation exchange resin, opens up an untapped area of green chemistry – the scientific initiative to find chemical reactions that produce the least waste. The best part? It wasn’t on purpose.

While working on an organic synthesis project in 2015, Turhanen noticed that the cation exchange resin he was using, Dowex, produced an unintended byproduct in the presence of sodium iodide (NaI), an iodide (I–) source. Further analysis unveiled that the byproduct was the result of an iodide addition reaction. This is a reaction where a double bond between two carbon atoms is converted into a single bond with a new atom on each carbon, one hydrogen and one iodine.

The novel and green iodide addition reaction discovered by Dr. Petri Turhanen

The source of this unique reactivity comes from the polymer known as Dowex. Dowex is a solid resin made of polystyrene sulfonate. Its main use is as a cation exchange resin, a type of solid that is able to exchange cations, such as H+, for other cations, such as Na+ or K+.

Why is this reaction significant? Iodinated molecules serve multiple purposes. They are often intermediate molecules in organic synthesis, acting as a precursor to building up larger, more complex organic molecules such as pharmaceuticals. Furthermore, radioactive iodine isotopes attached to organic molecules are used as tags in medical imaging.

The industrial processes used to iodinate compounds require toxic starting materials, harmful solvents and high temperatures. These include hazardous, or even carcinogenic, compounds such as iodine, hydrogen peroxide, trimethylsulfonium iodate and iodine monochloride and heavy metals catalysts. To contract, Dowex has low toxicity and can be reused after the reaction is complete.

Comparison of iodide addition reactions

Since the first experiment in 2015, Turhanen has expanded the library of reactions possible in the presence of Dowex, such as esterifications and the conversion ethylene to a di-iodide species. Continued organic synthesis initiatives such as Turhanen’s will pave the way for a greener future of science.

 

-Mark Rubinchik

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Revised: Breathe in the air… made from moon dust!

Posted on February 7, 2020 | Leave a comment

On January 17th 2020, the materials and electrical components laboratory of the European Space Research and Technology Centre (ESTEC) in Noordwijk, Netherlands announced the launch of an oxygen plant: a facility designed to extract oxygen from moon dust.

Using molten salt electrolysis, oxygen gas (O2) can be extracted from oxygen-rich compounds commonly found on the lunar surface. The ability to produce oxygen on the moon will benefit future lunar endeavors as oxygen is used for breathing and rocket fuel production.

Simulated moon dust before (left) and after (right) oxygen extraction by molten salt electrolysis. The byproducts (right) are metal alloys. (From ESA)

Moon dust, formally known as moon regolith, is rich in metal oxides. Metal oxides contain metals with strong bonds to one or more oxygen atoms. These oxygen atoms require a significant amount of energy to liberate in order to produce oxygen gas.

In molten salt electrolysis (see figure below), simulated moon regolith is placed in a metal basket with calcium chloride (CaCl2) and heated to 950oC to melt the calcium chloride. The molten calcium chloride is an electrolyte that makes the mixture highly conductive. An electric current is applied to the heated sample, reducing metal oxides to metals and oxygen dianions at the cathode. The oxygen dianions are oxidized to oxygen gas at the anode.

Molten salt electrolysis setup (Modified from Lomax et al., 2020)

The idea of making the most of lunar resources has been driven by space agencies’ (such as NASA and the European Space Agency) desire to start sending humans to the moon again, but this time with the intentions of staying and setting up a lunar base. The ability to self-sufficiently produce oxygen would be a vital asset to these missions, reducing the cost and urgency of supply missions to the moon.

The metal alloy byproduct may also benefit lunar missions as ESTEC researchers now work on identifying the most useful components of the byproduct and their potential applications.

 

-Mark Rubinchik

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Breathe in the air… made from moon dust!

Posted on January 25, 2020 | Leave a comment

On January 17th 2020, the materials and electrical components laboratory of the European Space Research and Technology Centre (ESTEC) in Noordwijk, Netherlands announced the launch of an oxygen plant: a facility designed to extract oxygen from moon dust. Using molten salt electrolysis, oxygen gas (O2) can be extracted from oxygen-rich compounds commonly found on the lunar surface. The ability to produce oxygen on the moon will benefit future lunar endeavors as oxygen is used for breathing and rocket fuel production.

Simulated moon dust before (left) and after (right) oxygen extraction by molten salt electrolysis. The byproducts (right) are metal alloys. (Credit: Beth Lomax, University of Glasgow)

Moon dust, formally known as moon regolith, is rich in metal oxides. Metal oxides contain metals with strong bonds to one or more oxygen atoms. These oxygen atoms require a significant amount of energy to liberate in order to produce oxygen gas. In molten salt electrolysis, simulated moon regolith is placed in a metal basket with calcium chloride (CaCl2) and heated to 950oC to melt the calcium chloride. An electric current is applied to the heated sample, producing oxygen gas and metal alloys.

The idea of making the most of lunar resources has been driven by space agencies’ (such as NASA and the European Space Agency) desire to start sending humans to the moon again, but this time with the intentions of staying and setting up a lunar base. The ability to self-sufficiently produce oxygen would be a vital asset to these missions, reducing the cost and urgency of supply missions to the moon. The metal alloy byproduct may also benefit lunar missions as ESTEC researchers now work on identifying the most useful components of the byproduct and their potential applications.

 

-Mark Rubinchik

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