You’ve probably already heard a lot of things about Metal Scavengers. You might know how their usefulness is unquestionable in removing metal impurities and that they work selectively to react and bind to excess metal complexes. Let’s review the other important facts and learn more with this list of 10 things you should know about metal scavenging.

1. Metal content in your products is bad

You might be used to checking your product’s purity by NMR, and that’s perfect to observe organic impurities or the absence thereof. Unfortunately, it does not detect metallic impurities, only organic ones. Metal impurities are equally just as important to avoid, as they might jeopardize your next synthetic steps.

If you are working in medicinal chemistry or the pharmaceutical industry, an active pharmaceutical ingredient (API) contaminated by metals is a major health concern. According to the ICH Harmonized guidelines for elemental impurities, the list of restricted metals includes many of the ones routinely used as catalysts in synthesis (Pd, Cu, Ru, Rh, Ni, Pt, etc.).1 Metal Scavengers eliminate them.

Residual catalysts not only cause toxicity issues, but they also affect the performance and stability of electronic components such as solar cells and transistors. Countless publications have discussed the importance to remove residual catalysts from organic compounds in these devices. Metal Scavengers eliminate them.

You don’t have to be in the pharmaceutical or organic electronics industries to care: labs across all industries must protect their equipment and residual metals are something that can mess up an HPLC column. Introducing metals in the column will damage it. Metal Scavengers eliminate them.

Unless you are working in the metal industry, metal content in your products is bad. Metal Scavengers eliminate it.

2. Metal Scavengers are SiliCycle’s avengers

Functionalized silicas acting as Scavengers can be considered as avengers protecting your molecules of interest from impurities. When in contact with the contaminated product, the Scavenger has a greater affinity for the impurities, aka the villains. It will thus capture them, leaving the product free from impurity. Since the Scavenger is on a solid support, filtering out the Scavenger (including the impurity trapped on it) leaves only the desired product in solution.

3. Metal Scavengers outperform other techniques

Other techniques are also known to achieve impurity removal such as crystallization, solvent extraction, chromatography, and activated carbons. However, these have some drawbacks:

  • The thermal degradation of the desired products caused by the high temperatures involved in crystallization;
  • The black dust that comes with handling bulk activated carbon;
  • The great amount of solvents needed for solvent extraction;
  • The time and despair spent on chromatography, and hardship of scaling it up.

Silica-supported Metal Scavengers circumvent many of the drawbacks associated with these methods. Moreover, none of these techniques are as selective and scalable as scavenging can be. For example, the removal of ruthenium was explored using different adsorbents and techniques, including a scavenger, activated carbon, and bare silica. SiliaMetS DMT was by far the most efficient.

4. Metal Scavengers are easy to scale up

Nobody wants to load columns like this one on the left. When it comes to scaling up, Metal Scavengers can offer the linearity that other methods can only dream of.

No need for special large equipment, you can just dump the Scavenger into your reactor and filter out the solid at the end. No mess, no worry, just happy easy purifications!

 

Happy with the conditions that worked on the lab scale?
They still work on a larger scale.

Just check our multiple case studies illustrating scaling up processes.

5. Metal Scavengers are in accordance with Green Chemistry Principles

Green chemistry is on everyone’s minds. Even our Scavengers’. While catalysis is one of the 12 Principles of Green Chemistry2, it calls for a way to remove the leftover catalysts from the final product. Another principle is waste reduction. Can you guess what creative solution helps for both?

Metal Scavengers reduce the amount of waste generated compared to other purification techniques with less solvent needed and smaller quantities of sorbent.

Since SiliaMetS are compatible with all organic solvents, and most are with aqueous solvents as well , it is super easy to green an existing method by swapping for an environmentally friendly solvent without cause for concern.

Automation also makes a process greener , and scavenging can be achieved using SiliaMetS in flow or microwave chemistry automated applications. You can place the functionalized silica in the solid-phase reactors and watch the magic (or chemistry?) as it happens.

6. Metal Scavengers can be used in different formats

They are available as a bulk powder, but also packed in solid-load cartridges for your flash system, in SPE tubes, in guard columns to protect your expensive HPLC columns, or in radial flow E-PAK cartridges.

I mentioned earlier the different industries that can benefit from Metal Scavengers. And there’s a perfect format for each one of them.

To purify large quantities of API, E-PAK cartridges could be an interesting avenue (available in lab scale to commercial scale). Bulk powder can also simply be thrown in the reactor ; quantities up to hundreds of kg for our star Scavengers like Thiol or DMT can be produced in a single batch.

To remove the metals before they enter your HPLC column, a SiliaMetS packed guard column is a safety net far from superfluous.

Before going any further with purifying your organic molecules, a scavenging step can be simply added to your usual work up. Just like you always use magnesium sulfate to remove leftover water, you can do the same with a scoop or two of SiliaMetS. Or a solid-load cartridge packed with SiliaMetS placed before your flash system is effortless.

7. Metal Scavengers are synergistic

Just like you, your crude product and your application are unique. For this reason, we recommend performing a screening test to find the one SiliaMetS Scavenger that works best for your purpose. The one? Or maybe the ones? More than one may offer a similar efficiency. Furthermore, many cases of scavenging synergies have been observed when mixing scavengers

Take this example of the purification of Mavatrep, a potent transient reception potential vanilloid-1 antagonist. A combination of SiliaMetS Thiourea and Thiol provided better scavenging yields than the two did separately for Pd removal:

 

Similarly, the same two helped to scavenge residual Pd from a Suzuki-Miyaura cross-coupling product:

These two case studies show that the same catalyst PdCl2(dppf) may need different Scavengers for optimal metal removal in different environments. This once again support the importance of screening Scavengers.

In some cases, more than one metal contaminates the crude, and you need to scavenge them all. Rather than finding a single Scavenger that can remove everything, it is easier to just mix Scavengers and observe their synergy. Two examples are shared below for the removal of Pd and Fe from using a (Pd(dtbpf)) catalyst. Both cases showed that a combination of SiliaMetS DMT or Cysteine and SiliaBond Tosic acid (in the synthesis of a DGAT-1 inhibitor) or SiliaMetS Thiol and SiliaBond Tosic acid (catalyst only in solvent) achieved the best scavenging of two metals.

 

8. You might not recover the metal

Even though metal catalysts are often the most expensive part of the reaction and, by definition, should be able to run other catalytic cycles, we do not recommend recovering them. The process of recovering catalysts after removing them from your products might be a lot more costly than the catalysts themselves. And the processes are somewhat nasty, using aqua regia.

Some customers stockpile their Scavenger filtrates until enough has been collected to make the process of sending them out cash positive. The quantity must be substantial to make economic sense, and they tend to work with companies specialized in metal recoveries rather than doing it themselves.

Nevertheless, a group from the University of Jyväskylä used SiliaMetS for a totally different purpose, with the aim of circular economy of electronic waste. They worked with Metal Scavengers to adsorb palladium and silver from waste printed circuit boards which was then desorbed using concentrated nitric acid. Again, a bit nasty.

In the end, recovery can be even more costly than simply buying new catalysts.

9. SiliaMetS Metal Scavengers have a history

SiliCycle did not start with manufacturing Metal Scavengers. When the company was founded in 1995, it was about recycling silica gel. Recycling and high purity were two of the founding values of the company.

With time, it became apparent that more precise ways to purify products were needed. Especially when it comes to larger scales. This led to the company’s diversification and, in 1999, to the commercialization of the first Metal Scavenger.

The portfolio kept expanding and is now the most diverse in terms of functionalized silica for scavenging.

10. You cannot eat Metal Scavengers

A question the scientific support team has been asked quite a few times is whether functionalized silica could be eaten (true story, I swear!). Even though it is vegan (we have BSE-TSE documents in case you need proof), Scavengers are not food products. It is safe to use and be in contact with food products, just not to ingest.

 

Is there anything else you wished to know about Metal Scavengers? Do not hesitate to reach out to our scientific support team!

There are no bad questions (we might laugh if you want to eat our scavengers to purify your gastrointestinal system, but we will answer tactfully I promise).

 

1 International council for harmonisation of technical requirements for pharmaceuticals for human use. (2019). Guideline for Elemental Impurities (Q3D(R1))
https://database.ich.org/sites/default/files/Q3D-R1EWG_Document_Step4_Guideline_2019_0322.pdf

2 Anastas, P. T., et al. Green Chemistry: Theory and Practice, Oxford University Press: New York, 1998, p.30. By permission of Oxford University Press.

 

Eliane, M.Sc

Eliane is the Scientific Content Specialist here at SiliCycle, with years of experience both in the lab and client support. She studied at Laval University, for both her Bachelor’s and Master’s in Chemistry. In fact, her thesis was in organic electronics in which purity is of the utmost essence, making her in-tune to the purification needs of chemists.