The challenging and dynamic world of analytical chemistry

Organic chemistry at Symeres has been proactively accommodating recent developments in drug discovery. Today, we are proud to say that we not only synthesize small molecules but also many nontraditional compounds, such as medium- to large-sized molecules, such as macrocycles and DEL-derived peptide-like molecules. However, this development would not have been possible if we could not analyze what we had made! In this article, one of the senior scientists from our Analytical Department, Colinda van Tilburg, talks about the challenges she encounters.

Colinda joined Mercachem (now Symeres) in 2007 after working for Organon (Oss) (now MSD) for 17 years. In her days at Organon, she switched from organic chemistry to analytical chemistry. In this interview, she explains the added benefit of having organic chemistry knowledge as an analytical chemist and passionately tells us how the analytical department solves new challenges every day.

I was conducting combinatorial chemistry, which was, at that time, regarded as the most advanced method to identify novel hit compounds. This emerging technology demanded analytical chemistry to become diversified and high throughput. Instead of only NMR, new analytical methods, such as GC-MS, LCMS, and IR, were introduced. Most analytical chemists see samples as numbers instead of structures. They needed someone with in-depth molecular knowledge, and I was fascinated to learn about this new world.

Learning new things! When I started in Nijmegen, the Process Research Group wanted to use DSC (differential scanning calorimetry). This technique is used for safety measurements of compounds. I had never heard about this method before, but I found it very interesting, more so because I had to learn fast.

In 2007, we ran 60 analyses a day. It is now 100 per day per machine and we have 8 machines, so it means circa 800 analyses per day. Compounds are usually measured at least 3 times: during the reaction, at the end of the reaction, and after purification. When all tests have been passed, a new compound is born!

We have 3 GC-MS, 2 NMR, 5 prep systems, 3 SFCs, 8 LCs, 8 LC-MS systems and 1 Orbitrap. Our capacity has grown rapidly in the last 10 years.

The complexity has grown exponentially. As the scope of our projects evolves, the questions the analytical department receives are more challenging and broader than they used to be. We used to only work with small molecules. Nowadays, we make many larger molecules like macrocycles, but also molecules you can hardly detect by LCMS: very fatty ones, polar ones, and also fragment-like tiny ones. The complexity of the structures is much more diverse now than it was in the past.

Yes! Synthetic chemists come to us with a lot of questions. At my previous job, it was accepted to come back with an answer in a week. Here, they expect us to find an answer in one hour. You have to think fast in order for the chemist to be able to continue with their work. Therefore, we read the literature, talk with chemists, and read their reports as well, so that we know in advance what is coming. We also look into suppliers’ markets, thinking ahead about whether or not it can be useful for Symeres. When we buy a column, we need to quickly learn about its scope. We quickly run some experiments and put it to use to find answers to the questions we get.

The scope of the projects in combination with the equipment we need. Our projects are more diverse now. Different compounds have different needs. Nothing is standard anymore. Therefore, you need a broad range of equipment to be able to accommodate all the questions, meaning the analytical department needs to expand. SFC is such an expansion. For high-throughput measurements, SFC is much faster and more comprehensive than LC-MS. It’s between GC and LC and has the advantages of both the GC and LC methods. This way, it speeds up the analyses and prep work, and it gives us the opportunity to use new methods for compounds we could not measure before. It gives us so much extra information. We cannot live without it anymore!

Everyone is very driven. Driven about the compounds; driven to making the best analysis and obtaining the compounds in the highest purity. When something goes wrong, we help them out and they can always come to us for support. And if I see something goes wrong, I will talk to that person. Also, every new colleague undergoes training when they analyze their first sample. We will show them how the equipment works and so on.

We visited our Groningen colleagues and talked about the differences, similarities, but also problems we encountered on both sites. We reach out to each other when we have an issue and help each other. This is very valuable to us both. We are using Microsoft Teams more and more, and this is a very useful. I am not specialized in validation work, but my colleagues who are have a similar experience working with Weert.

Curious to see if her colleagues agree with Colinda's assessment? Go see this round table discussion, with analytical chemists from all four chemistry sites!

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