Pharmaceutical researchers feel real pressure to increase their R&D productivity by ‘doing more with less’. Despite having limited internal resources and specialized expertise, discovery chemistry research labs are expected to be increasingly effective and efficient, and deliver drug targets faster to advance projects rapidly. However, a lack of effective tools and technologies results in low efficiency workflows, with slow and laborious lead generation and optimization as a result. To boost productivity, the iterative cycle of design-make-test-analyze (DMTA) must move to a ‘best-practices’ state to become faster, more predictable and less time-consuming. A key factor is availability of reliable purification systems from dependable vendors.
Isn’t amazing chemistry what you want to do every day? Don’t you strive for white crystalline final products? But things get in the way, such as other priorities, endless emails and frequent interruptions to your synthetic flow. Not to mention the challenges of designing new synthetic strategies, creating what could be the world’s most impactful new molecular entity. Finding the right reaction, the right reagents. Finding a way to get around yet another dead end. But those challenges are why you got into chemistry in the first place, right? After all, if it was easy, anyone could do it and you’re not just anyone. So let’s look at a few things that can put the fun back into chemistry.
Our recent survey of organic synthetic chemists showed that more than half of you feel that the most enjoyable aspect of your work is researching new chemistries, while 33% told us that preparing reactions was the best part of your day. Purifying products and writing up came in at distant 3rd and 4th places, and no one enjoyed doing work up. Sounds familiar? If you want to find out more about how to bring fun back into your chemistry then read on.
OK. We get it. You aren’t a molecule factory. Creating the right target molecule as soon as possible in order to keep your pharmaceutical research project moving isn’t easy or routine. Frankly, organic chemistry is hard and unpredictable. As Professor Gilbert Stork said, “Unless the molecule is very simple, it is not possible to go into the lab and make it within a short period of time.” His ‘Rule of Seven’ meant that, “however long you think a synthesis will take, multiply it by seven”.1
Creative productivity is the ability to find innovative ways to keep projects moving forward, including finding a way around the roadblocks that will inevitably show up as you go. So the real measure of productivity is not in molecules per day, but in your ability to find the synthetic pathway. Instrument manufacturers tend to want to tell you about the latest user-friendly ultra-fast instrument. Faster is nicer, but if you can cut 30 seconds off a column chromatography step, what does it matter when the reaction refluxed overnight and the reaction didn’t work? The thing is, many of the reliable techniques you apply to your organic chemistry work are considered unchangeable. There may be a better way, but that takes time and feels risky. So, you continue on, using what you learned as far back as college chemistry.
Organic reactions are generally inefficient, which means that crude reaction mixtures require work-up and purification to remove by-products and unreacted starting materials and/or catalysts. The goal in pharmaceutical research is to isolate the target compound with required purity and yield to be able to progress to the next synthetic sequence or biological testing with confidence. But the process of purification is viewed by synthetic chemists as a ‘means-to-an-end’ and the more rapidly and reliably the purification step can be performed the better. Easy enough to state, but hard to achieve when you need to be certain of purity and yield in a single, rapid purification attempt. As we will see here, flash column chromatography can help you achieve this.
First, join me on a flashback to my past as a discovery chemist just fresh out of grad school and eager to make a difference in pharmaceutical research. I was advised by my boss to model my behavior after a colleague and labmate with a reputation of being highly productive and successful. I was also informed that ‘chemist productivity’ was measured by 1) the number of compounds (of sufficient quantity and quality) he/she registered in the company’s database and 2) meeting project milestones.
Chemistry, by its very nature, involves the use of chemicals that can be harmful, toxic and potentially damaging to the environment, which means that drug discovery currently has a large and expensive environmental footprint. However, all is not lost. With a few small steps it is possible to make a big change to the impact that drug discovery has on our world. Let’s look at ways we can reduce the environmental impact of chemical processing and flash chromatography. This involves using green chemistry applications in the purification workflow to find a solution that reduces chemical waste to make it good for both the chemist and the environment.
Chromatographic purification methods such as flash chromatography can have a high environmental impact since they typically involve large quantities of harmful or toxic solvents run at high flow rates. In many laboratories the cost of procuring and then disposing of these solvents can be a major part of the overall cost of projects. For the chemist, trying to reduce the environmental impact of small molecule synthesis is part of being a good global citizen. Here are three strategies that greatly reduce the environmental impact of flash purifications. It can also save money in the long run by reducing the cost of chemical waste disposal.