Polymerisation success with biocatalysis

15th Jan 2025

Harnessing advanced analytical techniques and biocatalysis for precise polymer production

 

Polymers, especially biopolymers, have rapidly expanded their application in the pharmaceutical and biotechnology sectors. Their versatile structure, characterised by adjustable molecular weight, functional groups, and hydrophilic-hydrophobic balance, enables them to be tailored for various uses, such as enhancing targeted drug delivery and improving stability . 

However, producing polymers with precise structural and molecular weight control remains challenging. Ensuring uniformity and functional performance requires advanced analytical techniques for accurate characterisation and sizing, which are essential for consistency and efficacy in pharmaceutical applications. 

In this blog, we will explore how biocatalysis, combined with specialised analytical methods like size exclusion chromatography, can facilitate the efficient, reliable, and reproducible production of biopolymers that meet specific requirements. 

Biocatalysis, the use of enzymes to drive chemical reactions, has become a valuable tool in polymerisation over the last decade . It is appealing for several reasons:  

  • Specificity: Enzymes are highly selective, interacting only with specific substrates. This allows for greater control over the reaction process, enabling the reliable production of polymers with the desired properties without unwanted by-products or side reactions. 
  • Efficiency: Biocatalytic reactions support greater speed and lower energy consumption. They also take place under mild conditions, reducing the need for extreme temperatures or harsh chemicals. 
  • Versatility: Some monomers that are difficult to polymerise through traditional methods respond well to enzyme-driven reactions, expanding the scope of potential biocatalysis applications. 

In addition to the above, enzymes perform best in aqueous solutions, which can benefit the purification process by eliminating the need for organic solvents. The success of purification can be measured by using a copper-based colourimetry assay to determine how much enzyme remains, as copper ions will form a complex with amino acids in the enzyme.  

Achieving an optimal outcome in any polymerisation process depends on comprehensive development and small-scale synthesis to establish a robust and reproducible method before scaling up for commercial manufacture. Factors such as temperature, pH, and the presence of other chemicals can significantly impact biocatalytic reactions, making precision essential. For example, even a minor pH adjustment of 0.1 can alter the outcome, underscoring the need for careful monitoring and precise, reliable measurements. 

Size consistency is particularly important in polymerisation, as chain length and molecular weight can directly impact a polymer’s behaviour. These parameters are particularly crucial when synthesising biopolymers like RNA strands, where precise pairing of two strands depends on their size. 

One of the most reliable ways to measure polymer size and molecular weight is through size exclusion chromatography (SEC). Gel permeation chromatography (GPC), a subset of SEC, separates molecules by size as they pass through a column. For enhanced precision, a triple detection system that combines refractive index, viscosity, and light scattering detectors may be used. This powerful approach allows scientists to evaluate molecular weight with high levels of accuracy, ensuring that the polymer will consistently meet the required specifications and behave as desired under specific conditions. 

What does this look like in practice? Let’s examine a real-world application of size exclusion chromatography and biocatalysis in polymer production. 

A customer approached Sterling with a challenge: they needed to reliably produce polymer chains of a specific length to combine with another polymer in their therapeutic. Sterling’s chemistry and analytical teams collaborated both internally and with the customer to improve upon the original process, seeking a more repeatable and robust approach.  

Using biocatalysis, the Sterling team produced the polymer chain and adjusted the pH to achieve the desired molecular weight. The team added the enzyme in its diluted form and used specialised equipment to optimise delivery for maximum activity. The analytical team then employed gel permeation chromatography to confirm the molecular weight with precision. By fine-tuning the process and incorporating advanced analytical methods, Sterling was able to help the customer achieve consistent, reproducible results. 

Combining specialised technologies for polymerisation success

The combination of biocatalysis and size exclusion chromatography offers scientists a powerful combination of tools for the development of biopolymers. This approach aids scientists in maximising precision and control over polymer properties, enhancing process efficiency, and developing a robust process for smooth regulatory approvals. 

At Sterling, our combined expertise in enzymatic synthesis and analytical chemistry allows us to adapt to unique customer projects and tailor our approach to enhance their success. By closely collaborating across our specialised teams and with our customers, we ensure that all our customers’ objectives are met—whether they are developing novel polymers or overcoming challenges associated with difficult-to-polymerise materials. 

If you’d like to learn more about how we can support your polymerisation programme requirements, speak to an expert 

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