Using basic chemistry in manufacturing

A method of calculating solvation processes for chemical manufacture developed at UCL Chemistry has become integral to the work carried out by drug discovery teams at major pharmaceutical companies. Known as the Abraham solvation parameter approach, it is also used by research and development groups at international chemical companies.

Solvation processes have long been of interest, because dramatic changes in equilibria and reaction rates can be observed in different solvents. The Abraham solvation model is today a well-known and well-used equation in the chemical industries, where it provides a rapid and efficient way to compare solutes without conducting an actual experiment or even synthesising the molecule. It enables chemists to predict physicochemical and biochemical properties of chemicals, including drugs and agrochemicals. The method helps drug discovery teams to identify and optimise the most promising compounds, and often results in fewer compounds being made before a candidate is selected, saving time and resources.

In the pharmaceutical industry, the model is used for predicting the pharmacokinetics (absorption, distribution, metabolism, excretion and toxicity) of chemical agents, which is vital in determining their performance and pharmacological activity as drugs. Meanwhile, agri-businesses use the method to assess agrochemicals for efficacy and their long-term environmental risk assessment.

In recent years, commercial, open source and in-house computational modelling software has been developed based upon the Abraham solvation model. These provide a framework for analysing problems such as solubility and partitioning. For example, the Absolv software is used by chemists to calculate various solvation-associated properties from equations involving transfer from the gas phase to a condensed phase or between different condensed phases, and to carry out structure-based prediction of the solvation parameters required for those calculations.

The use of such software has become a fundamental part of how many drug discovery teams understand and optimise drug candidate solubility and partitioning. It has also become fundamental to how they establish vital parameters for determining whether a candidate can be formulated and delivered in sufficient quantities to be effective as a drug. The alternative approach is simply calculating the number of hydrogen-bond donor and acceptor groups and the size of the molecules, which often gives inferior information to the Abraham approach.

Outside of the pharmaceutical industry, physical chemists supporting Syngenta, one of the world's leading bioscience companies, use the approach to address chemical design issues related to expression of activity and environmental fate for agrochemicals, beyond conventional physical chemical properties.