Evaluation of polymer–preservative interactions for preservation efficacy: molecular dynamics simulation and QSAR approaches†

Preservatives are critical ingredients in various pharmaceutical and consumer products. In particular, a high efficacy preservative system is essential in enhancing the shelf-life and safety of these products. However, the development of such a preservative system heavily relies on experimental approaches. In this study, molecular dynamics (MD) simulation was complemented with quantitative structure–activity relationship (QSAR) modelling to comprehensively evaluate polymer–preservative interactions between three different polymers (polyethylene terephthalate, PET; polypropylene, PP; and cellulose) and a series of preservatives from the classes of aliphatic, aromatic, and organic acids. First, adsorption of preservatives onto polymer surfaces was simulated in an aqueous environment. The preservatives did not adhere to hydrophilic cellulose, but most preservatives were adsorbed by PET and PP in distinct configurations. Interaction energies (IEs) between the preservatives and the polymers generally increase from cellulose to PP and PET. The diffusion coefficients of preservatives are dependent on polymer nature, preservative structure, and their resulting molecular interactions. Linear and low molecular weight preservatives exhibit higher diffusion coefficients in polymers. For a particular preservative, diffusion coefficients increased in the order of cellulose < PET < PP. Finally, using MD properties and molecular descriptors of preservatives, QSAR models were developed to identify key descriptors of preservatives and predict their IEs and diffusion coefficients in polymers. This study demonstrates a computational approach for identifying critical materials properties, and predicting polymer–preservative molecular interactions in water. Such an approach streamlines the rational selection and design of high efficacy preservative systems for various pharmaceutical, food and cosmetic products. Furthermore, the integrated computational strategy also reduces trial-and-error experimental efforts, thereby accelerating the development of high efficacy preservative systems.