Designing Bioinspired Multifunctional Hybrid Materials: A Theoretical Protocol for <scp>MIP</scp> @Estradiol‐Like Steroids

ABSTRACT Over the years, synthetic receptors have been utilized as sensor elements, presenting a viable alternative to natural receptors. That way, the rational design of these types of receptors is currently one of the most extensively researched topics in molecular recognition. Molecularly imprinted polymers (MIP) have become increasingly prominent in polymer chemistry due to their wide range of applications and ability to be used in various environments. Their high chemical and thermal stability makes them ideal for use in fields such as sensors, drug delivery systems, and environmental monitoring. Additionally, MIP can be tailored to recognize specific molecules, enhancing their functionality and effectiveness in targeted applications. Thus, the present work aims to carry out a rational design of an MIP with specific cavities to accommodate estradiol using computational tools. To achieve this, theoretical calculations were performed using the Gaussian 09 program with DFT theory at the wb97xd/6‐31G(d,p) level, involving both optimization and frequency calculations. The main steps of an MIP preparation were simulated, and it was discovered that methacrylic acid (MAA) is the most suitable functional monomer for preparing MIP for estradiol, while EGDMA is found to be the optimal crosslinking agent due to its excellent performance in binding the target molecule effectively. Furthermore, the solvents acetonitrile and DMSO increase the stability of interactions between estradiol and functional monomer (Acrylic acid), being indicated when the objective is to attract or keep estradiol inside the MIP cavity. Finally, selectivity tests showed high affinity of the studied MIP for estradiol and chemically similar molecules. Furthermore, from a theoretical perspective, the computational analyses outlined in this paper provide a highly valuable protocol for predicting optimal experimental conditions. This has the potential to significantly reduce both the time and cost involved in preparing MIP. Additionally, it offers a systematic approach to enhance the efficiency of MIP preparation, thereby contributing to advancements in this field.