Fragment Templates in Molecularly Imprinted Polymer Synthesis: Design Strategies, Critical Factors, and Analytical Applications

The utilization of fragment templates in molecular imprinting polymer (MIP) synthesis attracts significant interest in its potential to create polymers with high specificity in recognizing target molecules. The primary advantage of fragment templates lies in their capacity to extract target molecules by focusing on specific components, thus forming precise and specific binding sites without necessitating the complete molecular structure of the target. While research has expanded, current literature often lacks a critical evaluation of the factors governing their effectiveness. This review provides a thorough examination of fragment template strategies across diverse analyte classes. We evaluate key performance determinants such as fragment size, polymerization technique, spatial accessibility, and binding energetics to elucidate why specific fragment designs outperform others for similar target analytes. Furthermore, the article explores emerging design principles, including computational modeling and advanced surface imprinting, while incorporating recent studies (2020–2024) to highlight key successes and systemic limitations. By synthesizing these comparative insights, this review serves as a definitive resource for the rational design of high‐performance fragment‐based MIPs across pharmaceutical, environmental, and clinical applications.