Enzymes orchestrate chemical transformations with unparalleled effectivity and specificity, a prowess derived from evolutionarily optimized lively websites and finely tuned microenvironments [1], [2], [3], [4], [5], [6]. Their catalytic perfection, nevertheless, is commonly circumscribed by inherent vulnerabilities—structural fragility, slender operational home windows (pH, temperature), and excessive manufacturing prices [7]. Consequently, appreciable efforts have been directed towards creating biomimetic alternate options that emulate enzymatic perform whereas enhancing robustness, substrate adaptability, and operational flexibility [8], [9], [10].
Molecularly imprinted polymers (MIPs), initially designed to imitate antibody-antigen recognition [11], [12], [13], [14], [15], [16], [17], [18], have emerged as a flexible platform for this function. When this recognition‑centered paradigm is prolonged to include catalytic performance inside nanoconfined areas, MIPs evolve into molecularly imprinted nanoreactors (MIRs) [19]. As a definite catalytic paradigm, MIRs intersects with, but meaningfully extends past, established classes of enzyme-mimetic methods. Whereas nanozymes focus totally on replicating the catalytic lively websites of enzymes—typically by means of inorganic nanomaterials [20]—MIRs combine molecular imprinting to create tailor-made binding cavities that confer substrate selectivity, thereby addressing a key limitation of standard nanozymes [21]. In contrast to molecular catalysts, which function in homogeneous media, MIRs provide heterogeneous, reusable platforms with programmable microenvironments that stabilize transition states and regulate response pathways [22], [23]. Moreover, MIRs differ from generic hybrid catalytic methods by emphasizing the synergistic co-design of tailor-made recognition websites, catalytic facilities, and nanoconfined response areas inside a unified structure [23]. Thus, MIRs are greatest considered as built-in nanoreactors that mix the selectivity of molecular imprinting, the tunability of artificial catalysis, and the robustness of engineered nanomaterials.
The elemental objective in MIR design is to faithfully emulate the core ideas of enzymatic catalysis. This includes: (1) mimicking the lively web site by exactly positioning catalytic moieties (e.g., acids, bases, nanozymes, steel complexes) throughout the imprinted cavity, typically utilizing transition-state analogues (TSAs) [24], [25], [26], product analogues (PAs) [27], [28], [29], or substrate analogues (SAs) [30], [31] as templates (Scheme 1, Scheme 2); (2) replicating the catalytic course of the place the pre-organized practical teams cooperate to facilitate bond cleavage/formation, with efficiency quantifiable through Michaelis-Menten kinetics (e.g., OkM, okcat, okcat/OkM) to permit direct comparability with pure enzymes [32], [47]; and (3) engineering the catalytic microenvironment, the place the polymer matrix surrounding the lively web site modulates native polarity, hydrophobicity, and electrostatics to pre-concentrate substrates, stabilize transition states, and management product diffusion [33], [34], [35]. Regardless of these advances, the sphere was constrained by persistent challenges—template leakage, binding-site heterogeneity, and mass-transfer limitations—that collectively undermine catalytic effectivity and reproducibility [32]. Whereas architectural improvements (e.g., hierarchically porous/core-shell construction [36], [37], [38], [39], [40]) and superior fabrication methods (like cryo-/micellar imprinting [41], [42], [43], [44], [45], [46]) have alleviated some points (Scheme 2), a unified framework to information the rational design of high-performance MIRs remains to be missing. Crucial questions stay unanswered: How can we standardize exercise metrics throughout numerous MIR platforms? What are the governing ideas for reaching excessive turnover? Most significantly, how can we obtain synergistic co-design of lively websites and microenvironments to bridge the hole between MIRs and enzymatic effectivity?
This evaluation goals to bridge these gaps by establishing a complete, structure-activity-oriented framework for MIRs. We first deconstruct the evolution from easy imprinted polymers to stylish nanoreactors, critically analyzing cutting-edge methods for active-site engineering (coordination anchoring, post-imprinting modification, spatial encapsulation) and microenvironment programming (cofactor regulation, tandem catalysis, nanoconfinement, digital results). We then consider their transformative functions in environmental remediation, biosensing, pharmaceutical synthesis, and vitality conversion, with a essential emphasis on efficiency relative to pure enzymes and real-world operational challenges. Lastly, we delineate future analysis trajectories, highlighting the mixing of single-atom catalysts, in situ spectral evaluation, and artificial biology interfaces as pathways to advance MIRs from laboratory towards industrial biocatalysis and programmable drugs.
