**1. Introduction**

Natural products have gained enormous popularity over the years as they are used in clinical settings [1]. They have made excellent contributions historically to drug development, and many of them have had profound effects on our lives [2]. Chrysin, chemically known as 5,7-dihydroxy flavone [3], is a kind of flavonoid compound with extensive pharmacological activity isolated from active ingredients of Chinese traditional medicine [4,5] and has great antioxidative [6] and anti-inflammatory effects [7]. Research has shown that chrysin inhibits tumor cell proliferation [8], induces tumor cell apoptosis [9], suppresses tumor angiogenesis [10] and circumvents drug resistance [11]. Therefore, studies on the extraction and identification of chrysin are of great value.

**Citation:** Li, L.; Li, L.; Cheng, G.; Wei, S.; Wang, Y.; Huang, Q.; Wu, W.; Liu, X.; Chen, G. Study of the Preparation and Properties of Chrysin Binary Functional Monomer Molecularly Imprinted Polymers. *Polymers* **2022**, *14*, 2771. https://doi.org/10.3390/ polym14142771

Academic Editors: Hao-Yang Mi, Chongxing Huang, Hui Zhao and Tao Liu

Received: 12 May 2022 Accepted: 1 July 2022 Published: 6 July 2022

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According to literature reviews, there are many methods for the separation of chrysin, including HPLC [12], column chromatography [13], solid-phase extraction (SPE) [14], gas chromatography–mass spectrometry(GC-MC) [15], macroporous resin [16] and other traditional methods. However, due to the problems of long extraction time and a large amount of solvent and waste, the instrumental methods are not suitable for industrial mass production applications. Although the traditional separation methods, such as extraction and precipitation, can be applied at a low cost, these approaches are restricted because of low recoveries and purities. At present, there is still a lack of efficient extraction methods of chrysin.

The molecularly imprinted polymer has been widely used for the separation and enrichment of active components from natural products [17–21]. Molecular imprinting is a technique for preparing polymers of desired and predetermined selectivity [22]. This polymer is a material with complementary spatial structure and functional group interaction with template molecule. The molecularly imprinted polymer has a strong affinity and recognition ability for the template molecule [23–28]. The method has excellent prospects for application in the field or market for easy and fast molecular identification. Due to their unique properties, molecularly imprinted polymers have been widely used in various applications, such as drug delivery [29], detection of viruses [30], chemical sensor [31,32], specific recognition of protein [33], chromatography [34], solid-phase extraction [35] and bioanalysis [36].

Generally speaking, most natural products have multiple active groups. Single functional monomers and template molecules are easily destroyed during hydrogen bond formation, which reduces adsorption capacity and separation factor and, thus, cannot be well separated and purified from traditional Chinese medicine. The synergistic effect of the two functional monomers is beneficial to the separation and purification of natural products. For example, Wan [37] selectively extracted myricetin from traditional Chinese medicine with an adsorption capacity of 10.58 mg/g using glycidyl methacrylate (GMA) and 4-vinylpyridine as bifocal monomers. Huan [38] used acrylamide and 2-vinylpyridine as bifocal monomers to prepare a solid-phase extraction column for the separation of rutin extract from traditional Chinese medicine, and the recovery rate was 85.93%, which was better than the traditional separation column. The calculation and practical experiments show that MIP synthesized from an acrylamide (AM) monomer has a higher specific factor and adsorption capacity [39]. Chrysin has a rigid benzene ring structure and contains both a hydroxyl group and an aldehyde group, belonging to polar flavonoids. The functional monomer methacrylic acid (MAA) was acidic and acrylamide (AM) neutral. Under the synergistic action of AM, the force of MAA on the hydrogen bonds, electrostatic and π–π stacking of chrysin increased, which is expected to improve the adsorption selectivity of molecularly imprinted polymers. Therefore, the strategy of multifunctional monomer is a valid synthetic option to synthesize imprinted materials for the template molecules of flavonoids with polar functional groups, such as chrysin.

In this paper, Bi-MIPs are used for the separation and enrichment chrysin for the first time. The Bi-MIPs were prepared by precipitation polymerization using methacrylic acid and acrylamide as functional monomers and ethylene glycol dimethacrylate as a crosslinking agent. The adsorption selectivity of the Bi-MIPs was evaluated by preparing Si-MIPs with methacrylic acid as a functional monomer as the control group. Furthermore, we also study the feasibility of the Bi-MIPs as effective sorptive materials for the dissociation and enrichment of chrysin. The equilibrium, kinetics and thermodynamics of the adsorption process were investigated to study the adsorption mechanism of chrysin on the Bi-MIPs. Thus, Bi-MIPs are presented for their promising output application toward the extraction of chrysin.
