An Artificial Riboflavin Receptor Prepared by a Template Analogue Imprinting Strategy

Abstract

Molecular imprinting has resulted in a range of robust polymer-based receptors that are being considered for use in a variety of applications based on molecular recognition. [1] The technique entails polymerization of mono-and polyfunctional monomers in the presence of a template, whose subsequent removal leaves sites that can be reoccupied by the template or a closely related compound. These synthetic receptors are distinguished by their robustness and ease of synthesis, but they also have drawbacks, notably their poor water compatibility and, with notable exceptions, [2][3][4][5] the lack of strategies for imprinting water-soluble target molecules. One approach towards overcoming the latter is to use a nonaqueous imprinting protocol, in which lipophilic templates representing a close structural analogue or substructure of the target are employed. [6,7] Here, a solvent/porogen is chosen such that the intrinsically weak monomer-template interactions based, for example, on hydrogen bonding, electrostatics, or charge transfer, are stabilized. Thus, the use of solvents with low polarity and hydrogen bonding strength is generally favored. Although polymers prepared by this route have displayed selective binding of their targets under aqueous conditions, the effects were typically too weak to be of practical value. Following this approach, we report here on molecularly imprinted polymers (MIPs) that recognize their targets (riboflavin) effectively under such conditions ( Figure 1). Careful fine-tuning of the synthesis conditions with respect to the choice of template and cross-linking monomer proved critical and resulted in a polymer which strongly and selectively bound riboflavin in water-rich media similar to those found in common alcoholic beverages. [8] For the design of the polymers, we first turned our attention to the functional monomer. The flavin ring system contains an imide functionality which contains an acceptordonor-acceptor (ADA) array of hydrogen-bonding sites capable of interacting with receptors containing a complimentary DAD array. Representative of such molecules are 2,6-bisamidopyridines, whose ability to bind to imide functionalities has been widely studied.[9] Accordingly, we chose 2,6-bis(acrylamido)pyridine (BAAPy) as our functional monomer (Scheme 1). [10,11] With regards the choice of template, we focused on flavin and riboflavin derivatives having high solubility in typical imprinting solvents, in this case chloroform (Scheme 1), initially attempting to use N(10)-alkylflavins.[12] However, the solubility of these compounds in chloroform was found to be too low (ca. 16 mm for 1 and only ca. 6 mm for 2) for a conventional template/monomer molar ratio to be used. As expected, polymers prepared using these analogues as templates exhibited low imprinting factors and capacities (see below). Riboflavin tetraesters performed better in this regard, their solubility in chloroform being far greater than that of the N(10)-alkylflavins described above (RfAc: 0.2 m, RfPr: 0.6 m, RfBu: 0.8 m). Furthermore...

Stoichiometric molecularly imprinted polymers for the recognition of anti-cancer pro-drug tegafur

“…The design of imprinted polymers for tegafur presented here was based on our prior experience in the development of recognition elements for uracil derivatives, which contain a hydrogen bond acceptordonor-acceptor (A-D-A) imide moiety [10,11]. Our previous work, as well as that of others' [12][13][14][15], has shown that polymerisable functional monomers with complementary donor-acceptor-donor (D-A-D) arrays result in highly selective imprinted polymers, capable of recognising the template substance even in the presence of strongly competing analytes.…”

Influence of salt ions on binding to molecularly imprinted polymers

“…Water may interfere with hydrogen bonds involved in the recognition and MIPs relying on non-covalent interactions to the template are therefore often prepared in aprotic organic media. Optimal rebinding is usually observed in similar aprotic organic solvents as the ones used during the imprinting, although several cases of successful rebinding in aqueous media have been reported [8,[16][17][18][19][20][21][22][23][24][25]. The pH and the ionic strength of the rebinding solvent mixture have been recognized as parameters affecting the binding capacity [16,19,26].…”

Twenty years since ‘antibody mimics’ by molecular imprinting were first proposed: A critical perspective

“…Such materials have been shown to outperform their biological counterparts in real sample applications, as they are capable of retaining their function in environments that fall outside of normal physiological conditions e.g. extremes temperatures and pH values [19].…”