A series of urea-based vinyl monomers was synthesized and investigated for their ability to function as polymerizable hosts for the molecular imprinting of N-Z-D- or L-glutamic acid in polar media (DMSO or DMF). The monomers were synthesized in one step from a polymerizable isocyanate and a nonpolymerizable amine or vice versa, with yields typically over 70%. Prior to polymerization their solution binding properties vis-a-vis tetrabutylammonium benzoate in DMSO were investigated by 1H NMR, UV-vis and fluorescence monitored titrations. The affinities of the urea monomers for benzoate depended upon the substitution pattern of the urea, with all diaryl ureas exhibiting high affinity. EDMA-based imprinted polymers prepared in DMF or DMSO against Z-D-(or L)-glutamic acid using 2 equiv of the urea monomer and 2 equiv of base were able to recognize the imprinted dianion as well as larger molecules containing the glutamic acid substructure. The affinity, reflected in liquid chromatography retention data, correlated with the solution binding properties of the corresponding monomers.

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Polymorphism of crystalline drugs is a common phenomenon. However, the number of reported polymorphic cocrystals is very limited. In this work, the synthesis and solid state characterisation of a polymorphic cocrystal composed of sulfadimidine (SD) and 4-aminosalicylic acid (4-ASA) is reported for the first time. By liquid-assisted milling, the SD:4-ASA 1:1 form I cocrystal, the structure of which has been previously reported, was formed. By spray drying, a new polymorphic form (form II) of the SD:4-ASA 1:1 cocrystal was discovered which could also be obtained by solvent evaporation from ethanol and acetone. Structure determination of the form II cocrystal was calculated using high resolution X-ray powder diffraction. The solubility of the SD:4-ASA 1:1 cocrystal was dependent on the pH and predicted by a model established for a two amphoteric component cocrystal. The form I cocrystal was found to be thermodynamically more stable in aqueous solution than form II, which showed transformation to form I. Dissolution studies revealed that the dissolution rate of SD from both cocrystals was enhanced when compared to a physical equimolar mixture and pure SD.

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...