Dynamic Molecular Recognition in Solid State for Separating Mixtures of Isomeric Dicarboxylic Acids

Abstract

Molecular recognition emerges from non-covalent interactions and is of paramount importance for understanding of biological processes, ranging from enzymatic activity to DNA base pairing, as well as in the design of functional supramolecular systems, for example, molecular motors, sensors, ion receptors, or systems used in waste management. In the specific area of selective anion binding, numerous anion receptors (hosts) and sensors have been developed. The study of anion binding has traditionally been performed in solution where the host often experiences conformational freedom to form complexes with a wide range of guests. However, selectivity in separation has usually been achieved only upon crystallization, emphasizing the importance of intermolecular interactions in rigid crystal environment which lock the conformation of the host giving rise to its selectivity. In this context, recent advances in chemical reactivity achieved using mechanochemistry indicate that the concepts of supramolecular chemistry, such as templating, may be applicable also to solvent-free reactions. Mechanochemical reactivity can be highly dynamic and has thus far been employed for solid-state differentiation between enantiomers, supramolecular metathesis reactions, and for thermodynamic product selection. Although these reactions show specific interaction patterns between molecules comprising their respective solid phases, the possibility of selective binding and separation of target guest molecules from solid mixtures is, besides the pioneering studies by Etter and Caira, still an unexplored area. Here we focus on recognition and separation of isomeric or geometrically similar dicarboxylic acids (Scheme 1) from either their solid or solution mixtures using principles of supramolecular chemistry. The chosen acids belong to a class of guests of high biological and industrial relevance, and a considerable effort has been put into developing their sensors and receptors. Typically, the receptor for each dicarboxylate had to be meticulously designed because of the specific geometry of each acid molecule and their differing physicochemical properties. The importance of separation of the maleic/fumaric acid (H2mal/H2fum) stereoisomeric pair is not only related to the specific diastereomer recognition, but also arises from their conflicting biochemical behavior and abundant use of H2fum in food and pharmaceutical industry. We show here that the flexible polyamine receptor L (Scheme 1) discriminates among H2mal/H2fum diastereomers, succinic acid (H2suc), and three isomers of benzenedicarboxylic acid, by adapting its conformation and finally forming different solid hydrogenbonded (HB) frameworks. Regardless of whether the recognition takes place in the solid state by milling or by crystallization from solution, the resulting supramolecular complexes are the same and the selectivity bias of L towards the guest acids is fully retained. Milling improved yields to quantitative and almost eliminated the use of solvent. L proved to be an exceptional receptor for H2mal, also on the gram scale, excluding it from solid mixtures with even five other acids or from mixtures where there is a large surplus of a competing acid. Reacting L and H2mal in methanol (MeOH) or ethanol (EtOH) solutions yielded isoskeletal solvated solids, 1a (Table 1 and Section S.2 in the Supporting Information), Scheme 1. Dicarboxylic acids and the polyamine host L. The host binds anions as a cation (HL) resulting from protonation of the central amino group.