Porous peptide frameworks generated by stacking non-self-complementary β-sheets

"One of major approaches in the design of cavity space in the solids utilizes non-self-complementary molecules[1]. The irregular shape of the molecules and/or specific directionality of potential H-bonds prevent close packing of the molecules and yields various architectures hosting a second component, from inclusion compounds and co-crystals to complex non-crystalline patterns in biology. The strategy of non-self-complementary molecules has been extended in our studies to 2D supramolecular polymers based on short peptides[2]. The formation of the peptide layer with a desired overall geometry is controlled by strong, charge-assisted H-bonds (arrows in the Figure) in a β-sheet-like network as well as the segregation of hydrophobic amino acid residues into the interlayer space. The H-bonds add stability to the whole architecture while the hydrophobic groups keep the stacking layers at a distance that generates a cavity space available to a second component (encircled ""G"" in the Figure). A wide range of inclusions and co-crystals have been prepared in our group based on a series of dipeptides and higher peptide oligomers. For example, the incorporation of various organic solvents and bioactive molecules have been demonstrated for leucyl-alanine and similar dipeptides: alcohols, amides, phenols, pyridines, polyols, vitamins, scents and flavors. The crystal structure studies reveal a surprisingly persistent structural motif that can be used for engineering of crystalline materials with a specific property. We believe this type of peptide matrix may be utilized in the solid state organic synthesis [3] as reactive molecules of the second component can be oriented in a predictable way with respect to each other. "

Co-crystals and inclusion compounds of leucyl-containing dipeptides

Short peptides are ecologically friendly and non-toxic molecules, so they can be safely utilized in green chemistry processes or incorporated in pharmaceuticals and food additives. It has been shown that some dipeptides can form crystals that incorporate other molecules through intermolecular hydrogen bonding and van der Waals interactions[1]. The utilization of such dipeptides for solid state organic synthesis or storage and stabilization of bioactive molecules would be of great practical interest, but the principles that define the successful combinations are not clear. In order to identify what factors lead to complementary pairs of a dipeptide and a second component, a series of leucine-containing dipeptides was screened against 40 organic solvents and solids. Direct or solvent-assisted grinding was used followed by PXRD analysis. It was found that each dipeptide was able to form new phases with some of the utilized reactive and bioactive molecules. The Figure illustrates three experimental powder patterns in the 5-35 2θ degree range. The dipeptide leucyl-valine (1) and the second component 5-acetylsalicylamide (2) combine to form a new crystalline phase (3). After screening was complete, a series of crystallizations was performed and several crystals comprised of both a dipeptide and another molecule have been isolated and studied. A number of structural motifs were observed, although a layered architecture with the second component included in the interlayer space prevailed.