nn2c09872_si_002.cif (545.95 kB)
Entropically-Driven Co-assembly of l‑Histidine and l‑Phenylalanine to Form Supramolecular Materials
datasetposted on 2023-02-06, 18:13 authored by Om Shanker Tiwari, Ruth Aizen, Massimiliano Meli, Giorgio Colombo, Linda J. W. Shimon, Noam Tal, Ehud Gazit
Molecular self- and co-assembly allow the formation of diverse and well-defined supramolecular structures with notable physical properties. Among the associating molecules, amino acids are especially attractive due to their inherent biocompatibility and simplicity. The biologically active enantiomer of l-histidine (l-His) plays structural and functional roles in proteins but does not self-assemble to form discrete nanostructures. In order to expand the structural space to include l-His-containing materials, we explored the co-assembly of l-His with all aromatic amino acids, including phenylalanine (Phe), tyrosine (Tyr), and tryptophan (Trp), all in both enantiomeric forms. In contrast to pristine l-His, the combination of this building block with all aromatic amino acids resulted in distinct morphologies including fibers, rods, and flake-like structures. Electrospray ionization mass spectrometry (ESI-MS) indicated the formation of supramolecular co-assemblies in all six combinations, but time-of-flight secondary-ion mass spectrometry (ToF-SIMS) indicated the best seamless co-assembly occurs between l-His and l-Phe while in the other cases, different degrees of phase separation could be observed. Indeed, isothermal titration calorimetry (ITC) suggested the highest affinity between l-His and l-Phe where the formation of co-assembled structures was driven by entropy. In accordance, among all the combinations, the co-assembly of l-His and l-Phe produced single crystals. The structure revealed the formation of a 3D network with nanocavities stabilized by hydrogen bonding between -N (l-His) and -NH (l-Phe). Taken together, using the co-assembly approach we expanded the field of amino acid nanomaterials and showed the ability to obtain discrete supramolecular nanostructures containing l-His based on its specific interactions with l-Phe.
phase separation couldnotable physical propertiesisothermal titration calorimetryion mass spectrometryform discrete nanostructuresespecially attractive duebiologically active enantiomeramino acid nanomaterialsaromatic amino acidsbest seamless codefined supramolecular structuresl ‑ phenylalaninephe ), tyrosinel ‑ histidineamino acidssupramolecular coincluding phenylalaninetyr ),trp ),like structuresassembled structurespristine linclude ltaken togetherstructure revealedstructural spacespecific interactionsplays structuralphe ).nanocavities stabilizedinherent biocompatibilityhydrogen bondinghighest affinityfunctional rolesflight secondaryenantiomeric formsdifferent degreescontaining materialsbuilding blockassociating molecules3d network