Covalently Linked Porphyrin-peptide Conjugates: Design, Synthesis And Supramolecular Self-assembly Properties

Precise control of supramolecular architecture is a great challenge in the field of molecular self-assembly, while precise and elegant arrangement of peptide-containing porphyrin conjugate systems is also very important for the purpose of conducting corresponding biological reactions in nature. As a result, the self-assemble property of porphyrin-peptide systems has formed the focus of research interests in this field. However, attention in this direction appears mainly focused on the self-assemble property of porphyrin hybrids with peptides depending on non-covalently interactions such as electrostatic interaction and hydrogen bonding. The self-assemble behavior of porphyrin conjugates covalently linked with peptides was also started to be investigated, but efforts toward this direction were still very limited.Porphyrins are of typical large conjugated molecular electronic structure with intrinsic intermolecularπ-πinteraction. Tuning the intermolecular interaction of such kind of tetrapyrrole derivatives can be easily reached by introducing functional groups (actually additional non-covalent interactions) onto the peripheral positions of porphyrin ring. On the other hand, peptides are well known for their hydrogen bond-forming ability and solvent-dependent secondary conformation nature. As a result, integration of peptide chain with porphyrin chromophore is expected to provide good chance to tune the optical and electronic properties of porphyrin self-assembled nanostructures on the basis of tuning the molecular packing mode depending on the interplay ofπ-πinteraction between porphyrin chromophores as well as the hydrogen bonding interaction and chiral discrimination between peptide chains.1. Morphology and Chirality Controlled Self-assembled Nanostructures of Porphyrin-pentapeptide Conjugate:Effect of the Peptide Secondary ConformationThe self-assembly properties of a novel covalently linked porphyrin-pentapeptide conjugate 1 in THF/n-hexane and THF/water were comparatively investigated by electronic absorption, circular dichroism (CD), IR spectroscopy, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and X-ray diffraction (XRD) technique. Associated with the different secondary conformation of pentapeptide chain covalently linked to the porphyrin ring in different solvent system, self-assembly of conjugate 1 leads to the formation of nanofibers with right-handed helical arrangement and nanotubes with left-handed helical arrangement in a stack of porphyrin chromophores according to the CD spectroscopic result in apolar THF/n-hexane (1:3) and polar THF/water (1:3) system depending on the cooperation between intramolecular or intermolecular hydrogen bonding interaction with chiral discrimination between pentapeptide chains and porphyrin-porphyrin interaction in the direction parallel to the tetrapyrrole ring of neighboring conjugate molecules. IR spectroscopic result clearly reveals theα-helix andβ-sheet secondary conformation, respectively, employed by the pentapeptide chain attached at the porphyrin core in the nanostructures formed in THF/n-hexane (1:3) and THF/water (1:3). The X-ray diffraction (XRD) result confirms that in the nanotubes a dimeric supramolecular bilayer structure was formed through an intermolecular hydrogen bonding interaction between two conjugate molecules, which as the building block self-assembles into the target nanostructures. These results clearly reveal the effect of secondary conformation of pentapeptide chain in the conjugate molecule on the packing mode of porphyrin chromophore, supramolecular chirality, and morphology of the self-assembled nanostructure. The present result represents not only the first example of organic nanostructures self-assembled from covalently linked porphyrin-pentapeptide conjugate, but more importantly the first effort towards controlling and tuning the morphology and in particular the supramolecular chirality of porphyrin nanostructures via tuning the secondary conformation of peptide in different solvent system, which is helpful towards understanding, designing, preparing, and mimicking the structure and role of naturally occurring porphyrin-peptide conjugates. In addition, both nanofibers and nanotubes were revealed to show good semiconducting properties. 2. Design, Synthesis and Characterization of Novel Covalently Linked Porphyrin-pentapeptide ConjugatesThe target novel covalently linked porphyrin-pentapeptide conjugates were synthesized in good yield from a simple solution-phase coupling reaction between a series of monocarboxylic porphyrin derivatives and a glycinyl-alanyl-glycinyl-alanyl-glycine (GAGAG) peptide in the presence of N, N-diisopropyl ethylamine (DIPEA) and o-benzotriazole-N, N, N', N'-tetramethyl-uronium-hexafluorophosphate (HBTU) in DMF. The obtained covalently linked porphyrin-pentapeptide conjugates were characterized by various methods such as MS, NMR, EA, IR, UV and CD. In addition, the synthesis route of monocarboxylic porphyrin derivatives was optimized and simplified by a novel and effective one-step method rather than multi-step method reported before. Finally, the solubility of obtained covalently linked porphyrin-pentapeptide conjugates were compared and studied systematically.