Date of Degree


Document Type


Degree Name





Rein V. Ulijn

Committee Members

Charles M. Drain

Dorthe Eisele

Donna McGregor

Raymond Tu

Subject Categories

Materials Chemistry | Physical Chemistry


Self-assembly, peptides, porphyrins, co-assembly


The diverse molecular functions of naturally occurring biomaterials designed from proteins are fundamentally based on a set of conserved building blocks, namely the 20 gene coded amino acids. The supramolecular structures and functions of proteins dictates by the self-assembly, where the complexity of proteins arise from a large number of amino acids. Generation of biomimetic systems that resemble the structures and functions of proteins is of great interest yet challenging due to the tremendous complexity of the natural systems. It is important to investigate alternative strategies to design much simpler systems that exhibit the same or similar function as proteins. Short peptides and aromatic peptide amphiphiles (2-5 amino acids short) are ideal candidates to generate minimalistic functional versions of complicated biological systems with same function and biocompatibility.

Thermodynamically driven fully reversible self-assembly of peptides is one the three main strategies (in addition to kinetically controlled and out-of-equilibrium assemblies) employed to create peptide based supramolecular structures. The fully reversible self-assembly of aromatic peptide amphiphiles via enzymatic hydrolysis and condensation of precursors to form peptide bonds in-situ can generate thermodynamically optimized conformations. These well-ordered nanostructures can act as scaffolds to effectively incorporate functional molecules (porphyrins as explained in chapters 3-5), via non-covalent interactions to generate soft nanomaterials. The co-assembled nanostructures get stabilized by hydrogen bonding interactions between amide backbones, and further stabilized by π- stacking interactions of aromatic moieties, with porphyrin molecules co-assembled into the aromatic stack. The resulting supramolecular structures organize porphyrin molecules inside the peptide nanostructures in such a way that they can facilitate the energy transfer by fulfilling the required spatial arrangement through highly ordered peptide nanostructures.

Cyclic dipeptides are simple yet versatile molecules with customizable supramolecular properties, which are dictated by the functionality of their two amino acid side chains. Their self-assembly propensity has typically been investigated using cyclic dipeptides obtained by separate chemical synthesis or other pathways not always compatible with self-assembly, such as extreme temperatures. The spontaneous, in situ formation of cyclic dipeptides in aqueous buffer from a variety of dipeptide methyl esters, through intramolecular amide bond formation is demonstrated in chapter 4 resulting nanoscale morphologies that are dictated by amino acid side chain functionality, which is presented on the nanostructure surface. The approach provides a straightforward means of producing supramolecular architectures with tunable nanoscale morphologies and surface chemical properties. The formation kinetics and consequent supramolecular properties of the resulting structures can be regulated by simply varying the concentration of starting materials, as demonstrated for a nanostructured hydrogel with tunable stiffness. Moreover, when the co-assembly between a functional cationic metalloporphyrin molecule and cyclic dipeptide hydrogels is achieved by introducing the functional porphyrin in the starting mixture it can lead to non-covalent functionalization and formation of supramolecular structures with customizable peroxidase-like activity.

Unprotected tri-peptides even with the presence of three amino acids exhibit 8000 different combinations providing a large sequence space to study. In chapter 5 we show that supramolecular structures formed thorough cationic tri-peptide self-assembly can utilized to serve as a supramolecular platform to organize charged porphyrin molecules in different arrangements depending on the primary sequence of the peptide. The differences in spatial organization of porphyrin molecules can be demonstrated by investigating the ability of the peptide-porphyrin assemblies to participated in energy transfer. The calculated energy transfer efficiencies will describe the degree of order the of porphyrin molecules inside the peptide supramolecular structures, thus enabling the controlled positioning of porphyrin molecules.