Nanometer-scale water-soluble macrocycles from nanometer-sized amino acids

Area of Science:

• Supramolecular Chemistry
• Organic Synthesis
• Materials Science

Background:

• The development of building blocks for creating complex molecular architectures is crucial in supramolecular chemistry.
• Previous work introduced Abc(2K), a linear building block for molecular rods.
• There is a need for novel amino acid derivatives that can form macrocycles with predictable geometries.

Purpose of the Study:

• To introduce and characterize two new unnatural amino acids, m-Abc(2K) and o-Abc(2K), as building blocks.
• To synthesize water-soluble macrocycles with well-defined shapes using these new amino acids.
• To investigate the conformational properties of the synthesized macrocycles.

Main Methods:

• Synthesis of Fmoc-protected unnatural amino acids Fmoc-m-Abc(2K(Boc))-OH (1a) and Fmoc-o-Abc(2K(Boc))-OH (1b).
• Fmoc-based solid-phase peptide synthesis to create macrocyclic structures (trimers to dodecamers).
• Molecular modeling, RP-HPLC, ESI-MS, and NMR spectroscopy for characterization and conformational analysis.

Main Results:

• Successful synthesis of macrocyclic "triangles", "parallelograms", and "rings" (24-114 atoms, 1-4 nm in size).
• Molecular modeling indicates well-defined shapes for most macrocycles under specific conditions.
• NMR studies confirm trans-amide linkages in CD(3)OD and D(2)O for some structures, while others show conformational changes in D(2)O.

Conclusions:

• m-Abc(2K) and o-Abc(2K) are effective nanometer-sized building blocks for constructing water-soluble macrocycles.
• The synthesized macrocycles exhibit predictable shapes and good solubility.
• Conformational flexibility exists, with some macrocycles adapting to different solvent environments.