J. Am. Chem. Soc. http://doi.org/44f (2015)

Credit: © 2015 ACS

Single-chain polymer nanoparticles are globular entities formed by intra-chain crosslinking — either covalent or non-covalent. When supramolecular linkages are used, the resulting nanoparticles can be thought of as crude analogues of folded peptide chains, and have been used to sequester catalytic sites in an effort to mimic enzymes. Unlike peptides, synthetic polymers display inherent variations from chain-to-chain, such as in chain length and the position of their crosslinking groups. This means that the exact nature and strength of their folding can be difficult to ascertain.

Now, Bert Meijer from Eindhoven University of Technology, Zhibin Guan from University of California, Irvine, and colleagues have used single-molecule force spectroscopy to investigate the strength of the intra-chain crosslinks in single-chain polymer nanoparticles. Two different bonding motifs were investigated: 2-ureido-4-[1H]-pyrimidinone (UPy), which contains a self-complementary H-bonding pattern and forms dimers; and benzene-1,3,5-tricarboxamine (BTA), which forms helical stacks of several BTA moieties. The polymer chains were attached at either end to a gold substrate and a gold-coated atomic force microscopy cantilever. Pulling the cantilever away from the substrate unfolded the nanoparticles and statistical analysis of the force-extension curves yielded some surprising insights into the folding of the nanoparticles.

For the nanoparticles held together with UPy dimers, one rupturing event in the force-extension curve for every two UPy functionalities on the chain was expected; however, for higher densities of UPy functionalities, fewer events were observed, suggesting that not all of the UPy groups dimerize during folding. For the BTA stacks, the situation is more complex as multiple BTA units are incorporated into one or more stacks — dependent on the density of BTA functionalities along the chain — within the nanoparticle. Using force spectroscopy analysis, the team were able to extract a dissociation rate constant for the BTA stacks. Interestingly, the stabilities of both UPy dimers and BTA stacks were lower in the polymer nanoparticles than alone in solution, due to the entropic cost of folding the polymer chain or the polarity of the nearby polymer backbone.