The balance between intramolecular hydrogen bonding, polymer solubility and rigidity in single-chain polymeric nanoparticles

Abstract

A library of copolymers with pendant, protected ureido-pyrimidinone (UPy) groups was prepared applying controlled polymerization techniques. The polymer backbones were based on polyacrylate, polymethacrylate, polystyrene and polynorbornene and differ in stiffness, molecular weight and the linking moiety between the backbone and the UPy group. In all cases, the percentage of protected UPy groups was kept constant. The effect of solvent on the behaviour of the polymers before and after removal of the protecting groups was evaluated in, among others, chloroform and tetrahydrofuran (THF).After deprotection of the UPy protecting group, the UPys dimerize via four-fold H-bonding in THF, inducing a collapse into single-chain polymeric nanoparticles (SCPNs), as evidenced by a combination of 1 H-NMR spectroscopy, size-exclusion chromatography and dynamic light scattering. In chloroform, on the other hand, dimerization of the UPy groups is present but interchain interactions occur as well, resulting in less-defined SCPNs. Remarkably, the flexibility of the polymer backbone, the polymer molecular weight and the nature of the linker unit all do not affect SCPN formation. In contrast, the interaction between solvent and the UPy moiety is a critical parameter for SCPN formation. For example, strong intramolecular dimerization of the UPys is observed in THF while interparticle interactions are suppressed. From this investigation we conclude that a wide variety of polymer backbones are suitable for polymer collapse via supramolecular interactions and thus allow for the formation of SCPNs but that the solvent choice is crucial to enhance intramolecular H-bonding and, at the same time, to suppress interparticle interactions.

Dynamic Single Chain Polymeric Nanoparticles: From Structure to Function

“…While the first studies on SCPNs relied strongly on the use of AFM and SEC to elucidate the single chain character of the particles obtained, Stals et al monitored the polymer backbone collapse of UPy functionalized SCPNs using a combination of DLS, NMR, SEC and AFM (42). Hereto, a library of polymers with varying backbone structures, molecular weights and linking groups was prepared that contained between 5-10% of photoprotected pendant UPy groups.…”

A brief user's guide to single-chain nanoparticles

“…Often, monomers are functionalized with hydrogen bonding units that are protected in some way to prevent the polymers from forming aggregates during their synthesis. 57 Benzene-1,3,5-tricarboxamide (BTA) has been exploited in the field of supramolecular chemistry for its ability to form helical assemblies via hydrogen bonding; 68 consequently, it has also found use in SCNP synthesis. 3).…”

Advances in single chain technology

“…We will not enter into details here; instead, we refer the interested reader to previously published reviews focused on intra-chain cross-linking techniques for SCNP construction. Hence, different non-covalent bonding-based strategies have been introduced over recent years to afford the preparation of responsive SCNPs, such as benzamide dimerization 77 developed in 2008, ureido-pyrimidinone (UPY) dimerization [78][79][80][81] in 2009, benzene-tricarboxamide (BTA) helical stacking 10,11,[82][83][84][85][86][87][88] in 2011, cucurbit[n]uril complexation, 89,90 hydrophobic L-phenylanaline (Phe)-Phe interactions 91,92 and 3,3 0 -bis(acylamino)-2,2 0 -bipyridine (BiPy-BTA) self-assembly 93 in 2012, Rh complexation, 94,95 charged amphiphilic random copolymer self-assembly [96][97][98][99][100][101] and Cu complexation in 2013, 13,72 and finally, neutral amphiphilic random copolymer self-assembly 102 in 2014. 11.…”