l-Histidine Salt-Bridged Monomer Preassembly and Polymerization-Induced Electrostatic Self-Assembly

Abstract

Salt bridges are predominant in protein construction and stabilization, yet largely unexplored for polymer nanoparticle synthesis. We herein report the use of l-histidine salt bridges to drive monomer preassembly and two-dimensional electrostatic self-assembly in aqueous photo-RAFT polymerization. l-histidine salt bridges drive the monomer clustering nucleation, complex coacervation, and Coulombic stabilization, leading to the 2 nm ultrasmall clusters and coacervate droplets. Homopolymerization leads to a precision two-dimensional electrostatic self-assembly via a droplet-monolayer-multilayer transition, i.e., salt-bridged homo-polymerization-induced self-assembly (PISA). Block copolymerization does not disturb the “salt-bridged homo-PISA” mechanism. Enhanced Coulombic repulsion via seeded polymerization of charged monomers using as-achieved multilayer lamellae (seeds) yields supercharged 5 nm ultrathin monolayer lamellae with high colloidal stability upon dilution, salting, and long-term storage, urgently needed for bioapplications. This work opens up a new avenue to use amino acid salt bridges for PISA synthesis of biologically important, yet hitherto inaccessible, salt-resistant ultrathin polyelectrolyte complex nanomaterials.

Site-Specific Polymerization-Induced Electrostatic Self-Assembly: Synthesis of Highly Charged Salt-Tolerant Polyion Complex Nanoreactors

“…It is seemingly axiomatic that net charge must be minimized for the precision shape/size control in PIESA. − Nevertheless, highly charged salt-tolerant subdomains are omnipresent in cellular proteins − organized via site-specific molecular recognition under thermodynamic and kinetic control . We found that aspartic acid ionic H-bonds and histidine salt bridges could stabilize salt-tolerant nanoparticles mainly via enthalpy control. Nevertheless, the electrostatic interactions of oppositely charged polyions lead to entropy gains from release of counterions associated with polymer chains that drive complexation.…”

Polymerization-induced self-assembly for the construction of nanostructured hydrogels

“…[46][47][48] The monomer/solvent toolkit of PISA has also been greatly enlarged. [49][50][51][52][53][54][55][56] Furthermore, the precise fabrication of polymer assemblies with a high concentration has greatly advanced their applications. In addition to drug and gene delivery, [57][58][59] polymer assemblies prepared via PISA have recently been used as Pickering emulsifiers, 60,61 nano-reactors, 62,63 functional gels, 64,65 coatings, 66,67 nano-splitters, 68 ice recrystallization inhibitors, 69,70 etc.…”