Self-Organized Nanoparticles of Random and Block Copolymers of Sodium 2-(Acrylamido)-2-methyl-1-propanesulfonate and Sodium 11-(Acrylamido)undecanoate as Safe and Effective Zika Virus Inhibitors.

A series of anionic homopolymers, poly(sodium 2-(acrylamido)-2-methyl-1-propanesulfonate) (PAMPS) and amphiphilic copolymers of AMPS and sodium 11-(acrylamido)undecanoate (AaU), both block (PAMPS75-b-PAaUn), and random (P(AMPSm-co-AaUn)), were synthesized and their antiviral activity against Zika virus (ZIKV) was evaluated. Interestingly, while the homopolymers showed limited antiviral activity, the copolymers are very efficient antivirals. This observation was explained considering that under the conditions relevant to the biological experiments (pH 7.4 PBS buffer) the macromolecules of these copolymers exist as negatively charged (zeta potential about -25 mV) nanoparticles (4-12 nm) due to their self-organization. They inhibit the ZIKV replication cycle by binding to the cell surface and thereby blocking virus attachment to host cells. Considering good solubility in aqueous media, low toxicity, and high selectivity index (SI) of the PAMPS-b-PAaU copolymers, they can be considered promising agents against ZIKV infections.

Fluorescence Study of the Interaction between Hydrophobically Modified Polymers and Charged Particles in Aqueous Media.

The interaction of hydrophobically randomly modified and end-modified poly(2-(acrylamido)-2-methylpropanesulfonate)s (PAMPSs) with nonionic and positively and negatively charged surfactants was studied with the fluorescence spectroscopic technique of labeled pyrene. The results indicated that the randomly modified PAMPS bound to the nonionic and positively charged surfactants and that the disruption of intrapolymer micelles formed by the polymer occurred. In contrast, end-modified PAMPS was bound to the surfactants without the disruption of multipolymer aggregates formed by the polymer in a comparably low concentration range of surfactants. The conformation of the polymer-surfactant complex was confirmed to depend on the position of the hydrophobic group in the polymer chains. In the case of negatively charged surfactant, the complex formation between the polymers and the surfactants was significantly restricted due to the electrostatic repulsion of anionic sites of the polymer chains and the negatively charged surfactants.

pH-Induced Association and Dissociation of Intermolecular Complexes Formed by Hydrogen Bonding between Diblock Copolymers.

Poly(sodium styrenesulfonate)⁻block⁻poly(acrylic acid) (PNaSS⁻b⁻PAA) and poly(sodium styrenesulfonate)⁻block⁻poly(N-isopropylacrylamide) (PNaSS⁻b⁻PNIPAM) were prepared via reversible addition⁻fragmentation chain transfer (RAFT) radical polymerization using a PNaSS-based macro-chain transfer agent. The molecular weight distributions (Mw/Mn) of PNaSS⁻b⁻PAA and PNaSS⁻b⁻PNIPAM were 1.18 and 1.39, respectively, suggesting that these polymers have controlled structures. When aqueous solutions of PNaSS⁻b⁻PAA and PNaSS⁻b⁻PNIPAM were mixed under acidic conditions, water-soluble PNaSS⁻b⁻PAA/PNaSS⁻b⁻PNIPAM complexes were formed as a result of hydrogen bonding interactions between the pendant carboxylic acids in the PAA block and the pendant amide groups in the PNIPAM block. The complex was characterized by ¹H NMR, dynamic light scattering, static light scattering, and transmission electron microscope measurements. The light scattering intensity of the complex depended on the mixing ratio of PNaSS⁻b⁻PAA and PNaSS⁻b⁻PNIPAM. When the molar ratio of the N-isopropylacrylamide (NIPAM) and acrylic acid (AA) units was near unity, the light scattering intensity reached a maximum, indicating stoichiometric complex formation. The complex dissociated at a pH higher than 4.0 because the hydrogen bonding interactions disappeared due to deprotonation of the pendant carboxylic acids in the PAA block.

pH-Responsive Intra- and Inter-Molecularly Micelle Formation of Anionic Diblock Copolymer in Water.

Poly(sodium2-(acrylamido)-2-methylpropanesulfonate)-block-poly(sodium11-(acrylamido)undecanoate) (PAMPS⁻PAaU) was synthesized via reversible addition-fragmentation chain transfer (RAFT)-controlled radical polymerization. The "living" polymerization of PAaU was evidenced by the fact that the molecular weight distribution was narrow (Mw/Mn = 1.23). The pH-induced association behavior of PAMPS⁻PAaU in 0.1 M NaCl aqueous solutions as a function of solution pH was investigated by ¹H NMR spin-spin relaxation time, dynamic light scattering (DLS), static light scattering (SLS), and fluorescence probe techniques. These results indicated that PAMPS⁻PAaU formed polymer micelles in 0.1 M NaCl aqueous solutions at pH < 9. At pH = 8⁻9, the polymer formed the micelles intramolecularly due to hydrophobic self-association of the PAaU block within the single polymer chain. On the other hand, at pH < 8, micellization occurred intermolecularly to form polymer micelles comprising hydrophobic PAaU cores and hydrophilic PAMPS shells.