Thiocyanate as a Local Probe of Ultrafast Structure and Dynamics in Imidazolium-Based Ionic Liquids: Water-Induced Heterogeneity and Cation-Induced Ion Pairing

Ultrafast two-dimensional infrared spectroscopy (2D-IR) of thiocyanate ([SCN]⁻) in 1-butyl-3-methylimidazolium bis­(trifluoromethylsulfonyl)­imide ([C₄C₁im]­[NTf₂]) and 1-butyl-2,3-dimethylimidazolium bis­(trifluoromethylsulfonyl)­imide ([C₄C₁C₁²im]­[NTf₂]) ionic liquids probes local structure and dynamics as a function of the water content, solute counterion, and solute concentration. The 2D-IR spectra of the water-saturated ionic liquids resolve two distinct kinds of dynamics. This dynamical heterogeneity is explained as two subensembles, one with and one without a water molecule in the first solvation shell. When the countercation is K⁺, ion pairs between K⁺ and [SCN]⁻ that persist for >100 ps are detected by long-lasting vibrational frequency correlations. The observed dynamics are invariant to [SCN]⁻concentration, which indicates that the [SCN]⁻ does not cluster in ionic liquid solution. Taken together, these results are consistent with a picture of thiocyanate as a local probe that can interrogate ultrafast structure and dynamics at a small spatial scale in ionic liquids

Single-Molecule Force Spectroscopy Studies of APOBEC3A–Single-Stranded DNA Complexes

APOBEC3A (A3A) inhibits the replication of a range of viruses and transposons and might also play a role in carcinogenesis. It is a single-domain deaminase enzyme that interacts with single-stranded DNA (ssDNA) and converts cytidines to uridines within specific trinucleotide contexts. Although there is abundant information that describes the potential biological activities of A3A, the interplay between binding ssDNA and sequence-specific deaminase activity remains controversial. Using a single-molecule atomic force microscopy spectroscopy approach developed by Shlyakhtenko et al. [(2015) <i>Sci. Rep. 5</i>, 15648], we determine the stability of A3A in complex with different ssDNA sequences. We found that the strength of the complex is sequence-dependent, with more stable complexes formed with deaminase-specific sequences. A correlation between the deaminase activity of A3A and the complex strength was identified. The ssDNA binding properties of A3A and those for A3G are also compared and discussed

Poly(4-styrenesulfonate) as an Inhibitor of Aβ40 Amyloid Fibril Formation

The formation of amyloid, a cross-β-sheet fibrillar aggregate of proteins, is associated with a variety of neurodegenerative diseases. Amyloidogenic proteins such as β-amyloid (Aβ) are known to exist with a large amount of polyelectrolyte macromolecules in vivo. The exact nature of Aβ–polyelectrolyte interactions and their roles in Aβ-aggregation are largely unknown. In this regard, we report the inhibiting effect of an anionic polyelectrolyte poly­(4-styrenesulfonate) (PSS) on the aggregation of Aβ40 peptide. The results demonstrate the strong inhibition potential of PSS on the aggregation of Aβ40 and imply the dominant role of hydrophobicity of the polyelectrolyte in reducing the propensity of Aβ40 amyloid formation. Additional studies with poly­(vinyl sulfate) (PVS) and <i>p</i>-toluenesulfonate (PTS), which share similar charge density with PSS except the former lacking the nonpolar aromatic side chain and the latter the aliphatic hydrocarbon backbone, reveal that the presence of both aliphatic backbone and aromatic side chain group in PSS is essential for its Aβ-aggregation inhibition activity. The interactions involved in the Aβ40–PSS complex were further investigated using molecular dynamics (MD) simulation. Our results provide new insights into the structural interplay between polyelectrolytes and Aβ peptide, facilitating the ultimate understanding of amyloid formation in Alzheimer’s disease. The results should assist in developing novel polyelectrolytes as potential chemical tools to study amyloid aggregation

Increased Heating Efficiency and Selective Thermal Ablation of Malignant Tissue with DNA-Encased Multiwalled Carbon Nanotubes

Nanoparticles, including multiwalled carbon nanotubes (MWNTs), strongly absorb near-infrared (nIR) radiation and efficiently convert absorbed energy to released heat which can be used for localized hyperthermia applications. We demonstrate for the first time that DNA-encasement increases heat emission following nIR irradiation of MWNTs, and DNA-encased MWNTs can be used to safely eradicate a tumor mass <i>in vivo</i>. Upon irradiation of DNA-encased MWNTs, heat is generated with a linear dependence on irradiation time and laser power. DNA-encasement resulted in a 3-fold reduction in the concentration of MWNTs required to impart a 10 °C temperature increase in bulk solution temperature. A single treatment consisting of intratumoral injection of MWNTs (100 μL of a 500 μg/mL solution) followed by laser irradiation at 1064 nm, 2.5 W/cm² completely eradicated PC3 xenograft tumors in 8/8 (100%) of nude mice. Tumors that received only MWNT injection or laser irradiation showed growth rates indistinguishable from nontreated control tumors. Nonmalignant tissues displayed no long-term damage from treatment. The results demonstrate that DNA-encased MWNTs are more efficient at converting nIR irradiation into heat compared to nonencased MWNTs and that DNA-encased MWNTs can be used safely and effectively for the selective thermal ablation of malignant tissue <i>in vivo</i>