4 research outputs found
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]<sup>−</sup>) in 1-butyl-3-methylimidazolium bisÂ(trifluoromethylsulfonyl)Âimide
([C<sub>4</sub>C<sub>1</sub>im]Â[NTf<sub>2</sub>]) and 1-butyl-2,3-dimethylimidazolium
bisÂ(trifluoromethylsulfonyl)Âimide ([C<sub>4</sub>C<sub>1</sub>C<sub>1</sub><sup>2</sup>im]Â[NTf<sub>2</sub>]) 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<sup>+</sup>, ion pairs between K<sup>+</sup> and [SCN]<sup>−</sup> that
persist for >100 ps are detected by long-lasting vibrational frequency
correlations. The observed dynamics are invariant to [SCN]<sup>−</sup>concentration, which indicates that the [SCN]<sup>−</sup> 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
polyÂ(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 polyÂ(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/cm<sup>2</sup> 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>