Water Dynamics at Protein Interfaces: Ultrafast Optical Kerr Effect Study

The behavior of water molecules surrounding a protein can have an important bearing on its structure and function. Consequently, a great deal of attention has been focused on changes in the relaxation dynamics of water when it is located at the protein surface. Here we use the ultrafast optical Kerr effect to study the H-bond structure and dynamics of aqueous solutions of proteins. Measurements are made for three proteins as a function of concentration. We find that the water dynamics in the first solvation layer of the proteins are slowed by up to a factor of 8 in comparison to those in bulk water. The most marked slowdown was observed for the most hydrophilic protein studied, bovine serum albumin, whereas the most hydrophobic protein, trypsin, had a slightly smaller effect. The terahertz Raman spectra of these protein solutions resemble those of pure water up to 5 wt % of protein, above which a new feature appears at 80 cm–1, which is assigned to a bending of the protein amide chain

Temperature dependence of protein dynamics simulated with three different water models

The effect of variation of the water model on the temperature dependence of protein and hydration water dynamics is examined by performing molecular dynamics simulations of myoglobin with the TIP3P, TIP4P, and TIP5P water models and the CHARMM protein force field at temperatures between 20 and 300 K. The atomic mean-square displacements, solvent reorientational relaxation times, pair angular correlations between surface water molecules, and time-averaged structures of the protein are all found to be similar, and the protein dynamical transition is described almost indistinguishably for the three water potentials. The results provide evidence that for some purposes changing the water model in protein simulations without a loss of accuracy may be possible

Novel self-assembly of an alternating copolymer into nanotubes : theoretical investigation and experimental characterisation

This thesis is aimed at understanding and fully characterising the association mechanism of an alternating copolymer in water and the effect of the association in solution on the conformation of the polymer chains at the air/water interface.Self-assembly is an elegant and efficient method to obtain well defined and usually defect-free nano-architectures. The association, variety of shapes and properties of block copolymers have been extensively studied. The present study led to a precise understanding of the complex behaviour of large molecules. The polymer studied is an alternating copolymer; poly(styrene- alt-maleic anhydride) (SMA). This polymer has various applications ranging from surface sizing of paper, to nanotechnology and pharmaceutical applications.The detailed theoretical investigation of the SMA association led to the discovery of a novel way to self-assemble polymer chains, and the prediction and characterisation of a tubular structure formed by this association. The nanotubes are several micrometers long and their conformation shows that the hydrophobic groups are mainly located inside the tube and the hydrophilic groups are mainly on the exterior surface of the tube.The predicted tubular structure of SMA in solution was also confirmed by neutron scattering experiments. This study showed that the tubes interact forming two-dimensional sheets of tubes and higher order structures. In addition, the SMA association has been shown to be thermally stable.Furthermore, neutron reflectivity experiments were performed on the SMA solution to determine the influence of the association in solution on the conformation of the polymer at the air-water interface. This study revealed an equilibrium between the conformation of the polymer in solution and at the interface.Using the knowledge of the association mechanism obtained from the complete theoretical and experimental characterisation of the association of poly(styrene-maleic anhydride) in water and at the air-water interface, a novel application for the polymer has been developed. This application uses the template formed by the nanotubes to form nanowires of intrinsically conducting polymers. Neutron scattering, neutron reflectivity, cryo-TEM and AFM experimental studies characterised the synthesis of the nanowires

The role of helicity in PFAS resistance to degradation: DFT simulation of electron capture and defluorination

Defluorination of perfluorinated alkyl substances (PFASs) via the direct capture of excess electrons poses a promising path to environmental decontamination. Herein we show that ab initio model optimization methods can be adapted to simulate the changes to molecular geometry that result from electron capture. These reaction pathways demonstrate that the introduction of an additional electron causes a loss of the helical arrangement along linear carbon tail chains. Regaining helicity is sufficiently favourable to enable fluoride release in C7-C10 carboxylate or sulfonate PFAS chains; shorter chains are enthalpically hindered from degradation while the additional charge is stabilized on longer chains by the greater entropy their flexibility permits. These results suggest that reductive PFAS treatment processes could be made more effective under high pressure or confined conditions

Improving Platinum Catalyst Durability with a Doped Graphene Support

Improving the durability of a platinum catalyst is an important step in increasing its utility when incorporated as the anode or cathode of a proton-exchange membrane fuel cell. Using density functional theory, the binding energy between a platinum atom and five graphene surfaces, one pure, and four others singly doped with beryllium, boron, nitrogen, and oxygen, was calculated. The oxygen-doped surface showed the highest binding energy and was calculated to be 7 times higher than the undoped surface. Each dopant modified the surface bonding arrangement within the graphene lattice, which then affected how the surface bonded to the platinum atom. Using molecular orbitals, natural bond orbitals, and the gradient of the electron density, these interactions were explored to explain the strength of the Pt–surface bond, which, in ascending order by dopant, was found to be undoped, nitrogen, boron, beryllium, and oxygen

Folic acid-conjugated amphiphilic alternating copolymer as a new active tumor targeting drug delivery platform

Xia Li,1 Myron R Szewczuk,2 Cecile Malardier-Jugroot1 1Department of Chemistry and Chemical Engineering, Royal Military College of Canada, 2Department of Biomedical and Molecular Sciences, Queen’s University, Kingston, ON, Canada Abstract: Targeted drug delivery using polymeric nanostructures is an emerging cancer research area, engineered for safer, more efficient, and effective use of chemotherapeutic drugs. A pH-responsive, active targeting delivery system was designed using folic acid functionalized amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA). The polymeric template is pH responsive, forming amphiphilic nanostructures at pH 7, allowing the encapsulation of hydrophobic drugs on its interior. Moreover, the structure is stable only at neutral pH and collapses in the acidic tumor microenvironment, releasing drugs on-site from its core. The delivery vehicle is investigated using human pancreatic PANC-1 cancer cells and RAW-Blue™ mouse macrophage reporter cell line, both of which have overly expression of folic acid receptors. To trace the cellular uptake by both cell lines, curcumin was selected as a dye and drug mimic owing to its fluorescence nature and hydrophobic properties. Fluorescent microscopy of FA-DABA-SMA loaded with curcumin revealed a significant internalization of the dye by human pancreatic PANC-1 cancer cells compared to those with unfunctionalized polymers (SMA). Moreover, the FA-DABA-SMA polymers exhibit rodlike association specific to the cells. Both empty SMA and FA-DABA-SMA show little toxicity to PANC-1 cells as characterized by WST-1 cell proliferation assay. These results clearly indicate that FA-DABA-SMA polymers show potential as an active tumor targeting drug delivery system with the ability to internalize hydrophobic chemotherapeutics after they specifically attach to cancer cells. Keywords: functionalized copolymers, folic acid receptors, curcumin, enhanced hydrophobic drug delivery, improved cellular uptak