Structure and Intermolecular Interactions in Aqueous Solutions of Polyethylene Glycol.

Aqueous solutions of polyethylene glycol are studied by small-angle neutron scattering over a broad range of polymer molecular masses and concentrations. The scattering data were modeled by a Gaussian chain form factor combined with random phase approximation, which provided good fits over the whole studied concentration range. The results showed that polyethylene glycol in the molecular mass range 0.4-20 kDa in water at physiological temperature T = 37 °C behaves like a random coil in nearly theta solvent conditions. The obtained results serve as a reference for the description of complex mixtures with PEG used in various applications.

Nanocrystallite-liquid phase transition in porous matrices with chemically functionalized surfaces.

Nanocrystallite-liquid phase transitions are studied for 1-octadecene confined in the pores of chemically functionalized silica gels. These silica gels possess similar fractal geometries of the pore system but differ in chemical termination of the surface, specific surface area (F) and pore volume (V). Linear dependencies of the melting temperature and specific melting heat on the F/V ratio are found for a series of silica gels with identical surface termination. A thermodynamic model based on experimental data is established, which explains the observed shift of the phase transition parameters for porous matrices with different surface chemistries. In addition, this model allows evaluation of actual changes in nanocrystallite density, surface tension and entropy upon melting.

Atomic charges for conformationally rich molecules obtained through a modified principal component regression.

A modification of the principal component regression model is proposed for obtaining a fixed set of atomic charges (referred to as dipole-derived charges) optimized for reproducing the dipole moment of a conformationally rich molecule, i.e., a molecule with multiple local minima on the potential energy surface. The method does not require any adjustable parameters and requires the geometries of conformers, their dipole moments and atomic polar tensor (APT) charges as the only input data. The fixed atomic charges generated by the method not only reproduce the molecular dipole moment in all the conformers accurately, but are also numerically close to the APT charges, thereby ensuring accurate reproduction of the dipole moment variations caused by small geometrical distortions (e.g., by vibrations) of the conformers. The proposed method has been applied to canonical 2'-deoxyribonucleotides, the model DNA monomers, and the dipole-derived charges have been shown to outperform both the averaged APT and RESP charges in reproducing the dipole moments of large sets of conformers, thus demonstrating a potential usefulness of the dipole-derived charges as a 'reference point' for modeling polarization effects in conformationally rich molecules.

Structural flexibility of DNA-like conformers of canonical 2'-deoxyribonucleosides.

Relaxed force constants (RFC) and vibrational root-mean-square (VRMS) deviations are used for comparative characterization of mechanical properties of canonical 2'-deoxyribonucleosides (2DRs) and 1,2-dideoxyribose molecule, their model sugar residue. It has been shown that RFC and VRMS should be preferred over traditional force constants when one needs to obtain the quantitative measure of the 'collective' parameter flexibility (furanose sugar pseudorotation phase P in particular) and compare it with classical torsion angles (ß, γ, ε, χ). It has been found that torsions ε and ß determining the 2DRs backbone hydroxyl orientations are as soft as the pseudorotation phase P with RFC values within 1-10 kcal mol(-1) rad(-2) depending on conformation. Torsion γ is the most rigid one with RFC 15-30 kcal mol(-1) rad(-2), while the glycosidic torsion χ is characterized by intermediate values of RFC (typically 5-10 kcal mol(-1) rad(-2)) and its RFC changes by 10 times, depending on the furanose sugar conformation (K(χ)≈ 3 kcal mol(-1) rad(-2) in B- vs. K(χ)≈ 21 kcal mol(-1) rad(-2) in A-DNA-like conformation of 2'-deoxycytidine). Quantum zero-point motion of the nuclei makes the dominant contribution to VRMS deviations of molecules structural parameters: 9-22° for ß, ε and P, 5-7° for γ and χ at the temperature of 0 K, and 15-38° for ß, ε and P, 9-26° for γ and χ at the room temperature (298.15 K). Obtained results can be used in constructing simple dynamical models of the DNA fragments.

Bridging QTAIM with vibrational spectroscopy: the energy of intramolecular hydrogen bonds in DNA-related biomolecules.

Physical properties of over 8000 intramolecular hydrogen bonds (iHBs), including 2901 ones of the types OH···O, OH···N, NH···O and OH···C, in 4244 conformers of the DNA-related molecules (four canonical 2'-deoxyribonucleotides, 1,2-dideoxyribose-5-phosphate, and 2-deoxy-D-ribose in its furanose, pyranose and linear forms) have been investigated using quantum theory of atoms in molecules (QTAIM) and vibrational analysis. It has been found that for all iHBs with positive red-shift of the proton donating group stretching frequency the shift value correlates with ρ(cp)-the electron charge density at the (3,-1)-type bond critical point. Combining QTAIM and spectroscopic data new relationships for estimation of OH···O, OH···N, NH···O and OH···C iHB enthalpy of formation (kcal mol(-1)) with RMS error below 0.8 kcal mol(-1) have been established: E(OH···O) = -3.09 + 239·ρ(cp), E(OH···N) = 1.72 + 142·ρ(cp), E(NH···O) = -2.03 + 225·ρ(cp), E(OH···C) = -0.29 + 288·ρ(cp), where ρ(cp) is in e a(0)(-3) (a(0)- the Bohr radius). It has been shown that XHY iHBs with red-shift values over 40 cm(-1) are characterized by the following minimal values of the XHY angle, ρ(cp) and nubla(2)ρ(cp): 112°, 0.005 e a(0)(-3) and 0.016 e a(0)(-5), respectively. New relationships have been used to reveal the strongest iHBs in canonical 2'-deoxy- and ribonucleosides and the O(5')H···N(3) H-bond in ribonucleoside guanosine was found to have the maximum energy (8.1 kcal mol(-1)).

Fullerenes as an Effective Amyloid Fibrils Disaggregating Nanomaterial.

Nowadays, determining the disassembly mechanism of amyloids under nanomaterials action is a crucial issue for their successful future use in therapy of neurodegenerative and overall amyloid-related diseases. In this study, the antiamyloid disassembly activity of fullerenes C60 and C70 dispersed in 1-methyl-2-pyrrolidinone (NMP) toward amyloid fibrils preformed from lysozyme and insulin was investigated using a combination of different experimental techniques. Thioflavin T fluorescence assay and atomic force microscopy were applied for monitoring of disaggregation activity of fullerenes. It was demonstrated that both types of fullerene-based complexes are very effective in disassembling preformed fibrils, and characterized by the low apparent half-maximal disaggregation concentration (DC50) in the range of ∼22-30 µg mL-1. Small-angle neutron scattering was employed to monitor the different stages of the disassembly process with respect to the size and morphology of the aggregates. Based on the obtained results, a possible disassembly mechanism for amyloid fibrils interacting with fullerene/NMP complexes was proposed. The study is a principal step in understanding of the fullerenes destruction mechanism of the protein amyloids, as well as providing valuable information on how macromolecules can be engineered to disassemble unwanted amyloid aggregates by different mechanisms.

Sedimentation of a suspension of rods: Monte Carlo simulation of a continuous two-dimensional problem.

The sedimentation of a two-dimensional suspension containing rods was studied by means of Monte Carlo (MC) simulations. An off-lattice model with continuous positional and orientational degrees of freedom was considered. The initial state before sedimentation was produced using a model of random sequential adsorption. During such sedimentation, the rods undergo translational and rotational Brownian motions. The MC simulations were run at different initial number densities (the numbers of rods per unit area), ρ_{i}, and sedimentation rates, u. For sediment films, the spatial distributions of the rods, the order parameters, and the electrical conductivities were examined. Different types of sedimentation-driven self-assembly and anisotropy of the electrical conductivity were revealed inside the sediment films. This anisotropy can be finely regulated by changes in the values of ρ_{i} and u.

The Complexation of the Anticancer Drug ThioTEPA with Methylated DNA Base Guanine: Combined Ab Initio and QTAIM Investigation.

Non-covalent complexes of methylated nitrogenous DNA base guanine (m(9) Gua) with 1 to 6 molecules of anticancer drug ThioTEPA (1,1',1''-phosphorothioyltriaziridine) have been investigated by molecular modeling techniques (molecular docking and DFT geometry optimization), ab initio wavefunction calculations and the quantum theory of atoms in molecules (QTAIM). The accuracy of complex structures predicted by standard molecular docking techniques have been assessed by comparing them with ab initio calculations, and the most important differences have been discussed. Obtained stabilization enthalpies (kcal/mol) for the m(9) Gua⋅⋅⋅(ThioTEPA)n complexes with n=1…6 have been found to be -15.6, -26.5, -38.4, -49.6, -60.5 and -69.3 respectively. The non-covalent interactions revealed by the QTAIM method have been shown to be a dominating factor responsible for the complex stability, with hydrogen bonds of NH⋅⋅⋅N type being the most important interactions in small (n=1 to 4) and CH⋅⋅⋅N bonds - in large (n=5, 6) complexes. The obtained results may help to understand ThioTEPA-DNA interactions and clarify the mechanism of the drug action.

The spatial diamond-graphite transition in detonation nanodiamond as revealed by small-angle neutron scattering.

A spatial transition of the carbon state in detonation nanodiamond (DND) from crystalline diamond inside the particle to a graphite-like state at the DND surface is proposed on the basis of small-angle neutron scattering (SANS) analysis. The SANS contrast variation from concentrated (5 wt%) dispersions of DND in liquids (water, dimethylsulfoxide) reveals a shift in the mean scattering length density of DND as compared to pure diamond, which is related to the presence of a non-diamond component in the DND structure. At the same time, the diffusive character of the particle surface is deduced based on the deviation from the Porod law. The two observations are combined to conclude that the continuous radial density profile over the whole particle volume conforms to a simple power law. The profile naturally suggests that non-diamond states are concentrated mainly close to the particle surface; still there is no sharp boundary between the radial distributions of the two states of carbon in DND.