Oleg N. Antzutkin

A Hexameric Peptide Barrel as Building Block of Amyloid‐β Protofibrils

Oligomeric and protofibrillar aggregates formed by the amyloid-β peptide (Aβ) are believed to be involved in the pathology of Alzheimers disease. Central to Alzheimer pathology is also the fact that the longer Aβ42 peptide is more prone to aggregation than the more prevalent Aβ40 . Detailed structural studies of Aβ oligomers and protofibrils have been impeded by aggregate heterogeneity and instability. We previously engineered a variant of Aβ that forms stable protofibrils and here we use solid-state NMR spectroscopy and molecular modeling to derive a structural model of these. NMR data are consistent with packing of residues 16 to 42 of Aβ protomers into hexameric barrel-like oligomers within the protofibril. The core of the oligomers consists of all residues of the central and C-terminal hydrophobic regions of Aβ, and hairpin loops extend from the core. The model accounts for why Aβ42 forms oligomers and protofibrils more easily than Aβ40 .

Halogen-free pyrrolidinium bis(mandelato)borate ionic liquids : some physicochemical properties and lubrication performance as additives to polyethylene glycol

This work reports on the synthesis and physicochemical characterisation of novel halogen-free boron containing ionic liquids (hf-BILs) with dialkylpyrrolidinium cations [CnC1Pyrr]+, n = 4–14, and bis(mandelato)borate anion [BMB]−. All the synthesised compounds are liquids at room temperature. It was found that the thermal properties and density of these hf-BILs are affected by the length of the longest alkyl chain connected to the nitrogen atom in the pyrrolidinium cations. Differential scanning calorimetry measurements revealed that glass transition temperatures of these ionic liquids are in the temperature range from 218 to 241 K. Interestingly, the glass transition temperatures follow the “odd–even” effect related to the number of carbons (n) in one of the alkyl chains of [CnC1Pyrr]+. It was also found that hf-BILs density decreases with an increase in the alkyl chain length of [CnC1Pyrr]+. It is suggested that the “odd–even” effect is associated with the difference in packing and specific interactions of cations and anions of this class of hf-BILs. Their lubricating properties, as 3 wt% additives in polyethylene glycol (PEG), were evaluated in steel–steel contacts. PEG with hf-BILs additive provided significantly lower wear and friction compared to the neat PEG and 5W40 engine oil. It was found that shortening the length of the longest alkyl chain in the cations of [CnC1Pyrr][BMB] significantly reduces frictional losses. Antiwear properties of [CnC1Pyrr][BMB] in PEG follow the same trend.

Atomistic Insight into Orthoborate-Based Ionic Liquids : Force Field Development and Evaluation

We have developed an all-atomistic force field for a new class of halogen-free chelated orthoborate-phosphonium ionic liquids. The force field is based on an AMBER framework with determination of force field parameters for phosphorus and boron atoms, as well as refinement of several available parameters. The bond and angle force constants were adjusted to fit vibration frequency data derived from both experimental measurements and ab initio calculations. The force field parameters for several dihedral angles were obtained by fitting torsion energy profiles deduced from ab initio calculations. To validate the proposed force field parameters, atomistic simulations were performed for 12 ionic liquids consisting of tetraalkylphosphonium cations and chelated orthoborate anions. The predicted densities for neat ionic liquids and the [P6,6,6,14][BOB] sample, with a water content of approximately 2.3-2.5 wt %, are in excellent agreement with available experimental data. The potential energy components of 12 ionic liquids were discussed in detail. The radial distribution functions and spatial distribution functions were analyzed and visualized to probe the microscopic ionic structures of these ionic liquids. There are mainly four high-probability regions of chelated orthoborate anions distributed around tetraalkylphosphonium cations in the first solvation shell, and such probability distribution functions are strongly influenced by the size of anions.

Atomistic Insight into Tetraalkylphosphonium-Bis(oxalato)borate Ionic Liquid/Water Mixtures. I. Local Microscopic Structure.

Atomistic simulations have been performed to investigate the microscopic structural organization of aqueous solutions of trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL). The evolution of the microscopic liquid structure and the local ionic organization of IL/water mixtures as a function of the water concentration is visualized and systematically analyzed via radial and spatial distribution functions, coordination numbers, hydrogen bond network, and water clustering analysis. The microscopic liquid structure in neat IL is characterized by a connected apolar network composed of the alkyl chains of [P6,6,6,14] cations and isolated polar domains consisting of the central segments of [P6,6,6,14] cations and [BOB] anions, and the corresponding local ionic environment is described by direct contact ion pairs. In IL/water mixtures with lower water mole fractions, the added water molecules are dispersed and embedded in cavities between neighboring ionic species and the local ionic structure is characterized by solvent-shared ion pairs through cation-water-anion triple complexes. With a gradual increase in the water concentration in IL/water mixtures, the added water molecules tend to aggregate and form small clusters, intermediate chain-like structures, large aggregates, and eventually a water network in water concentrated simulation systems. A further progressive dilution of IL/water mixtures leads to the formation of self-organized micelle-like aggregates characterized by a hydrophobic core and hydrophilic shell consisting of the central polar segments in [P6,6,6,14] cations and [BOB] anions in a highly branched water network. The striking structural evolution of the [P6,6,6,14][BOB] IL/water mixtures is rationalized by the competition between favorable hydrogen bonded interactions and strong electrostatic interactions between the polar segments in ionic species and the dispersion interactions between the hydrophobic alkyl chains in [P6,6,6,14] cations.

NMR self-diffusion study of a phosphonium bis(mandelato)borate ionic liquid

Newly synthesised halogen-free boron based ionic liquids (hf-BILs) composed of chelated orthoborate anions and phosphonium cations have hydrolytic stability, low melting point and outstanding wear and friction reducing properties. We report here the peculiarities of self-diffusion in one representative from this class, trihexyltetradecylphosphonium bis(mandelato)borate, [P6,6,6,14][BMB], in the temperature range of its practical interest, 20-100 °C. NMR techniques demonstrated complicated diffusional behaviour - the ionic liquid can exist in one or two liquid phases. In the low-temperature range (20-50 °C), two phases coexist where the cations, [P6,6,6,14], are contained mainly in the phase with slower diffusion coefficients while the anions, [BMB], are in the phase with faster diffusion coefficients. Cations have lower diffusion coefficients with a factor of 20 as compared with the anions, an effect which is caused by aggregation of cations into domains due to so-called hydrophobic interaction of their hydrocarbon chains. As the temperature rises above 60 °C, the two phases merge into one where both ions have equal diffusion coefficients. This is caused by thermal motion making the cation domains smaller in size and more easily interacting with anions. As a result, anions and cations diffuse in this high-temperature range as a pair.

Atomistic Insight into Tetraalkylphosphonium Bis(oxalato)borate Ionic Liquid/Water Mixtures. 2. Volumetric and Dynamic Properties

Atomistic molecular dynamics simulations have been performed to investigate volumetric quantities and dynamic properties of binary trihexyltetradecylphosphonium bis(oxalato)borate ([P6,6,6,14][BOB]) ionic liquid (IL)/water mixtures with different water concentrations. The predicted liquid densities for typical [P6,6,6,14][BOB] IL/water mixtures are consistent with available experimental data with a relative discrepancy of less than 3%. The liquid densities and excess molar volumes of all studied [P6,6,6,14][BOB] IL/water mixtures are characterized by concave and convex features, respectively, within full water concentration range. The dynamic properties of [P6,6,6,14] cations, [BOB] anions, and water molecules are particularly analyzed through calculation of velocity autocorrelation functions, diffusion coefficients, and reorientational autocorrelation functions and correlation times. The translational and reorientational mobilities of three species become faster upon increasing water concentration in [P6,6,6,14][BOB] IL/water mixtures and present complex dynamical characteristics arising from three distinct microscopic diffusion features within the full water concentration range. The obtained striking volumetric quantities and particular dynamic properties are well correlated to microscopic liquid structural organization and distinct local ionic environment of all studied [P6,6,6,14][BOB] IL/water mixtures.

A Solid-State Nuclear Magnetic Resonance Study of Post-Plasma Reactions in Organosilicone Microwave Plasma-Enhanced Chemical Vapor Deposition (PECVD) Coatings

Plasma-polymerized organosilicone coatings can be used to impart abrasion resistance and barrier properties to plastic substrates such as polycarbonate. Coating rates suitable for industrial-scale deposition, up to 100 nm/s, can be achieved through the use of microwave plasma-enhanced chemical vapor deposition (PECVD), with optimal process vapors such as tetramethyldisiloxane (TMDSO) and oxygen. However, it has been found that under certain deposition conditions, such coatings are subject to post-plasma changes; crazing or cracking can occur anytime from days to months after deposition. To understand the cause of the crazing and its dependence on processing plasma parameters, the effects of post-plasma reactions on the chemical bonding structure of coatings deposited with varying TMDSO-to-O2 ratios was studied with (29)Si and (13)C solid-state magic angle spinning nuclear magnetic resonance (MAS NMR) using both single-pulse and cross-polarization techniques. The coatings showed complex chemical compositions significantly altered from the parent monomer. (29)Si MAS NMR spectra revealed four main groups of resonance lines, which correspond to four siloxane moieties (i.e., mono (M), di (D), tri (T), and quaternary (Q)) and how they are bound to oxygen. Quantitative measurements showed that the ratio of TMDSO to oxygen could shift the chemical structure of the coating from 39% to 55% in Q-type bonds and from 28% to 16% for D-type bonds. Post-plasma reactions were found to produce changes in relative intensities of (29)Si resonance lines. The NMR data were complemented by Fourier transform infrared (FTIR) spectroscopy. Together, these techniques have shown that the bonding environment of Si is drastically altered by varying the TMDSO-to-O2 ratio during PECVD, and that post-plasma reactions increase the cross-link density of the silicon-oxygen network. It appears that Si-H and Si-OH chemical groups are the most susceptible to post-plasma reactions. Coatings produced at a low TMDSO-to-oxygen ratio had little to no singly substituted moieties, displayed a highly cross-linked structure, and showed less post-plasma reactions. However, these chemically more stable coatings are less compatible mechanically with plastic substrates, because of their high stiffness.

Amyloid Hydrogen Bonding Polymorphism Evaluated by 15N{17O}REAPDOR Solid-State NMR and Ultra-High Resolution Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

A combined approach, using Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) and solid-state NMR (Nuclear Magnetic Resonance), shows a high degree of polymorphism exhibited by Aβ species in forming hydrogen-bonded networks. Two Alzheimers Aβ peptides, Ac-Aβ(16-22)-NH2 and Aβ(11-25), selectively labeled with (17)O and (15)N at specific amino acid residues were investigated. The total amount of peptides labeled with (17)O as measured by FTICR-MS enabled the interpretation of dephasing observed in (15)N{(17)O}REAPDOR solid-state NMR experiments. Specifically, about one-third of the Aβ peptides were found to be involved in the formation of a specific >C═(17)O···H-(15)N hydrogen bond with their neighbor peptide molecules, and we hypothesize that the rest of the molecules undergo ± n off-registry shifts in their hydrogen bonding networks.

Self‐diffusion and interactions in mixtures of imidazolium bis(mandelato)borate ionic liquids with polyethylene glycol: 1H NMR study

We used 1H nuclear magnetic resonance pulsed‐field gradient to study the self‐diffusion of polyethylene glycol (PEG) and ions in a mixture of PEG and imidazolium bis(mandelato)borate ionic liquids (ILs) at IL concentrations from 0 to 10u2009wt% and temperatures from 295 to 370u2009K. PEG behaves as a solvent for these ILs, allowing observation of separate lines in 1H NMR spectra assigned to the cation and anion as well as to PEG. The diffusion coefficients of PEG, as well as the imidazolium cation and bis(mandelato)borate (BMB) anion, differ under all experimental conditions tested. This demonstrates that the IL in the mixture is present in at least a partially dissociated state, while the lifetimes of the associated states of the ions and ions with PEG are less than ~30u2009ms. Generally, increasing the concentration of the IL leads to a decrease in the diffusion coefficients of PEG and both ions. The diffusion coefficient of the anion is less than that of the cation; the molecular mass dependence of diffusion of ions can be described by the Stokes–Einstein model. NMR chemical shift alteration analysis showed that the presence of PEG changes mainly the chemical shifts of protons belonging to imidazole ring of the cation, while chemical shifts of protons of anions and PEG remain unchanged. This demonstrated that the imidazolium cation interacts mainly with PEG, which most probably occurs through the oxygen of PEG and the imidazole ring. The BMB anion does not strongly interact with PEG, but it may be indirectly affected by PEG through interaction with the cation, which directly interacts with PEG. Copyright

The effect of the cation alkyl chain length on density and diffusion in dialkylpyrrolidinium bis(mandelato)borate ionic liquids

The physicochemical properties of ionic liquids are strongly affected by the selective combination of the cations and anions comprising the ionic liquid. In particular, the length of the alkyl chains of ions has a clear influence on the ionic liquids performance. In this paper, we study the self-diffusion of ions in a series of halogen-free boron-based ionic liquids (hf-BILs) containing bis(mandelato)borate anions and dialkylpyrrolidinium cations with long alkyl chains CnH2n+1 with n from 4 to 14 within a temperature range of 293-373 K. It was found that the hf-BILs with n = 4-7 have very similar diffusion coefficients, while hf-BILs with n = 10-14 exhibit two liquid sub-phases in almost the entire temperature range studied (293-353 K). Both liquid sub-phases differ in their diffusion coefficients, while values of the slower diffusion coefficients are close to those of hf-BILs with shorter alkyl chains. To explain the particular dependence of diffusion on the alkyl chain length, we examined the densities of the hf-BILs studied here. It was shown that the dependence of the density on the number of CH2 groups in long alkyl chains of cations can be accurately described using a mosaic type model, where regions of long alkyl chains of cations (named aliphatic regions) and the residual chemical moieties in both cations and anions (named ionic regions) give additive contributions. Changes in density due to an increase in temperature and the number of CH2 groups in the long alkyl chains of cations are determined predominantly by changes in the free volume of the ionic regions, while aliphatic regions are already highly compressed by van der Waals forces, which results in only infinitesimal changes in their free volumes with temperature.