Chemoselective Staudinger Reactivity of Bis(azido)phosphines Supported with a π-Donating Imidazolin-2-iminato Ligand.

Synthesis and characterization of new P(III) and P(V) bis(azido)phosphines/phosphoranes supported by an N,N'-bis(2,6-diisopropylphenyl) imidazolin-2-iminato (IPrN) ligand and their reactivity with various secondary and tertiary phosphines result in the formation of chiral and/or asymmetric mono(phosphinimino)azidophosphines via the Staudinger reaction. The reaction of IPrNP(N3)2 (2) or IPrNP(S)(N3)2 (4S) with an excess of tertiary phosphine resulted in the chemoselective formation of IPrNP(N3)(NPMe3) (7) or IPrNP(S)N3(NPR3) (5R), respectively. The chemoselective Staudinger reactivity was also observed in reactions using a secondary phosphine (HPCy2) to produce IPrNP(S)N3[NP(H)Cy2] (6a), which exists in equilibrium with a tautomeric IPrNP(S)N3[N(H)PCy2] form (6b), as confirmed by 31P-31P nuclear Overhauser effect spectroscopy (NOESY). Density functional theory (DFT) calculations point to a combination of energetically unfavorable lowest unoccupied molecular orbitals (LUMOs) and the accumulation of increasing negative charge at the terminal azido-nitrogen upon a single azide-to-phosphinimine conversion that gave rise to the observed chemoselectivity.

A Molecular Dynamics Simulation Study of the Effects of ßGln114 Mutation on the Dynamic Behavior of the Catalytic Site of the Tryptophan Synthase.

L-tryptophan (l-Trp), a vital amino acid for the survival of various organisms, is synthesized by the enzyme tryptophan synthase (TS) in organisms such as eubacteria, archaebacteria, protista, fungi, and plantae. TS, a pyridoxal 5'-phosphate (PLP)-dependent enzyme, comprises α and ß subunits that typically form an α2ß2 tetramer. The enzyme's activity is regulated by the conformational switching of its α and ß subunits between the open (T state) and closed (R state) conformations. Many microorganisms rely on TS for growth and replication, making the enzyme and the l-Trp biosynthetic pathway potential drug targets. For instance, Mycobacterium tuberculosis, Chlamydiae bacteria, Streptococcus pneumoniae, Francisella tularensis, Salmonella bacteria, and Cryptosporidium parasitic protozoa depend on l-Trp synthesis. Antibiotic-resistant salmonella strains have emerged, underscoring the need for novel drugs targeting the l-Trp biosynthetic pathway, especially for salmonella-related infections. A single amino acid mutation can significantly impact enzyme function, affecting stability, conformational dynamics, and active or allosteric sites. These changes influence interactions, catalytic activity, and protein-ligand/protein-protein interactions. This study focuses on the impact of mutating the ßGln114 residue on the catalytic and allosteric sites of TS. Extensive molecular dynamics simulations were conducted on E(PLP), E(AEX1), E(A-A), and E(C3) forms of TS using the WT, ßQ114A, and ßQ114N versions. The results show that both the ßQ114A and ßQ114N mutations increase protein backbone root mean square deviation fluctuations, destabilizing all TS forms. Conformational and hydrogen bond analyses suggest the significance of ßGln114 drifting away from cofactor/intermediates and forming hydrogen bonds with water molecules necessary for l-Trp biosynthesis. The ßQ114A mutation creates a gap between ßAla114 and cofactor/intermediates, hindering hydrogen bond formation due to short side chains and disrupting ß-sites. Conversely, the ßQ114N mutation positions ßAsn114 closer to cofactor/intermediates, forming hydrogen bonds with O3 of cofactors/intermediates and nearby water molecules, potentially disrupting the l-Trp biosynthetic mechanism.

Elucidating lipid conformations in the ripple phase: Machine learning reveals four lipid populations.

A new mixed radial-angular, three-particle correlation function method in combination with unsupervised machine learning was applied to examine the emergence of the ripple phase in dipalmitoylphosphatidylcholine (DPPC) lipid bilayers using data from atomistic molecular dynamics simulations of system sizes ranging from 128 to 4096 lipids. Based on the acyl tail conformations, the analysis revealed the presence of four distinct conformational populations of lipids in the ripple phases of the DPPC lipid bilayers. The expected gel-like (ordered; Lo) and fluid-like (disordered; Ld) lipids are found along with their splayed tail equivalents (Lo,s and Ld,s). These lipids differ, based on their gauche distribution and tail packing. The disordered (Ld) and disordered-splayed (Ld,s) lipids spatially cluster in the ripple in the groove side, that is, in an asymmetric manner across the bilayer leaflets. The ripple phase does not contain large numbers of Ld lipids; instead they only exist on the interface of the groove side of the undulation. The bulk of the groove side is a complex coexistence of Lo,Lo,s, and Ld,s lipids. The convex side of the undulation contains predominantly Lo lipids. Thus, the structure of the ripple phase is neither a simple coexistence of ordered and disordered lipids nor a coexistence of ordered interdigitating gel-like (Lo) and ordered-splayed (Lo,s) lipids, but instead a coexistence of an ordered phase and a complex mixed phase. Principal component analysis further confirmed the existence of the four lipid groups.

Effect of oxidation on POPC lipid bilayers: anionic carboxyl group plays a major role.

Phospholipids with unsaturated acyl chains are major targets of reactive oxygen species leading to formation of oxidized lipids. Oxidized phospholipids have a pronounced role in cell membrane damage. We investigated the effect of oxidation on physiological properties of phospholipid bilayers using atomistic molecular dynamics simulations. We studied phospholipid bilayer systems of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and its two stable oxidized products, 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC). Structural properties of the POPC lipid bilayer upon the addition of PoxnoPC or PazePC with concentration ranging from 10% to 30% were described. The key finding is that PazePC lipids bend their polar tails toward the bilayer-water interface whereas PoxnoPC lipids orient their tail toward the bilayer interior. The bilayer thickness decreases such that the thickness reduction in bilayers containing PazePC is stronger than in bilayers containing PoxnoPC. The average area per lipid decreases with a stronger effect in bilayers containing PoxnoPC. The addition of PoxnoPC makes both POPC acyl chains slightly more ordered whereas the addition of PazePC reduces the order in the two POPC acyl chains. These structural changes lead to an enhancement in the permeabilities of the bilayers containing these two oxidized products depending on the type, and the amount of oxidation. This enhancement can be achieved with a lower concentration of PazePC (10% or 15%), whereas a higher concentration of PoxnoPC (20%) is required to achieve an apparent enhancement in permeability. While the permeability of bilayers containing PazePC is higher than bilayers containing PoxnoPC in the 10-20% concentration range, by increasing the concentration of the oxidized products to higher than 20%, permeability of the bilayers containing PazePC is reduced such that it is slightly smaller than those containing PoxnoPC.

Identification of Catechins' Binding Sites in Monomeric Aß42 through Ensemble Docking and MD Simulations.

The assembly of the amyloid-ß peptide (Aß) into toxic oligomers and fibrils is associated with Alzheimer's disease and dementia. Therefore, disrupting amyloid assembly by direct targeting of the Aß monomeric form with small molecules or antibodies is a promising therapeutic strategy. However, given the dynamic nature of Aß, standard computational tools cannot be easily applied for high-throughput structure-based virtual screening in drug discovery projects. In the current study, we propose a computational pipeline-in the framework of the ensemble docking strategy-to identify catechins' binding sites in monomeric Aß42. It is shown that both hydrophobic aromatic interactions and hydrogen bonding are crucial for the binding of catechins to Aß42. Additionally, it has been found that all the studied ligands, especially EGCG, can act as potent inhibitors against amyloid aggregation by blocking the central hydrophobic region of Aß. Our findings are evaluated and confirmed with multi-microsecond MD simulations. Finally, it is suggested that our proposed pipeline, with low computational cost in comparison with MD simulations, is a suitable approach for the virtual screening of ligand libraries against Aß.

Highly Similar Sequence and Structure Yet Different Biophysical Behavior: A Computational Study of Two Triosephosphate Isomerases.

Homodimeric triosephosphate isomerases (TIMs) from Trypanosoma cruzi (TcTIM) and Trypanosoma brucei (TbTIM) have markedly similar amino-acid sequences and three-dimensional structures. However, several of their biophysical parameters, such as their susceptibility to sulfhydryl agents and their reactivation speed after being denatured, have significant differences. The causes of these differences were explored with microsecond-scale molecular dynamics (MD) simulations of three different TIM proteins: TcTIM, TbTIM, and a chimeric protein, Mut1. We examined their electrostatic interactions and explored the impact of simulation length on them. The same salt bridge between catalytic residues Lys 14 and Glu 98 was observed in all three proteins, but key differences were found in other interactions that the catalytic amino acids form. In particular, a cation-π interaction between catalytic amino acids Lys 14 and His 96 and both a salt bridge and a hydrogen bond between catalytic Glu 168 and residue Arg 100 were only observed in TcTIM. Furthermore, although TcTIM forms less hydrogen bonds than TbTIM and Mut1, its hydrogen bond network spans almost the entire protein, connecting the residues in both monomers. This work provides new insight into the mechanisms that give rise to the different behavior of these proteins. The results also show the importance of long simulations.

Multiscale Computational Study of the Conformation of the Full-Length Intrinsically Disordered Protein MeCP2.

The malfunction of the methyl-CpG binding protein 2 (MeCP2) is associated with the Rett syndrome, one of the most common causes of cognitive impairment in females. MeCP2 is an intrinsically disordered protein (IDP), making its experimental characterization a challenge. There is currently no structure available for the full-length MeCP2 in any of the databases, and only the structure of its MBD domain has been solved. We used this structure to build a full-length model of MeCP2 by completing the rest of the protein via ab initio modeling. Using a combination of all-atom and coarse-grained simulations, we characterized its structure and dynamics as well as the conformational space sampled by the ID and transcriptional repression domain (TRD) domains in the absence of the rest of the protein. The present work is the first computational study of the full-length protein. Two main conformations were sampled in the coarse-grained simulations: a globular structure similar to the one observed in the all-atom force field and a two-globule conformation. Our all-atom model is in good agreement with the available experimental data, predicting amino acid W104 to be buried, amino acids R111 and R133 to be solvent-accessible, and having a 4.1% α-helix content, compared to the 4% found experimentally. Finally, we compared the model predicted by AlphaFold to our Modeller model. The model was not stable in water and underwent further folding. Together, these simulations provide a detailed (if perhaps incomplete) conformational ensemble of the full-length MeCP2, which is compatible with experimental data and can be the basis of further studies, e.g., on mutants of the protein or its interactions with its biological partners.

AlphaFold2: A Role for Disordered Protein/Region Prediction?

The development of AlphaFold2 marked a paradigm-shift in the structural biology community. Herein, we assess the ability of AlphaFold2 to predict disordered regions against traditional sequence-based disorder predictors. We find that AlphaFold2 performs well at discriminating disordered regions, but also note that the disorder predictor one constructs from an AlphaFold2 structure determines accuracy. In particular, a naïve, but non-trivial assumption that residues assigned to helices, strands, and H-bond stabilized turns are likely ordered and all other residues are disordered results in a dramatic overestimation in disorder; conversely, the predicted local distance difference test (pLDDT) provides an excellent measure of residue-wise disorder. Furthermore, by employing molecular dynamics (MD) simulations, we note an interesting relationship between the pLDDT and secondary structure, that may explain our observations and suggests a broader application of the pLDDT for characterizing the local dynamics of intrinsically disordered proteins and regions (IDPs/IDRs).

Computer Simulations of Deep Eutectic Solvents: Challenges, Solutions, and Perspectives.

Deep eutectic solvents (DESs) are one of the most rapidly evolving types of solvents, appearing in a broad range of applications, such as nanotechnology, electrochemistry, biomass transformation, pharmaceuticals, membrane technology, biocomposite development, modern 3D-printing, and many others. The range of their applicability continues to expand, which demands the development of new DESs with improved properties. To do so requires an understanding of the fundamental relationship between the structure and properties of DESs. Computer simulation and machine learning techniques provide a fruitful approach as they can predict and reveal physical mechanisms and readily be linked to experiments. This review is devoted to the computational research of DESs and describes technical features of DES simulations and the corresponding perspectives on various DES applications. The aim is to demonstrate the current frontiers of computational research of DESs and discuss future perspectives.

Structural Investigation of DHICA Eumelanin Using Density Functional Theory and Classical Molecular Dynamics Simulations.

Eumelanin is an important pigment, for example, in skin, hair, eyes, and the inner ear. It is a highly heterogeneous polymer with 5,6-dihydroxyindole-2-carboxylic acid (DHICA) and 5,6-dihydroxyindole (DHI) building blocks, of which DHICA is reported as the more abundant in natural eumelanin. The DHICA-eumelanin protomolecule consists of three building blocks, indole-2-carboxylic acid-5,6-quinone (ICAQ), DHICA and pyrrole-2,3,5-tricarboxylic acid (PTCA). Here, we focus on the self-assembly of DHICA-eumelanin using multi-microsecond molecular dynamics (MD) simulations at various concentrations in aqueous solutions. The molecule was first parameterized using density functional theory (DFT) calculations. Three types of systems were studied: (1) uncharged DHICA-eumelanin, (2) charged DHICA-eumelanin corresponding to physiological pH, and (3) a binary mixture of both of the above protomolecules. In the case of uncharged DHICA-eumelanin, spontaneous aggregation occurred and water molecules were present inside the aggregates. In the systems corresponding to physiological pH, all the carboxyl groups are negatively charged and the DHICA-eumelanin model has a net charge of -4. The effect of K+ ions as counterions was investigated. The results show high probability of binding to the deprotonated oxygens of the carboxylate anions in the PTCA moiety. Furthermore, the K+ counterions increased the solubility of DHICA-eumelanin in its charged form. A possible explanation is that the charged protomolecules favor binding to the K+ ions rather than aggregating and binding to other protomolecules. The binary mixtures show aggregation of uncharged DHICA-eumelanins; unlike the charged systems with no aggregation, a few charged DHICA-eumelanins are present on the surface of the uncharged aggregation, binding to the K+ ions.

Role of cholesterol flip-flop in oxidized lipid bilayers.

We performed a series of molecular dynamics simulations of cholesterol (Chol) in nonoxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) bilayer and in binary mixtures of PLPC-oxidized-lipid-bilayers with 0-50% Chol concentration and oxidized lipids with hydroperoxide and aldehyde oxidized functional groups. From the 60 unbiased molecular dynamics simulations (total of 161 µs), we found that Chol inhibited pore formation in the aldehyde-containing oxidized lipid bilayers at concentrations greater than 11%. For both pure PLPC bilayer and bilayers with hydroperoxide lipids, no pores were observed at any Chol concentration. Furthermore, increasing cholesterol concentration led to a change of phase state from the liquid-disordered to the liquid-ordered phase. This condensing effect of Chol was observed in all systems. Data analysis shows that the addition of Chol results in an increase in bilayer thickness. Interestingly, we observed Chol flip-flop only in the aldehyde-containing lipid bilayer but neither in the PLPC nor the hydroperoxide bilayers. Umbrella-sampling simulations were performed to calculate the translocation free energies and the Chol flip-flop rates. The results show that Chol's flip-flop rate depends on the lipid bilayer type, and the highest rate are found in aldehyde bilayers. As the main finding, we shown that Chol stabilizes the oxidized lipid bilayer by confining the distribution of the oxidized functional groups.

How to control interactions of cellulose-based biomaterials with skin: the role of acidity in the contact area.

Being able to control the interactions of biomaterials with living tissues and skin is highly desirable for many biomedical applications. This is particularly the case for cellulose-based materials which provide one of the most versatile platforms for tissue engineering due to their strength, biocompatibility and abundance. Achieving such control, however, requires detailed molecular-level knowledge of the dominant interaction mechanisms. Here, we employed both biased and unbiased atomic-scale molecular dynamics simulations to explore how cellulose crystals interact with model stratum corneum bilayers, ternary mixtures of ceramides, cholesterol, and free fatty acids. Our findings show that acidity in the contact area directly affects binding between cellulose and the stratum corneum bilayer: Protonation of free fatty acids in the bilayer promotes attractive cellulose-bilayer interactions. We identified two major factors that control the cellulose-skin interactions: (i) the electrostatic repulsion between a cellulose crystal and the charged (anionic due to deprotonated fatty acids) surface of a stratum corneum bilayer and (ii) the cellulose-stratum corneum hydrogen bonding. When less than half of the fatty acids in the bilayer are protonated, the first factor dominates and there is no binding to skin. At a larger degree of fatty acid protonation the cellulose-stratum corneum hydrogen bonding prevails yielding a tight binding. Remarkably, we found that ceramide molecules are the key component in hydrogen bonding with cellulose. Overall, our findings highlight the critical role of fatty acid protonation in biomaterial-stratum corneum interactions and can be used for optimizing the surface properties of cellulose-based materials aimed at biomedical applications such as wound dressings.

Fine-Tuning the Polarizable CL&Pol Force Field for the Deep Eutectic Solvent Ethaline.

Polarizable force fields are gradually becoming a common choice for ionic soft matter, in particular, for molecular dynamics (MD) simulations of ionic liquids (ILs) and deep eutectic solvents (DESs). The CL&Pol force field introduced in 2019 is the first general, transferable, and polarizable force field for MD simulations of different types of DESs. The original formulation contains, however, some problems that appear in simulations of ethaline and may also have a broader impact. First, the originally proposed atomic diameter parameters are unbalanced, resulting in too weak interactions between the chlorides and the hydroxyl groups of the ethylene glycol molecules. This, in turn, causes an artificial phase separation in long simulations. Second, there is an overpolarization of chlorides due to strong induced dipoles that give rise to the presence of peaks and antipeaks at very low q-vector values (2.4 nm-1) in the partial components of the structure factors. In physical terms, this is equivalent to overestimated spatial nanoscale heterogeneity. To correct these problems, we adjusted the chloride-hydroxyl radial distribution functions against ab initio data and then extended the use of the Tang-Toennis damping function for the chlorides' induced dipoles. These adjustments correct the problems without losing the robustness of the CL&Pol force field. The results were also compared with the nonpolarizable version, the CL&P force field. We expect that the corrections will facilitate reliable use of the CL&Pol force field for other types of DESs.

KEAP1 Cancer Mutants: A Large-Scale Molecular Dynamics Study of Protein Stability.

We have performed 280 µs of unbiased molecular dynamics (MD) simulations to investigate the effects of 12 different cancer mutations on Kelch-like ECH-associated protein 1 (KEAP1) (G333C, G350S, G364C, G379D, R413L, R415G, A427V, G430C, R470C, R470H, R470S and G476R), one of the frequently mutated proteins in lung cancer. The aim was to provide structural insight into the effects of these mutants, including a new class of ANCHOR (additionally NRF2-complexed hypomorph) mutant variants. Our work provides additional insight into the structural dynamics of mutants that could not be analyzed experimentally, painting a more complete picture of their mutagenic effects. Notably, blade-wise analysis of the Kelch domain points to stability as a possible target of cancer in KEAP1. Interestingly, structural analysis of the R470C ANCHOR mutant, the most prevalent missense mutation in KEAP1, revealed no significant change in structural stability or NRF2 binding site dynamics, possibly indicating an covalent modification as this mutant's mode of action.

Symmetry-breaking transitions in the early steps of protein self-assembly.

Protein misfolding and subsequent self-association are complex, intertwined processes, resulting in development of a heterogeneous population of aggregates closely related to many chronic pathological conditions including Type 2 Diabetes Mellitus and Alzheimer's disease. To address this issue, here, we develop a theoretical model in the general framework of linear stability analysis. According to this model, self-assemblies of peptides with pronounced conformational flexibility may become, under particular conditions, unstable and spontaneously evolve toward an alternating array of partially ordered and disordered monomers. The predictions of the theory were verified by atomistic molecular dynamics (MD) simulations of islet amyloid polypeptide (IAPP) used as a paradigm of aggregation-prone polypeptides (proteins). Simulations of dimeric, tetrameric, and hexameric human-IAPP self-assemblies at physiological electrolyte concentration reveal an alternating distribution of the smallest domains (of the order of the peptide mean length) formed by partially ordered (mainly ß-strands) and disordered (turns and coil) arrays. Periodicity disappears upon weakening of the inter-peptide binding, a result in line with the predictions of the theory. To further probe the general validity of our hypothesis, we extended the simulations to other peptides, the Aß(1-40) amyloid peptide, and the ovine prion peptide as well as to other proteins (SOD1 dimer) that do not belong to the broad class of intrinsically disordered proteins. In all cases, the oligomeric aggregates show an alternate distribution of partially ordered and disordered monomers. We also carried out Surface Enhanced Raman Scattering (SERS) measurements of hIAPP as an experimental validation of both the theory and in silico simulations.

Cholesterol sequestration by xenon nano bubbles leads to lipid raft destabilization.

Combined coarse-grained (CG) and atomistic molecular dynamics (MD) simulations were performed to study the interactions of xenon with model lipid rafts consisting of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) and cholesterol (Chol). At a concentration of 2 Xe/lipid we observed an unexpected result: spontaneous nucleation of Xe nano bubbles which rapidly plunged into the bilayer. In this process Chol, essential for raft stabilization, was pulled out from the raft into the hydrophobic zone. When concentration was further increased (3 Xe/lipid), the bubbles increase in size and disrupted both the membrane and raft. We computed the radial distribution functions, pair-wise potentials, second virial coefficients and Schlitter entropy to scrutinize the nature of the interactions. Our findings, concurring with a recent report on the origin of general anaesthesia (M. A. Pavel, E. N. Petersen, H. Wang, R. A. Lerner and S. B. Hansen, Proc. Natl. Acad. Sci. U. S. A., 2020, 117(24), 13757-13766), suggest that the well-known anaesthetic effect of Xe could be mediated by sequestration of Chol, which, in turn, compromises the stability of rafts where specialized proteins needed to produce the nervous signal are anchored.

Self-Assembly of Phosphocholine Derivatives Using the ELBA Coarse-Grained Model: Micelles, Bicelles, and Reverse Micelles.

The ELBA coarse-grained force field was originally developed for lipids, and its water model is described as a single-site Lennard-Jones particle with electrostatics modeled by an embedded point-dipole, while other molecules in this force field have a three (or four)-to-one mapping scheme. Here, ELBA was applied to investigate the self-assembly processes of dodecyl-phosphocholine (DPC) micelle, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine/1,2-dihexaoyl-sn-glycero-3-phosphocholine (DPPC/DHPC) bicelles, and DPPC/cyclohexane/water reverse micelles through coarse-grained molecular dynamics (MD) simulations. New parameters were obtained using a simplex algorithm-based calibration procedure to determine the Lennard-Jones parameters for cyclohexane, dodecane, and cyclohexane-dodecane cross-interactions. Density, self-diffusion coefficient, surface tension, and mixture excess volume were found to be in fair agreement with experimental data. These new parameters were used in the simulations, and the obtained structures were analyzed for shape, size, volume, and surface area. Except for the shape of DPC micelles, all other properties match well with available experimental data and all-atom simulations. Remarkably, in agreement with experiments the rodlike shape of the DPPC reverse micelle is well described by ELBA, while all-atom data in the literature predicts a disclike shape. To further check the consistency of the force field in reproducing the correct shapes of reverse micelles, additional simulations were performed doubling the system size. Two distinct reverse micelles were obtained both presenting the rodlike shape and correct aggregation number.

Molecular Dynamics Simulations of Polymer-Ionic Liquid (1-Ethyl-3-methylimidazolium Tetracyanoborate) Ternary Electrolyte for Sodium and Potassium Ion Batteries.

We have performed molecular dynamics (MD) simulations of 1-ethyl-3-methylimidazolium tetracyanoborate ([EMIM]+[B(CN)4]-) ionic liquid to investigate the impact of addition of Na+/K+[B(CN)4]- salts and poly(ethylene oxide) (PEO6) on transport properties. These ternary mixtures are promising electrolyte materials for Na+-ion and K+-ion batteries as alternatives to the traditional Li+-ion ones. In addition, local structure was assessed through radial distribution functions. Our main findings are the following: (1) when compared to systems with larger amounts of Na+ and K+, it was observed that lower concentrations enhance the overall ionic conductivity and decrease viscosity; (2) Na+ and K+ cations prefer to be coordinated to the polymer chains rather than the [B(CN)4]- anions; (3) transport properties are improved when PEO6 oligomers are included in the electrolyte medium but these improvements continue only up to an optimum amount of PEO6. Beyond this amount, further addition of PEO6 did not have any additional impact on transport properties.

Manipulation of Diatomic Molecules with Oriented External Electric Fields: Linear Correlations in Atomic Properties Lead to Nonlinear Molecular Responses.

Oriented external electric fields (OEEFs) have been shown to have great potential in being able to provide unprecedented control of chemical reactions, catalysis, and selectivity with applications ranging from H2 storage to molecular machines. We report a theoretical study of the atomic origins of molecular changes because of OEEFs since understanding the characteristics of OEEF-induced couplings between atomic and molecular properties is an important step toward comprehensive understanding of the effects of strong external fields on the molecular structure, stability, and reactivity. We focus on the atomic and molecular (bond) properties of a set of homo- (H2, N2, O2, F2, and Cl2) and heterodiatomic (HF, HCl, CO, and NO) molecules under intense external electric fields in the context of quantum theory of atoms in molecules (QTAIM). It is shown that the atomic properties (atomic charges, energies, and localization indices) correlate linearly with the field strengths, but molecular properties (bond length, electron density at the bond critical point, and electron delocalization index) exhibit nonlinear responses to the imposed fields. In particular, the changes in the electron density distribution alter the shapes and locations of the zero-flux surfaces, atomic volumes, atomic electron population, and localization/delocalization indices. The topography and topology of the molecular electrostatic potential undergo dramatic changes. External fields also perturb the covalent-polar-ionic characteristic of the studied chemical bonds, hallmarking the impact of electric fields on the stability and reactivity of chemical compounds. The findings are well-rationalized within the framework of the QTAIM and form a coherent conceptual understanding of these effects in prototypical diatomic molecules.

Controlled On-Off Switching of Tight-Binding Hydrogen Bonds between Model Cell Membranes and Acetylated Cellulose Surfaces.

Controlling interactions between cellulose-based materials and membranes of living cells is critical in medicine and biotechnology in, for example, wound dressing, tissue engineering, hemodialysis membranes, and drug transport. Cellulose acetylation is a widely used approach to tuning those interactions. Surprisingly, however, detailed interactions of acetylated cellulose and membranes have thus far not been characterized. Using atomistic molecular dynamics (MD) simulations, we show that the key to such control is hydrogen bonds: by tuning the number of hydrogen bonds between tissue (cell membranes) and cellulose, binding can be controlled in a precise manner. We demonstrate that the acetylation of each hydroxymethyl group reduces the free energy of cellulose-membrane binding by an order of magnitude as compared to that of pristine cellulose. Remarkably, this acetylation-induced weakening does not occur gradually and is characterized by a sharp threshold in the degree of substitution, beyond which the microscopic character of lipid-cellulose interactions changes drastically. When the degree of substitution does not exceed 0.125, the cellulose-lipid interactions are mainly driven by hydrogen bonding between cellulose's hydroxyl groups and phosphate groups of lipid molecules. This results in the tight binding of a cellulose crystal and a lipid bilayer. Larger degrees of substitution (here, 0.25 and 0.5) prevent hydrogen bonding, leading to rather weak and unstable cellulose-bilayer binding. In this case, the lipid-cellulose binding is controlled by the interactions of lipid choline groups with hydroxyl(hydroxymethyl) groups and carbonyl groups of acetyl moieties of acetylated cellulose.