Long-lasting dashed waves in a reactive microemulsion

In the Belousov-Zhabotinsky (BZ) reaction carried out in a reverse microemulsion with Aerosol OT as surfactant, the existence of two different sizes of droplets containing the BZ reactants leads to the emergence of segmented (dashed) waves. This bimodal distribution of sizes is stabilized by adding small amounts of the homopolymer poly(ethylene oxide) (PEO). Addition of PEO lengthens the period during which these patterns are observed, so that dashed waves can persist for 12-14 h, in contrast to the 2-3 h found in earlier studies without added polymer.     

Quantum and molecular mechanical study of the first proton transfer in the catalytic cycle of cytochrome P450cam and its mutant D251N

In the catalytic cycle of cytochrome P450cam, the hydroperoxo intermediate (Cpd 0) is formed by proton transfer from a reduced oxyheme complex (S5). This process is drastically slowed down when Asp251 is mutated to Asn (D251N). We report quantum mechanical/molecular mechanical (QM/MM) calculations that address this proton delivery in the doublet state through a hydrogen-bond network in the Asp251 channel, both for the wild-type enzyme and the D251N mutant, using four different active-site models. For the wild-type, we find a facile concerted mechanism for proton transfer from protonated Asp251 via Wat901 and Thr252 to the FeOO moiety, with a barrier of about 1 kcal/mol and a high exothermicity of more than 20 kcal/mol. In the D251N mutant with a neutral Asn251 residue, the proton transfer is almost thermoneutral or slightly exothermic in the three models considered. It is still very facile when the Asn251 residue adopts a conformation analogous to Asp251 in the wild-type enzyme, but the barrier increases significantly when the Asn251 side chain flips (as indicated by classical molecular dynamics simulations). This flip disrupts the hydrogen-bond network and hence the proton-transfer pathway, which causes a longer lifetime of S5 in the D251N mutant (consistent with experimental observations). The entry of an additional water molecule into the active site of D251N with flipped Asn251 regenerates the hydrogen-bond network and provides a viable mechanism for proton delivery in the mutant, with a moderate barrier of about 7 kcal/mol.     

Formation of the active species of cytochrome p450 by using iodosylbenzene: a case for spin-selective reactivity

The generation of the active species for the enzyme cytochrome P450 by using the highly versatile oxygen surrogate iodosylbenzene (PhIO) often produces different results compared with the native route, in which the active species is generated through O(2) uptake and reduction by NADPH. One of these differences that is addressed here is the deuterium kinetic isotope effect (KIE) jump observed during N-dealkylation of N,N-dimethylaniline (DMA) by P450, when the reaction conditions change from the native to the PhIO route. The paper presents a theoretical analysis targeted to elucidate the mechanism of the reaction of PhIO with heme, to form the high-valent iron-oxo species Compound I (Cpd I), and define the origins of the KIE jump in the reaction of Cpd I with DMA. It is concluded that the likely origin of the KIE jump is the spin-selective chemistry of the enzyme cytochrome P450 under different preparation procedures. In the native route, the reaction proceeds via the doublet spin state of Cpd I and leads to a low KIE value. PhIO, however, diverts the reaction to the quartet spin state of Cpd I, which leads to the observed high KIE values. The KIE jump is reproduced here experimentally for the dealkylation of N,N-dimethyl-4-(methylthio)aniline, by using intra-molecular KIE measurements that avoid kinetic complexities. The effect of PhIO is compared with N,N-dimethylaniline-N-oxide (DMAO), which acts both as the oxygen donor and the substrate and leads to the same KIE values as the native route.     

Chiral separation: mechanism modeling in two-dimensional systems

Fluid phase separations of racemates are difficult because the subtle, short-ranged differences in intermolecular interactions of like and unlike pairs of chiral molecules are typically smaller than the thermal energy. A surface restricts the configurational space available to the pair of interacting molecules, thus changing the effective interactions between them. Because of this restriction, a surface can promote chiral separation of mixtures that are racemic in bulk. In this paper, we investigate chiral symmetry breaking induced by an achiral surface in a racemate. A parallel tempering Monte Carlo algorithm with tempering over the temperature domain is used to examine the interplay between molecular geometry and energetics in promoting chiral separations. The system is restricted to evolve in two dimensions. By controlling the balance between electrostatic and steric interactions, one can direct the surface assembly of the chiral molecules toward formation of small clusters of identical molecules. When molecular shape asymmetry is complemented by dipolar alignment, chiral micellar clusters of like molecules are assembled on the surface. We examine the case of small model molecules for which the two-dimensional restriction of the pair potential is sufficient to induce chiral segregation. An increase in molecular complexity can change the balance of intermolecular interactions to the point that heterochiral pairs are energetically more favored. In this case, we find conditions in which formation of homochiral micelles is still achieved, due to a combination of multibody and entropic effects. In such systems, an examination of the pair potential alone is insufficient to predict whether the multimolecular racemate will or will not segregate.     

Compound I of nitric oxide synthase: the active site protonation state

A quantum mechanical/molecular mechanical (QM/MM) study of the formation of the elusive active species Compound I (Cpd I) of nitric oxide synthase (NOS) from the oxyferrous intermediate shows that two protons have to be provided to produce a reaction that is reasonably exothermic and that leads to the appearance of a radical on the tetrahydrobiopterin cofactor. Molecular dynamics and energy considerations show that a possible source of proton is the water H-bond chain formed from the surface to the active site, but that a water molecule by itself cannot be the source of the proton; an H3O+ species that is propagated along the chain is more likely. The QM/MM calculations demonstrate that Cpd I and H2O are formed from the ferric-hydrogen peroxide complex in a unique heterolytic O-O cleavage mechanism. The properties of the so-formed Cpd I are compared with those of the known species of chloroperoxidase, and the geometry and spin densities are found to be compatible. The M?ssbauer parameters are calculated and may serve as experimental probes in attempts to characterize NOS Cpd I.     

Effects of block copolymer's architecture on its association with lipid membranes: experiments and simulations

Triblock copolymers of the form poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) have been shown to effectively interact with and restore activity of damaged cell membranes. To better understand the interaction between these polymers and cell membranes, we have modeled the outer leaflet of a cell membrane with a lipid monolayer spread at the air-water interface and injected poloxamers of varying architectures into the subphase beneath the monolayer. Subsequent interactions of the polymer with the monolayer upon compression were monitored with concurrent Langmuir isotherm and fluorescence microscopy measurements. Monte Carlo simulations were run in parallel using a coarse-grained model to capture interactions between lipids and poloxamers. Changing the ratio of the PEO to PPO block lengths (NPEO:NPPO) affects the equilibrium spreading pressure of the polymer. Poloxamers with a relatively longer central hydrophobic block are less soluble, resulting in more polymer adsorbed to the interface and therefore a higher equilibrium spreading pressure. Simulation results show that changing the poloxamer structure effectively affects its solubility. This is also reflected in the degree of lipid corralling as poloxamers with a higher chemical potential (and resulting higher equilibrium spreading pressure) cause the neighboring lipid domains to be more ordered. Upon lateral compression of the monolayers, the polymer is expelled from the film beyond a certain squeeze-out pressure. A poloxamer with a higher NPEO:NPPO ratio (with either NPEO or NPPO held constant in each series) has a lower squeeze-out pressure. Likewise when the total size of the polymer is varied with a constant hydrophilic:hydrophobic ratio, smaller poloxamers are squeezed out at a lower pressure. Our simulation results capture the trends of our experimental observations, both indicating how the interactions between lipids and poloxamers can be tuned by the polymer architecture.     

A Generalized Information-Theoretic Approach for Bounding the Number of Independent Sets in Bipartite Graphs

This paper studies the problem of upper bounding the number of independent sets in a graph, expressed in terms of its degree distribution. For bipartite regular graphs, Kahn (2001) established a tight upper bound using an information-theoretic approach, and he also conjectured an upper bound for general graphs. His conjectured bound was recently proved by Sah et al. (2019), using different techniques not involving information theory. The main contribution of this work is the extension of Kahn’s information-theoretic proof technique to handle irregular bipartite graphs. In particular, when the bipartite graph is regular on one side, but may be irregular on the other, the extended entropy-based proof technique yields the same bound as was conjectured by Kahn (2001) and proved by Sah et al. (2019).     

Halide affinity for the water-air interface in aqueous solutions of mixtures of sodium salts

The water-air interface plays a critical role in many physical and chemical processes of the Earth's atmosphere. In particular, heavy halide ions are strongly involved in processes of fundamental importance in determining the prevalence of many atmospheric components through heterogeneous reactions at the water-air interface. In this work, molecular dynamics simulations are used to study the halide enhancements at the water-air interface in the case of mixtures of Cl(-), Br(-), and I(-) ions. The results show a pattern of enhancement directly correlated to the anion polarizability. This effect is explained in terms of the charge distribution across the slab resembling an electrical double layer. As a result, the anions with higher polarizability lower the system's potential energy by enhancing their presence at the interface.