Optical and molecular features of negatively curved surfaces created by POPE lipids: A crucial role of the initial conditions.

Membrane fusion is closely related to plasma membrane domains rich in cone-shaped phosphatidylethanolamine (PE) lipids that can reverse membrane curvature under certain conditions. The phase transition of PE-based lipid membranes from the lamellar fluid phase (Lα) to the inverse hexagonal phase (HII) is commonly taken as a general model in reconstructing the membrane fusion pathway, and whose structural features have been mostly described so far using structural and microscopic techniques. The aim of this paper is to decipher the optical and molecular features of Lߠ→ Lα and especially of Lα â†’ HII transition of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) lipids at pH = 7.0 when they are initially prepared in the form of both multi- and unilamellar liposomes (MLVs and LUVs). The distinction between optical properties of MLS- and LUVs-derived HII phase, provided from turbidity-sensitive temperature-dependent UV-Vis spectra, was attributed to different formation mechanisms of HII phase. Most importantly, from FTIR spectroscopic data of POPE lipids in Lß (15 °C), Lα (50 °C) and HII (85 °C) phases we identified the changes in molecular features of POPE lipids during phase transitions. Among the latter, by far the most significant is different hydration pattern of POPE lipids in MLVs- and LUVs-derived HII phase which extends from the polar-apolar interface all the way to the terminal amino group of the POPE lipid, along with the changes in the conformation of glycerol backbone as evidenced by the signature of α-methylene groups. Molecular dynamics simulations confirmed higher water penetration in HII phase and provided insight into hydrogen bonding patterns.

Size and Polarizability of Boron Cluster Carriers Modulate Chaotropic Membrane Transport.

Perhalogenated closo-borates represent a new class of membrane carriers. They owe this activity to their chaotropicity, which enables the transport of hydrophilic molecules across model membranes and into living cells. The transport efficiency of this new class of cluster carriers depends on a careful balance between their affinity to membranes and cargo, which varies with chaotropicity. However, the structure-activity parameters that define chaotropic transport remain to be elucidated. Here, we have studied the modulation of chaotropic transport by decoupling the halogen composition from the boron core size. The binding affinity between perhalogenated decaborate and dodecaborate clusters carriers was quantified with different hydrophilic model cargos, namely a neutral and a cationic peptide, phalloidin and (KLAKLAK)2. The transport efficiency, membrane-lytic properties, and cellular toxicity, as obtained from different vesicle and cell assays, increased with the size and polarizability of the clusters. These results validate the chaotropic effect as the driving force behind the membrane transport propensity of boron clusters. This work advances our understanding of the structural features of boron cluster carriers and establishes the first set of rational design principles for chaotropic membrane transporters.

Novel pyrene-calix[4]arene derivatives as highly sensitive sensors for nucleotides, DNA and RNA.

Covalent functionalization of a calix[4]arene with one or two pyrene arms at one rim and two imidazoles at the opposite rim of the macrocyclic basket, yields fluorescent conjugates characterized by intramolecular pyrene-calixarene exciplex emission of a mono-pyrene conjugate, whereas the bis-pyrene derivative exhibits pyrene excimer fluorescence. The pyrene emission in these novel compounds is shown to be sensitive to non-covalent interactions with both mono- and polynucleotides. Pyrene-calixarene conjugates, acting as host molecules, strongly interact with nucleotides, as monitored by moderate emission quenching, reaching 0.1 µM affinities, comparable to some of the most effective supramolecular sensors for nucleotides. These compounds are efficiently inserted into ds-DNA/RNA grooves, with a high, 0.1-1 µM affinity, not influencing significantly any of the ds-polynucleotide native properties, whereby complete emission quenching allows the detection of DNA at nM concentration.

Reactions of a hydrogen atom with haloacetates in aqueous solutions: Computational evidence for proton-coupled electron transfer and competing mechanisms.

A computational study of the mechanisms and kinetics of the aqueous reactions of a hydrogen atom with haloacetates is presented. Several mechanisms in the close competition are observed, such as proton-coupled electron transfer (PCET), hydrogen atom transfer (HAT), and halogen abstraction (XA). Computations predict that dechlorination takes place via PCET mechanisms and not via XA, as stated earlier, while XA is the fastest mechanism for IAc - . The reaction rate constants are reasonably well predicted within the theoretically most reliable canonical variational transition state theory with small curvature tunneling corrections and compared with the experimental ones. To reproduce the experimental rate constants of the debromination process it is necessary to include the PCET and XA cumulative values. Small curvature tunneling corrections to the rate constants are the highest for HAT and PCET mechanisms, up to 70 times larger than the Wigner, while variational effects for XA mechanisms are very small.

Comparing the performances of various density functionals for modelling the mechanisms and kinetics of bimolecular free radical reactions in aqueous solution.

We carried out an investigation of the performances of 18 density functionals (DFs) for modelling the mechanisms and kinetics of the aqueous phase reactions between the α-hydroxyisopropyl radical and 9 organic substrates. The primary goal was to evaluate the applicability of density functional theory specifically in conjunction with the polarizable continuum model (DFT/PCM) for a fully implicit description of the aqueous environment. Accordingly, the solute is augmented with the explicit molecule(s) of the water solvent only when it is confirmed that the water participates in the reaction mechanism directly and not just as a potential donor or acceptor of additional hydrogen bonds. The tested DFs are chosen by systematically ascending the Jacob's ladder of DFs with particular emphasis on the versatile Minnesota family. For most of the DFs we used the empirical corrections for the dispersion in accordance with Grimme's D3 or D3-BJ models. The optimum DFs are determined on the basis of the lowest mean absolute errors (MAEs) and the largest Pearson correlation coefficients (PCCs) with respect to the set of experimentally determined rate constants. The studied substrates are carbon tetrachloride (CCl4), chloroform (CHCl3), trichloroacetate (Cl3Ac-), chloral hydrate (ClH), iodoacetate (IAc-), iodoacetamide (IAm), 5-bromouracil (BrU), 5-nitrouracil (NO2U), and cysteamine (Cys+). The mechanisms that contribute dominantly to the observed rate constants are: chlorine abstractions for CCl4, CHCl3, Cl3Ac-, and ClH; proton-coupled electron transfer (PCET) for IAc-; water-assisted PCET and iodine abstraction for IAm; ortho-addition for BrU and NO2U; and hydrogen atom abstraction from the sulphur atom for Cys+. It is found that in the DFT/PCM setting climbing up the Jacob's ladder does not necessarily imply a systematically increasing accuracy. Thus, M06-D3 and PBE0-D3 exhibit the best performance according to the lowest MAEs (1.10 and 1.26 kcal mol-1 MAEs in the Gibbs free energies of activation), and M06-D3, M06-2X-D3 and MN15 according to the largest PCCs (0.95, 0.94, and 0.94). In a surprising contrast, the three tested double-hybrid DFs, B2PLYP-D3, DSD-PBEP86, and PBEQIDH, all exhibit comparatively large MAEs and poor PCCs, and therefore do not appear well-suited for use in the DFT/PCM framework.

Proton-coupled electron transfer is the dominant mechanism of reduction of haloacetates by the α-hydroxyethyl radical in aqueous media.

The reaction systems of α-hydroxyalkyl radicals with halogenated organics in aqueous solutions are uniquely suited for studying the fundamentally important proton-coupled electron transfer (PCET) mechanism in competition with alternatives such as substitution, hydrogen abstraction, halogen atom abstraction etc. We report experimental (steady state γ-radiolysis) and theoretical (density functional theory) studies of reactions of the α-hydroxyethyl radical (˙EtOH) with the four monohaloacetate anions (XAc-): fluoroacetate (FAc-), chloroacetate (ClAc-), bromoacetate (BrAc-) and iodoacetate (IAc-). The reactions are conducted in non-buffered and buffered (bicarbonate or phosphate) aqueous solutions of ethanol. In these conditions, only IAc- and BrAc- are reduced by ˙EtOH, and the PCET is predicted to be the most feasible reaction mechanism. In contrast to analogous reaction systems with alkyl halides, halophenols and 5-bromouracil, the radical-mediated one-electron reduction and subsequent dehalogenation of IAc- and BrAc- proceed regardless of the presence of buffers as the external proton acceptors. This implies that the proton can be efficiently transferred to the carboxyl group. The proton transfer is predicted to take place directly as interposition of one water molecule raises the barriers to the PCET. The addition of HCO3- or HPO42- accelerates the PCET owing to their larger proton affinities compared to that of the carboxyl group. The reduction of IAc- and BrAc- generates daughter carboxymethyl radicals thus initiating a radical chain reaction which considerably enhances the Br- and I- yields. In contrast, ClAc- and FAc- are not degraded by ˙EtOH even at elevated temperatures. These comparatively simple reaction systems enable general insights into PCET processes in which the carboxyl group may assume the role of proton acceptor.

Solvation Effect on Complexation of Alkali Metal Cations by a Calix[4]arene Ketone Derivative.

The medium effect on the complexation of alkali metal cations with a calix[4]arene ketone derivative (L) was systematically examined in methanol, ethanol, N-methylformamide, N,N-dimethylformamide, dimethyl sulfoxide, and acetonitrile. In all solvents the binding of Na+ cation by L was rather efficient, whereas the complexation of other alkali metal cations was observed only in methanol and acetonitrile. Complexation reactions were enthalpically controlled, while ligand dissolution was endothermic in all cases. A notable influence of the solvent on NaL+ complex stability could be mainly attributed to the differences in complexation entropies. The higher NaL+ stability in comparison to complexes with other alkali metal cations in acetonitrile was predominantly due to a more favorable complexation enthalpy. The 1H NMR investigations revealed a relatively low affinity of the calixarene sodium complex for inclusion of the solvent molecule in the calixarene hydrophobic cavity, with the exception of acetonitrile. Differences in complex stabilities in the explored solvents, apart from N,N-dimethylformamide and acetonitrile, could be mostly explained by taking into account solely the cation and complex solvation. A considerable solvent effect on the complexation equilibria was proven to be due to an interesting interplay between the transfer enthalpies and entropies of the reactants and the complexes formed.