Low Dielectric Solvents Research Articles

Molecular dynamics simulation of discontinuous volume phase transitions in highly-charged crosslinked polyelectrolyte networks with explicit counterions in good solvent

The volumetric properties of highly-charged defect-free polyelectrolyte networks with tetrafunctional crosslinks are studied through molecular dynamics simulations in the canonical ensemble. The network backbone monomers, which are monovalent, and the counterions, which are mono-, di-, or trivalent, are modeled explicitly in the simulations, but the solvent is treated implicitly as a dielectric medium of good solvation quality. The osmotic pressure of the network-solvent system is found to depend greatly on the strength of electrostatic interactions. Discontinuous volume phase transitions are observed when the electrostatic interactions are strong, and the onset of these transitions shifts to higher solvent dielectricity as the counterion valency increases. The roles of the various virial contributions to the osmotic pressure are examined. The network elasticity entropy is found to behave nearly classically. As the network contracts and collapses with increasing strength of electrostatic interactions, the loss of counterion entropy leads to increased counterion osmotic pressure contributions via two mechanisms. The reduction in available configurational space increases the counterion translational entropy contribution to the ideal part of the osmotic pressure, and the greater number of counterion-monomer contacts formed due to counterion condensation and confinement increases the counterion excluded-volume entropy contribution to the excess part of the osmotic pressure. These observations contrast the decrease in the single ideal-gas-like counterion translational entropy contribution to the osmotic pressure predicted by the counterion condensation-charge renormalization theory. An accompanying decrease in the total electrostatic energy balances the loss of counterion excluded-volume entropy as the polyelectrolyte networks collapse in low-dielectric solvents. This interplay between the electrostatic energy and the counterion excluded-volume entropy appears to be responsible for the discontinuous volume phase transitions that are observed in polyelectrolyte networks. The structure of the polyelectrolyte network is also found to be affine in the swollen state, with constituent chains nearly fully extended, and nonaffine in the collapsed state, with the chains adopting a Gaussian conformation.

Ion mobility-mass spectrometry applied to cyclic peptide analysis: conformational preferences of gramicidin S and linear analogs in the gas phase

In this paper, we present an investigation of the gas-phase structural differences between cyclic and linear peptide ions by matrix-assisted laser desorption ionization-ion mobility-mass spectrometry. Specifically, data is shown for gramicidin S (cyclo-VOLFPVOLFP where phenylalanines are D rather than L-type amino acids and the O designates the non-standard amino acid ornithine) and five linear gramicidin S analogues. Results are interpreted as evidence for a β-sheet (or β-hairpin) conformational preference in both linear-protonated and sodiated-cyclic gramicidin S gas-phase peptides, and a preference for the protonated-cyclic peptide to adopt a collapsed, random coil-type conformation. A comparison with solution-phase circular dicrhoism measurements is performed, and structures similar to those observed in the gas phase appear to be favored in low-dielectric solvents such as 2,2,2-triflouroethanol. The utility of ion mobility-mass spectrometry (IM-MS) as a means of rapidly distinguishing between linear and cyclic peptide forms in also discussed.

Ion mobility-mass spectrometry applied to cyclic peptide analysis: conformational preferences of gramicidin S and linear analogs in the gas phase

In this paper, we present an investigation of the gas-phase structural differences between cyclic and linear peptide ions by matrix-assisted laser desorption ionization-ion mobility-mass spectrometry. Specifically, data is shown for gramicidin S (cyclo-VOLFPVOLFP where phenylalanines are D rather than L-type amino acids and the O designates the non-standard amino acid ornithine) and five linear gramicidin S analogues. Results are interpreted as evidence for a β-sheet (or β-hairpin) conformational preference in both linear-protonated and sodiated-cyclic gramicidin S gas-phase peptides, and a preference for the protonated-cyclic peptide to adopt a collapsed, random coil-type conformation. A comparison with solution-phase circular dicrhoism measurements is performed, and structures similar to those observed in the gas phase appear to be favored in low-dielectric solvents such as 2,2,2-triflouroethanol. The utility of ion mobility-mass spectrometry (IM-MS) as a means of rapidly distinguishing between linear and cyclic peptide forms in also discussed.

Free energy of solvation from molecular dynamics simulations for low dielectric solvents.

Using molecular dynamics simulation, we present new results for the free energy of solvation for solvents with low dielectric constants (CCl(4), CHCl(3), benzene). The solvation free energy is computed as the sum of three contributions originated at the cavitation of the solute by the solvent, the solute-solvent repulsion and dispersion interactions, and the electrostatic solvation of the solute. The cavitational contribution has been obtained from the Claverie-Pierotti model applied to excluded volumes obtained from distances for nearest neighbor configurations between the solute's atoms and a spherical solvent description. An electrostatic continuum model has been adapted for the computation of the electrostatic free energy of solvation, whereas the van der Waals contribution has been calculated directly from the intermolecular interactions defined by the force fields applied to the simulations. For each solvent, a large set of solute molecules containing most of the chemically interesting functionalities has been treated. The simulated solvation free energies are in very good agreement with experimental data, although a small systematical overestimation of the free energy of solvation indicates a failure of the spherical approach to the solvent molecules in the case of benzene.

Alkyl halide charge transfer complexes with hard Lewis bases

The unusual charge transfer complexes formed between alkyl halide acceptors and hard Lewis base donors (amines and alcohols) in low dielectric solvent were examined using ultraviolet spectroscopy. The λ max of the complex decreases with increasing ionization potential of the donor. The complex formation equilibria were probed by thermodynamic analysis and concentration variation. At ambient temperatures complex formation is generally slightly exergonic with a negative complexation entropy. The complex extinction coefficients are much lower (<10 l mol −1 cm −1) than for typical charge transfer complexes. These complexes are extraordinary within a classical context since the halide acceptors have a negative electron affinity. They exhibited an atypical hypsochromic shift with increasing solvent dielectric constant.

Electrostatic interactions between substituents as regioselectivity control elements in Diels-Alder cycloadditions. A DFT study of cycloadditions of 1-methoxy-4-trimethylsiloxy dienes with acrylonitrile.

The regioselectivities of Diels-Alder reactions of 1-methoxy-4-trimethylsiloxy-1,3-butadiene and the corresponding o-xylylene with acrylonitrile were explored with density functional theory. The transition state of the reaction of the diene with acrylonitrile was studied in both the gas phase and in a low dielectric (epsilon = 2.247) solvent. The regioselectivities of these reactions are predicted to be controlled by the direct electrostatic interactions between the diene and dienophile substituents. The electron-donating capacities of methoxy and trimethylsiloxy substituents are shown to be very similar and to not contribute to regioselectivity control. A prediction is made that the cycloadditions of the o-xylylene will be unselective, while 1-methoxy-4-trimethylsiloxy-1,3-butadiene will give a small preference ( approximately 5:1) in favor of the proximal methoxy and cyano groups. The thermochromic behavior of trans-disubstituted disiloxy benzocyclobutene was also explored.

A bis-acetonitrile two-coordinate copper(I) complex: synthesis and characterization of highly soluble B(C(6)F(5))(4)(-) salts of [Cu(MeCN)(2)](+) and [Cu(MeCN)(4)](+).

Copper(I)-acetonitrile complexes are exceedingly useful starting materials for the synthesis of copper(I) complexes with polydentate ligands. To extend the utility of such chemistry to solution studies in relatively low-dielectric solvents (i.e., diethyl ether, toluene) and to aid in obtaining products amenable to X-ray diffraction studies, we have recently begun to employ counteranions such as B(C(6)F(5))(4)(-) for bioinorganic studies. Thus, the synthesis of [Cu(MeCN)(4)]B(C(6)F(5))(4) (1) is presented. Its recrystallization from CH(2)Cl(2)/pentane yields the linear, two-coordinate complex [Cu(MeCN)(2)]B(C(6)F(5))(4) (2), whose centrosymmetric X-ray structure shows that its Cu-N distance is significantly shorter than that in other two-coordinate Cu(I) complexes with nitrogen ligands or that in the tetrahedral complex [Cu(MeCN)(4)]ClO(4). Infrared spectroscopy indicates interesting and diagnostically useful differences between the nu(CN) of 1 and 2.

Chemistry Inside Carbon Nanotubes: the Menshutkin SN2 Reaction

In an effort to gain insight into the effect of carbon nanotube confinement on reaction enthalpies and activation energies, calculations using hybrid density functional theory have been carried out for the Menshutkin SN2 reaction in gas phase and inside carbon nanotubes. The polarizability of the carbon nanotubes provides an interaction mechanism, which leads to the stabilization of confined dipolar species. Inside hydrogen-terminated (8,0) and (9,0) carbon nanotubes, the activation energy and reaction endothermicity for the Menshutkin SN2 reaction are significantly reduced compared to those in the gas phase. Polarizable continuum models, using dielectric constants calculated from the carbon nanotube polarizabilities, are found to provide results in remarkable agreement with all electron nanotube-confined calculations, confirming the stabilization mechanism and offering a cost-effective approach for further exploration of the effects of the carbon nanotube environment. Overall, the effect of carbon nanotube confinement on reaction enthalpies closely resembles solvation in a low-dielectric solvent. Therefore, chemical reactions in which there is a separation of charge along the reaction coordinate may be enhanced inside fullerene-based materials because of their large electronic polarizabilities.

Voltammetric probes of cytochrome electroreactivity: the effect of the protein matrix on outer-sphere reorganization energy and electronic coupling probed through comparisons with the behavior of porphyrin complexes.

Using surface-modified electrodes composed of omega-hydroxyalkanethiols, an experimentally based value for the inner-sphere reorganization energy of the bis(imidazole)iron porphyrin system has been obtained by examining the solvent dependence of the reorganization energy of bis(N-methylimidazole)meso-tetraphenyl iron porphyrin. The value obtained (0.41 +/- 0.06 eV) is remarkably similar to values we have recently reported for the reorganization energy of cytochrome b(5) (0.43 +/- 0.02 eV) and cytochrome c (0.58 +/- 0.06 eV). This strongly suggests that the protein matrix mimics the behavior of a low dielectric solvent and effectively shields the heme from the solvent. The effect of the orientation of the heme relative to the electrode was also explored by sytematically varying the steric bulk of the axial ligands. On the basis of a good linear correlation between the electronic coupling and the cosine of the angle between the heme plane and the surface of the electrode, it is suggested that a parallel orientation of the heme yields a maximum in the electronic coupling. Relevance to interheme protein electron transfer is discussed.

Specific Binding of Ethanol to Cholesterol in Organic Solvents

Although ethanol has been reported to affect cholesterol homeostasis in biological membranes, the molecular mechanism of action is unknown. Here, nuclear magnetic resonance (NMR) spectroscopic techniques have been used to investigate possible direct interactions between ethanol and cholesterol in various low dielectric solvents (acetone, methanol, isopropanol, DMF, DMSO, chloroform, and CCl 4). Measurement of 13C chemical shifts, spin-lattice and multiplet relaxation times, as well as self-diffusion coefficients, indicates that ethanol interacts weakly, yet specifically, with the HC-OH moiety and the two flanking methylenes in the cyclohexanol ring of cholesterol. This interaction is most strong in the least polar-solvent carbon tetrachloride where the ethanol–cholesterol equilibrium dissociation constant is estimated to be 2 × 10 −3 M. 13C-NMR spin-lattice relaxation studies allow insight into the geometry of this complex, which is best modeled with the methyl group of ethanol sandwiched between the two methylenes in the cyclohexanol ring and the hydroxyl group of ethanol hydrogen bonded to the hydroxyl group of cholesterol.

Coexistence curve of the ionic binary mixture tetra- n-butylammonium picrate in 1-dodecanol

The coexistence curve of the ionic binary mixture tetra- n-butylammonium picrate in the low dielectric solvent 1-dodecanol is measured in the reduced temperature range 4.2×10 −5<( T c − T)/ T c<4.2×10 −3, with T c the critical temperature. The asymptotic critical exponent β is found to be close to the 3-D Ising value with one negative correction-to-scaling term. However, when the data are corrected for a small drift of T c, no cross-over behavior is observed in the studied temperature range. The mean diameter can be fitted by a simple linear law showing no anomaly within the accuracy of our measurements.

Changes in polypeptide conformer populations induced by the solvent environment

Changes in the solvent dielectric properties are correlated with changes in polypeptide conformer populations. Gramicidin A, a peptide native to membrane environments, forms a variety of well defined dimeric conformations in relatively low dielectric organic solvents. However, changes in this environment lead to changes in the conformer populations with the lowest dielectric solvents favoring the conformers with the lowest net dipole moment. Such changes were characterized by cross-peak intensities in GCOSY solution NMR spectra. In studying membrane-bound polypeptides, it is very important to recognize that the structure is not dictated by just the amino acid sequence, but that the environment plays a very significant role in defining the polypeptide conformation. © 1998 John Wiley & Sons, Ltd.

Protein stability and conformational rearrangements in lipid bilayers: linear gramicidin, a model system

The replacement of four tryptophans in gramicidin A by four phenylalanines (gramicidin M) causes no change in the molecular fold of this dimeric peptide in a low dielectric isotropic organic solvent, but the molecular folds are dramatically different in a lipid bilayer environment. The indoles of gramicidin A interact with the anisotropic bilayer environment to induce a change in the molecular fold. The double-helical fold of gramicidin M, as opposed to the single-stranded structure of gramicidin A, is not compatible with ion conductance. Gramicidin A/gramicidin M hybrid structures have also been prepared, and like gramicidin M homodimers, these dimeric hybrids appear to have a double-helical fold, suggesting that a couple of indoles are being buried in the bilayer interstices. To achieve this equilibrium structure (i.e., minimum energy conformation), incubation at 68 degrees C for 2 days is required. Kinetically trapped metastable structures may be more common in lipid bilayers than in an aqueous isotropic environment. Structural characterizations in the bilayers were achieved with solid-state NMR-derived orientational constraints from uniformly aligned lipid bilayer samples, and characterizations in organic solvents were accomplished by solution NMR.

NON-AQUEOUS TITRATIONS AS A TOOL IN THE STUDY OF MOLECULAR RECOGNITION PHENOMENA. USES IN DISTINGUISHING HYDROGEN BONDING FROM PROTON TRANSFER, THE MEASUREMENT OF COMPLEX INDUCED pKa SHIFTS, AND THE ABILITY TO DISTINGUISH THE CATALYTIC ROLES OF GENERAL ACIDS AND BASES

Whenever hydrogen bonding is involved in molecular recognition, the possibility of a proton transfer from the donor to the acceptor arises. In most cases the pKa of the donor is far enough above the pKa of the conjugate acid of the acceptor for it to be clear that no proton transfer will occur. However, as the difference between the donor and acceptor pKas decreases, it can become difficult to predict whether a proton transfer will occur. Since most hydrogen bond-driven molecular recognition is studied in low dielectric solvents, non-aqueous titrations can be used to measure the pKas and therefore predict proton transfers. In this paper three studies which involved non-aqueous titrations are summarized. The first deals with distinguishing simple proton transfer from host–guest complex formation. The second involves measuring pKa shifts upon host–guest complex formation. The last is a study of the catalysis of a phosphoryl transfer. In all three scenarios the non-aqueous titration method gave results which would have been difficult to obtain by other means, and which proved crucial for a complete understanding of the molecular recognition process. © 1997 John Wiley & Sons, Ltd.

Molecular dynamics simulations of ion clustering and conductivity in NaI/ether solutions. II. Effect of ion concentration

Molecular dynamics simulations of sodium iodide dissolved in dimethyl ether or 1,2-dimethoxyethane (glyme) were studied at a range of salt concentrations. The interactions among the species were represented with Lennard-Jones and Coulomb forces. Dimethyl ether and glyme were represented by a rigid three-site model and a six-site model with flexible dihedral angles, respectively. Glyme is demonstrated to be a much better solvent than dimethyl ether, although both are low-dielectric solvents. At the highest concentration studied in glyme, which corresponds to an oxygen/cation ratio of 16:1, free ions make up about 50% of the total ion concentration, and neutral pairs make up about 20%. A quantitative analysis of the species important in conductivity shows that the current is primarily the result of the movement of free ions and the relative movement of ions within loosely bound ion pairs. At higher salt concentrations, many different ionic species can make contributions to the conductivity.

An ESR‐Electrochemical Cell Which Can Be Used in High and Low Dielectric Solvents Over Wide Ranges of Temperature and Time Domain

A robust small volume (0.2 ml) electrochemical cell has been designed which enables simultaneous rapid scan voltam‐metric (linear diffusion conditions) and electron spin resonance (ESR) experiments to be undertaken directly in the cavity of the spectrometer over a wide temperature range in low (e.g., dichloromethane) or high (e.g., acetonitrile) dielectric solvents. Additionally, the design facilitates the study of electrochemically generated highly oxygen and/or moisture sensitive radicals. The close proximity of the specially designed reference electrode to the working electrode and the thick layer solution conditions enables small cell (RC) time constants to be achieved. These conditions allow the ESR signal at constant field to be measured at fast scan rates. Alternatively, ensemble averaging of the complete ESR spectrum at constant potential enables high quality ESR spectra to be obtained for reactive electrochemically generated radicals. Data on the oxidation of and reduction of [, acac = acetylacetone], tetramethrin, and 5,5‐dipropylpyridine‐2,6‐dicarbothioate are presented to demonstrate the features of the newly designed cell. Lowering the temperature down to 130 K does not lead to destruction of the cell, so that frozen solution spectra of electrochemically generated radicals may be obtained.

Turbidity of a near-critical ionic fluid

We report the critical behavior of osmotic compressibility (% T ), that was deduced from turbidity, in an ionic fluid mixture comprised of tetra-n-butyl ammonium picrate in a low dielectric solvent, 1-dodecanol. The liquid-liquid phase separation in this system is driven, predominantly, by Coulombic interactions. Measurements covered the reduced temperature, t, range 7 x 105 ⩽ / ⩽ 7 × 10− 2. The critical behavior of Z, indicates acrossover from the mean-field to the Ising critical exponent, as the critical temperature (T c) is approached.

Effect of intravenous administration of hydroxyethyl-starch-deferoxamine on oxygen-derived free radical generation in cancellous bone specimens obtained from dogs

Summary The ability of iv administered hydroxyethyl-starch-deferoxamine to attenuate radical production in freshly procured cancellous bone specimens was investigated, using spin-trapping and electron spin resonance (esr) techniques. A core cancellous bone specimen 10 mm long and 5.6 mm in diameter was obtained, using aseptic technique, from the proximal portion of the humerus of 30 adult mixed-breed dogs. After procurement of the initial bone specimen, 10 dogs received a 10 % solution of hydroxyethyl-starch-deferoxamine in 0.9% NaCl (50 mg/kg of body weight, iv), 10 dogs received an equivalent volume (5 ml/kg, iv) of a 10% solution of hydroxyethyl-starch in 0.9 % NaCl, and 10 dogs received 0.9 % saline solution (5 ml/kg, iv). A second core cancellous bone specimen was obtained from the contralateral humerus of each dog 45 minutes after treatment. All specimens were individually incubated in the spin trap α-phenyl-N-tert-butylnitrone in Eagle's minimum essential medium, at 26 C for 45 minutes, then were frozen at -20 C until they were prepared for analysis by esr spectroscopy. Each specimen was thawed, homogenized, and extracted in a low-dielectric organic solvent prior to obtaining an esr spectrum, which was analyzed for hyperfine splitting constants for radical identification. Each first-derivative spectrum was digitally double-integrated to obtain an area; these areas were used to compare intensities of the spin adducts. Difference in the area obtained before and after treatment for each dog was expressed as a ratio of that dog's pretreatment area ([pretreatment-posttreatment ]/pretreatment). The calculated ratios for saline-, hydroxyethyl-starch-, and hydroxyethyl-starch-deferoxamine-treated dogs were compared, using a Kruskal-Wallis (KW) nonparametric test for multiple comparisons of ranked data. Significance was determined at P ≤ 0.05. Ad hoc comparisons were performed, using the KW procedure for individual comparisons, with a set at 0.05. The mean ± sd and median ratio for each of the treatment groups were: saline-treated dogs, 0.005 ± 0.40 and 0.045; hydroxyethyl-starch-treated dogs, -0.063 0.27 and -0.025; hydroxyethyl-starch-deferoxamine-treated dogs, 0.261 ± 0.278 and 0.335, respectively. There was a significant (P &lt; 0.01, KW) difference in the ratios between treatment groups. Ratios for hydroxyethyl-starch-deferoxamine-treated dogs were significantly (P &lt; 0.05, KW) higher than that for hydroxyethyl-starch-treated dogs but not for saline-treated dogs. The ratios for saline- and hydroxyethyl-starch-treated dogs were not significantly different. We could not associate significant attenuation of radical generation in freshly harvested core cancellous bone specimens with iv administration of hydroxyethyl-starch-deferoxamine. The potential for unconjugated hydroxyethyl-starch to function as an oxidant must considered.

Investigation of oxygen-derived free radical generation in cancellous bone specimens obtained from dogs

Summary Generation of free radicals and the ability ofvarious antioxidants to attenuate radical production in freshly procured cancellous bone specimens was investigated, using spin-trapping and electron spin resonance (esr) techniques. Seven core cancellous bone specimens, 10 mm long and 7.9 mm in diameter, were obtained using aseptic technique, from the proximal portion of the humerus of 9 adult mixedbreed dogs. One core cancellous bone specimen from each dog was incubated in spin trap α-phenyl-N tert-butylnitrone in Eagle's minimum essential medium and served as a control. The other 6 specimens from each dog were incubated in α-phenyl-N-tertbutylnitrone/Eagle's minimum essential medium plus 1 of the following antioxidants: superoxide dismutase, catalase, superoxide dismutase/catalase, indomethacin, allopurinol, or deferoxamine mesylate. All specimens were incubated at 26 C for 90 minutes, then frozen at -20 C until they were prepared for analysis by esr spectroscopy. Each specimen was thawed, homogenized, and extracted in a low-dielectric organic solvent prior to obtaining an esr spectrum which was analyzed for hyperfine splitting constants to identify radicals. Each first-derivative spectrum was digitally double-integrated to obtain an area: these areas were used to compare intensities of the spin. For each treatment group, the areas from the treated specimens were compared with the areas from the control specimens, using a paired t-test. Significance was accepted at P ≤ 0.05. Spin adducts were detected in all cancellous bone specimens. Specimens incubated in deferoxamine (P = 0.0017) and superoxide dismutase/catalase (P = 0.0452) had significantly smaller areas than did control specimens. The areas for the other treatment groups did not differ significantly from controls. Our results substantiate free radical production in freshly procured cancellous bone specimens and that radical formation is attenuated by in vitro incubation with deferoxamine or superoxide dismutase/catalase.

8-Amino-2′-deoxyadenosine:2′-Deoxythymidine Base Pairing: Identification of Novel Reverse Hoogsteen Mode in Solution

A novel reversed Hoogsteen mode is observed for the base-pairing of 8-amino-2′-deoxyadenosine with 2′-deoxythymidine in low dielectric solvent. The results may have important significance for designing novel DNA duplexes and triplexes incorporating 8-amino-dA.