Treatment of charge singularities in implicit solvent models

This paper presents a novel method for solving the Poisson-Boltzmann (PB) equation based on a rigorous treatment of geometric singularities of the dielectric interface and a Green's function formulation of charge singularities. Geometric singularities, such as cusps and self-intersecting surfaces, in the dielectric interfaces are bottleneck in developing highly accurate PB solvers. Based on an advanced mathematical technique, the matched interface and boundary (MIB) method, we have recently developed a PB solver by rigorously enforcing the flux continuity conditions at the solvent-molecule interface where geometric singularities may occur. The resulting PB solver, denoted as MIBPB-II, is able to deliver second order accuracy for the molecular surfaces of proteins. However, when the mesh size approaches half of the van der Waals radius, the MIBPB-II cannot maintain its accuracy because the grid points that carry the interface information overlap with those that carry distributed singular charges. In the present Green's function formalism, the charge singularities are transformed into interface flux jump conditions, which are treated on an equal footing as the geometric singularities in our MIB framework. The resulting method, denoted as MIBPB-III, is able to provide highly accurate electrostatic potentials at a mesh as coarse as 1.2 A for proteins. Consequently, at a given level of accuracy, the MIBPB-III is about three times faster than the APBS, a recent multigrid PB solver. The MIBPB-III has been extensively validated by using analytically solvable problems, molecular surfaces of polyatomic systems, and 24 proteins. It provides reliable benchmark numerical solutions for the PB equation.     

Influence of the solvent on the charge distribution of anomeric compounds

Conformational preferences of methanediol, dimethoxymethane, methanediamine, and fluoromethanol in the presence of solvents of diverse polarity (water, acetone, and chloroform), modeled with the polarizable continuum model, were analyzed within the framework of the Quantum Theory of Atoms in Molecules. The results indicate that the hydrogens bonded to the anomeric carbon experience the largest reorganization of electron density upon conformational change, as was obtained from previous calculations in the gas phase. When the water solvation is simulated by explicit inclusion of water molecules, the electron density reorganization involved in the cluster formation is significantly different for each conformer of methanediol. As a consequence, similar depletions of electron population are displayed by the hydrogens of hydroxyl and methylene groups in the cluster obtained for the most stable conformer of methanediol, with regard to that built for the completely antiperiplanar conformer.     

Antihydrophobic solvent effects: an experimental probe for the hydrophobic contribution to enzyme-inhibitor binding

The hydrophobic component to the binding affinities of one acyclic phosphinate (4) and three macrocyclic phosphonamidate inhibitors (1-3) to the zinc peptidase thermolysin was probed by varying the solvent composition. Increasing the percentage of ethanol in the buffer solution over the range 0-9% increases the inhibition constants, K(i), by up to an order of magnitude. This approach represents an experimental method for distinguishing solvation from conformational or other effects on protein-ligand binding. The size of the "antihydrophobic effect" is correlated with the amount of hydrophobic surface area sequestered from solvent on association of the inhibitor and enzyme, although it is attenuated from that calculated from the surface tension of ethanol-water mixtures. The results are consistent with the Lum-Chandler-Weeks explanation for the size dependence of the hydrophobic effect.     

Recent developments of charge injection and charge transfer in DNA

The question of whether and how electrons migrate through DNA was a matter of controversial discussion over the last ten years. Today, there is no doubt that long distance charge migration through DNA exists and most scientists explain this process by a multistep hopping mechanism. This feature article presents recent developments of our group on the injection of a positive charge into DNA bases and the transfer of the charge between the DNA bases. The influence of the donor, the nature of the bridge, and the distance between the donor and the acceptor are discussed.     

DNA charge transport leading to disulfide bond formation

Here, we show that DNA-mediated charge transport (CT) can lead to the oxidation of thiols to form disulfide bonds in DNA. DNA assemblies were prepared possessing anthraquinone (AQ) as a photooxidant spatially separated on the duplex from two SH groups incorporated into the DNA backbone. Upon AQ irradiation, HPLC analysis reveals DNA ligated through a disulfide. The reaction efficiency is seen to vary in assemblies containing intervening DNA mismatches, confirming that the reaction is DNA-mediated. Interestingly, one intervening mismatch near the thiols promotes an increase in efficiency, which we attribute to increased base dynamics. Hence, here, where the reaction is on the backbone rather than within the base stack, stacking perturbations do not necessarily lead to an inhibitory effect on DNA CT.     

Application of the energy gap law to the decay of charge transfer excited states,solvent effects

Values of non-radiative decay rate constants (k_nr) and emission energies (E_cm) have been obtained for Os(Phen₃)²⁺ in a series of solvents and the results are consistent with the energy gap law. For hydroxylic solvents like water or methanol related studies suggest the existence of strong, specific contributions to the vibrational trapping energy of the solvent.     

Oscillations in solvent fraction of polyelectrolyte multilayers driven by the charge of the terminating layer

We have investigated polyelectrolyte multilayers of poly(styrene sulfonate) (PSS) and poly(allylamine hydrochloride) in contact with D2O by neutron reflectometry. The study particularly focuses on the changes in the solvent fraction of the system upon addition of a layer. When the layers are deposited at a low salt concentration (0.25 M NaCl), no significant changes in the solvent fraction are detected. In contrast, at a larger salt concentration (1 M NaCl), oscillations in the solvent fraction are detected when a new layer is deposited. In this case, addition of PSS systematically increases the solvent volume fraction, and addition of PAH decreases the solvent fraction. The results suggest that one of the parameters driving the oscillations in solvent fraction is the uncompensated charges present in the layers. This study opens new perspectives on results previously published by other authors: in addition to polymer desorption, water uptake or release might contribute to the different regimes of multilayer growth reported in the literature (linear, asymmetric, or exponential growth). In addition, comparison to NMR results previously reported allows for conclusions about the mobility of the solvent in the multilayers: the average rotational correlation time of the water molecules in the polyelectrolyte layers decreases upon addition of PSS and increases upon addition of PAH.     

Electron correlation as the driving force for charge transfer: charge migration following ionization in N-methyl acetamide

A hole charge created in a molecule, for instance, by ionization, can migrate through the system solely driven by electron correlation. The migration of a hole charge following ionization in N-methyl acetamide (a molecular system containing a peptide bond) is investigated. The initial hole charge is localized at one specific site of the molecule. Ab initio calculations show that nearly 90% of the hole migrates to a remote site of the molecule in 4.2 fs. This migration of charge is highly efficient and ultrafast. The underlying mechanism for this migration of a hole charge is identified and compared with a simple model.     

Effects of solvent on the maximum charge state and charge state distribution of protein ions produced by electrospray ionization

The effects of solvent composition on both the maximum charge states and charge state distributions of analyte ions formed by electrospray ionization were investigated using a quadrupole mass spectrometer. The charge state distributions of cytochrome c and myoglobin, formed from 47%/50%/3% water/solvent/acetic acid solutions, shift to lower charge (higher m/z) when the 50% solvent fraction is changed from water to methanol, to acetonitrile, to isopropanol. This is also the order of increasing gas-phase basicities of these solvents, although other physical properties of these solvents may also play a role. The effect is relatively small for these solvents, possibly due to their limited concentration inside the electrospray interface. In contrast, the addition of even small amounts of diethylamine (<0.4%) results in dramatic shifts to lower charge, presumably due to preferential proton transfer from the higher charge state ions to diethylamine. These results clearly show that the maximum charge states and charge state distributions of ions formed by electrospray ionization are influenced by solvents that are more volatile than water. Addition of even small amounts of two solvents that are less volatile than water, ethylene glycol and 2-methoxyethanol, also results in preferential deprotonation of higher charge state ions of small peptides, but these solvents actually produce an enhancement in the higher charge state ions for both cytochrome c and myoglobin. For instruments that have capabilities that improve with lower m/z, this effect could be taken advantage of to improve the performance of an analysis.     

Analysis of charge transport in gels containing polyoxometallates using methods of different sensitivity to migration

Two methods have been used for examination of transport of charge in gels soaked with DMF and containing dissolved polyoxometallates. The first method is based on the analysis of both Cottrellian and steady-state currents and therefore is capable of giving the concentration of the electroactive redox centres and their transport (diffusion-type) coefficient. The second method provides the real diffusion coefficients, i.e. transport coefficients free of migrational influence, for both the substrate and the product of the electrode reaction. Several gels based on poly(methyl methacrylate), with charged (addition of 1-acrylamido-2-methyl-2-propanesulphonic acid to the polymerization mixture) and uncharged chains, have been used in the investigation. The ratio obtained for the diffusion coefficient (second method) and transport coefficient (first method) was smaller for the gels containing charged polymer chains than for the gels with uncharged chains. In part these changes could be explained by the contribution of migration to the transport of polyoxomatallates in the gels. However, the impact of the changes in the polymer-channel capacity at the electrode surface while the electrode process proceeds was also considered. These structural changes should affect differently the methods based on different time domains.     

Conformational energy contribution to the heat of solution in polymer–solvent systems. Part I. Theory

The conformational energy contribution (ΔU_conf) to the heat of solution in polymer-solvent systems is presented and discussed in connection with chain conformational properties. In particular, ΔU_conf has been discussed in terms of various possible mechanisms of coil deformation.     

Characteristics of migration patterns of DNA oligomers in gels and the relationship to the question of intrinsic DNA bending

We have developed a methodology that is capable of quantitatively describing the electrophoretic mobility patterns of oligomeric B-DNA through polyacrylamide gels (PAG) in the presence of varying concentration of the organic solvent 2-methyl-2,4-pentanediol (MPD), used routinely to induce DNA crystallization. The model includes the ion atmosphere and its polarization, electrostatic excluded volume, hydrodynamic interactions, and fluctuation effects that characterize the overall size of the migrating polyion. Using this model, and by critically examining the mobility patterns of linear random-sequence B-DNA molecules in PAG as a function of MPD, we address the question of the discrepancy between current models used to explain the molecular origins of A-tract-induced DNA bending. Direct analysis of the mobility of B-DNA oligomers on PAG, and comparison to the mobility of A-tract-containing oligomers, shows a significant apparent effect of MPD on the mobility of generic B-DNA sequences, which is larger than the effect on A-tract-containing oligomers. The effect is chain-length dependent, especially at lower MPD concentration. Thus, the apparent reduction in gel mobility, as a function of MPD, is not unique to A-tract regions or A-tract-containing molecules. However, our analysis suggests that MPD molecules are probably excluded from the surface of both B-DNA and A-tract molecules. This is supported by circular dichroism studies on A-tract and B-DNA molecules in solutions containing various MPD concentrations.     

食品包装材料中7种光引发剂向水性模拟液中的迁移测定

为了考察食品包装材料中光引发剂向食品中迁移的情况,以水性模拟液作为迁移溶剂,用65 μm聚二甲基硅氧烷/二乙烯基苯(PDMS-DVB)纤维头进行固相微萃取结合气相色谱-质谱(SPME/GC-MS)分析方法同时测定食品包装材料中7种光引发剂(PIs)的迁移量。方法的检出限为0.0012～0.0069 μg/L,线性范围为0.03～1.0 μg/L (r2＞0.9909),在3种浓度的添加水平下,加标回收率为70.8%～112.0%,相对标准偏差不大于14.0%。利用建立的方法对20个实际样品进行测定,发现所有样品中均检出二苯甲酮,其中10个样品中检出4-甲基二苯甲酮,3个样品中检出1-羟基环己基苯基甲酮,1个样品中检出安息香双甲醚。该方法的灵敏度高,样品前处理过程简单,无需使用有机溶剂,为食品接触材料表面印刷油墨中PIs向水性样品中的迁移测定提供了参考。     

Influence of solvent on the energetics of hole transfer in DNA

We have investigated the contribution of molecular environment to the exchange reactions in the DNA molecule taking into account different geometries of the reaction centers in oxidized and reduced states. We have observed the influence of the ionization potential of the donor and the acceptor on the free energy of the hole transfer reaction in the solvated DNA molecule: A decrease of the free energy occurs if IPA > or = IPD and an increase if IPA < or = IPD. The corresponding decrease of the potential barrier by 0.244 eV for hole migration from (G-C) to (A-T) and increase for migration from (G-C) to (G-C)n in solvent have been determined. The prevalence of oxidation of the redox states in the molecule center in comparison to the molecule sides due to the nonuniform charge distribution along the phosphate backbone was found to be stronger for the non-neutralized backbone than for the neutralized case. The influence of the single counterion on the electrostatic interactions within the solute DNA molecule has been found to be smoothly spread over a long distance approximately 7-8 base pairs. Therefore, each counterion contributes to the oxidation potential of the 7-8 nearest nucleosides and any irregularity due to phosphate neutralization would not significantly modify the potential profile for the hole migration through the DNA molecule.     

Energy migration and transfer in polymer systems

Theoretical treatments of singlet energy transfer are reviewed with the objective of determining the expressions most relevant for polymeric systems. Observations of singlet energy transfer from 1,3 diphenyl oxazole to 1,4 di[2-(4-methyl 5-phenyl oxazolyl)]-benzene, anthracene and benzophenone confirm that the Förster relationships are valid for dilute solutions of these small molecules. For a polymer donor in which there exists spectral overlap in absorption and emission, there is the possibility of energy migration along the chain. Under these conditions, and where acceptor diffusion may be important, it is found that relationships due to Yokota and Tanimoto are the most useful in both fluid and polymeric environments. Coefficients for migration of singlet energy down chains of poly(N-vinyl carbazole), poly(2-vinyl) naphthalene) and copolymers of N-vinyl carbazole with methyl acrylate have been evaluated. They are consistent with a model in which energy is transferred by a random walk series of Förster interactions between spectroscopically active nearest neighbours.     

Conformational energy contribution to the heat of solution in polymer–solvent systems. Part II. Experimental results

Heats of solution (ΔH_exp) in solvents of increasing thermodynamic power have been measured for four polymers: polystyrene (PS), poly(vinyl acetate) (PVAc), polyisobutylene (PIB) and polydimethylsiloxane (PDMS). After subtraction from ΔH_exp of an interaction term (calculated by the Hildebrand treatment based on solubility parameters) and the excess volume term, the quantity remaining is interpreted as the conformational energy contribution (ΔU_conf) to the heat of solution. ΔU_conf appears to correlate well with some basic conformational properties of the chain, such as the sign of the temperature coefficient of unperturbed dimensions derived from solution properties, and shows a monotonic behavior with α, the expansion coefficient of the polymer coil in the final solution. Numerical values of ΔU_conf, at least for those cases in which polymer solubility parameters are known with some certainty, are much larger than those evaluated from rubber elasticity experiments (through the experimentally accessible value of the energy component of the force of retraction im simple elongation).