Selective binding of monovalent cations to the stacking G-quartet structure formed by guanosine 5'-monophosphate: a solid-state NMR study

We report a solid-state multinuclear ((23)Na, (15)N, (13)C, and (31)P) NMR study on the relative affinity of monovalent cations for a stacking G-quartet structure formed by guanosine 5'-monophosphate (5'-GMP) self-association at pH 8. Two major types of cations are bound to the 5'-GMP structure: one at the surface and the other within the channel cavity between two G-quartets. The channel cation is coordinated to eight carbonyl oxygen atoms from the guanine bases, whereas the surface cation is close to the phosphate group and likely to be only partially hydrated. On the basis of solid-state (23)Na NMR results from a series of ion titration experiments, we have obtained quantitative thermodynamic parameters concerning the relative cation binding affinity for each of the two major binding sites. For the channel cavity site, the values of the free energy difference (Delta G degrees at 25 degrees C) for ion competition between M(+) and Na(+) ions are K(+) (-1.9 kcal mol(-1)), NH(4)(+) (-1.8 kcal mol(-1)), Rb(+) (-0.3 kcal mol(-1)), and Cs(+) (1.8 kcal mol(-1)). For the surface site, the values Delta G degrees are K(+) (2.5 kcal mol(-1)), NH(4)(+) (-1.3 kcal mol(-1)), Rb(+) (1.1 kcal mol(-1)), and Cs(+) (0.9 kcal mol(-1)). Solid-state NMR data suggest that the affinity of monovalent cations for the 5'-GMP structure follows the order NH(4)(+) > Na(+) > Cs(+) > Rb(+) > K(+) at the surface site and K(+) > NH(4)(+) > Rb(+) > Na(+) > Cs(+) > Li(+) at the channel cavity site. We have found that the cation-induced stability of a 5'-GMP structure is determined only by the affinity of monovalent cations for the channel site and that the binding of monovalent cations to phosphate groups plays no role in 5'-GMP self-ordered structure. We have demonstrated that solid-state (23)Na and (15)N NMR can be used simultaneously to provide mutually complementary information about competitive binding between Na(+) and NH(4)(+) ions.     

Cation exchange in lipophilic G-quadruplexes: not all ion binding sites are equal

Lipophilic guanosine derivatives that form G-quadruplexes are promising building blocks for ionophores and ion channels. Herein, cation exchange between solvated cations (K+ and NH4+) and bound cations in the G-quadruplex [G1]16.4Na+.4DNP- was studied by electrospray ionization mass spectrometry and solution 1H, 15N NMR spectroscopy. The ESI-MS and 1H NMR data provided evidence for the formation of mixed-cationic Na+, K+ G-quadruplexes. The use of 15NH4+ cations in NMR titrations, along with 15N-filtered 1H NMR and selective NOE experiments, identified two mixed-cationic intermediates in the cation exchange pathway from [G1]16.4Na+.4DNP- to [G1]16.4NH4+.4DNP-. The central Na+, bound between the two symmetry-related G8-Na+ octamers, exchanges with either K+ or NH4+ before the two outer Na+ ions situated within the C4 symmetric G8 octamers. A structural rationale, based on differences in the cations' octahedral coordination geometries, is proposed to explain the differences in site exchange for these lipophilic G-quadruplexes. Large cations such as Cs+ can be exchanged into the central cation binding site that holds the two symmetry-related C4 symmetric G8 octamer units together. The potential relevance of these findings to both supramolecular chemistry and DNA G-quadruplex structure are discussed.     

Structural characterization of G-quadruplexes in deoxyguanosine clusters using ion mobility mass spectrometry

The aggregation and conformation of deoxyguanosine (dG) in an ammonium acetate buffer solution were examined using mass spectrometry, ion mobility, and molecular mechanics/dynamics calculations. The nano-ESI mass spectrum indicated that 4 and 6 dGs cluster with 1 NH4+; 11 dGs with 2 NH4+; 14, 16, and 17 dGs with 3 NH4+; and 23 dGs with 4 NH4+. The collision cross sections with helium were measured and compared with calculated cross sections of theoretical structures generated by molecular mechanics/dynamics calculations. Three distinct arrival time distribution (ATD) peaks were observed for (4dG + NH4)+. One peak was assigned to the quadruplex structure of (4dG + NH4)+, while the other two peaks corresponded to the quadruplex structures of (8dG + 2NH4)2+ and (12dG + 3NH4)3+, all with the same m/z. Four ATD peaks were observed for (6dG + NH4)+ and assigned to the globular structure of (6dG + NH4)+, and the quadruplex structures of (12dG + 2NH4)2+, (18dG + 3NH4)3+, and (24dG + 4NH4)4+. Two ATD peaks were observed for (11dG + 2NH4)2+ and assigned to the quadruplex structures of (11dG + 2NH4)2+ and (22dG + 4NH4)4+. All of the other clusters in the mass spectrum (14, 16, and 17 dGs with 3 NH4+ and 23 dGs with 4 NH4+) only had one peak in their ATDs and in all cases the theoretical structures in a quadruplex arrangement agreed with the experimental cross sections. These results provide compelling evidence that quadruplexes are present in solution and retain their structure during the spray process, dehydration, and detection.     

Mechanism of ion stacking in aqueous partition chromatographic processes

It has been reported that ion enrichment phenomena are observed in liquid chromatographic processes with an aqueous mobile phase on the columns packed with nonionic materials. However, the mechanism of the ion enrichment is not at all well understood. In this study, we investigated the retention and enrichment behaviors of simple inorganic anions on a C18‐bonded silica column and a cross‐linked hydroxylated methacrylic polymer gel column with pure aqueous mobile phases containing various electrolytes. We show that the stacking of ionic solutes can successfully be accounted for by the ion partition model, and it takes place due to the effect of the background coion in the eluent and/or sample solution on the distribution of the ions between the bulk water and the water incorporated in the packing material, which acts as the stationary phase. Using the ion exclusion effect of fixed anionic charges on a packing material as well as the ion stacking by partition, we developed a simple and versatile method for effective enrichment of anionic solutes in aqueous solutions. The enrichment factor and the elution time of the stacked ion zone can be predicted by the ion partition model.     

Four-stranded nucleic acids: structure, function and targeting of G-quadruplexes

There are many structures that can be adopted by nucleic acids other than the famous Watson-Crick duplex form. This tutorial review describes the guanine rich G-quadruplex structure, highlighting the chemical interactions governing its formation, and the topological variants that exist. The methods that are used to study G-quadruplex structures are described, with examples of the information that may be derived from these different methods. Next, the proposed biological functions of G-quadruplexes are discussed, highlighting especially their presence in telomeric regions and gene promoters. G-quadruplex structures are the subject of considerable interest for the development of small-molecule ligands, and are also the targets of a wide variety of natural proteins.     

Energy-loss straggling of low energetic 16O ion in Co, Ni and Lu

The energy-loss straggling for low-energetic ¹⁶O ion in Co, Ni and Lu was measured. The obtained results were compared with various theoretical predictions. The variance of foil thickness was measured by different methods and the target quality was discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Ab initio rigid water: effect on water structure, ion hydration, and thermodynamics

We investigate the liquid structure, ion hydration, and some thermodynamic properties associated with the rigid geometry approximation to water by applying ab initio molecular dynamics simulations (AIMD) with the Perdew-Burke-Ernzerhof (PBE) exchange-correlation functional at T = 320 K. We vary the rigid water geometry in order to locate a class of practical water models that yield reasonable liquid structure and dynamics, and to examine the progression of AIMD-predicted water behavior as the OH bond length varies. Water constrained at the optimal PBE gas phase geometry yields reasonable pair correlation functions. The predicted liquid phase pressure, however, is large ( approximately 8.0 kbar). Although the O-H bond in water should elongate when transferred from gas to the condensed phase, when it is constrained to 0.02, or even just 0.01 A longer than the optimal gas phase value, liquid water is predicted to be substantially overstructured compared to experiments. Zero temperature calculations of the thermodynamic properties of cubic ice underscore the sensitivity toward small variations in the O-H bond length. We examine the hydration structures of potassium, chloride, and formate ions in one rigid PBE water model. The results are in reasonable agreement with unconstrained AIMD simulations.     

Lipophilic G-quadruplexes are self-assembled ion pair receptors,and the bound anion modulates the kinetic stability of these complexes

With an eye toward the eventual selective modification of noncovalent structures, we used ESI-MS, X-ray crystallography, and NMR spectroscopy to study the anion's influence on the structure and dynamics of self-assembled ion pair receptors formed from guanosine G 1. We compared five complexes of formula (G 1)(16).2Ba(2+).4A(-) containing different organic anions: 2,4,6-trinitrophenolate (2), 2,6-dinitrophenolate (3), 4-methyl-2,6-dinitrophenolate (4), 4-methoxy-2,6-dinitrophenolate (5), and 2,5-dinitrophenolate (6). Crystallography reveals that anion-nucleobase hydrogen bond geometry is sensitive to both phenolate basicity and structure. For the 2,6-substituted anions 2-5, progressive shortening of anion-nucleobase hydrogen bonds is correlated with increased phenolate basicity. Lipophilic G-quadruplexes with different anions also have much different kinetic stabilities in CD(2)Cl(2) solution. Proton NMR shows that free 6 exchanges faster with G-quadruplex-bound anion than do the 2,6-dinitrophenolates 2-5. The increased lability of 6 is probably because, unlike the 2,6-dinitrophenolates, this anion cannot effectively chelate separate G(8).M(2+) octamers via anion-nucleobase hydrogen bonds. In addition to these structural effects, the anion's basicity modulates the anion exchange rate between its free and bound states. 2D EXSY NMR shows that 3 and 5 exchange about 7 times slower than the less basic picrate (2). The use of 3, a relatively basic dinitrophenolate that hydrogen bonds with the amino groups of the two "inner" G(4)-quartets, resulted in extraordinary kinetic stabilization of the G-quadruplex in CD(2)Cl(2). Thus, no isomerization product (G 1)(8).Ba(2+).(G 1)(8).Sr(2+).4(3) was observed even 2 months after the separate G-quadruplexes (G 1)(16).2Ba(2+).4(3) and (G 1)(16).2Sr(2+).4(3) were combined in CD(2)Cl(2). In sharp contrast, G-quadruplexes containing the isomeric 6 anion have isomerization half-lives of approximately t(1/2) = 30 min under identical conditions. All the evidence indicates that the structure and electronics of the organic anions, bound to the assembly's periphery, are crucial for controlling the kinetic stability of these cation-filled G-quadruplexes.     

Experimental apparatus for investigation of sputtering and secondary ion emission induced by energetic ion beams

The construction of an experimental apparatus, for investigation of implantation, secondary ion emission and sputtering processes, during irradiation of samples with an ion beam of up to 70 keV energy, is described. The basis of the apparatus is an electromagnetic mass separator equipped with a quadrupole mass spectrometer located in the collector chamber. The computer data acquisition control system makes it possible to perform the experimental measurements with high accuracy and precision. Preliminary results of secondary ion mass spectral measurements, obtained for C, Al, Si and Cu targets bombarded with Ar(+) and Kr(+) ions, are presented.     

The effects of energetic ion irradiation on metal-to-polymer adhesion

In this study, the simple and effective surface modification of polymers through ion irradiation is described to improve metal-to-polymer adhesion. The surface of polymer films was irradiated with 150 keV Xe⁺ ions at various fluences, and copper (Cu) was then deposited onto the surface-modified polymer films. The surface properties of the modified films were investigated in terms of their wettability, chemical composition, and surface morphology. The metal-to-polymer adhesion strength was estimated using a nano-indenter. As a result, the surface environment of the polymer films was physiochemically changed by ion irradiation, which could have a significant effect on the metal-to-polymer adhesion. The irradiated polymer films exhibited a higher adhesion strength than the control film, and the strength depended on the fluence. The maximum adhesion strength (8.45 mN) of the Cu deposited on the irradiated PEN films was obtained at a fluence of 5×10¹⁴ ions/cm².     

Aromatic stacking of a perylenetetracarboxylic tetraester: Self-assembly in both water and chloroform

The self-assembly features of a water soluble perylenetetracarboxylic tetraester (PTTE) have been investigated by concentration dependent UV–Vis, steady-state fluorescence, and ¹H NMR titration experiments. The results showed that the PTTE molecules self-assemble cooperatively to form supramolecular aggregates in both water and chloroform by the combined action of hydrophobic effects, hydrogen bonding, and π–π stacking. To determine the mechanism of aggregation, the Goldstein–Stryer nucleation-elongation model was applied to the concentration-dependent data, starting from a dimeric nucleus. Scanning electron microscopy revealed different morphologies for assemblies stemming from different aggregation propensities of the monomers in water and chloroform.     

Assessing long-range contributions to the charge asymmetry of ion adsorption at the air–water interface

Anions generally associate more favorably with the air–water interface than cations. In addition to solute size and polarizability, the intrinsic structure of the unperturbed interface has been discussed as an important contributor to this bias. Here we assess quantitatively the role that intrinsic charge asymmetry of water''s surface plays in ion adsorption, using computer simulations to compare model solutes of various size and charge. In doing so, we also evaluate the degree to which linear response theory for solvent polarization is a reasonable approach for comparing the thermodynamics of bulk and interfacial ion solvation. Consistent with previous works on bulk ion solvation, we find that the average electrostatic potential at the center of a neutral, sub-nanometer solute at the air–water interface depends sensitively on its radius, and that this potential changes quite nonlinearly as the solute''s charge is introduced. The nonlinear response closely resembles that of the bulk. As a result, the net nonlinearity of ion adsorption is weaker than in bulk, but still substantial, comparable to the apparent magnitude of macroscopically nonlocal contributions from the undisturbed interface. For the simple-point-charge model of water we study, these results argue distinctly against rationalizing ion adsorption in terms of surface potentials inherent to molecular structure of the liquid''s boundary.

Cations and anions have different affinities for the air-water interface. The intrinsic orientation of surface molecules suggests such an asymmetry, but the bias is dominated by solvent response that is spatially local and significantly nonlinear.

Counter to expectations from conventional theories of solvation, there is a large body of both computational and experimental evidence indicating that small ions can adsorb to the air–water interface.^1–9 Implications across the biological, atmospheric and physical sciences have inspired efforts to understand the microscopic driving forces for ions associating with hydrophobic interfaces in general.^10–21 A particular emphasis has been placed on understanding ion specificity, i.e., why some ions exhibit strong interfacial affinity while others do not. Empirical trends indicate that ion size and polarizability are important factors, as could be anticipated from conventional theory. More surprisingly, the sign of a solute''s charge can effect a significant bias, with anions tending to adsorb more favorably than cations.Here we examine the microscopic origin of this charge asymmetry in interfacial ion adsorption. We specifically assess whether the thermodynamic preference can be simply and generally understood in terms of long-range biases that are intrinsic to an aqueous system surrounded by vapor. By “long-range” and “nonlocal” we refer to macroscopically large scales, i.e., collective forces that are felt at arbitrarily long distance. Such a macroscopically long-range bias is expected from the air–water interface due to its average polarization, and by some measures the bias is quite strong. By contrast, “local” contributions comprise the entire influence of a solute''s microscopic environment, including electrostatic forces from molecules that are many solvation shells away – any influence that decays over a sub-macroscopic length scale.The importance of macroscopically nonlocal contributions has been discussed extensively in the context of ion solvation in bulk liquid water, which we review in Section 1 as a backdrop for interfacial solvation. The notion that such contributions strongly influence charge asymmetry of solvation at the air–water interface has informed theoretical approaches and inspired criticism of widely used force fields for molecular simulation.^22,23 A full understanding of their role in interfacial adsorption, however, is lacking.In the course of this study, we will also evaluate the suitability of dielectric continuum theory (DCT) to describe the adsorption process. DCT has provided an essential conceptual framework for rationalizing water''s response to electrostatic perturbations. But a more precise understanding of its applicability is needed, particularly for the construction of more elaborate models (e.g., with heterogeneous polarizability near interfaces^24–26) and for the application of DCT to evermore complex (e.g., nanoconfined^27,28) environments.     

Influence of metal ion on chelate–aryl stacking interactions

CCSD(T)/CBS and DFT methods are employed to study the stacking interactions of acetylacetonate‐type (acac‐type) chelates of nickel, palladium, and platinum with benzene. The strongest chelate–aryl stacking interactions are formed by nickel and palladium chelate, with interaction energies of −5.75 kcal mol⁻¹ and −5.73 kcal mol⁻¹, while the interaction of platinum chelate is weaker, with interaction energy of −5.36 kcal mol⁻¹. These interaction energies are significantly stronger than stacking of two benzenes, −2.73 kcal mol⁻¹. The strongest nickel and palladium chelate–aryl interactions are with benzene center above the metal area, while the strongest platinum chelate–aryl interaction is with the benzene center above the C2 atom of the acac‐type chelate ring. These preferences arise from very different electrostatic potentials above the metal ions, ranging from very positive above nickel to slightly negative above platinum. While the differences in electrostatic potentials above metal atoms cause different geometries with the most stable interaction among the three metals, the dispersion (correlation energy) component is the largest contribution to the total interaction energy for all three metals.     

Predicting ion concentration polarization and analyte stacking/focusing at nanofluidic interfaces

We report on the investigation of electropreconcentration phenomena in micro-/nanofluidic devices integrating 100 μm long nanochannels using 2D COMSOL simulations based on the coupled Poisson–Nernst–Planck and Navier–Stokes system of equations. Our numerical model is used to demonstrate the influence of key governing parameters such as electrolyte concentration, surface charge density, and applied axial electric field on ion concentration polarization (ICP) dynamics in our system. Under sufficiently extreme surface-charge-governed transport conditions, ICP propagation is shown to enable various transient and stationary stacking and counter-flow gradient focusing mechanisms of anionic analytes. We resolve these spatiotemporal dynamics of analytes and electrolyte ICP over disparate time and length scales, and confirm previous findings that the greatest enhancement is observed when a system is tuned for analyte focusing at the charge, excluding microchannel, nanochannel electrical double layer (EDL) interface. Moreover, we demonstrate that such tuning can readily be achieved by including additional nanochannels oriented parallel to the electric field between two microchannels, effectively increasing the overall perm-selectivity and leading to enhanced focusing at the EDL interfaces. This approach shows promise in providing added control over the extent of ICP in electrokinetic systems, particularly under circumstances in which relatively weak ICP effects are observed using only a single channel.     

Unfolding of proteins monitored by electrospray ionization mass spectrometry: a comparison of positive and negative ion modes

Electrospray ionization (ESI) mass spectrometry (MS) in both the positive and negative ion mode has been used to study protein unfolding transitions of lysozyme, cytochrome c (cyt c), and ubiquitin in solution. As expected, ESI of unfolded lysozyme leads to the formation of substantially higher charge states than the tightly folded protein in both modes of operation. Surprisingly, the acid-induced unfolding of cyt c as well as the acid and the base-induced unfolding of ubiquitin show different behavior: In these three cases protein unfolding only leads to marginal changes in the negative ion charge state distributions, whereas in the positive ion mode pronounced shifts to higher charge states are observed. This shows that ESI MS in the negative ion mode as a method for probing conformational changes of proteins in solution should be treated with caution. The data presented in this work provide further evidence that the conformation of a protein in solution not its charge state is the predominant factor for determining the ESI charge state distribution in the positive ion mode. Furthermore, these data support the hypothesis of a recent study (Konermann and Douglas, Biochemistry 1997, 36, 12296–12302) which suggested that ESI in the positive ion mode is not sensitive to changes in the secondary structure of proteins but only to changes in the tertiary structure.     

Amination of energetic anions: high-performing energetic materials

The new energetic materials 2-amino-5-nitrotetrazole (ANT, 1), 1-amino-3,4-dinitro-1,2,4-triazole (ADNT, 2), and both 1,1'-diamino-5,5'-bistetrazole and 1,2'-diamino-5,5'-bistetrazole (11DABT, 3 and 12DABT, 4) have been prepared by the amination of the parent anion with O-tosylhydroxylamine. The 5-H-tetrazolate anion has also been aminated using hydroxylamine O-sulfonic acid to both 1-aminotetrazole and 2-aminotetrazole (1AT, 5 and 2AT, 6). The prepared materials have been characterized chemically (XRD (1-4, 6·AtNO(2), 8), multinuclear NMR, IR, Raman) and as explosives (mechanical and electrostatic sensitivity) and their explosive performances calculated using the EXPLO5 computer code. The prepared N-amino energetic materials, which can also be used as new ligands for high energy-capacity transition metal complexes, exhibit high explosive performances (in the range of hexogen and octogen) and a range of sensitivities from low to extremely high.     

Surface-charge induced ion depletion and sample stacking near single nanopores in microfluidic devices

We report integrated nanopore/microchannel devices in which single nanopores are isolated between two microfluidic channels. The devices were formed by sandwiching track-etched conical nanopores in a poly(ethylene terephthalate) membrane between two poly(dimethylsiloxane) microchannels. Integration of the nanopores into microfluidic devices improves mass transport to the nanopore and allows easy coupling of applied potentials. Electrical and optical characterization of these individual nanopores suggests double layer overlap is not required to form an ion depletion region adjacent to the nanopore in the microchannel; rather, excess surface charge in the nanopore contributes to the formation of this ion depletion region. We used fluorescent probes to optically map the ion depletion region and the stacking of fluorescein near the nanopore/microchannel junction, and current measurements confirmed formation of the ion depletion region.     

Electron response of metallic clusters to strong laser pulses and energetic ion collisons

We investigate the electron dynamics of Na₉ ⁺ excited by strong fs laser pulses and fast proton collisions. Non-perturbative numerical simulations are performed using time-dependent density-functional methods on a semiclassical and fully quantal level. Both excitation mechanisms induce pronounced dipole oscillations accompanied by rapid ionization.     

The reactions of energetic tritium atoms with water molecules

Hard sphere excitation functions are derived for the reactions of T atoms with H₂O molecules, and the results compared with the available experimental data.