Intercalators. 1. Nature of stacking interactions between intercalators (ethidium, daunomycin, ellipticine, and 4',6-diaminide-2-phenylindole) and DNA base pairs. Ab initio quantum chemical, density functional theory, and empirical potential study

Properties of isolated intercalators (ethidium (E), daunomycin (D), ellipticine (EL), and 4,6'-diaminide-2-phenylindole (DAPI)) and their stacking interactions with adenine...thymine (AT) and guanine...cytosine (GC) nucleic acid base pairs were investigated by means of a nonempirical correlated ab initio method. All intercalators exhibit large charge delocalization, and none of them (including the DAPI dication) exhibits a site with dominant charge. All intercalators have large polarizability and are good electron acceptors, while base pairs are good electron donors. MP2/6-31G*(0.25) stabilization energies of intercalator...base pair complexes are large (E...AT, 22.4 kcal/mol; D...GC, 17.8 kcal/mol; EL...GC, 18.2 kcal/mol; DAPI...GC, 21.1 kcal/mol) and are well reproduced by modified AMBER potential (van der Waals radii of intercalator atoms are enlarged and their energy depths are increased). Standard AMBER potential underestimates binding, especially for DAPI-containing complexes. Because the DAPI dication is the best electron acceptor (among all intercalators studied), this difference is explained by the importance of the charge-transfer term, which is not included in the AMBER potential. For the neutral EL molecule, the standard AMBER force field provides correct results. The Hartree-Fock and DFT/B3LYP methods, not covering the dispersion energy, fail completely to reveal any energy minimum at the potential energy curve of the E...AT complex, and these methods thus cannot be recommended for a study of intercalation process. On the other hand, an approximate version of the DFT method, which was extended to cover London dispersion energy, yields for all complexes very good stabilization energies that are well comparable with referenced ab initio data. Besides the vertical dependence of the interaction, an energy twist dependence of the interaction energy was also investigated by a reference correlated ab initio method and empirical potentials. It is concluded that, despite the cationic (E +1, D +1, DAPI +2) or polar (EL) character of the intercalators investigated, it is the dispersion energy which predominantly contributes to the stability of intercalator...base pair complexes. Any procedure which does not cover dispersion energy is thus not suitable for studying the process of intercalation.     

Molecular dynamics simulations and thermodynamics analysis of DNA-drug complexes. Minor groove binding between 4',6-diamidino-2-phenylindole and DNA duplexes in solution

An extended set of nanosecond-scale molecular dynamics simulations of DNA duplex sequences in explicit solvent interacting with the minor groove binding drug 4',6-diamidino-2-phenylindole (DAPI) are investigated for four different and sequence specific binding modes. Force fields for DAPI have been parametrized to properly reflect its internal nonplanarity. Sequences investigated include the binding modes observed experimentally, that is, AATT in d(CGCGAATTCGCG)(2) and ATTG in d(GGCCAATTGG)(2) and alternative shifted binding modes ATTC and AATT, respectively. In each case, stable MD simulations are obtained, well reproducing specific hydration patterns seen in the experiments. In contrast to the 2.4 A d(CGCGAATTCGCG)(2) crystal structure, the DAPI is nonplanar, consistent with its gas-phase geometry and the higher resolution crystal structure. The simulations also suggest that the DAPI molecule is able to adopt different conformational substates accompanied by specific hydration patterns that include long-residing waters. The MM_PBSA technology for estimating relative free energies was utilized. The most consistent free energy results were obtained with an approach that uses a single trajectory of the DNA-DAPI complex to estimate all free energy terms. It is demonstrated that explicit inclusion of a subset of bound water molecules shifts the calculated relative binding free energies in favor of both crystallographically observed binding modes, underlining the importance of structured hydration.     

On the Discrepancy for Boxes and Polytopes

 We consider so-called Tusnády’s problem in dimension d: Given an n-point set P in R ^d , color the points of P red or blue in such a way that for any d-dimensional interval B, the number of red points in differs from the number of blue points in by at most Δ, where should be as small as possible. We slightly improve previous results of Beck, Bohus, and Srinivasan by showing that , with a simple proof. The same asymptotic bound is shown for an analogous problem where B is allowed to be any translated and scaled copy of a fixed convex polytope A in R ^d . Here the constant of proportionality depends on A and we give an explicit estimate. The same asymptotic bounds also follow for the Lebesgue-measure discrepancy, which improves and simplifies results of Beck and of Károlyi.     

Analysis of artichoke (Cynara cardunculus L.) extract by means of micellar electrokinetic capillary chromatography

The main constituents of artichoke extract were separated by micellar electrokinetic chromatography (MEKC), using a buffer consisting of 100 mM sodium dodecyl sulfate (SDS) in 20 mM sodium dihydrogen phosphate, 20 mM disodium tetraborate (pH 8.6) as background electrolyte. Optimum separation voltage of 28 kV (positive polarity) and a capillary temperature of 25 degrees C gave the best analysis. The UV detection was performed at 200 nm. The method was successfully used to analyze plant and drug samples as well as for the study of artichoke antioxidant activity. The quantitative MEKC results were in good agreement to those obtained previously by reversed-phase high-performance liquid chromatography (RP-HPLC).     

Localization properties of strain-softening gradient plasticity models. Part II: Theories with gradients of internal variables

The second part of this paper compares and evaluates enhancements of the conventional plasticity theory by gradients of internal variables. Attention is focused on their performance as localization limiters. Both explicit and implicit gradient formulations are considered. It is shown that certain models suffer by serious mathematical deficiencies that would complicate their numerical implementation. Some other models are appropriate only at early stages of the softening process but later exhibit locking accompanied by a spurious expansion of the localized plastic zone. The comparative study indicates that a convenient and robust tool for regularized modeling of the entire localization process is provided by the implicit gradient approach combined with a suitable form of the hardening/softening law.     

Three empirical correlations connecting gaseous cluster energies and solvation energies of alkali metal and halide ions.

This paper gives two empirical correlations of formation Gibbs energies of gaseous clusters DeltaG(f)n as function of number of solvent molecules attached to the ion, n, and one correlation connecting the DeltaG(f)n for each individual cluster with the total DeltaG(o)hydr value. The experimental ratios of DeltaG(f)2/DeltaG(f)1 and DeltaG(f)3/DeltaG(f)1 for both alkali metal and halide ions are on average equal to 0.75 and 0.5, respectively. DeltaG(f)n values for n > or = 4 are correlated with n as DeltaG(f)n = [a/(n - 1)] DeltaG(f)1 + b DeltaG(f)1. For all available data on cluster energies and each individual cluster, the DeltaG(f)n's are straight-line functions of DeltaG(o)hydr. This well corresponds to another empirical rule stating that the Gibbs energies of transfer of ions between two solvents are often as well straight-line functions of DeltaG(o)(hydr) [J. Rais and T. Okada, J. Phys. Chem. A, 2000, 104, 7314]. Tentative models of the found behavior are proposed. A full data set of the gaseous cluster energies of formation based on inclusion of new, usually not used entries from the literature is provided.     

C,N‐chelated triorganotin(IV) diesters of 4‐ketopimelic acid and their fungicidal activity

The set of four triorganotin(IV) diesters of 4‐ketopimelic acid containing {2‐[(CH₃)₂NCH₂]C₆H₄}‐ as a C,N‐chelating ligand was prepared. Their structures were studied by the help of IR, NMR and X‐ray crystallographic techniques in the case of {{2‐[(CH₃)₂NCH₂]C₆H₄}SnPh₂}₂[(OOCCH₂CH₂)₂C?]. All these compounds are monomeric both in solid state and solution with five‐coordinated tin atoms and medium strong intramolecular Sn? N connection. The antimycotical activity of these compound was studied and compared with the triorganotin(IV) derivatives of 4‐ketopimelic acid and antimycotical drugs in clinical use. Copyright © 2008 John Wiley & Sons, Ltd.     

Stochastic equations on compact groups in discrete negative time

In this paper a stochastic equation on compact groups in discrete negative time is studied. The diagonal group action on the extreme points of solutions is proved to be transitive by means of the coupling method. This result is applied to generalize Yor’s work which is closely related to Tsirelson’s stochastic differential equation and to give criteria for existence of a strong solution and for uniqueness in law. This research was supported by Open Research Center Project for Private Universities: matching fund subsidy from MEXT, 2004–2008.     

Solvent-induced textural changes of as-synthesized mesoporous alumina, as reported by spin probe electron spin resonance spectroscopy

The effect of solvent used during the synthesis and postsynthesis treatment on textural properties of organized mesoporous aluminas was investigated and related to the behavior of spin probes studied by electron spin resonance (ESR) spectroscopy. It was found that the structure of surfactant aggregates serving in the as-synthesized precipitates as templates could be easily modified by treatment with different solvents. This treatment induces corresponding variations in surface areas, mesopore volumes, and mesopore diameters of the final products. The ESR spectrum of 5-doxyl stearic acid spin probe properly reflects the changes in template structure based on changes of the solvent used and represents an early indicator of the corresponding textural modifications of the mesoporous alumina.     

Unexpectedly strong energy stabilization inside the hydrophobic core of small protein rubredoxin mediated by aromatic residues: correlated ab initio quantum chemical calculations

The formation of a hydrophobic core of globular proteins is believed to be the consequence of exterior hydrophobic forces of entropic nature. This, together with the low occurrence of hydrogen bonds in the protein core, leads to the opinion that the energy contribution of core formation to protein folding and stability is negligible. We show that stabilization inside the hydrophobic core of a small protein, rubredoxin, determined by means of high-level correlated ab initio calculations (complete basis set limit of MP2 stabilization energy + CCSD(T) correction term), amounted to approximately 50 kcal/mol. These results clearly demonstrate strong attraction inside a hydrophobic core. This finding may lead to substantial changes in the current view of protein folding. We also point out the inability of the DFT/B3LYP method to describe a strong attraction between studied amino acids.