Ekaterina A. Nikitina

The 1:1 host-guest complexation between cucurbit[7]uril and styryl dye.

The photophysical properties of aqueous solution of styryl dye, 4-[(E)-2-(3,4-dimethoxyphenyl)ethenyl]-1-ethylpyridinium perchlorate (dye 1), in the presence of cucurbit[7]uril (CB[7]) was studied by means of fluorescence spectroscopy methods. The production of 1:1 host-guest complexes in the range of CB[7] concentrations up to 16 μM with K = 1.0 × 10(6) M(-1) has been observed, which corresponds to appearance of the isosbestic point at 396 nm in the absorption spectra and a 5-fold increase in fluorescence intensity. The decay of fluorescence was found to fit to double-exponential functions in all cases; the calculated average fluorescence lifetime increases from 145 to 352 ps upon the addition of CB[7]. Rotational relaxation times of dye 1 solutions 119 ± 14 ps without CB[7] and 277 ± 35 ps in the presence of CB[7] have been determined by anisotropy fluorescence method. The comparison of the results of quantum-chemical calculations and experimental data confirms that in the host cavity dye 1 rotates as a whole with CB[7].

A tricotage-like failure of nanographene

The response of a nanographene sheet to external stresses was considered in terms of a mechanochemical reaction. The quantum chemical realization of the approach was based on the coordinate-of-reaction concept for the purpose of introducing a mechanochemical internal coordinate (MIC) that specifies a deformational mode. The related force of response is calculated as the energy gradient along the MIC, while the atomic configuration is optimized over all of the other coordinates under the MIC constant-pitch elongation. The approach is applied to the benzene molecule and (5,5) nanographene. A drastic anisotropy in the microscopic behavior of both objects under elongation along a MIC was observed when the MIC was oriented either along or normally to the C–C bond chain. Both the anisotropy and the high stiffness of the nanographene originate from the response of the benzenoid unit to stress.

Structure-sensitive mechanism of nanographene failure

The quantum-mechanochemical-reaction-coordinate approach has disclosed atomically matched peculiarities that accompany the deformation-failure-rupture process occurring in nanographenes. The high stiffness of the graphene body is provided by the benzenoid unit. The anisotropy of the unit mechanical behavior in combination with different configurations of the unit packing with respect to the body C-C bond chains forms the ground for the structure-sensitive mechanism of the mechanical behavior that is drastically different for two different deformation modes. The zig-zag deformation mode is particularly manifested with the formation of one-atom chains. The approach allows tracing a deformation-stimulated change in the chemical reactivity of both the nanographene body and its individual atoms.

Preferential solvation of spherical ions in binary DMSO/benzene mixtures.

We consider a new qualitative approach for treating theoretically the solvation of single-atomic ionic solutes in binary mixtures of polar and nonpolar aprotic solvents. It is based on the implicit continuum electrostatic model of the solvent mixture involving distance-dependent dielectric permittivity epsilon(R) (where R is the distance from the ion) and local concentrations C(1)(R) and C(2)(R) of the solvent ingredients. For a given R, the condition for local thermodynamic equilibrium provides the transcendental equation for explicitly establishing the permittivity and concentration profiles. Computations performed with real Cl(-) and model Cl(+) ions as solutes in benzene/DMSO mixtures are compared with the molecular dynamics simulations of the same systems. A significant discrepancy of molecular and continuum results is revealed for the concentration profiles in the close vicinity of the ion boundary, although the general trends are similar. The continuum methodology cannot account for the formation of rigid solvent structures around ions, which is most significant for the case of Cl(+). Such defect, however, proves to become of less importance in calculations of the solvation free energy, which are quite satisfactory for Cl(-) ion. Free energy calculations for Cl(+) are less successful in the range of low DMSO concentration.

Advanced dielectric continuum model of preferential solvation.

A continuum model for solvation effects in binary solvent mixtures is formulated in terms of the density functional theory. The presence of two variables, namely, the dimensionless solvent composition y and the dimensionless total solvent density z, is an essential feature of binary systems. Their coupling, hidden in the structure of the local dielectric permittivity function, is postulated at the phenomenological level. Local equilibrium conditions are derived by a variation in the free energy functional expressed in terms of the composition and density variables. They appear as a pair of coupled equations defining y and z as spatial distributions. We consider the simplest spherically symmetric case of the Born-type ion immersed in the benzene/dimethylsulfoxide (DMSO) solvent mixture. The profiles of y(R) and z(R) along the radius R, which measures the distance from the ion center, are found in molecular dynamics (MD) simulations. It is shown that for a given solute ion z(R) does not depend significantly on the composition variable y. A simplified solution is then obtained by inserting z(R), found in the MD simulation for the pure DMSO, in the single equation which defines y(R). In this way composition dependences of the main solvation effects are investigated. The local density augmentation appears as a peak of z(R) at the ion boundary. It is responsible for the fine solvation effects missing when the ordinary solvation theories, in which z=1, are applied. These phenomena, studied for negative ions, reproduce consistently the simulation results. For positive ions the simulation shows that z>>1 (z=5-6 at the maximum of the z peak), which means that an extremely dense solvation shell is formed. In such a situation the continuum description fails to be valid within a consistent parametrization.

Implicit electrostatic solvent model with continuous dielectric permittivity function

The modification of the electrostatic continuum solvent model considered in the present work is based on the exact solution of the Poisson equation, which can be constructed provided that the dielectric permittivity epsilon of the total solute and solvent system is an isotropic and continuous spatial function. This assumption allows one to formulate a numerically efficient and universal computational scheme that covers the important case of a variable epsilon function inherent to the solvent region. The obtained type of solution is unavailable for conventional dielectric continuum models such as the Onsager and Kirkwood models for spherical cavities and the polarizable continuum model (PCM) for solute cavities of general shape, which imply that epsilon is discontinuous on the boundary confining the excluded volume cavity of the solute particle. Test computations based on the present algorithm are performed for water and several nonaqueous solvents. They illustrate specific features of this approach, called the smooth boundary continuum model (SBCM), as compared to the PCM procedure, and suggest primary tentative results of its parametrization for different solvents. The calculation for the case of a binary solvent mixture with variable epsilon in the solvent space region demonstrates the applicability of this approach to a novel application field covered by the SBCM.

[Systemic regulation of genetic and cytogenetic processes by a signal cascade of actin remodeling: locus agnostic in Drosophila].

The concept on systemic regulation of genetic and cytogenetic processes has acquired a new perspective after the completion of the Human Genome project, when the view on systemic realization of genetic activity in the dynamic spatial organization of the genome in the nucleus was generally accepted. This organization underlies plasticity of complex biological systems. Chromosome position within the nucleus determines both processes of normal development and the development of genomic diseases, i.e., changes according to the environmental requirements, current needs of the organism, and its individual experience. Nuclear actin has been envisioned as a main factor bridging three levels of the genome organization (nucleotide, structural, and spatial), due to its capability of (1) regulating transcription by activating all three classes of RNA polymerase; (2) participating in chromatin remodeling by interacting with numerous proteins; and (3) lining the nuclear membrane, determining the chromosome attachment points and regulating export from the nucleus. In view of this, the role of actin remodeling factors (LIMK1, cofilin, actin) in the development of neurodegenerative diseases, including prionic ones, and in the mechanisms of generation of genomic diseases, syndromes resulting from unequal recombination, has been intensely studied. Drosophila is a helpful model organism to determine the sequence of events in this system of hierarchical relationships. Using spontaneous and mutant variants of the agnostic locus, we have designed a model for the Williams syndrome, which also reproduces main diagnostic traits of neurodegenerative diseases.

Pathogenic chaperone-like RNA induces congophilic aggregates and facilitates neurodegeneration in Drosophila

Abstract Protein aggregation is a hallmark of many neurodegenerative diseases. RNA chaperones have been suggested to play a role in protein misfolding and aggregation. Noncoding, highly structured RNA recently has been demonstrated to facilitate transformation of recombinant and cellular prion protein into proteinase K-resistant, congophilic, insoluble aggregates and to generate cytotoxic oligomers in vitro. Transgenic Drosophila melanogaster strains were developed to express highly structured RNA under control of a heat shock promoter. Expression of a specific construct strongly perturbed fly behavior, caused significant decline in learning and memory retention of adult males, and was coincident with the formation of intracellular congophilic aggregates in the brain and other tissues of adult and larval stages. Additionally, neuronal cell pathology of adult flies was similar to that observed in human Parkinsons and Alzheimers disease. This novel model demonstrates that expression of a specific highly structured RNA alone is sufficient to trigger neurodegeneration, possibly through chaperone-like facilitation of protein misfolding and aggregation.

Association constants and distribution functions for ion pairs in binary solvent mixtures: Application to a cyanine dye system

The computations of the association constants K(ass) were performed at the microscopic level for the ion pair Cy(+)I(-) composed of the complex cyanine dye cation Cy(+) coupled to the negative iodine counterion. The wide array of K(ass) values is arranged by a variation of the composition of the binary solvent mixtures toluene/dimethylsulfoxide with the accompanying change of the solvent polarity. The potentials of mean force (PMFs) are calculated for a set of interionic separations R in the Cy(+)I(-) by a methodology which combines the quantum-chemical techniques for the treatment of the electronic structure of the Cy(+)I(-) system with the recent dielectric continuum approach which accounts for the solvation effects. For a given solute/solvent system the probability function P(R), which describes the distribution of interionic separations, is constructed in terms of the PMFs and implemented for the evaluation of the K(ass).

Combination of Hypomorphic Mutations of the Drosophila Homologues of Aryl Hydrocarbon Receptor and Nucleosome Assembly Protein Family Genes Disrupts Morphogenesis, Memory and Detoxification

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans.