Andrea Michalkova

Using nano-QSAR to predict the cytotoxicity of metal oxide nanoparticles

It is expected that the number and variety of engineered nanoparticles will increase rapidly over the next few years, and there is a need for new methods to quickly test the potential toxicity of these materials. Because experimental evaluation of the safety of chemicals is expensive and time-consuming, computational methods have been found to be efficient alternatives for predicting the potential toxicity and environmental impact of new nanomaterials before mass production. Here, we show that the quantitative structure-activity relationship (QSAR) method commonly used to predict the physicochemical properties of chemical compounds can be applied to predict the toxicity of various metal oxides. Based on experimental testing, we have developed a model to describe the cytotoxicity of 17 different types of metal oxide nanoparticles to bacteria Escherichia coli. The model reliably predicts the toxicity of all considered compounds, and the methodology is expected to provide guidance for the future design of safe nanomaterials.

Effect of charge distribution on RDX adsorption in IRMOF-10.

Quantum mechanical (QM) calculations, classical grand canonical Monte Carlo (GCMC) simulations, and classical molecular dynamics (MD) simulations are performed to test the effect of charge distribution on hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) adsorption and diffusion in IRMOF-10. Several different methods for mapping QM electron distributions onto atomic point charges are explored, including the electrostatic potential (ESP) method, Mulliken population analysis, Lowdin population analysis, and natural bond orbital analysis. Classical GCMC and MD simulations of RDX in IRMOF-10 are performed using 15 combinations of charge sources of RDX and IRMOF-10. As the charge distributions vary, interaction potential energies, the adsorption loading, and the self-diffusivities are significantly different. None of the 15 combinations are able to quantitatively capture the dependence of the energy of adsorption on local configuration of RDX as observed in the QM calculations. We observe changes in the charge distributions of RDX and IRMOF-10 with the introduction of an RDX molecule into the cage. We also observe a large dispersion contribution to the interaction energy from QM calculations that is not reproduced in the classical simulations, indicating that the source of discrepancy may not lie exclusively with the assignment of charges.

Thermodynamics and Kinetics of Intramolecular Water Assisted Proton Transfer in Na+-1-Methylcytosine Water Complexes

High-level ab initio predictions of the tautomerization equilibrium and rate constants of water-assisted proton transfer of 1-methyl-cytosine (MeC) to its MeC* imino tautomeric form in the presence of up to two water molecules (W) and the Na(+) cation were carried out. The calculated energy values were used to obtain the thermodynamic parameters and equilibrium concentration of MeC, its rare tautomer, and their complexes with up to two water molecules and the Na (+) cation. The rate constants for the tautomerization were obtained by using the instanton approach (a quasiclassical method based on the least-action principle). Hydration of MeC by one water molecule leads to an increase of the concentration of the MeC* tautomer in the equilibrium mixture and a decrease of the barrier of the MeC* formation (to 15.6 kcal/mol). If the Na(+) cation is present, the tautomeric form is much less favored, and the tautomerization barrier increases to 25.2 kcal/mol. It was found that MeC monohydrate has both the highest equilibrium (2.9 x 10(-2)) and rate (7.9 x 10(5) s(-1)) constants of tautomerization in comparison to the MeC*NaW and MeC*Na2W complexes containing the Na(+) cation. Moreover, this study also allows one to estimate the concentration of MeC present in the cell during DNA synthesis as the unwanted tautomer, which in forming a mismatched base pair can cause spontaneous point mutations. Kinetic simulations have demonstrated that the low values of equilibrium (10(-14)-10(-13)) and rate constants (10(-17)-10(-16) s(-1)) of tautomerization make contribution of the MeC*Na(+)W and MeC*Na(+)2W complexes to the point mutations in DNA unlikely. In contrast to these Na(+) complexes, MeC*W can reach an equilibrium concentration of 2.9 x 10(-2) within 10(-7) s; thus, it can increase the probability of the point mutations.

Theoretical study of the surface properties of poly(dimethylsiloxane) and poly(tetrafluoroethylene)

Molecular dynamics (MD) simulations of poly(dimethylsiloxane) (PDMS) and poly(tetrafluoroethylene) (PTFE) were carried out to determine their surface properties and energies. This study helps to gain better insight into the molecular modeling of PDMS and PTFE, in particular how different approaches affect calculations of surface energy. Current experimental and theoretical data were used to further understand the surface properties of PDMS and PTFE as well as to validate and verify results obtained from the combination of density functional theory (DFT) calculations (including periodic boundary conditions) and MD simulations. Detailed analysis of the structure and electronic properties (by calculation of the projected density of states) of the bulk and surface models of PDMS and PTFE was performed. The sensitivity of the surface energy calculation of these two polymers to the chemistry and model preparation was indicated. The balance between the molecular density, weight (which also reflects bond orientation in the surface region), bond flexibility, and intramolecular interactions including bond stretching was revealed to govern the results obtained. In modeling, the structural organization of polymer near a given surface (types and number of end groups and broken bonds due to application of different cut offs of the periodic structure) also significantly affects the final results. Besides the structural differences, certain simulation parameters, such the DFT functionals and simulation boxes utilized, play an important role in determining surface energy. The models used here were shown to be sufficient due to their good agreement with experimental and other theoretical data related to surface properties and surface energies.

Towards Involvement of Interactions of Nucleic Acid Bases with Minerals in the Origin of Life: Quantum Chemical Approach

This review describes the results of studies of interactions of nucleic acid bases with water, cations and minerals. It focuses on three areas investigated computationally: (1) carbon fixation cycle; (2) 1-methylcytosine tautomerism due to presence of water and cation; (3) adsorption of thymine and uracil on clay minerals. It reveals how the individual reactions responsible for the generation of acetic acid on iron-nickel sulfide surfaces as catalysts could have operated to produce carboxylic acids from carbon oxide and water. The importance of these results in terms of a primordial chemistry on iron-nickel sulfide surfaces is discussed. The interaction with the Na+ cation has a dramatic effect on equilibrium between oxo-amino and oxo-imino tautomers of methylcytosine and can lead to a decrease in concentration of imino-oxo tautomer (present in the cell during DNA synthesis) responsible for the point mutations in DNA during formation of a mismatched base pair. Thymine and uracil interact quite strongly with the kaolinite mineral surfaces but uracil is slightly better stabilized than thymine on these clays. The adsorption leads to their structural changes, which are induced by the deposition way and are driven by the surface potential. Explicit addition of water molecule changes only slightly its adsorption properties, comparing the presence of the sodium cation.

A Quest for Efficient Methods of Disintegration of Organophosphorus Compounds: Modeling Adsorption and Decomposition Processes

The problem with a contamination of soil and groundwater by organophosphorus compounds is a widespread environmental concern with environmental deterioration. However, the high cost of remediation becomes evident. Organophosphorus compounds have several applications (agricultural, industrial, and military). Nevertheless, assessments of the hazards from these applications quite often do not take into account chemical processes. The management of contaminants requires considerable knowledge and understanding of contaminant behavior. Unique properties of transition metals and metal oxides such as having high adsorption and catalytic ability have resulted in their applications as natural adsorbents and catalysts in the development of clean-up technologies. An understanding of the physical characteristics of the adsorption sites of selected parts of soil (metal oxides) and transition metals, the physical and chemical characteristics of the contaminant, details of sorption of contaminants on soil, on soil in water solution, and on transition metals, and its distribution within the system is of practical interest. Quantum-chemical calculations provide more insight into the aforementioned characteristics of organophosphorus compounds. This review summarizes experimental studies and the computational techniques and applications which are used to develop theoretical models that explain and predict how transition metals and metal oxides can affect the adsorption and decomposition of selected organophosphorus compounds. The results can contribute to a better knowledge of impact of such processes in existing remedial technologies and in a development of new removal and decomposition techniques