How Water's Properties Are Encoded in Its Molecular Structure and Energies.

How are water's material properties encoded within the structure of the water molecule? This is pertinent to understanding Earth's living systems, its materials, its geochemistry and geophysics, and a broad spectrum of its industrial chemistry. Water has distinctive liquid and solid properties: It is highly cohesive. It has volumetric anomalies-water's solid (ice) floats on its liquid; pressure can melt the solid rather than freezing the liquid; heating can shrink the liquid. It has more solid phases than other materials. Its supercooled liquid has divergent thermodynamic response functions. Its glassy state is neither fragile nor strong. Its component ions-hydroxide and protons-diffuse much faster than other ions. Aqueous solvation of ions or oils entails large entropies and heat capacities. We review how these properties are encoded within water's molecular structure and energies, as understood from theories, simulations, and experiments. Like simpler liquids, water molecules are nearly spherical and interact with each other through van der Waals forces. Unlike simpler liquids, water's orientation-dependent hydrogen bonding leads to open tetrahedral cage-like structuring that contributes to its remarkable volumetric and thermal properties

Setchenov parameters for naphthalene

It is the purpose of this work to study the solubility of naphthalene, the simplest polycyclic aromatic hydrocarbon as a function of the salt content and the temperature, in ranges that span those likely to be found in natural ecosystems. Another goal is to set up a high-pressure generator, to study the effect of pressure on the solubility of hydrocarbons

Toward an understanding of the aqueous solubility of amino acids in the presence of salts : a molecular dynamics simulation study

Ion-specific effects on the aqueous solubilities of biomolecules are relevant in many areas of biochemistry and life sciences. However, a general and well-supported molecular picture of the phenomena has not yet been established. In order to contribute to the understanding of the molecular-level interactions governing the behavior of biocompounds in aqueous saline environments, classical molecular dynamics simulations were performed for aqueous solutions of four amino acids (alanine, valine, isoleucine, and 2-aminodecanoic acid), taken as model systems, in the presence of a series of inorganic salts. The MD results reported here provide support for a molecular picture of the salting-in/salting-out mechanism based on the presence/absence of interactions between the anions and the nonpolar moieties of the amino acids. These results are in good qualitative agreement with experimental solubilities and allow for a theoretical interpretation of the available data

APPLICATION OF LINEAR FREE ENERGY RELATIONSHIPS IN THE PREDICTION OF TRIGLYCERIDE/WATER PARTITION COEFFICIENTS AND LIPID BILAYER PERMEABILITY COEFFICIENTS OF SMALL ORGANIC MOLECULES AND PEPTIDES

Computational methods such as linear free energy relationships (LFERs) offer a useful high-throughput solution to quickly evaluate drug developability, e.g. membrane permeability, organic solvent/water partition coefficients, and solubility. LFERs typically assume the contribution of structural components/functional groups to the overall properties of a given molecule to be constant and independent. This dissertation describes a series of studies in which linear free energy relationships were developed to predict solvation of small organic molecules in lipid formulations, specifically, triglyceride containing solvents and phospholipid-based liposomes. The formation of intermolecular HBs in triglyceride solvents (homogenous with H-bond accepting ability) and intramolecular HBs within the bilayer barrier domain (hydrocarbon-like) proved to be the major factors to consider in developing LFERs to account for the increased oil/water partition coefficients and enhanced bilayer permeability of small organic molecules. The triglyceride solvent/water partition coefficients of a series of model compounds varying in polarity and H-bond donating/accepting capability were used to establish a correlation between the solvent descriptors and the ester concentration in these solvents using the Abraham LFER approach. The LFER analyses showed that the descriptors representing the polarizability and H-bond basicity of the solvents vary systematically with the ester concentration. A fragment-based LFER to predict membrane permeability or 1,9- decadiene/water partition coefficients of small organic molecules including small peptides was systematically constructed using a total of 47 compounds. Significant nonadditivity was observed in peptides in that the contribution of the peptide backbone amide to the apparent transfer free energy from water into the bilayer barrier domain is considerably smaller than that of a “well-isolated” amide and greatly affected by adjacent polar substituents on the C-termini. In order to explain the phenomenon of nonadditivity, the formation of intramolecular HBs and inductive effects of neighboring polar groups on backbone amide, were investigated using FTIR and MD simulations. Both spectroscopic and computational results provided supportive evidence for the hypothesis that the formation of intramolecular HBs in peptides is the main reason for the observed nonadditivity of Δ(ΔG°)-CONH-. The MD simulation results showed that the inductive effect of neighboring groups is not as important as the effect of intramolecular HBs

Hydrophobization of Cellulose-Based Fibers for Packaging Applications with Alkyl Ketene Dimers (AKD) and Food-Grade Waxes via Supercritical Impregnation with Carbon Dioxide – Experimental and Thermodynamic Modeling Approaches

This modified material has applications in food packaging, where frequently water-repellant surfaces are required. This method is preferable to traditional coating methods because it sizes across the entire thickness of the substrate rather than just the surface and can be used for non-planar surfaces; uses significantly less material than traditional methods and will be an excellent technique for multilayered and intelligent coating

Review of Computational approaches for predicting the physicochemical and biological properties of nanoparticles

In the growing field of nanotechnology there is a need to determine the physicochemical and potential toxicological properties of nanomaterials since many industrial, medical and consumer applications are based on an understanding of these properties and on a controlled exposure to the materials. This document provides a literature review on the current status of computational studies aimed at predicting the physicochemical properties and biological effects (including toxicity) of nanomaterials, with an emphasis on medical applications. Although a number of models have been published for physicochemical property prediction, very few models have been published for predicting biological effects, toxicity or the underlying mechanisms of action. This is due to two main reasons: a) nanomaterials form a colloidal phase when in contact with biological systems making the definition and calculation of properties (descriptors) suitable for the prediction of toxicity a new and challenging task, and b) nanomaterials form a very heterogeneous class of materials, not only in terms of their chemical composition, but also in terms of size, shape, agglomeration state, and surface reactivity. There is thus an urgent need to extend the traditional structure-activity paradigm to develop methods for predicting the toxicity of nanomaterials, and to make the resulting models readily available. This document concludes by proposing some lines of research to fill the gap in knowledge and predictive methodologyJRC.I.6-Systems toxicolog

A Computational Simulation Study of Benzamidine Derivatives Binding to Arginine-Specific Gingipain (HRgpA) from Periodontopathogen Porphyromonas gingivalis

We have shown that the binding free energy calculation from molecular dynamics can be adapted successfully to cysteine proteinases, such as arginine-specific gingipain (HRgpA) from Porphyromonas gingivalis. The binding free energy obtained is in good agreement with the available experimental data for eight benzamidine derivatives including urea and ether linker. The calculations showed that the electrostatic energies between HRgpA and inhibitors were important in determining the relative affinities of the inhibitors to the HRgpA, with an average binding free energy of about −5 kcal/mol. The average structures of the eight complexes suggest that benzamidine inhibitors interact with Asp387, His435, and Cys468 by hydrogen bonding and with Trp508 by hydrophilic interactions that are essential for the activities of benzamidine inhibitors. It can therefore be expected that the method provides a reliable tool for the investigation of new HRgpA inhibitors. This finding could significantly benefit the future design of HRgpA inhibitors

Formulation, Structure, and Applications of Therapeutic, Amino Acid, and Water-Based Deep Eutectic Solvents

In the design of greener chemicals, deep eutectic solvents (DESs) are considered as one of the most versatile alternative solvents with widespread applications. DESs have the advantages of being nonflammable with negligible vapor pressure compared to traditional solvents. They share many characteristics of ionic liquids, but DESs are cheaper to formulate, typically nontoxic, recyclable, biodegradable, and are suitable for use with biological systems. In my Ph.D. research, three types of emerging and unconventional types of DESs, namely therapeutic DES (THEDES), amino acid-based DES (AADES), and water-based DES (WDES), have been investigated. To formulate these DES easily available and cheaper chemicals, such as water, choline chloride, menthol, aspirin, glutamic acid, arginine, and glycerol, were used. Besides formulation, experimental structural characterization, and rigorous computational studies, some of their preliminary applications have been explored to understand their potential area of applications. Formulation for poorly soluble drugs as THEDESs could enhance their solubility significantly and AADES were used to selectively depolymerize lignin. A complete characterization of WDES and solubility of salt or drug was explored. The structures and structural properties of the DES studied were explored rigorously, as these insights can help to make them more effective. The major aim of the research projects was to find out the gaps of the DES research and provide a solid background for future research. Combining the molecular dynamics (MD), density functional theory (DFT), spectroscopic (Raman, IR, and VCD) techniques, solvatochormism, cheminformatics, and chromatographic techniques helped to understand the behavior and potential of the studied formulations. For example, atom-atom radial distribution functions (RDFs) based on MD simulation reveal that hydrogen bonds are formed between Cl-…HOCh+ and Cl- …HOCOOH of the THEDES, where Cl- works as a bridge between ASA and Ch+. Cationanion electrostatic attractions are disrupted by highly interconnected hydrogen bonds. Nonsalt HBA-HBD THEDES (1:1 L-Menthol: acetic acid) is also explored and found that their depression of melting point is mainly because of long network of hydrogen bond. Since menthol is a chiral molecular, VCD was found as a good tool to understand the behavior of chiral molecule-based DES. Melting points of WDESs (1:3 and 1:4 choline chloride: H2O) were found significantly low, -79.21 and -79.25 °C, respectively. TGA study proved that water could be relatively stable at a higher temperature when it forms the DESs. Solvent selectivity triangle (SST) of Kamlet-Taft parameters proved that the DESs possess similar solvatochromic properties to ionic liquids. A simple analytical method was developed employing ion chromatography and atomic absorption spectroscopy to investigate the solubility of sodium halides, alkali chlorides, and cobalt chloride in the studied water-based DESs. Solubility trends of the metal halides in both DESs were found same, NaCl \u3e NaBr \u3e NaI \u3e NaF for sodium halides and LiCl \u3e NaCl \u3e KCl for alkali metal chlorides. Solubilities of the studied drug molecules such as aspirin were found to be 1.3 to 6.7 times higher in the solvents than their solubilities in water. Cell viability assay of the WDES1 (1:3 ChCl:H2O) compared to dimethyl sulfoxide (DMSO) against HEK293 cell line proved that the solvent is applicable to the biological system. The eutectic points of the formulated AADESs were -0.14°C for Glu-Gly and -1.36°C for Arg-Gly. FT-IR, 1HNMR spectroscopy, and mass spectrometry studies found that Glu-Gly formed ester impurities. However, mass spectrometry showed that the impurities are negligible. TGA revealed that both DESs could be applied up to 150-160°C without losing weight, while Glu-Gly could be used up to 200°C. AADESs are excellent pretreatment media for biomass, lignin was treated as a model biomass in this study with the formulated AADESs to determine their reaction products. It was found that Arg-Gly can isolate only one monomeric compound (4-methyl benzaldehyde), while Glu-Gly can isolate three monomeric compounds. Oxidative depolymerization of the lignin residues validated the outcomes obtained from the AADES-lignin reactions. Overall, this work helped to understand how to formulate novel DESs, their wide variety of characterizations, and possible application