John P. O’Connell

Infinite dilution partial molar properties of aqueous solutions of nonelectrolytes. I. Equations for partial molar volumes at infinite dilution and standard thermodynamic functions of hydration of volatile nonelectrolytes over wide ranges of conditions

A semitheoretical expression for partial molar volumes at infinite dilution of aqueous nonelectrolyte solutes has been developed employing the collection of properties from fluctuation solution theory for use over wide ranges of temperature and pressure. The form of the solution expression was suggested by a comparison of solute/solvent and solvent/solvent direct correlation function integrals (DCFI). The selection of solvent density and compressibility as model variables provides a correct description in the critical region while second virial coefficients have been used to give a rigorous expression in the low density region. The formulation has been integrated to obtain analytic expressions for thermodynamic properties of hydration at supercritical temperatures. The equation is limited to solutes for which B12 (the second cross virial coefficient between water and a solute molecule) is known or can be estimated. Regression of the three remaining parameters gives good correlations of the available experimental data. A strategy for estimating these parameters allows prediction from readily available data.

Infinite dilution partial molar properties of aqueous solutions of nonelectrolytes. II. equations for the standard thermodynamic functions of hydration of volatile nonelectrolytes over wide ranges of conditions including subcritical temperatures

Abstract The volumetric equation proposed previously (Plyasunov et al., 2000) , for estimating the infinite dilution Gibbs energy of hydration of volatile nonelectrolytes at temperatures exceeding the critical temperature of pure water, T c , is extended to subcritical temperatures. The basis for the extension without inclusion of new fitting parameters besides the experimental values of the thermodynamic functions of hydration at 298.15 K, 0.1 MPa, is an auxiliary function, Δ h Cp 0 ( T , P r ), for the variation of the infinite dilution partial molar heat capacity of hydration of a solute in liquid-like water between temperatures T = 273.15 K and T = T s = 658 K along the isobar P r = 28 MPa. The analytical form of Δ h Cp 0 ( T , P r ) was found by globally fitting all available data for the seven best-studied solutes (CH 4 , CO 2 , H 2 S, NH 3 , Ar, Xe, and C 2 H 4 ). Four constraints were used to determine the values of four terms of the Δ h Cp 0 ( T , P r ) function: the numerical values of the temperature increments between T = 298.15 K and T = T s = 658 K for the Gibbs energy and the enthalpy of hydration, and numerical value of the heat capacity at T s and at 298.15 K, all at the selected isobar P r . This approach, in combination with the volumetric equation, may be used to describe and predict all the infinite dilution thermodynamic functions of hydration for nonelectrolytes over extremely wide ranges of temperature and pressure. The model allows calculation of the standard state partial molar properties, including the Gibbs energy of aqueous solutes in a single framework for conditions from high-temperature magmatic processes through hydrothermal phenomena to low-temperature conditions of hypergenesis.

A new thermodynamic model describes the effects of ligand density and type, salt concentration and protein species in hydrophobic interaction chromatography

A new thermodynamic model is derived that describes both loading and pulse-response behavior of proteins in hydrophobic interaction chromatography (HIC). The model describes adsorption in terms of protein and solvent activities, and water displacement from hydrophobic interfaces, and distinguishes contributions from ligand density, ligand type and protein species. Experimental isocratic response and loading data for a set of globular proteins on Sepharose resins of various ligand types and densities are described by the model with a limited number of parameters. The model is explicit in ligand density and may provide insight into the sensitivity of protein retention to ligand density in HIC as well as the limited reproducibility of HIC data.

Analysis of Infinite Dilution Activity Coefficients of Solutes in Hydrocarbons from UNIFAC

Molecular structural effects on infinite dilution activity coefficients of solutes in n-alkanes and other hydrocarbons are studied within the UNIFAC model. Characteristic chain-length dependencies and other structural relationships imbedded in the model are discussed with emphasis to the consequences this has for model development. The cases treated have subtle but major implications for the correlation of activity coefficients and derivatives since these imply that combinatorial terms may not be small and they can be essential to the success of correlations based on UNIFAC. We have examined a number of infinite dilution properties and find that current expressions do not adequately describe these and other cases. The analysis is described and comparisons of the expressions with data for important systems are presented. New models are not presented, but improvements with either modified group definitions or revised relationships are discussed. The importance of such adjustments, for adding new terms to the existing equations, is stressed.

Changes in solvent exposure reveal the kinetics and equilibria of adsorbed protein unfolding in hydrophobic interaction chromatography.

Hydrogen exchange has been a useful technique for studying the conformational state of proteins, both in bulk solution and at interfaces, for several decades. Here, we propose a physically based model of simultaneous protein adsorption, unfolding and hydrogen exchange in HIC. An accompanying experimental protocol, utilizing mass spectrometry to quantify deuterium labeling, enables the determination of both the equilibrium partitioning between conformational states and pseudo-first order rate constants for folding and unfolding of adsorbed protein. Unlike chromatographic techniques, which rely on the interpretation of bulk phase behavior, this methodology utilizes the measurement of a molecular property (solvent exposure) and provides insight into the nature of the unfolded conformation in the adsorbed phase. Three model proteins of varying conformational stability, alpha-chymotrypsinogen A, beta-lactoglobulin B, and holo alpha-lactalbumin, are studied on Sepharose HIC resins possessing assorted ligand chemistries and densities. alpha-Chymotrypsinogen, conformationally the most stable protein in the set, exhibits no change in solvent exposure at all the conditions studied, even when isocratic pulse-response chromatography suggests nearly irreversible adsorption. Apparent unfolding energies of adsorbed beta-lactoglobulin B and holo alpha-lactalbumin range from -4 to 3 kJ/mol and are dependent on resin properties and salt concentration. Characteristic pseudo-first order rate constants for surface-induced unfolding are 0.2-0.9 min(-1). While poor protein recovery in HIC is often associated with irreversible unfolding, this study documents that non-eluting behavior can occur when surface unfolding is reversible or does not occur at all. Further, this hydrogen exchange technique can be used to assess the conformation of adsorbed protein under conditions where the protein is non-eluting and chromatographic methods are not applicable.

Thermodynamics and Fluctuation Solution Theory with Some Applications to Systems at Near- or Supercritical Conditions

The first sections (1–3) give some general thermodynamic analyses of fluids, with representative applications involving near-critical systems. Thorough discussion is given of standard states for phase equilibria and results for various sets of independent thermodynamic variables such as in the Lewis-Randall, Kirkwood-Buff and McMillan-Mayer systems. Differences with sets of composition variables based on species and groups for systems with “reactive” components are illustrated. The second portion (Sections 4–8) describes the fundamentals and applications of fluctuation solution theory (FST) to correlate and predict thermodynamic properties of mixtures. This analysis includes a variety of relations from molecular theory and the behavior of integrals of molecular correlation functions for mixtures, including near-critical conditions. The emphasis is placed on activity coefficients and high dilution partial molar volumes of supercritical substances and salts in liquids at extreme temperatures and pressures. Comments are made about the insight that FST formulations can provide for critical-region systems. FST properties show relatively simple behavior over wide ranges of conditions.

Aprotinin conformational distributions during reversed-phase liquid chromatography. Analysis by hydrogen-exchange mass spectrometry.

Hydrogen-exchange mass spectrometry analysis of the stable protein aprotinin during reversed-phase liquid chromatography shows both native and unfolded protein. The behavior is consistent with only two conformational states, a near-native state and a fully solvent-accessible state, with reversible interchange of species within and between the mobile and stationary phases. The amount of unfolded form is greater on C18 relative to C4 alkyl modified silica surfaces. The addition of (NH4)2SO4, Na2SO4, NaCl, or NaSCN to the mobile phase stabilized native conformation on the chromatographic surface, especially on the C4 media. Finally, the retention and the proportion of denatured form increases with added salts in anorder consistent with the lyotropic series, but reversed from that observed for small molecules.

Unfolding of a model protein on ion exchange and mixed mode chromatography surfaces

Recent studies with proteins indicate that conformational changes and aggregation can occur during ion exchange chromatography (IEC). Such behavior is not usually expected, but could lead to decreased yield and product degradation from both IEC and multi mode chromatography (MMC) that has ligands of both hydrophobic and charged functionalities. In this study, we used hydrogen exchange mass spectrometry to investigate unfolding of the model protein BSA on IEC and MMC surfaces under different solution conditions at 25°C. Increased solvent exposure, indicating greater unfolding relative to that in solution, was found for protein adsorbed on cationic IEC and MMC surfaces in the pH range of 3.0 to 4.5, where BSA has decreased stability in solution. There was no effect of anionic surfaces at pH values in the range from 6.0 to 9.0. Differences of solvent exposure of whole molecules when adsorbed and in solution suggest that adsorbed BSA unfolds at lower pH values and may show aggregation, depending upon pH and the surface type. Measurements on digested peptides showed that classifications of stability can be made for various regions; these are generally retained as pH is changed. When salt was added to MMC systems, where electrostatic interactions would be minimized, less solvent exposure was seen, implying that it is the cationic moieties, rather than the hydrophobic ligands, which cause greater surface unfolding at low salt concentrations. These results suggest that proteins of lower stability may exhibit unfolding and aggregation during IEC and MMC separations, as they can with hydrophobic interaction chromatography.

Molecular dynamics simulations of hydrocarbon chains

Molecular dynamics methods are used to study the conformation of single model hydrocarbon chains in a monatomic Lennard‐Jones fluid of methylene segments. Simulations of 7, 9, 11, 13, 15, 17, and 21 segment chains were made with 100–500 spheres. The forces of the skeletal chains involve intramolecular effects of bond vibration, angle bending, and rotation among quartets of adjacent segments. The average trans fraction of the hydrocarbon chains shows no significant effect of chain length, and the end‐to‐end distance and radius of gyration vary linearly with chain length.

A Framework for the Modelling of Biphasic Reacting Systems

Biphasic reacting systems have a broad application range from organic reactions in pharmaceutical and agro-bio industries to CO2 capture. However, mathematical modelling of biphasic reacting systems is a formidable challenge due to many phenomena underlying the process such as chemical equilibrium, biphasic equilibrium, reaction kinetics, and transport/mixing. In this study, a framework for modelling biphasic reacting systems is proposed to facilitate the model development in support of model-based process design-analysis. This framework is successfully applied to describe two biphasic reaction systems: a PTC-based reaction system and pseudo-PTC system.