Volume 75, Issue 7

As biotechnology sweeps the world, it is appropriate to remember that the great virtue of thermodynamics is its broad range of applicability. As a result, there is a growing literature describing how chemical thermodynamics can be used to inform processes for old and new biochemical products for industry and medicine.A particular application of molecular thermodynamics concerns separation of aqueous proteins by selective precipitation. For this purpose, we need phase diagrams; for constructing such diagrams, we need to understand not only the qualitative nature of phase equilibria of aqueous proteins, but also the quantitative intermolecular forces between proteins in solution. Some examples are given to show how aqueous protein-protein forces can be calculated or measured to yield a potential of mean force and how that potential is then used along with a statistical-thermodynamic model to establish liquid -liquid and liquid -crystal equilibria. Such equilibria are useful not only for separation processes, but also for understanding diseases like Alzheimer’s, eye cataracts, and sickle-cell anemia that appear to be caused by protein agglomeration.

Reliable knowledge of the thermophysical properties of pure compounds and their mixtures in the whole composition and a wide temperature and pressure range is a vital prerequisite for computer-aided synthesis, design, and optimization of chemical processes. Knowledge of the various phase equilibria is most important for the development of thermal separation processes (but also for other applications,such as the design of multiphase reactors, the prediction of the fate of a chemical in the environment,etc.). Whereas 25 years ago, the main interest was directed to the development of predictive tools for vapor–liquid equilibria of subcritical compounds of similar size (ASOG, UNIFAC), 15 years later a proper description of the temperature dependence (excess enthalpies), the activity coefficients at infinite dilution, and solid–liquid equilibria of eutectic mixtures (including strong asymmetric systems) was achieved. After the combination with cubic equations of state [Soave–Redlich–Kwong (SRK), Peng–Robinson (PR)], the group contribution concept was extended to supercritical compounds [predictive SRK (PSRK)]. With the development of an adequate electrolyte model (LIFAC), the equation-of-state approach can even be used for systems with strong electrolytes. With the revision of the group interaction parameters, the extension of the parameter matrix (introduction of new structural groups, filling of parameter gaps), and the help of a large database (Dortmund Data Bank), the predicted results of group contribution methods were significantly improved and the range of applicability greatly extended. Furthermore, still-existing problems with the group contribution approach (proximity effects,etc.) were reduced. With the help of a volume-translated PR equation of state and application of temperature-dependent and improved mixing rules, the remaining weaknesses of group contribution equations of state (such as poor results for liquid densities, excess enthalpies, and the problems with asymmetric systems) were minimized.

In materials that are exposed to thermodynamic potential gradients (i.e., gradients of chemical potentials, electrical potential, temperature, or pressure), transport processes of the mobile components occur. These transport processes and the coupling between different processes are not only of fundamental interest, but are also the origin of degradation processes, such as kinetic demixing and decomposition and changes in the morphology of the material, all of which are of great practical relevance.Two classes of materials will be considered: semi-and ion-conducting oxides and ion-conducting halides. In oxides, kinetic demixing of the cations in a multicomponent oxide and kinetic decomposition of the oxide under the influence of an applied thermodynamic potential gradient will be considered for homovalent oxide solid solutions and for heterovalently doped oxides. In ion-conducting halides, the morphological stability of solid/solid interfaces, which are driven by an external electrical potential gradient, is studied. Monte Carlo simulations show that the morphological stability of the interface is determined by the difference in the ionic conductivities of the two crystals.

Zwitterionic or polar lipids that form lamellar phases swell in the presence of water to take up between 10 and 30 water molecules per lipid. The degree of the water uptake depends both on the state of the alkyl chains, liquid or solid, and on the nature of the polar group. The swelling behavior has been extensively characterized on the free-energy level through measuring the relation between the chemical potential of the water and the degree of swelling. In spite of the extensive studies of this type, consensus is still lacking concerning the molecular mechanism causing the swelling. The two main ideas that explain the existence of the effectively repulsive force between two opposing bilayers are (i) a water structure effect and (ii) thermal excitations of the lipid molecules. The first is from a thermodynamic perspective caused by a negative partial molar enthalpy of the water, whereas for the second, the repulsion is caused by positive entropy. A further insight into the swelling behavior is obtained by simultaneously measuring the partial molar free energy and the partial molar enthalpy using a twin double calorimeter. Such measurements show for binary lipid–water and for ternary lipid –cholesterol –water systems that the first four water molecules enter the bilayer driven by a favorable enthalpic interaction, whereas for higher water contents, the partial free energy and the partial enthalpy have opposite signs. In spite of the fact that the partial free energy varies with water content in a similar way, the partial enthalpies depend strongly on the nature of the lipid sample. Thus, it is obvious that a molecular interpretation of the enthalpy values has to involve the lipid degrees of freedom. This is a strong indication that the interpretation of the free energies should also include the same degrees of freedom. This gives experimental evidence in favor of an interpretation of the molecular mechanism causing the swelling that involves changes in the thermal excitation of the lipid degrees of freedom.

Some of the molecular and ionic crystals containing hydrogen undergo phase transitions only when they are deuterated. This indicates that not only the intermolecular potential energy, but also the kinetic energy of the nuclei are involved in an essential way in the mechanisms of the transitions. The quantum effects implied by these observations are discussed in terms of tunneling of protons and deuterons. Experimental evidence for deuteration-induced phase transitions and nuclear tunneling states accumulated by low temperature calorimetry, far infrared spectroscopy,and neutron diffraction is discussed.

A protein in solution is a thermodynamic entity, spanning, in principle, the entire allowed conformational space from the fully folded N to the fully unfolded U. Although some alternately or partially folded higher-energy conformers may coexist with N and U, they are seldom detected spectroscopically because their populations are usually quite low under physiological conditions. I describe here a new type of experiment, a combination of multidimensional NMR spectroscopy with pressure, that is capable of detecting and analyzing structures and thermodynamic stability of these higher-energy conformers. The idea is based on the finding that under physiological conditions the conformational order of a globular protein normally decreases in parallel with its partial molar volume (negative δ V ), so that under equilibrium conditions, the population is shifted to a less and-less-ordered conformer with increasing pressure. In principle, with the high space resolution of the multidimensional NMR, the method enables one to explore protein structure and stability in atomic detail in a wide conformational space from N to U with pressure and temperature as variables. The method will provide us with a strong basis for understanding the fundamental phenomena of proteins:function, folding, and aggregation.

There may be substantial differences in the chemical composition of technical-grade products of the same active ingredient manufactured under different conditions, from different raw materials, or by different routes of synthesis. Resulting differences in impurity content may significantly affect the toxicological properties of pesticide products. Relevant impurities are those that may exhibit pronounced toxic effects compared to the active ingredient, affect phytotoxicity or physical properties of formulations, result in undesirable residues in food,or cause environmental contamination. The first safety assessment of an active ingredient by a regulatory body considers toxicological data developed on a representative batch of technical products, with the assumption that the material produced commercially by the original or generic manufacturers has an equal or higher content of active ingredient and contains the same or fewer impurities at equal or lower concentrations as the fully characterized technical product used in the toxicological tests. Three steps are essential for ensuring the safety of commercial technical- grade pesticide products, whether produced by the original manufacturer or by generic manufacturers. First, the identity and chemical structure of the impurities must be elucidated.This should include positive identification of major (=1 %) and all toxicologically or environmentally relevant impurities, and characterization of minor impurities (>0.1 %). Second, in addition to recognition of a minimum active ingredient content, official specifications should also list relevant impurities and their maximum permissible concentrations.Implementation of these specifications should be aided by a decision-making scheme for establishing similarity of subsequently evaluated technical products. Third, appropriate analytical methods for the detection and quantification of impurity levels should be developed and employed in a quality-monitoring program associated with the manufacturing and formulation process.

When cooled to a temperature of a few K using supersonic jet expansion into a vacuum, a molecule exists in the lowest vibrational level of the ground electronic state and is isolated at collision-free conditions. The absorption or excitation/fluorescence spectrum is then greatly simplified, when transitions occur from this single vibrational level to a limited number of vibrational levels in the excited electronic state. This method, called supersonic jet spectrometry, is a powerful analytical technique because of its high selectivity, since the chemical species can be accurately identified and selectively quantified using the sharp spectral features even for large molecules. Supersonic jet spectrometry has distinct advantages over other low-temperature spectrometries,in that it can be combined with gas-phase separation and detection techniques such as chromatography or mass spectrometry. Therefore, this spectrometric technique can be used as a versatile analytical means, not only for basic research on pure substances, but also for practical trace analysis of chemical species in multicomponent samples (e.g., in biological monitoring or in environmental monitoring).