Glückliche Reise.

Following Forest Hills High School in New York City, I attended Cornell University for a five-year program leading to a Bachelor of Chemical Engineering degree. After spending one year at the University of Rochester to obtain a Master of Science in Chemical Engineering, I came to Princeton University in 1951. Four years later, with a fresh PhD, I joined the faculty at the University of California, Berkeley, where I remained, interrupted only by sabbatical leaves in Switzerland, Germany, England, New Zealand, and Australia. Most of my professional work has been in applied chemical thermodynamics for process design, in particular, development of molecular-thermodynamic models for calculating phase equilibria for large-scale separation operations. I have also worked on the properties of electrolytes and hydrates, critical phenomena in fluid mixtures, properties of polymers and gels, adsorption of fluid mixtures, and separation of biomolecules. For many years I was a consultant for Air Projects and Chemicals and for the Fluor Corporation. Throughout my long teaching career, I have stressed the importance of context and of integrating science and engineering with humanities and with the needs of society. Such integration makes better engineers and contributes to personal happiness.

Wetting behavior of four polar organic solvents containing one of three lithium salts on a lithium-ion-battery separator.

HYPOTHESIS: The wetting behavior of an electrolyte solution on the separator, determined by contact-angle measurements, has a significant effect on the internal resistance of the battery and on its cycle life. The solvent, the lithium-salt type and its concentration may affect the wettability. However, few systematic studies address the effect of salt concentration on surface tension and contact angle. EXPERIMENTS: Surface tensions and advancing contact angles were measured for dimethyl sulfoxide (DMSO), propylene carbonate (PC), dimethyl carbonate (DMC), and a PC/DMC mixture (1:1 mass ratio) with various concentrations of a lithium salt (LiClO4, LiPF6, and LiTFSI) at 23 °C. Measurements were made by a Krüss Drop Shape Analyzer 100, with a video camera mounted on a microscope to record the drop image. FINDINGS: For DMSO, PC and PC/DMC, surface tensions increase by adding LiClO4 or LiPF6 but decrease upon addition of LiTFSI. For DMC, the lithium salts have little impact on the surface tensions. For each solvent, contact angles and adhesion energies follow the same trend as those for surface tensions. The TFSI- anion reduces the surface tension of the solvent, favoring good wettability of the separator. The optimal surface tension for wettability of Celgard 2500 is at or below 26.1 mN/m.

Henry's Constants of Persistent Organic Pollutants by a Group-Contribution Method Based on Scaled-Particle Theory.

A group-contribution method based on scaled-particle theory was developed to predict Henry's constants for six families of persistent organic pollutants: polychlorinated benzenes, polychlorinated biphenyls, polychlorinated dibenzodioxins, polychlorinated dibenzofurans, polychlorinated naphthalenes, and polybrominated diphenyl ethers. The group-contribution model uses limited experimental data to obtain group-interaction parameters for an easy-to-use method to predict Henry's constants for systems where reliable experimental data are scarce. By using group-interaction parameters obtained from data reduction, scaled-particle theory gives the partial molar Gibbs energy of dissolution, Δg̅2, allowing calculation of Henry's constant, H2, for more than 700 organic pollutants. The average deviation between predicted values of log H2 and experiment is 4%. Application of an approximate van't Hoff equation gives the temperature dependence of Henry's constants for polychlorinated biphenyls, polychlorinated naphthalenes, and polybrominated diphenyl ethers in the environmentally relevant range 0-40 °C.

Delignification of miscanthus using ethylenediamine (EDA) with or without ammonia and subsequent enzymatic hydrolysis to sugars.

Pretreatment of miscanthus is essential for efficient enzymatic production of cellulosic ethanol. This study reports a possible pretreatment method for miscanthus using aqueous ethylenediamine (EDA) for 30 min at 180 °C with or without ammonia. The mass ratio of miscanthus to EDA was varied from 1:3, 1:1, and 1:0.5, keeping the mass ratio of miscanthus to liquid (EDA + Water) constant at 1:8. The ammonia-to-miscanthus ratio was 1:0.25. After pretreatment with a ratio of 1:3 miscanthus to EDA, about 75 % of the lignin was removed from the raw miscanthus with 90 % retention of cellulose and 50 % of hemicellulose in the recovered solid. Enzymatic hydrolysis of the recovered solid miscanthus gave 63 % glucose and 62 % xylose conversion after 72 h. EDA provides an effective pretreatment for miscanthus, achieving good delignification and enhanced sugar yield by enzyme hydrolysis. Results using aqueous EDA with or without ammonia are much better than those using hot water and compare favorably with those using aqueous ammonia. The delignification efficiency of EDA pretreatment is high compared to that for hot-water pretreatment and is nearly as efficient as that obtained for aqueous-ammonia pretreatment.

A simplified electrostatic model for hydrolase catalysis.

Toward the development of an electrostatic model for enzyme catalysis, the active site of the enzyme is represented by a cavity whose surface (and beyond) is populated by electric charges as determined by pH and the enzyme's structure. The electric field in the cavity is obtained from electrostatics and a suitable computer program. The key chemical bond in the substrate, at its ends, has partial charges with opposite signs determined from published force-field parameters. The electric field attracts one end of the bond and repels the other, causing bond tension. If that tension exceeds the attractive force between the atoms, the bond breaks; the enzyme is then a successful catalyst. To illustrate this very simple model, based on numerous assumptions, some results are presented for three hydrolases: hen-egg white lysozyme, bovine trypsin and bovine ribonuclease. Attention is given to the effect of pH.

Water-soluble drug partitioning and adsorption in HEMA/MAA hydrogels.

Two-photon confocal microscopy and back extraction with UV/Vis-absorption spectrophotometry quantify equilibrium partition coefficients, k, for six prototypical drugs in five soft-contact-lens-material hydrogels over a range of water contents from 40 to 92%. Partition coefficients were obtained for acetazolamide, caffeine, hydrocortisone, Oregon Green 488, sodium fluorescein, and theophylline in 2-hydroxyethyl methacrylate/methacrylic acid (HEMA/MAA, pKa≈5.2) copolymer hydrogels as functions of composition, aqueous pH (2 and 7.4), and salinity. At pH 2, the hydrogels are nonionic, whereas at pH 7.4, hydrogels are anionic due to MAA ionization. Solute adsorption on and nonspecific electrostatic interaction with the polymer matrix are pronounced. To express deviation from ideal partitioning, we define an enhancement or exclusion factor, E ≡ k/φ1, where φ1 is hydrogel water volume fraction. All solutes exhibit E > 1 in 100 wt % HEMA hydrogels owing to strong specific adsorption to HEMA strands. For all solutes, E significantly decreases upon incorporation of anionic MAA into the hydrogel due to lack of adsorption onto charged MAA moieties. For dianionic sodium fluorescein and Oregon Green 488, and partially ionized monoanionic acetazolamide at pH 7.4, however, the decrease in E is more severe than that for similar-sized nonionic solutes. Conversely, at pH 2, E generally increases with addition of the nonionic MAA copolymer due to strong preferential adsorption to the uncharged carboxylic-acid group of MAA. For all cases, we quantitatively predict enhancement factors for the six drugs using only independently obtained parameters. In dilute solution for solute i, Ei is conveniently expressed as a product of individual enhancement factors for size exclusion (Ei(ex)), electrostatic interaction (Ei(el)), and specific adsorption (Ei(ad)):Ei≡Ei(ex)Ei(el)Ei(ad). To obtain the individual enhancement factors, we employ an extended Ogston mesh-size distribution for Ei(ex); Donnan equilibrium for Ei(el); and Henry's law characterizing specific adsorption to the polymer chains for Ei(ad). Predicted enhancement factors are in excellent agreement with experiment.

High solubilities of small hydrocarbons in trihexyl tetradecylphosphonium bis(2,4,4-trimethylpentyl) phosphinate.

Experimental solubilities are reported for methane, ethane, ethylene, propane, and propylene in trihexyl tetradecylphosphonium bis(2,4,4-trimethylpentyl) phosphinate [P(14)666][TMPP] from 313 to 353 K up to 6.7 MPa. A literature review on solubilities of small hydrocarbons in ionic liquids shows that solubilities in [P(14)666][TMPP] are appreciably larger than those in other ionic liquids. Contrary to solubilities in ionic liquids studied earlier, solubilities of paraffins (ethane and propane) in [P(14)666][TMPP] are larger than those of the corresponding olefins (ethylene and propylene). Because, at fixed temperature, the vapor pressure of an olefin is larger than that of the corresponding paraffin, the relative volatility of the olefin exceeds that of the corresponding paraffin, contrary to the relative volatility observed in conventional extractive distillation with polar solvents where the volatility of the paraffin exceeds that of the corresponding olefin.

Aqueous-ammonia delignification of miscanthus followed by enzymatic hydrolysis to sugars.

This work concerns the effect of aqueous ammonia pretreatment at four temperatures and at 10, 20 or 30 wt.% ammonia. After 1h, more than 65% delignification is achieved at 150 or 180 °C for high and for low concentrations of ammonia. When the delignified miscanthus is enzymatically hydrolyzed for 96 h using cellulases and beta-glucosidase, conversion of the recovered solid to glucose is 53.4% and to xylose 70.0%. Additional glucose and xylose can be obtained from the ammonia-containing aqueous phase. Increased ammonia concentration leads to better conversion. Fourier-transform infrared and Two-dimensional (13)C-(1)H Heteronuclear Single Quantum Coherence (HSQC) Nuclear Magnetic Resonance spectroscopy provide data for the composition of the pretreated miscanthus and for that of the liquid extract. These spectra indicate that pretreatment with ammonia leads to de-acetylation of the xylan-backbone. The ß-O-4' linked aryl ether remains the most abundant linkage in the pretreated miscanthus.

Extraction of lignins from aqueous-ionic liquid mixtures by organic solvents.

The commercial development of ionic liquids (ILs) to pretreat lignocellulose by dissolution of whole biomass and cellulose precipitation by addition of water is hindered by the absence of an effective technique to recover the lignin content of the biomass from the IL. Three organic solvents [ethyl acetate, 1,4-dioxane, and tetrahydrofuran (THF)] were studied for their ability to form a two-liquid-phase system with water and 1-ethyl-3-methylimidazolium acetate ([C(2)mim][OAc]), and for partitioning model lignins and lignin monomers between the two liquid phases. Ternary diagrams were obtained for three [C(2)mim][OAc]/organic solvent/water systems at 22°C. Partition coefficients were measured for several types of lignin in these three systems. Partition coefficients increase with rising water content in the IL phase, and depend strongly on the type of lignin and on the organic solvent. Partition coefficients rise as the pH of the ionic-liquid-rich phase falls. Small molecule model lignin monomer compounds (guaiacol, syringaldehyde) are also readily extracted from the IL/water system by THF.

Addition of ammonia and/or oxygen to an ionic liquid for delignification of miscanthus.

Ammonia and/or oxygen were used to enhance the delignification of miscanthus dissolved in 1-ethyl-3-methylimidazolium acetate at 140°C. After dissolution of the gas at 9 bar, water was added as antisolvent to regenerate the dissolved biomass. In a next step, an acetone/water mixture was used to remove carbohydrate-free lignin from the regenerated biomass. The lignin content in the final product was around 10%, much lower than the ca. 23% lignin content of the raw dry miscanthus. This lignin reduction is achieved without diminution of cellulose or of total carbohydrates recovered, relative to the recovery achieved with the ionic liquid pretreatment in contact with air or nitrogen.

Ionic liquid pretreatment of cellulosic biomass: enzymatic hydrolysis and ionic liquid recycle.

Ionic liquids (ILs) are promising solvents for the pretreatment of biomass as certain ILs are able to completely solubilize lignocellulose. The cellulose can readily be precipitated with an anti-solvent for further hydrolysis to glucose, but the anti-solvent must be removed for the IL to be recovered and recycled. We describe the use of aqueous kosmotropic salt solutions to form a three-phase system that precipitates the biomass, forming IL-rich and salt-rich phases. The phase behavior of [Emim][Ac] and aqueous phosphate salt systems is presented, together with a process for recycling the [Emim][Ac] and enzymatically hydrolyzing the cellulose. This process reduces the amount of water to be evaporated from recycled IL, permitting efficient recycle of the IL. Material balances on the process, with multiple recycles of the [Emim][Ac], quantify the major components from a Miscanthus feedstock through the pretreatment, separation, and enzymatic hydrolysis steps. A more rapid and higher yielding conversion of cellulose to glucose is obtained by use of the three-phase system as compared to the cellulose obtained from biomass pretreated with IL and precipitated with water. The addition of a kosmotropic salt during the precipitation results in partial delignification of the biomass, which makes the substrate more accessible, enhancing the enzymatic hydrolysis.

Modeling corneal metabolism and oxygen transport during contact lens wear.

PURPOSE: A metabolic model is developed for cornea-contact-lens system to elucidate the role of glucose metabolism in oxygenation of the cornea and to gauge the role that contact lens oxygen transmissibility plays in avoiding hypoxia-induced corneal abnormalities for extended wear applications. METHODS: Oxygen transport through the cornea and contact lens system is typically described by oxygen diffusion with reactive loss. Oxygen in the cornea, however, interacts with other metabolic species, specifically glucose, lactate ion, bicarbonate ion, hydrogen ion, and carbon dioxide via aerobic glycolysis (Krebs or tricarboxylic acid cycle) and anaerobic glycolysis. Here, corneal aerobic and anaerobic metabolic reactions are incorporated into a six-layer (endothelium, stroma, epithelium, postlens tear film, contact lens, and prelens tear film) steady-state continuum reaction-diffusion model to quantify oxygen transport. We also define a new index, the oxygen deficiency factor (ODF), for gauging corneal oxygenation. As opposed to other current gauges of hypoxia, ODF is a local and sensitive measure of both the extent and severity of corneal oxygen deprivation. RESULTS: We calculate not only oxygenation of the cornea but also its coupled glucose, lactate, and acidosis behavior. For the first time, the metabolic shift from aerobic to anaerobic glycolysis is explicitly incorporated into the transport and consumption of oxygen in the cornea on closed-eye contact lens wear. Adoption of enzymatic Monod kinetics for the metabolic reactions permits realistic assessment of local species concentrations throughout the cornea. We find that anerobic-produced lactate transports out of the cornea into the anterior chamber, whereas buffering bicarbonate ion transports into the comea from the anterior chamber. CONCLUSIONS: The coupling of oxygen with other reactive species in corneal metabolism provides useful insight into the transport of oxygen in cornea-contact-lens system. Specifically, we find that in addition to oxygen depletion and acidosis in the cornea, lactate concentration increases while glucose and bicarbonate concentrations decrease from the endothelium toward the epithelium. Unlike other indices of corneal oxygenation, ODF is sensitive specifically to regions of cornea with local oxygen deficiency. Accordingly, ODF is a useful physiologic index to assess the extent and severity of hypoxia in the cornea.

In vitro cytotoxicities of ionic liquids: effect of cation rings, functional groups, and anions.

In vitro cytotoxicities were measured for ionic liquids (ILs) containing various cations and anions using the MCF7 human breast cancer cell line. We measured the cytotoxicities of ionic liquids containing the cations pyridinium, pyrrolidinium, piperidinium, or imidazolium with various alkyl chain lengths, and the anions bromide, bis(trifluoromethanesulfone)imide (Tf(2)N), trifluoromethylsulfonate (TfO), or nonafluoromethylsulfonate (NfO). Three new hydrophobic, task-specific ionic liquids (TSILs), namely, [MBCNPip](+)[Tf(2)N](-), [MPS(2)Pip](+)[Tf(2)N](-), and [MPS(2)Pyrro](+)[Tf(2)N](-) designed for metal-ion extraction were also evaluated. IC(50) values of the ionic liquids toward the MCF7 cells ranged from 8 microM to 44 mM. The toxicity depended significantly on the nature of the cations and anions, especially when the cations contained a long side chain. TSILs studied in this work were less toxic than the classical ILs.

Diffusion and Monod kinetics to determine in vivo human corneal oxygen-consumption rate during soft contact-lens wear.

The rate of oxygen consumption is an important parameter to assess the physiology of the human cornea. Metabolism of oxygen in the cornea is influenced by contact-lens-induced hypoxia, diseases such as diabetes, surgery, and drug treatment. Therefore, estimation of in vivo corneal oxygen-consumption rate is essential for gauging adequate oxygen supply to the cornea. Phosphorescence quenching of a dye coated on the posterior of a soft contact lens provides a powerful technique to measure tear-film oxygen tension (Harvitt and Bonanno, Invest Ophthalmol Vis Sci 1996;37:1026-1036; Bonanno et al., Invest Ophthalmol Vis Sci 2002;43:371-376). Unfortunately, previous work in establishing oxygen-consumption kinetics from transient postlens tear-film oxygen tensions relies on the simplistic assumption of a constant corneal-consumption rate. A more realistic model of corneal metabolism is needed to obtain reliable oxygen-consumption kinetics. Here, physiologically relevant nonlinear Monod kinetics is adopted for describing the local oxygen-consumption rate, thus avoiding aphysical negative oxygen tensions in the cornea. We incorporate Monod kinetics in an unsteady-state reactive-diffusion model for the cornea contact-lens system to determine tear-film oxygen tension as a function of time when changing from closed-eye to open-eye condition. The model was fit to available experimental data of in vivo human postlens tear-film oxygen tension to determine the corneal oxygen-consumption rate. Reliance on corneal oxygen diffusivity and solubility data obtained from rabbits is no longer requisite. Excellent agreement is obtained between the proposed model and experiment. We calculate the spatial-averaged in vivo human maximum corneal oxygen-consumption rate as Q(c)(max) = 1.05 x 10(-4) mL/(cm(3) s). The calculated Monod constant is K(m) = 2.2 mmHg.

Pairwise-additive hydrophobic effect for alkanes in water.

Pairwise additivity of the hydrophobic effect is indicated by reliable experimental Henry's constants for a large number of linear and branched low-molecular-weight alkanes in water. Pairwise additivity suggests that the hydrophobic effect is primarily a local phenomenon and that the hydrophobic interaction may be represented by a semiempirical force field. By representing the hydrophobic potential between two methane molecules as a linear function of the overlap volume of the hydration layers, we find that the contact value of the hydrophobic potential (-0.72 kcal/mol) is smaller than that from quantum mechanics simulations (-2.8 kcal/mol) but is close to that from classical molecular dynamics (-0.5 approximately -0.9 kcal/mol).

Solvent polarities and kamlet-taft parameters for ionic liquids containing a pyridinium cation.

Five recently synthesized pyridinium ionic liquids [(1-butyl-4-methylpyridinium, 1-octylpyridinium, 1-octyl-2-methylpyridinium, 1-octyl-3-methylpyridinium, and 1-octyl-4-methylpyridinium, all with anion bis(trifluoromethylsulfonyl)imide], were investigated to establish the influence of substituting a methyl group and the influence of alkyl chain length on the cation on polarity ET(N) and on three Kamlet-Taft parameters: dipolarity/polarizabilty (pi*), hydrogen-bond acidity (alpha), and hydrogen-bond basicity (beta). Experimental measurements cover the range 25 to 65 degrees C.

Water-Nafion equilibria. absence of Schroeder's paradox.

Water-Nafion phase equilibria and proton conductivities were measured in two ways. First, Nafion was in contact with saturated water vapor. Second, Nafion was in contact with liquid water at the same temperature. At 29 degrees C, for preboiled, vapor-equilibrated Nafion exposed to water with an activity = 1 and air pressures ranging from 0 to 0.96 bar, the water content was lambda = 23 +/- 1 mol H(2)O/mol SO3-. For the preboiled, liquid-equilibrated membrane, lambda = 24 +/- 2. At 100% relative humidity (RH), the water content of preboiled Nafion decreased as the temperature rose from 30 to 80 degrees C but did not recover its initial water content when the temperature returned to 30 degrees C. The water content of predried Nafion at 1 atm and 30 degrees C was lambda = 13.7 +/- 0.2 when vapor-equilibrated and lambda = 13.1 +/- 0.5 when liquid-equilibrated. A Nafion membrane originally boiled in water had much higher liquid- and 100% RH vapor-equilibrated proton conductivities than the same membrane originally dried at 110 degrees C with a RH less than 2%. The liquid-equilibrated and 100% RH vapor-equilibrated membrane conductivities were the same when the membrane had the same thermal history. The conductivity data was fit to a model, and the water content was determined at different temperatures. The predried membrane water content increased with temperature, and the preboiled membrane's water content changed slightly with temperature. Both water sorption and proton-conductivity data do not exhibit Schroeder's paradox. These studies and previous results suggest that Schroeder's paradox is resolved when attention is given to the thermal history of the absorbing polymer.

A single-lens polarographic measurement of oxygen permeability (Dk) for hypertransmissible soft contact lenses.

A novel polarographic apparatus is described that requires only a single soft contact lens (SCL) to ascertain oxygen permeabilities of hypertransmissible lenses. Unlike conventional methods where a range of lens thickness is needed for determining oxygen permeabilities of SCLs, the apparatus described here requires only a single-lens thickness. This is accomplished by minimizing (or completely eliminating) edge effects, boundary-layer resistances, and lens desiccation in the polarographic apparatus. By taking these effects into account, we measure reliable oxygen permeabilities of hypertransmissible SCLs (i.e., above 100 barrer). Results are reported for nine commercial SCLs ranging in permeability from 9 to 180 barrer. Measured single-lens oxygen permeabilities are in excellent agreement with those claimed by commercial manufacturers. Our new single-lens permeameter provides a reliable, efficient, and economical method for measuring oxygen permeabilities of commercial SCLs. The single-lens method offers a potential international standard for measuring oxygen permeabilities of SCLs up to 250 barrer.

Protein aggregation in silico.

Protein aggregation is a challenge to the successful manufacture of protein therapeutics; it can impose severe limitations on purification yields and compromise formulation stability. Advances in computer power, and the wealth of computational studies pertaining to protein folding, have facilitated the development of molecular simulation as a tool to investigate protein misfolding and aggregation. Here, we highlight the successes of protein aggregation studies carried out in silico, with a particular emphasis on studies related to biotechnology. To conclude, we discuss future prospects for the field, and identify several biotechnology-related problems that would benefit from molecular simulation.

Molecular simulation of protein aggregation.

Computer simulation offers unique possibilities for investigating molecular-level phenomena difficult to probe experimentally. Drawing from a wealth of studies concerning protein folding, computational studies of protein aggregation are emerging. These studies have been successful in capturing aspects of aggregation known from experiment and are being used to refine experimental methods aimed at abating aggregation. Here we review molecular-simulation studies of protein aggregation conducted in our laboratory. Specific attention is devoted to issues with implications for biotechnology.