Biomedical subjects

Dor Ben-Amotz

Publications and source records attributed to Dor Ben-Amotz.

At least 19 recordsLinked to original sources

PubMed2006

Note on the energy density in the solvent induced by a solute.

The question of how far the effect of the presence of a solute molecule propagates into the solvent is studied in a lattice model that had been used earlier to describe hydrophobic interactions. The local energy density in the model solvent is obtained as an explicit function of distance from the solute and is found to decay to its bulk-phase value with the same decay length as that of the solvent-mediated part of the potential of mean force between a pair of solute molecules. The integrated deviation of the energy density from its bulk-phase value is evaluated in Bethe-Guggenheim approximation and shown to be identical to the energy change accompanying the dissolution of the solute as obtained from the temperature dependence of its solubility.

Journal Article↗

PubMed2006

Generalized solvation heat capacities.

The partial molar heat capacity associated with a constant-pressure solvation process is extended to define a total of six generalized solvation heat capacities, each of which contain unique physical information. These arise from all the possible cross derivatives of the reversible heat of solvation (with respect to T and N), each evaluated at either constant pressure or constant volume. The resulting quantities may be interconverted using expressions that depend on the solvent equation of state and the solute partial molar volume. Moreover, contributions to each of the solvation heat capacities arising from the temperature dependence of the solute-solvent interaction energy and the solvent-reorganization energy (at either constant pressure or constant volume) are formally identified. For the self-solvation of a molecule in its own pure fluid, the latter quantities may be extracted directly from experimental data, while for more general solvation processes additional input is required, either from computer simulation or from theoretical approximations. The results are used to experimentally quantify the generalized heat capacities pertaining to the self-solvation of xenon, difluoromethane, n-hexane, and water, as well as the hydration of xenon, cyclohexane, and three hard sphere solutes (of about the same size as water, xenon, and cyclohexane).

Journal Article↗

PubMed2006

Revisiting Bohr's semiclassical quantum theory.

Bohr's atomic theory is widely viewed as remarkable, both for its accuracy in predicting the observed optical transitions of one-electron atoms and for its failure to fully correspond with current electronic structure theory. What is not generally appreciated is that Bohr's original semiclassical conception differed significantly from the Bohr-Sommerfeld theory and offers an alternative semiclassical approximation scheme with remarkable attributes. More specifically, Bohr's original method did not impose action quantization constraints but rather obtained these as predictions by simply matching photon and classical orbital frequencies. In other words, the hydrogen atom was treated entirely classically and orbital quantized emerged directly from the Planck-Einstein photon quantization condition, E = h nu. Here, we revisit this early history of quantum theory and demonstrate the application of Bohr's original strategy to the three quintessential quantum systems: an electron in a box, an electron in a ring, and a dipolar harmonic oscillator. The usual energy-level spectra, and optical selection rules, emerge by solving an algebraic (quadratic) equation, rather than a Bohr-Sommerfeld integral (or Schroedinger) equation. However, the new predictions include a frozen (zero-kinetic-energy) state which in some (but not all) cases lies below the usual zero-point energy. In addition to raising provocative questions concerning the origin of quantum-chemical phenomena, the results may prove to be of pedagogical value in introducing students to quantum mechanics.

Journal Article↗

PubMed2006

The rectified second law of thermodynamics.

Equilibrium thermodynamics is combined with Jarzynski's irreversible work theorem to quantify the excess entropy produced by irreversible processes. The resulting rectified form of the second law parallels the first law, in the sense that it facilitates the experimental measurement of excess entropy changes resulting from irreversible work and heat exchanges, just as the first law quantifies energy changes produced by either reversible or irreversible work and heat exchanges. The general form of the rectified second law is further applied to a broad class of quasi-static irreverisble (QSI) processes, for which all of the thermodynamic functions of both the system and surroundings remain continuously well-defined, thus facilitating excess entropy measurements by integrating exact differential functions along QSI paths. The results are illustrated by calculating the mechanical and thermal excess entropy produced by the irreversible unfolding of an RNA molecule.

Algorithms↗

PubMed2006

Validation of the drop coating deposition Raman method for protein analysis.

Drop coating deposition Raman (DCDR) spectroscopy is critically evaluated to establish the limits to which it may be used to detect changes in protein conformation, binding, and purity. Difference spectroscopy is used to evaluate the reproducibility of the DCDR spectra under various experimental conditions. The results indicate (i) the absence of thermal/photochemical laser damage induced by the Raman excitation laser under typical DCDR data collection conditions, (ii) the reproducibility of DCDR spectra from samples with different volumes or concentrations, (iii) the water content of DCDR protein deposits and associated spectral signatures, and (iv) the degree of similarity between solution Raman spectra and DCDR spectra.

Deuterium Oxide↗

PubMed2006

Average entropy dissipation in irreversible mesoscopic processes.

The Clausius inequality is rectified to obtain expressions for the entropy produced as the result of irreversible work and/or heat exchanges. These are combined with the Jarzynski equality and its generalizations to explicitly relate mean (as opposed to transient) entropy dissipation to experimental or simulation observables. The results are extended to nonisothermal processes which begin and end at nonequilibrium steady states, leading to a new exact expression and positive lower bound for the resulting average entropy dissipation. The Carnot engine emerges as a limiting case of a family of irreversible processes arising from an interface between materials at different temperatures, whose mapping onto reversible and irreversible molecular extension experiments is discussed.

Journal Article↗

PubMed2005

Global thermodynamics of hydrophobic cavitation, dewetting, and hydration.

Pure water experimental and simulation results are combined to predict the thermodynamics of cavity formation, spanning atomic to macroscopic length scales, over the entire ambient liquid temperature range. The resulting cavity equation of state is used to quantify dewetting excess contributions to cavity formation thermodynamics and construct a thermodynamic perturbation theory of hydrophobic hydration. Predictions are compared with large cavity simulations and experimental rare-gas hydration thermodynamics data (for He, Ne, Ar, Kr, Xe, and Rn). Key findings include the strong temperature dependence of the critical length scale for hydrophobic dewetting and the evaluation of fundamental solute-solvent interaction contributions to rare-gas hydration chemical potentials.

Journal Article↗

PubMed2005

Adaptive silver films for detection of antibody-antigen binding.

Antibody-antigen binding events at a monolayer protein concentration have been demonstrated on nanostructured adaptive silver films (ASFs) using surface-enhanced Raman scattering (SERS) and luminescence-based assays. It is shown that proteins stabilize and restructure the ASF to increase the SERS signal while preserving antigen-binding activity. Evidence for antibody-antigen binding on the ASF substrates is the distinct SERS spectral changes of the surface-bound antibody or antigen without special tags. The activity of the surface-bound proteins and their practical application are validated by independent immunochemical assays. Results are presented to demonstrate that these surfaces can be extended to protein arrays with detection applications distinct from current SERS, fluorescence, or luminescence methods.

Antibodies↗

PubMed2005

Detection of amino acid and peptide phosphate protonation using Raman spectroscopy.

Raman spectra of phosphorylated amino acids and peptides undergo pH-dependent changes attributed to protonation of -OPO(3)(2-) (dibasic) to -OPO(3)H(-) (monobasic). Bands at approximately 980 and 1080cm(-1) in solution Raman spectra of phosphoserine and phosphothreonine are assigned to the monobasic and dibasic phosphate groups, respectively. Calibrated Raman peak area ratio measurements, performed as a function of pH, are used to determine the corresponding pKa values of 5.6 (phosphoserine) and 5.9 (phosphothreonine). In peptides, the phosphate Raman bands are difficult to distinguish due to interference from other neighboring bands (particularly those derived from aromatic amino acid residues) as well as the relatively low solubility of peptides. Nevertheless, drop coating deposition Raman (DCDR) spectra obtained from 100-microM peptide solutions reveal pH-dependent second derivative features at approximately 980 and 1080cm(-1), which are indicative of phosphate protonation.

Amino Acid Sequence↗

PubMed2005

Isotope edited internal standard method for quantitative surface-enhanced Raman spectroscopy.

A new isotope edited internal standard (IEIS) method for quantitative surface-enhanced Raman spectroscopy (SERS) is demonstrated using rhodamine 6G (R6G-d0) and rhodamine 6G (R6G-d4) edited with deuterium. The reproducibility and accuracy of the IEIS method is investigated both under optical resonance (SERRS) and nonresonance (SERS) conditions. A batch-to-batch concentration measurement reproducibility of better than 3% is demonstrated over a concentration range of 200 pM-2 microM with up to a factor of 3 difference between the concentration of the analyte and its IEIS. The superior performance of the IEIS method is further illustrated by comparing results obtained using absolute SERS/SERRS intensity calibration (with no internal standard) or using adenine (rather than R6G-d4) as an internal standard for R6G concentration quantization. Potential biomedical gene expression and comparative proteomic applications of the IEIS method are discussed.

Adenine↗

PubMed2005

Solvation thermodynamics: theory and applications.

Potential distribution and coupling parameter theories are combined to interrelate previous solvation thermodynamic results and derive several new expressions for the solvent reorganization energy at both constant volume and constant pressure. We further demonstrate that the usual decomposition of the chemical potential into noncompensating energetic and entropic contributions may be extended to obtain a Gaussian fluctuation approximation for the chemical potential plus an exact cumulant expansion for the remainder. These exact expressions are further related to approximate first-order thermodynamic perturbation theory predictions and used to obtain a coupling-parameter integral expression for the sum of all higher-order terms in the perturbation series. The results are compared with the experimental global solvation thermodynamic functions for xenon dissolved in n-hexane and water (under ambient conditions). These comparisons imply that the constant-volume solvent reorganization energy has a magnitude of at most approximately kT in both experimental solutions. The results are used to extract numerical values of the solute-solvent mean interaction energy and associated fluctuation entropy directly from experimental solvation thermodynamic measurements.

Journal Article↗

PubMed2005

Detection of the site of phosphorylation in a peptide using Raman spectroscopy and partial least squares discriminant analysis.

Normal (non-enhanced) Raman spectroscopy is used to determine the site of phosphorylation on a 13-residue peptide whose sequence derives from the cellular protein pp60(c-src) (protein tyrosine kinase). Raman spectra of serine, threonine and tyrosine amino acids and their phosphorylated derivatives are used to aid in the interpretation of peptide spectra. The purity of the synthetic peptides are confirmed by mass spectroscopy. Peptide Raman measurements are performed using the recently reported drop-coating deposition Raman (DCDR) method, followed by Savistky-Golay second derivative (SGSD) pre-processing and multivariate spectral classification using partial least squares (PLS) discriminant analysis. Leave-one-out training/testing results are displayed using a PLS psuedo-probability score plot and shown to facilitate error-free spectral determination of the site of phosphorylation.

Humans↗

PubMed2004

Identification of insulin variants using Raman spectroscopy.

Drop coating deposition Raman (DCDR) spectroscopy is used to obtain high-quality normal Raman spectra from small volumes (10 microl) of dilute insulin solutions (3-400 microM) for spectral identification and chromatographic detection. The results are used to demonstrate the spectroscopic classification (identification) of three natural insulin variants-human, bovine, and porcine-that differ by between one and three amino acid residues. DCDR measurements were performed on solutions obtained from reverse phase high-performance liquid chromatography (RP-HPLC) eluent fractions, either before or after lyophilization. Classification is demonstrated using replicate DCDR measurements, followed by normalized Savitsky-Golay second derivative preprocessing and partial least squares training with either leave-one-out or batch-to-batch testing.

Amino Acid Sequence↗

PubMed2004

The Raman detection of peptide tyrosine phosphorylation.

Drop-coating-deposition-Raman (DCDR) is used to detect spectral changes induced by phosphorylation of tyrosine amino acid residues in peptides. Four peptides are investigated, with sequences derived from the human protein-tyrosine kinase, p60c-src, with Y-216, Y-419, and Y-530 phosphorylation sites. Although the spectra of the four peptides are quite different, tyrosine phosphorylation is found to invariably induce the collapse of a doublet at 820-850cm(-1) and the attenuation of a peak around 1205cm(-1). Moreover, amide III band shifts suggest that tyrosine phosphorylation may promote beta sheet formation, particularly in peptides that lack phenylalanine residues. The degree of tyrosine phosphorylation in peptide mixtures is determined using DCDR combined with partial least squares multivariate calibration with a 2% root mean standard error of prediction.

Amino Acid Sequence↗

PubMed2004

Hard sphere perturbation theory for fluids with soft-repulsive-core potentials.

The thermodynamic properties of fluids with very soft repulsive-core potentials, resembling those of some liquid metals, are predicted with unprecedented accuracy using a new first-order thermodynamic perturbation theory. This theory is an extension of Mansoori-Canfield/Rasaiah-Stell (MCRS) perturbation theory, obtained by including a configuration integral correction recently identified by Mon, who evaluated it by computer simulation. In this work we derive an analytic expression for Mon's correction in terms of the radial distribution function of the soft-core fluid, g(0)(r), approximated using Lado's self-consistent extension of Weeks-Chandler-Andersen (WCA) theory. Comparisons with WCA and MCRS predictions show that our new extended-MCRS theory outperforms other first-order theories when applied to fluids with very soft inverse-power potentials (n< or =6), and predicts free energies that are within 0.3 kT of simulation results up to the fluid freezing point.

Journal Article↗

PubMed2004

Oligosaccharide identification and mixture quantification using Raman spectroscopy and chemometric analysis.

This work demonstrates the feasibility of using Raman spectroscopy for the analysis of small quantities of chemically similar oligosaccharides and their mixtures. Raman spectra were obtained from 10-microL aliquots of 1 mM solutions of maltotetraose and/or stachyose after deposition onto an electrochemically roughened silver substrate (and the resulting spectral features are attributed to a combination of normal and surface-enhanced Raman scattering). These compounds were selected because they are representative of glycans derived from post-translationally modified proteins which, like these compounds, often consist of isomers of equal mass and similar shape. Replicate spectral measurements were recorded and processed using a partial-least-squares (PLS) classification and quantification algorithms with a leave-one-batch-out (LOBO) training and testing procedure. Spectra derived from solutions of individual sugars were identified with 100% accuracy, and mixtures of the two sugars were quantified with an average error of 2.7% in the relative maltotetraose/stachyose composition for mixtures with a total oligosaccharide concentration of 1 mM.

Algorithms↗

PubMed2004

Chemical segregation and reduction of Raman background interference using drop coating deposition.

A new application of the recently described drop coating deposition Raman (DCDR) method facilitates the segregation and independent spectral characterization of mixture components. The quality of the normal (un-enhanced) Raman spectra are significantly improved as a result of reduced spectral interference from fluorescent impurities and buffer compounds. Fluorescence of commercial amino acid (O-phospho-L-serine) and protein (myoglobin) samples is reduced by over an order of magnitude using DCDR, more effectively than prolonged photo-bleaching. Furthermore, DCDR is used to obtain high-quality Raman spectra of proteins, lysozyme, and insulin, derived from solutions with up to 1000-fold excess buffer concentration. Possible thermodynamic and kinetic contributions to the observed segregation phenomena are discussed.

Amino Acids↗

PubMed2004

Second-derivative variance minimization method for automated spectral subtraction.

A new second-derivative variance minimization (SDVM) procedure is used to automatically extract spectra of a dilute component (solute) from a mixture whose spectrum is dominated by a major component (solvent). This procedure involves the subtraction of Savitzky-Golay second-derivative preprocessed pure solvent and mixture spectra by minimizing the variance of the difference spectrum. The resulting undifferentiated output spectra contain primarily features associated with the solute and/or solute-induced perturbations of the solvent. The SDVM method is found to outperform several related methods, including a previously proposed derivative minimization method, as demonstrated using 1000 randomly generated solute/solvent synthetic spectral pairs and experimental Raman spectra of dilute solutions of benzene in n-hexane and water in acetone. The former experimental solution produced SDVM difference spectra containing benzene bands with virtually no n-hexane interference, while the latter revealed water-induced shifts in acetone spectral features. Several other types of SDVM applications, such as the spectroscopic analysis of layered composites, are discussed.

Journal Article↗