Determination of the acid/base properties of MgY and NH4Y molecular sieves by inverse gas chromatography

The surface characterization of MgY and NH(4)Y zeolites was performed using inverse gas chromatography (IGC). The adsorption thermodynamic parameters (the standard enthalpy (DeltaH degrees ), standard entropy change (DeltaS degrees ), and free energy change of adsorption (DeltaG degrees ), the dispersive component of the surface free energies (gamma(S)(d)), and the acid-base character of the surface of MgY and NH(4)Y zeolites were estimated using the retention time of different non-polar and polar probes at infinite dilution region. The specific free energy of adsorption (DeltaG(sp)), the specific enthalpy of adsorption (DeltaH(sp)), and the specific entropy of adsorption (DeltaS(sp)) of polar probes on MgY and NH(4)Y zeolites were determined. The values of the DeltaH(sp) were correlated with both the donor and acceptor numbers of the probes to quantify the acidic K(A) and the basic K(D) parameters of the zeolite surfaces. The values obtained for the K(A) and K(D) parameters indicated a basic character for the surface of MgY and NH(4)Y zeolites.     

Equilibrium constants for dehydration of water adducts of aromatic carbon-carbon double bonds

Equilibrium constants (K(de)) are reported for the dehydration of hydrates of benzene, naphthalene, phenanthrene, and anthracene. Free energies of formation of the hydrates (DeltaG(o) (f)(aq)) are derived by combining free energies of formation of the parent (dihydroaromatic) hydrocarbon with estimates of the increment in free energy (DeltaG(OH)) accompanying replacement of a hydrogen atom of the hydrocarbon by a hydroxyl group. Combining these in turn with free energies of formation of H(2)O and of the aromatic hydrocarbon products furnishes the desired equilibrium constants. The method depends on the availability of thermodynamic data (i) for the hydrocarbons from which the hydrates are derived by hydroxyl substitution and (ii) for a sufficient range of alcohols to assess the structural dependence of DeltaG(OH). The data comprise chiefly heats of formation and standard entropies in the gas phase and free energies of transfer from the gas phase to aqueous solution (the latter being derived from vapor pressures and solubilities). They also include experimental measurements of equilibrium constants for dehydration of alcohols, especially cyclic, allylic, and benzylic alcohols. In general DeltaG(OH) depends on whether the alcohol is (a) primary, secondary, or tertiary; (b) allylic or benzylic; and (c) open chain or cyclic. Differences in geminal interactions of the hydroxyl group of the alcohol with alpha-alkyl and vinyl or phenyl groups account for variations in DeltaG(OH) of 5 kcal mol(-1). Weaker variations which arise from beta-vinyl/OH or beta-phenyl/OH interactions present in the aromatic hydrates but not in experimentally studied analogues are estimated as 1.0 kcal mol(-1). Equilibrium constants for dehydration may be expressed as their negative logs (pK(de)). Reactions yielding the following aliphatic, aromatic, and antiaromatic unsaturated products then have pK(de) values: +4.8, ethene; +15.0, ethyne; +22.1, cyclopropene; +28.4 cyclobutadiene; -22.2, benzene; -14.6, naphthalene; -9.2, phenanthrene; -7.4, anthracene. Large positive values are associated with formation of strained or antiaromatic double bonds and large negative values with aromatic double bonds. Trends in pK(de) parallel those of heats of hydrogenation. The results illustrate the usefulness of a substituent treatment for extending the range of currently available free energies of formation. In addition to hydroxyl substituent effects, DeltaG(OH), values of DeltaG(pi) for substitution of a pi-bond in a hydrocarbon are reported.     

Alpha7 nicotinic acetylcholine receptor agonists: prediction of their binding affinity through a molecular mechanics Poisson-Boltzmann surface area approach

A group of agonists for the alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies of binding DeltaG(bind) were calculated by applying the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) approach. This method, based on molecular dynamics simulations of fully solvated protein-ligand complexes, allowed us to estimate the contribution of both polar and nonpolar terms as well as the entropy to the overall free energy of binding. The calculated results were in a good agreement with the experimentally determined DeltaG(bind) values, thereby pointing to the MM-PBSA protocol as a valuable computational tool for the rational design of specific agents targeting the neuronal alpha7 nAChR subtypes.     

Three empirical correlations connecting gaseous cluster energies and solvation energies of alkali metal and halide ions.

This paper gives two empirical correlations of formation Gibbs energies of gaseous clusters DeltaG(f)n as function of number of solvent molecules attached to the ion, n, and one correlation connecting the DeltaG(f)n for each individual cluster with the total DeltaG(o)hydr value. The experimental ratios of DeltaG(f)2/DeltaG(f)1 and DeltaG(f)3/DeltaG(f)1 for both alkali metal and halide ions are on average equal to 0.75 and 0.5, respectively. DeltaG(f)n values for n > or = 4 are correlated with n as DeltaG(f)n = [a/(n - 1)] DeltaG(f)1 + b DeltaG(f)1. For all available data on cluster energies and each individual cluster, the DeltaG(f)n's are straight-line functions of DeltaG(o)hydr. This well corresponds to another empirical rule stating that the Gibbs energies of transfer of ions between two solvents are often as well straight-line functions of DeltaG(o)(hydr) [J. Rais and T. Okada, J. Phys. Chem. A, 2000, 104, 7314]. Tentative models of the found behavior are proposed. A full data set of the gaseous cluster energies of formation based on inclusion of new, usually not used entries from the literature is provided.     

The demicellization of alkyltrimethylammonium bromides in 0.1 M sodium chloride solution studied by isothermal titration calorimetry

The demicellization of the cationic detergents dodecyltrimethylammonium bromide, tetradecyltrimetylammonium bromide, and cetyltrimethylammonium bromide was studied at temperatures between 20 and 60 degrees C in 0.1 M NaCl (pH 6.4) using isothermal titration calorimetry (ITC). We determined the critical micellization concentration (cmc) of the cationic detergents which show a minimum at temperatures between 20 and 34 degrees C. In accordance with the lengthening of the hydrophobic tail of the detergents the cmc decreases with increasing alkyl chain length. The thermodynamic parameters describing the changes of enthalpy (DeltaH(demic)), the changes of entropy (DeltaS(demic)) and the Gibbs free energy change (DeltaG(demic)) for demicellization were first obtained using the pseudophase-separation model. The aggregation number n at the cmc as well as the demicellization enthalpy, entropy and Gibbs free energy change were also calculated using a simulation based on the mass-action model. Furthermore, we investigated the demicellization of CTAB in deionized water in comparison to demicellization in sodium chloride solution to determine the influence of counter ion binding on the demicellization.     

Accurate pK(a) calculations for carboxylic acids using complete basis set and Gaussian-n models combined with CPCM continuum solvation methods

Complete Basis Set and Gaussian-n methods were combined with CPCM continuum solvation methods to calculate pK(a) values for six carboxylic acids. An experimental value of -264.61 kcal/mol for the free energy of solvation of H(+), DeltaG(s)(H(+)), was combined with a value for G(gas)(H(+)) of -6.28 kcal/mol to calculate pK(a) values with Cycle 1. The Complete Basis Set gas-phase methods used to calculate gas-phase free energies are very accurate, with mean unsigned errors of 0.3 kcal/mol and standard deviations of 0.4 kcal/mol. The CPCM solvation calculations used to calculate condensed-phase free energies are slightly less accurate than the gas-phase models, and the best method has a mean unsigned error and standard deviation of 0.4 and 0.5 kcal/mol, respectively. The use of Cycle 1 and the Complete Basis Set models combined with the CPCM solvation methods yielded pK(a) values accurate to less than half a pK(a) unit.     

FAMBE-pH: a fast and accurate method to compute the total solvation free energies of proteins

A fast and accurate method to compute the total solvation free energies of proteins as a function of pH is presented. The method makes use of a combination of approaches, some of which have already appeared in the literature; (i) the Poisson equation is solved with an optimized fast adaptive multigrid boundary element (FAMBE) method; (ii) the electrostatic free energies of the ionizable sites are calculated for their neutral and charged states by using a detailed model of atomic charges; (iii) a set of optimal atomic radii is used to define a precise dielectric surface interface; (iv) a multilevel adaptive tessellation of this dielectric surface interface is achieved by using multisized boundary elements; and (v) 1:1 salt effects are included. The equilibrium proton binding/release is calculated with the Tanford-Schellman integral if the proteins contain more than approximately 20-25 ionizable groups; for a smaller number of ionizable groups, the ionization partition function is calculated directly. The FAMBE method is tested as a function of pH (FAMBE-pH) with three proteins, namely, bovine pancreatic trypsin inhibitor (BPTI), hen egg white lysozyme (HEWL), and bovine pancreatic ribonuclease A (RNaseA). The results are (a) the FAMBE-pH method reproduces the observed pK a's of the ionizable groups of these proteins within an average absolute value of 0.4 p K units and a maximum error of 1.2 p K units and (b) comparison of the calculated total pH-dependent solvation free energy for BPTI, between the exact calculation of the ionization partition function and the Tanford-Schellman integral method, shows agreement within 1.2 kcal/mol. These results indicate that calculation of total solvation free energies with the FAMBE-pH method can provide an accurate prediction of protein conformational stability at a given fixed pH and, if coupled with molecular mechanics or molecular dynamics methods, can also be used for more realistic studies of protein folding, unfolding, and dynamics, as a function of pH.     

Studies of the equilibrium and thermodynamics of the adsorption of Cu(2+) onto as-produced and modified carbon nanotubes

This study evaluates the Cu(2+) adsorption efficiency of as-produced carbon nanotubes (CNTs) and those modified by HNO(3) and NaOCl. The surface area, pH(pzc), pore volume, FTIR analyses, and average pore size of CNTs were determined to compare the differences between nanotubes before and after HNO(3) and NaOCl modification. The HNO(3) and NaOCl modifications increased the pore volume and the average pore size of CNTs; in contrast, the pH(pzc) was decreased. The modification processes produced some functional groups. The adsorption capacity of Cu(2+) on as-produced and modified CNTs increased with the pH and temperature; however, the effects of the ionic strength on the adsorption of Cu(2+) on as-produced and modified CNTs were negligible. The linear correlation coefficients of Langmuir and Freundlich isotherms were obtained and the results revealed that the Langmuir isotherm fitted the experimental results better than did the Freundlich isotherm. The adsorption capacity of Cu(2+) followed the order NaOCl-modified CNTs > HNO(3)-modified CNTs > as-produced CNTs. Changes in the free energy of adsorption (DeltaG(o)), enthalpy (DeltaH(o)), and entropy (DeltaS(o)) were determined. All DeltaG(o) values were negative; the DeltaH(o) values of as-produced, HNO(3)-modified, and NaOCl-modified CNTs were 10.84, 17.08, and 67.77 kJ/mol and the DeltaS(o) values were 96.89, 122.88, and 319.76 J/mol K, respectively.     

N-(1-piperidinepropionyl)amphotericin B methyl ester (PAME)--a new derivative of the antifungal antibiotic amphotericin B: searching for the mechanism of its reduced toxicity

N-(1-piperidinepropionyl)amphotericin B methyl ester (in short, PAME), a low-toxicity amphotericin B derivative, has been investigated in Langmuir monolayers at the air/water interface alone and in mixtures with cellular membrane sterols (a mammalian sterol, cholesterol, and a fungal sterol, ergosterol) and a model phospholipid (DPPC). The analysis of the strength of interaction between PAME and both sterols as well as DPPC was based, on surface pressure measurements and analysis of the isothermal compressibility (C(s)(-1)), the mean area per molecule (A(12)), the excess free energy of mixing (DeltaG(Exc)) and the total free energy of mixing (DeltaG(M)). It has been found that the interactions between PAME and sterols are attractive; however, their strength is significantly weaker for mixtures of PAME with cholesterol than with ergosterol. This casts light on the improved selectivity of PAME toward fungal cells. The strongest interactions, found for PAME/DPPC mixtures, proved an important role of DPPC in the mechanism of reduced toxicity of PAME as compared to amphotericin B. Due to stable complex formation between PAME and DPPC the antibiotic is immobilized with DPPC molecules, which reduces the concentration of free antibiotic, which is capable of interacting with membrane sterols.     

The sorption of divalent metal ions on AlPO4

The sorption of Cu(2+), Pb(2+), Ni(2+), and Cd(2+) ions on the aluminum(III) phosphate was observed to increase with increases in the concentration, temperature, and pH of the system. The apparent dissociation (pK(a)), binding (pK(b)) and exchange (pK(ex)) constants of aluminum(III) phosphate were evaluated and found to be dependent upon the temperature and nature of the metal cations. The values of the dissociation constants (pK(a)) followed the order Pb(2+)相似文献   

Computation of hydration free energies of organic solutes with an implicit water model

A new approach for computing hydration free energies DeltaG(solv) of organic solutes is formulated and parameterized. The method combines a conventional PCM (polarizable continuum model) computation for the electrostatic component DeltaG(el) of DeltaG(solv) and a specially detailed algorithm for treating the complementary nonelectrostatic contributions (DeltaG(nel)). The novel features include the following: (a) two different cavities are used for treating DeltaG(el) and DeltaG(nel). For the latter case the cavity is larger and based on thermal atomic radii (i.e., slightly reduced van der Waals radii). (b) The cavitation component of DeltaG(nel) is taken to be proportional to the volume of the large cavity. (c) In the treatment of van der Waals interactions, all solute atoms are counted explicitly. The corresponding interaction energies are computed as integrals over the surface of the larger cavity; they are based on Lennard Jones (LJ) type potentials for individual solute atoms. The weighting coefficients of these LJ terms are considered as fitting parameters. Testing this method on a collection of 278 uncharged organic solutes gave satisfactory results. The average error (RMSD) between calculated and experimental free energy values varies between 0.15 and 0.5 kcal/mol for different classes of solutes. The larger deviations found for the case of oxygen compounds are probably due to a poor approximation of H-bonding in terms of LJ potentials. For the seven compounds with poorest fit to experiment, the error exceeds 1.5 kcal/mol; these outlier points were not included in the parameterization procedure. Several possible origins of these errors are discussed.     

Kinetics and thermodynamics of sorption of nitroaromatic compounds to as-grown and oxidized multiwalled carbon nanotubes

The sorption kinetics and thermodynamics of 1,3-dinitrobenzene (DNB), m-nitrotoluene (mNT), p-nitrophenol (pNP), and nitrobenzene (NB) on as-grown and nitric acid-oxidized multiwalled carbon nanotubes (MWCNTs) were investigated. The sorption kinetics was well described by a pseudo-second-order rate model, while both Langmuir and Freundlich models described the sorption isotherms well and the sorption thermodynamic parameters of equilibrium constant (K(0)), standard free energy (DeltaG), standard enthalpy (DeltaH), and standard entropy changes (DeltaS) were measured. The values of DeltaH and DeltaG suggested that the sorption of nitroaromatics (NACs) onto MWCNTs was exothermic and spontaneous. The structure, number, and position of nitro groups of NACs were the main factors affecting the sorption rate and capacity. Treatment of the MWCNTs with nitric acid increased both the surface area and the pore volume and introduced oxygen-containing functional groups to the MWCNTs, which depressed the sorption of NACs onto MWCNTs.     

Reactions of cisplatin and glycine in solution with constant pH: a computational study

In this study interaction between glycine and cisplatin was explored. The structures were optimized in both gas phase and implicit water solution at the B3LYP/6-31G(p)/IEFPCM/UAKS computational level. Vibrational analysis confirms the corresponding character of all the complexes from examined reaction coordinates. The enthalpy and entropy contributions to Gibbs free energies were estimated from the vibrational frequencies and statistical canonical ensemble model. In the solution, several deprotonated forms were considered, and pK(a) values of the reactants and products were determined. The reaction Gibbs free energies and pK(a) values were used for determination of the transformed thermodynamic potential ΔG' with pH as a natural variable.     

pH dependence of uranyl retention in a quartz/solution system: an XPS study

We have investigated the pH dependence of U(VI) retention in quartz/10(-4) M uranyl solution systems, under conditions favoring formation of polynuclear aqueous species and of colloids of amorphous schoepite as U(VI) solubility-limiting phases. X-ray photoelectron spectroscopy was used to gain insights into the coordination environments of sorbed/precipitated uranyl ions in the centrifuged quartz samples. The U4f XPS spectra made it possible to identify unambiguously the presence of two uranyl components. A high binding energy component, whose relative proportion increases with pH, exhibits the U4f lines characteristic of a reference synthetic metaschoepite. Such a high binding energy component is interpreted as a component having a U(VI) oxide hydrate character, either as polynuclear surface oligomers and/or as amorphous schoepite-like (surface) precipitates. Its pH dependence suggests that a binding of polynuclear species at quartz surfaces and/or a formation of amorphous schoepite-like (surface) precipitates is favored when the proportion of aqueous polynuclear species increases. A second surface component exhibits binding energies for the U4f core levels at values significantly lower (DeltaE(b)=1.2 eV) than for metaschoepite, evidencing uranyl ions in a distinct coordination environment. Such a low binding energy component may be attributed to monomeric uranyl surface complexes on the basis of published EXAFS data. Such a hypothesis is supported by a major contribution of the low binding energy component to the U4f XPS spectra of reference samples for uranyl sorbed on quartz from very acidic 10(-3) M uranyl solutions where UO(2)(2+) ions predominate.     

Energetics of binding and protein unfolding upon amphiphilic drug complexation with a globular protein in different aqueous media

The interactions and complexation process of the structurally related amphiphilic phenothiazines promazine and triflupromazine hydrochlorides with horse myoglobin in aqueous buffered solutions of pH 2.5, 5.5 and 9.0 have been examined by zeta-potential, isothermal titration calorimetry (ITC), UV-vis spectroscopy and dynamic light-scattering techniques with the aim of analyzing the effect of hydrophobic and electrostatic forces, the alteration of protein conformation and the effect of substituents in the drug molecular structure on the binding mechanism and structure of the resulting complexes. The energetics and stoichiometry of the binding process was derived from ITC. The enthalpies of binding obtained are small and exothermic, and the Gibbs energies of binding are dominated by large increases in entropy consistent with hydrophobic interactions. Binding isotherms were obtained from microcalorimetric data by using a theoretical model based on the Langmuir isotherm. zeta-Potential data showed a reversal in the sign of the protein charge at pH 9.0 as a consequence of drug binding. Gibbs energies of drug binding per mole of drug were also derived from zeta-potential data. On the other hand, binding of the phenothiazines causes a conformational transition on protein structure which was followed as a function of drug concentration by using UV-vis spectroscopy. These data were analyzed to obtain the Gibbs energy of the transition in water (DeltaG(w)(degrees)) and in a hydrophobic environment (DeltaG(hc)(degrees)). Finally, the population distribution of the different species in solution and their size was analyzed through dynamic light scattering. The existence of an aggregation process of drug/protein complexes, mainly at pH 2.5, was observed. We think this is a consequence of the already expanded structure of the protein at this pH and the subsequent binding of drug molecules to the protein.     

Heuristic molecular lipophilicity potential (HMLP): lipophilicity and hydrophilicity of amino acid side chains

Heuristic molecular lipophilicity potential (HMLP) is applied in the study of lipophilicity and hydrophilicity of 20 natural amino acids side chains. The HMLP parameters, surface area S(i), lipophilic indices L(i), and hydrophilic indices H(i) of amino acid side chains are derived from lipophilicity potential L(r). The parameters are correlated with the experimental data of phase-transferring free energies of vapor-to-water, vapor-to-cyclohexane, vapor-to-octanol, cyclohexane-to-water, octanol-to-water, and cyclohexane-to-octanol through a linear free energy equation DeltaG(0)(tr,i) = b(0) + b(1)S(i) (+) + b(2)S(i) (-) + b(3)L(i) + b(4)H(i). For all above six phase-transfer free energies, the HMLP parameters of 20 amino acid side chains give good calculation results using linear free energy equation. HMLP is an ab initio quantum chemical approach and a structure-based technique. Except for atomic van der Waals radii, there are no other empirical parameters used. The HMLP has clear physical and chemical meaning and provides useful lipophilic and hydrophilic parameters for the studies of proteins and peptides.     

In silico prediction of drug solubility: 1. Free energy of hydration

As a first step in the computational prediction of drug solubility the free energy of hydration, DeltaG*(vw) in TIP4P water has been computed for a data set of 48 drug molecules using the free energy of perturbation method and the optimized potential for liquid simulations all-atom force field. The simulations were performed in two steps, where first the Coulomb and then the Lennard-Jones interactions between the solute and the water molecules were scaled down from full to zero strength to provide physical understanding and simpler predictive models. The results have been interpreted using a theory assuming DeltaG*(vw) = A(MS)gamma + E(LJ) + E(C)/2 where A(MS) is the molecular surface area, gamma is the water-vapor surface tension, and E(LJ) and E(C) are the solute-water Lennard-Jones and Coulomb interaction energies, respectively. It was found that by a proper definition of the molecular surface area our results as well as several results from the literature were found to be in quantitative agreement using the macroscopic surface tension of TIP4P water. This is in contrast to the surface tension for water around a spherical cavity that previously has been shown to be dependent on the size of the cavity up to a radius of approximately 1 nm. The step of scaling down the electrostatic interaction can be represented by linear response theory.     

Acid-base equilibria of diazepam and prazepam in montmorillonite suspensions

The distribution of ionic species of diazepam and prazepam in aqueous and aqueous montmorillonite clay suspensions at several pH conditions (pH 1-12) was monitored spectrophotometrically. Measurements were performed at 284 and 365 nm for diazepam and 285 and 361 nm for prazepam. The interaction between the negative clay surface and protonated species of the drugs studied relative to the unchanged species is responsible for the apparent displacement of pK(a) values from 3.3 and 2.7 to 4.4 and 3.9 for diazepam and prazepam respectively. Changes in the partial molar free energy of the ionic species of both drugs (DeltaG(i)) as a result of interactions with montmorillonite suspensions was -1.47 and -1.72 for diazepam and prazepam respectively. The effect of an additional ionic solute i.e. sodium chloride was also studied. The recovered amounts of both drugs from five different concentrations of veegum at pH 2, 5 and 10 indicates the effect of drug-clay interactions in drug analysis.     

Adding explicit solvent molecules to continuum solvent calculations for the calculation of aqueous acid dissociation constants

Aqueous acid dissociation free energies for a diverse set of 57 monoprotic acids have been calculated using a combination of experimental and calculated gas and liquid-phase free energies. For ionic species, aqueous solvation free energies were calculated using the recently developed SM6 continuum solvation model. This model combines a dielectric continuum with atomic surface tensions to account for bulk solvent effects. For some of the acids studied, a combined approach that involves attaching a single explicit water molecule to the conjugate base (anion), and then surrounding the resulting anion-water cluster by a dielectric continuum, significantly improves the agreement between the calculated pK(a) value and experiment. This suggests that for some anions, particularly those concentrating charge on a single exposed heteroatom, augmenting implicit solvent calculations with a single explicit water molecule is required, and adequate, to account for strong short-range hydrogen bonding interactions between the anion and the solvent. We also demonstrate the effect of adding several explicit waters by calculating the pK(a) of bicarbonate (HCO(3)(-)) using as the conjugate base carbonate (CO(3)(2-)) bound by up to three explicit water molecules.     

A free energy calculation study of the effect of H-->F substitution on binding affinity in ligand-antibody interactions

Changes in binding affinity to catalytic antibody 6D9 of chloramphenicol phosphonate derivatives (CPDs) containing H or F were investigated by performing free energy calculations based on molecular dynamics simulations. We calculated the binding free energy, enthalpy, and entropy changes (DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS) attributable to H-->F substitution by comparing results for CPDs containing a trifluoroacetylamino group (CPD-F) or an acetylamino group (CPD-H). The calculated DeltaDeltaG, DeltaDeltaH, and -TDeltaDeltaS values were -2.9, -6.3, and 3.5 kcal mol(-1) and close to experimental values observed for a series of similar ligands, chloramphenicol phosphonates with F and H (-1.4, -3.5, and 2.1 kcal mol(-1)). Therefore, CPD-F binds more strongly to 6D9 than does CPD-H. To clarify the origin of the large difference in DeltaDeltaG, we apportioned the calculated values of DeltaDeltaG and DeltaG for the associated and dissociated states into contributions from various atomic interactions. We found that the H-->F substitution increased the binding affinity mainly by decreasing the hydration free energy and not by increasing favorable interactions with the antibody. The decreased hydration free energy of the ligand was mainly due to unfavorable coulombic interactions between the trifluoroacetylamino group and solvent waters, which increased the free energy of the dissociated state (by about 3.7 kcal mol(-1)). Also, the trifluoroacetylamino group slightly increased the free energy level of the associated state (about 0.8 kcal mol(-1)) because favorable van der Waals interactions compensated for unfavorable coulombic interactions with antibody atoms. In addition, the enthalpy and entropy changes, DeltaDeltaH and -TDeltaDeltaS (computationally -6.3 and 3.5 kcal mol(-1)), originated mainly from a decrease in hydration free energy in the dissociated state. The CPD-F and CPD-H ligands had substantially different structures in the dissociated and complexed states.