Prediction of soil adsorption coefficients from retention parameters on three reversed-phase liquid chromatographic columns

Reversed-phase high-performance liquid chromatographic (RP-HPLC) retention parameters, which are determined by the intermolecular interactions in retention process, can be considered as the chemical molecular descriptors in linear free energy relationships (LFERs). On the basis of the characterization and comparison of octadecyl-bonded silica gel (ODS), cyano-bonded silica gel (CN), and phenyl-bonded silica gel (Ph) columns with linear solvation energy relationships (LSERs), a new multiple linear regression model using RP-HPLC retention parameters on ODS and CN columns as variables for estimation of soil adsorption coefficients was developed. It was tested on a set of reference substances from various chemical classes. The results showed that the multicolumn method was more promising than a single-column method was for the estimation of soil adsorption coefficients. The accuracy of the suggested model is identical with that of LSERs.

Quantitative structure-hydrophobicity relationships of molecular fragments and beyond

Quantitative structure-property relationship (QSPR) models were firstly established for the hydrophobic substituent constant (πX) using the theoretical descriptors derived solely from electrostatic potentials (EPSs) at the substituent atoms. The descriptors introduced are found to be related to hydrogen-bond basicity, hydrogen-bond acidity, cavity, or dipolarity/polarizability terms in linear solvation energy relationship, which endows the models good interpretability. The predictive capabilities of the models constructed were also verified by rigorous Monte Carlo cross-validation. Then, eight groups of meta- or para- disubstituted benzenes and one group of substituted pyridines were investigated. QSPR models for individual systems were achieved with the ESP-derived descriptors. Additionally, two QSPR models were also established for Rekker's fragment constants (foct), which is a secondary-treatment quantity and reflects average contribution of the fragment to logP. It has been demonstrated that the descriptors derived from ESPs at the fragments, can be well used to quantitatively express the relationship between fragment structures and their hydrophobic properties, regardless of the attached parent structure or the valence state. Finally, the relations of Hammett σ constant and ESP quantities were explored. It implies that σ and π, which are essential in classic QSAR and represent different type of contributions to biological activities, are also complementary in interaction site.

Experimental Evidence of the Occurrence of Intramolecular Electron Transfer in Catalyzed 1,2-Dioxetane Decomposition

The activation parameters for the thermal decomposition of 13 acridinium-substituted 1,2-dioxetanes, bearing an aromatic moiety, were determined and their chemiluminescence emission quantum yields estimated, utilizing in situ photosensitized 1,2-dioxetane generation and observation of its thermal decomposition kinetics, without isolation of these highly unstable cyclic peroxides. Decomposition rate constants show linear free-energy correlation for electron-withdrawing substituents, with a Hammett reaction constant of rho = 1.3 +/- 0.1, indicating the occurrence of an intramolecular electron transfer from the acridinium moiety to the 1,2-dioxetane ring, as postulated by the intramolecular chemically initiated electron exchange luminescence (CIEEL) mechanism. Emission quantum yield behavior can also be rationalized on the basis of the intramolecular CIEEL mechanism, additionally evidencing its occurrence in this transformation. Both relations constitute the first experimental evidence for the occurrence of the postulated intramolecular electron transfer in the catalyzed and induced decomposition of properly substituted 1,2-dioxetanes.

Direct Kinetic Observation of the Chemiexcitation Step in Peroxyoxalate Chemiluminescence

A high-energy intermediate in the peroxyoxalate reaction can be accumulated at room temperature under specific reaction conditions and in the absence of any reducing agent in up to micromolar concentrations. Bimolecular interaction of this intermediate, accumulated in the reaction of oxalyl chloride with hydrogen peroxide, with an activator (highly fluorescent aromatic hydrocarbons with low oxidation potential) added in delay shows unequivocally that this intermediate is responsible for chemiexcitation of the activator. Activation parameters for the unimolccular decomposition of this intermediate (Delta H(double dagger) = 11.2 kcal mol(-1); Delta S(double dagger) = -23.2 cal mol(-1) K(-1)) and for its bimolecular reaction with 9,10-diphenylanthracene (Delta H(double dagger) = 4.2 kcal mol(-1); Delta S(double dagger) = -26.9 cal mol(-1) K(-1)) show that this intermediate is much less stable than typical 1,2-dioxetanes and 1,2-dioxetanones and demonstrate its highly favored interaction with the activator. Therefore, it can be inferred that structural characterization of the high-energy intermediate in the presence of an activator must be highly improbable. The observed linear free-energy correlation between the catalytic rate constants and the oxidation potentials of several activators definitely confirms the occurrence of the chemically initiated electron-exchange luminescence (CIEEL) mechanism in the chemiexcitation step of the peroxyoxalate system.

Complexation of some trivalent lanthanides, scandium(III) and thorium(IV) by benzylidenepyruvates in aqueous solution

The protonation constants of 4-methylbenzylidenepyruvate (4Me-BP) and 4-isopropylbenzylidenepyruvate (4IP-BP) as well as the stability constants of their binary 1:1 complexes with Cu(II), La(III), Pr(III), Sm(III), Eu(III), Yb(III), Sc(III) and Th(IV) have been determined spectrophotometrically in aqueous solution at 25°C and ionic strength 0.500 M, maintained with sodium perchlorate. For all metal ions considered, the stability changes move in the same direction as the pKa of the ligands. Linear free energy relationships, as applied to oxygen donor substances, suggest the -COCOO- moiety as the metal binding site of the ligands. The results are discussed mainly taking into account that benzylidenepyruvates, besides the α-keto canonical form, may display other forms in aqueous solution with changing pH and the possible occurrence of extra intra-ligand charge polarization, induced by metal ions.

Multiscale modeling of lamellar mesophases

The mesoscale simulation of a lamellar mesophase based on a free energy functional is examined with the objective of determining the relationship between the parameters in the model and molecular parameters. Attention is restricted to a symmetric lamellar phase with equal volumes of hydrophilic and hydrophobic components. Apart from the lamellar spacing, there are two parameters in the free energy functional. One of the parameters, r, determines the sharpness of the interface, and it is shown how this parameter can be obtained from the interface profile in a molecular simulation. The other parameter, A, provides an energy scale. Analytical expressions are derived to relate these parameters to r and A to the bending and compression moduli and the permeation constant in the macroscopic equation to the Onsager coefficient in the concentration diffusion equation. The linear hydrodynamic response predicted by the theory is verified by carrying out a mesoscale simulation using the lattice-Boltzmann technique and verifying that the analytical predictions are in agreement with simulation results. A macroscale model based on the layer thickness field and the layer normal field is proposed, and the relationship between the parameters in the macroscale model from the parameters in the mesoscale free energy functional is obtained.

Adsopption isotherms-A critique

The possibility or the impossibility of separating the particle and the electrode interactions is discussed in a wider context of the effects due to any two interaction potentials on the equation of state. The involved nature of the pressure dependence on two individually definable forces is illustrated through the Percus Yevick results for the adhesive hard spheres. An alternative form of the adsorption isotherm is given to bring home the intimate relationship between the actual equation of state and the free energy of adsorption. Thermodynamic consequences of congruence with respect to E (or q) as reflected through the linear plots of q (or E) vs. θ are well known. Mathematical consequences of simultaneous congruence have been pointed out recently. In this paper, the physical nature of congruence hypothesis is revealed. In passing "the pseudo-congruence" is also discussed. It is emphasised that the problem is no less ambiguous with regard to modelling the particle/particle interaction. The ad hoc nature of our dependence of the available equations of state is emphasised through a discussion on the HFL theory. Finally, a heuristic method for modelling ΔG mathematically-incorporating its behaviour at saturation coverages-is advanced. The more interesting aspects of this approach, which generalises almost all isotherms hitherto known, are sketched.

Absolute Entropy and Energy of Carbon Dioxide Using the Two-Phase Thermodynamic Model

The two-phase thermodynamic (2PT) model is used to determine the absolute entropy and energy of carbon dioxide over a wide range of conditions from molecular dynamics trajectories. The 2PT method determines the thermodynamic properties by applying the proper statistical mechanical partition function to the normal modes of a fluid. The vibrational density of state (DoS), obtained from the Fourier transform of the velocity autocorrelation function, converges quickly, allowing the free energy, entropy, and other thermodynamic properties to be determined from short 20-ps MD trajectories. The anharmonic effects in the vibrations are accounted for by the broadening of the normal modes into bands from sampling the velocities over the trajectory. The low frequency diffusive modes, which lead to finite DoS at zero frequency, are accounted for by considering the DoS as a superposition of gas-phase and solid-phase components (two phases). The analytical decomposition of the DoS allows for an evaluation of properties contributed by different types of molecular motions. We show that this 2PT analysis leads to accurate predictions of entropy and energy of CO2 over a wide range of conditions (from the triple point to the critical point of both the vapor and the liquid phases along the saturation line). This allows the equation of state of CO2 to be determined, which is limited only by the accuracy of the force field. We also validated that the 2PT entropy agrees with that determined from thermodynamic integration, but 2PT requires only a fraction of the time. A complication for CO2 is that its equilibrium configuration is linear, which would have only two rotational modes, but during the dynamics it is never exactly linear, so that there is a third mode from rotational about the axis. In this work, we show how to treat such linear molecules in the 2PT framework.

Structural Transformations, Composition Anomalies and a Dramatic Collapse of Linear Polymer Chains in Dilute Ethanol-Water Mixtures

Water-ethanol mixtures exhibit many interesting anomalies, such as negative excess partial molar volume of ethanol, excess sound absorption coefficient at low concentrations, and positive deviation from Raoult's law for vapor pressure, to mention a few. These anomalies have been attributed to different, often contradictory origins, but a quantitative understanding is still lacking. We show by computer simulation and theoretical analyses that these anomalies arise from the sudden emergence of a bicontinuous phase that occurs at a relatively low ethanol concentration of x(eth) approximate to 0.06-0.10 (that amounts to a volume fraction of 0.17-0.26, which is a significant range!). The bicontinuous phase is formed by aggregation of ethanol molecules, resulting in a weak phase transition whose nature is elucidated. We find that the microheterogeneous structure of the mixture gives rise to a pronounced nonmonotonic composition dependence of local compressibility and nonmonotonic dependence in the peak value of the radial distribution function of ethyl groups. A multidimensional free energy surface of pair association is shown to provide a molecular explanation of the known negative excess partial volume of ethanol in terms of parallel orientation and hence better packing of the ethyl groups in the mixture due to hydrophobic interactions. The energy distribution of the ethanol molecules indicates additional energy decay channels that explain the excess sound attenuation coefficient in aqueous alcohol mixtures. We studied the dependence of the solvation of a linear polymer chain on the composition of the water-ethanol solvent. We find that there is a sudden collapse of the polymer at x(eth) approximate to 0.05-a phenomenon which we attribute to the formation of the microheterogeneous structures in the binary mixture at low ethanol concentrations. Together with recent single molecule pulling experiments, these results provide new insight into the behavior of polymer chain and foreign solutes, such as enzymes, in aqueous binary mixtures.

Structure-rheology relationship in a sheared lamellar fluid

The structure-rheology relationship in the shear alignment of a lamellar fluid is studied using a mesoscale model which provides access to the lamellar configurations and the rheology. Based on the equations and free energy functional, the complete set of dimensionless groups that characterize the system are the Reynolds number (rho gamma L-2/mu), the Schmidt number (mu/rho D), the Ericksen number (mu(gamma)/B), the interface sharpness parameter r, the ratio of the viscosities of the hydrophilic and hydrophobic parts mu(r), and the ratio of the system size and layer spacing (L/lambda). Here, rho and mu are the fluid density and average viscosity, (gamma) over dot is the applied strain rate, D is the coefficient of diffusion, B is the compression modulus, mu(r) is the maximum difference in the viscosity of the hydrophilic and hydrophobic parts divided by the average viscosity, and L is the system size in the cross-stream direction. The lattice Boltzmann method is used to solve the concentration and momentum equations for a two dimensional system of moderate size (L/lambda = 32) and for a low Reynolds number, and the other parameters are systematically varied to examine the qualitative features of the structure and viscosity evolution in different regimes. At low Schmidt numbers where mass diffusion is faster than momentum diffusion, there is fast local formation of randomly aligned domains with ``grain boundaries,'' which are rotated by the shear flow to align along the extensional axis as time increases. This configuration offers a high resistance to flow, and the layers do not align in the flow direction even after 1000 strain units, resulting in a viscosity higher than that for an aligned lamellar phase. At high Schmidt numbers where momentum diffusion is fast, the shear flow disrupts layers before they are fully formed by diffusion, and alignment takes place by the breakage and reformation of layers by shear, resulting in defects (edge dislocations) embedded in a background of nearly aligned layers. At high Ericksen number where the viscous forces are large compared to the restoring forces due to layer compression and bending, shear tends to homogenize the concentration field, and the viscosity decreases significantly. At very high Ericksen number, shear even disrupts the layering of the lamellar phase. At low Ericksen number, shear results in the formation of well aligned layers with edge dislocations. However, these edge dislocations take a long time to anneal; the relatively small misalignment due to the defects results in a large increase in viscosity due to high layer stiffness and due to shear localization, because the layers between defects get pinned and move as a plug with no shear. An increase in the viscosity contrast between the hydrophilic and hydrophobic parts does not alter the structural characteristics during alignment. However, there is a significant increase in the viscosity, due to pinning of the layers between defects, which results in a plug flow between defects and a localization of the shear to a part of the domain.

Molecular Dynamics Simulation Of Adhesion Forces In A Dipalmitoylphosphatidylcholine Membrane

Adhesion forces of Dipalmitoylphosphatidylcholine ( DPPC) membrane in the gel phase are investigated by molecular dynamics ( MD) simulation. In the simulations, individual DPPC molecules are pulled out of DPPC membranes with different rates and we get the maximum adhesion forces of DPPC membrane. We find that the maximum adhesion forces increase with pull rate, from about 400 to 700 pN when pull rates are from 0.001 to 0.03 nm/ps. We analyze the relationship between pull rate and adhesion forces of different origins using Brownian dynamics and notice that viscosity of solvent plays an important role in adhesion forces. Then we simulate the motion of a single DPPC molecule in solvent and it elucidates that the maximum drag force is almost linear with respect to the pull rate. We use Stokes' relation to describe the motion of a single DPPC molecule and deduce the effective length of a DPPC molecule. Conformational analyses indicate that the free energy variation of a DPPC molecule inside and outside of the DPPC membrane is an essential part of adhesion energy.

Molecular dynamics simulation of adhesion forces in a dipalmitoylphosphatidylcholine membrane

Adhesion forces of Dipalmitoylphosphatidylcholine ( DPPC) membrane in the gel phase are investigated by molecular dynamics ( MD) simulation. In the simulations, individual DPPC molecules are pulled out of DPPC membranes with different rates and we get the maximum adhesion forces of DPPC membrane. We find that the maximum adhesion forces increase with pull rate, from about 400 to 700 pN when pull rates are from 0.001 to 0.03 nm/ps. We analyze the relationship between pull rate and adhesion forces of different origins using Brownian dynamics and notice that viscosity of solvent plays an important role in adhesion forces. Then we simulate the motion of a single DPPC molecule in solvent and it elucidates that the maximum drag force is almost linear with respect to the pull rate. We use Stokes' relation to describe the motion of a single DPPC molecule and deduce the effective length of a DPPC molecule. Conformational analyses indicate that the free energy variation of a DPPC molecule inside and outside of the DPPC membrane is an essential part of adhesion energy.

A study of capacitance-voltage characteristics of lead zirconate titanate ferroelectric thin films and their usage to investigate polarization and coercive field.

Capacitance-voltage (C-V) characteristics of lead zirconate titanate (PZT) thin films with a thickness of 130 nm were measured between 300 and 533 K. The transition between ferroelectric and paraelectric phases was revealed to be of second order in our case, with a Curie temperature at around 450 K. A linear relationship was found between the measured capacitance and the inverse square root of the applied voltage. It was shown that such a relationship could be fitted well by a universal expression of C/A = k(V+V(0))(-1/2) and that this expression could be derived by expanding the Landau-Devonshire free energy at an effective equilibrium position of the Ti/Zr ion in a PZT unit cell. By using the derived equations in this work, the free energy parameters for an individual material can be obtained solely from the corresponding C-V data, and the temperature dependences of both remnant polarization and coercive voltage are shown to be in quantitative agreement with the experimental data.

A Correlation between the Dynamic Viscosity and Crystallisation of Felodipine from its Amorphous Polymer Solid Dispersion

Purpose Previously, it has been reported that molecular mobility determines the rate of molecular approach to crystal surfaces, while entropy relates to the probability of that approaching molecule having the desirable configuration for further growth of the existing crystal; and the free energy dictates the probability of that molecule not returning to the liquid phase1. If we plot the crystal growth rate and viscosity of a supercooled liquid in a log-log format, the relationship between the two is linear, indicating the influence viscosity has upon crystal growth rate. However, such approximation has been derived from pure drug compounds and it is apparent that further understanding of crystallization from drug-polymer solid dispersion is required in order to stabilise drugs embedded within amorphous polymeric solid dispersions. Methods Mixtures of felodipine and polymer (HPMCAS-HF, PVPK15 and Soluplus®) at specified compositions were prepared using a Restch MM200 ball mill. To examine crystal growth within amorphous solid dispersions, samples were prepared by melting 5-10 mg of ball milled mixture at 150°C for 3-5 minutes on a glass slip pre-cleaned with methanol and acetone. All prepared samples were confirmed to be crystal free by visual observation using a polarised light microscope (Olympus BX50). Prepared samples were stored at 0% RH (P2O5), inside desiccators, maintained in ovens at 80°C. For the dynamic viscosity measurement, approximately 100-200mg ball milled mixture was heated on the base plate of a rotational rheometer at 150°C for 5 minutes and the top plate was lowered to a defined gap to form a good contact with the material. The sandwiched amorphous material was heated to 80°C and the viscosity was measured. Results The equation was used to probe the correlation of viscosity to crystal growth rate. In comparison to the value of xi in log-log equation reported from pure drug compound, a value of 1.63 was obtained for FD-polymer solid dispersions irrespective of the polymer involved. &#8733 Conclusion The high xi value suggests stronger viscosity dependence may exist for amorphous FD once incorporated with amorphous polymer.