Intrinsic Partition Coefficient Research Articles

Experimental estimation of transient evolution of three thermal parameters characterizing a dry friction interface

Several studies have been performed to understand the occurred phenomena in a sliding contact interface. Due to a generated heat flux, the sliding contact necessarily induces an increase of the temperature. These temperatures could reach critical value for the system. Thus, it is imperative to anticipate the temperature increase to avoid severe issues. The aim of this study is to be able to determine the evolution of the thermal parameters characterizing sliding interfaces. In order to do this, we develop a new methodology which involves three transient parameters, the intrinsic partition coefficient, the thermal contact resistance and the heat flux generated by friction. The estimation of time dependent thermal sliding contact parameters is performed by an inverse heat conduction problem (IHCP) from temperature measurements. A parametrization technic with a constrained Levenberg Marquardt algorithm is used to regularize and decorrelate the IHCP. An experimental estimation of the evolution of the thermal contact parameters is performed. Several friction scenarios are investigated and show the relevance of the developed methodology.

PENETAPAN NILAI PARAMETER LIPOFILISITAS (LOG P, JUMLAH TETAPAN  HANSCH DAN TETAPAN f REKKER) ASAM PIPEMIDAT

Lipophilicity is the most often used physicochemical property in quantitative structure-activity relationships (QSAR) studies because it is related to the absorption across biological membrane and the distribution between body fluid and lipid-rich phase of drugs. Its quantitative descriptor is the octanol-water partition coefficient (usually expressed as log P). The 1-octanol-water partition coefficient of pipemidic acid was determined by an experimental using the shake-flask method and by calculating from p Hansch and f Rekker constant. The values of logarithmic intrinsic partition coefficient (IPC) and apparent partition coefficient (APC) of pipemidic acid were -2,03 ± 0,25 and -3,932 ± 0,25. The values of logarithmic partition coefficient, which were obtained by calculating of p Hansch and f Rekker constant were -1,65 and -1,981, respectively.

An investigation into the ability of alendronate ion pairs to increase oral absorption

The purpose of this study is to increase oral absorption of the highly charged drug alendronate using an ion pair strategy. Ion pairing is a formulation approach in drug delivery that is performed to improve the lipophilicity of ionized drugs. Cationic counter ions, such as arginine, phenazopyridine, hyoscine and pyridostigmine, were selected to enhance the lipophilicity and permeability of alendronate. Data obtained from quasi-equilibrium analysis were used to calculate the binding constant and intrinsic partition coefficient of ion pairs in an octanol/water system. The results of the partitioning study in an octanol/water system were confirmed using in vitro transport models with PAMPA and Caco-2 monolayer assays. Two counter ions, phenazopyridine and arginine, substantially increased the partition coefficient of alendronate by up to 1.15 and 0.73 units, respectively, in the octanol/water system. Binding constants of 117M−1 for alendronate-arginine and 90M−1 for alendronate-phenazopyridine ion pairs were obtained using quasi equilibrium analysis. Arginine and phenazopyridine enhanced the apparent permeability of alendronate by 14- and 26-fold in the PAMPA model and 6.5- and 4.4-fold across caco-2 cell monolayers, respectively. Based on this study, the lipophilicity and permeability of alendronate across lipophilic membranes was increased by suitable counter ions and could be used to establish a new formulation to increase the oral absorption of alendronate.

Influence of the natural colloids on the multi-phase distributions of antibiotics in the surface water from the largest lake in North China

Understanding antibiotic adsorption on natural colloids is crucial for prediction of the behavior, bioavailability and toxicity of antibiotics in natural waters. In the present study, the filtered water (dissolved phase, <0.7μm) was further separated into colloidal phase (1kDa-0.7μm) and soluble phase (<1kDa) by cross-flow ultrafiltration (CFUF), and the spatial-temporal variation and distribution of six antibiotics in multi-phases were investigated in Baiyangdian Lake. Results indicated that antibiotic concentrations differed significantly with sampling location and time. The mean concentrations of antibiotics ranged between 13.65 and 320.44ngL−1 in the dissolved phase, and the colloidal phase accounted for 4.7–49.8% of all antibiotics, suggesting that natural colloids play an important role as carriers of antibiotics in aquatic environments. Because of the influence of colloids, the partition coefficients of antibiotics between suspended particulate matter (SPM) and soluble phase (intrinsic partition coefficients, Kpint) were found to be 6.18–109.60% higher than corresponding observed partition coefficients (Kpobs, between SPM and dissolved phase). The mean partition coefficients between colloidal and soluble phase (Kcol.) ranged between 6218 and 117,374Lkg−1, which were 1–2 orders of magnitude greater than Kpint values. In order to explore the adsorption mechanism of antibiotics on colloids, Pearson's correlations were performed. The results showed that log Kcol. were negatively correlated with cations in natural colloids; especially with Mg (r, −0.643, P<0.01) for oxytetracycline (OTC), and with both Ca (−0.595, P<0.01) and Mg (−0.593, P<0.01) in the case of ofloxacin (OFL). This result revealed that the competitive effect between cations and antibiotics was the main factor influencing the adsorption behavior of antibiotics on natural colloids in the lake.

A method to Quantify the Affinity of Cabazitaxel for PLA-PEG Nanoparticles and Investigate the Influence of the Nano-Assembly Structure on the Drug/Particle Association.

To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier. An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as Kp. The determination was made from apparent values (referred to as Kp (ap)) measured in the presence of solubilizing agents (albumin and hydroxypropyl-βcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering. Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different Kp values. The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.

Solid effect in solvent extraction treatment of pre-treated oily sludge

Oil recovery from oily sludge generated from the petroleum industry has been investigated by solvent extraction using four organic solvents, cyclohexane, n-hexanol, n-butanol and kerosene. Special emphasis was placed on the effect of sludge (solid) concentration (CS) on the oil recovery efficiency (RO) and partition coefficient (KD). The KD was found to vary with CS. This phenomenon can be described as the “solid concentration effect” or “solid effect” (CS-effect). The CS-effect can be explained using the surface component activity (SCA) model that we developed previously. In this model, the activity coefficient of solid surface sites (fS) was proposed as a function of CS rather than unity because of interactions among solid particles. Based on the SCA model, we provide a CS-dependent function of partition coefficient (termed the SCA-partition coefficient function), in which the intrinsic (or thermodynamic) partition coefficient KD0 independent of CS can be simulated from extraction experimental data and can be used to characterize the extraction equilibrium. It was confirmed that the SCA-partition coefficient function could describe the CS-effect observed in our solvent extraction experiments accurately. In addition, the fS of the sludge was independent of the solvent in our tests and decreased with increasing temperature.

Physicochemical Characterization of 9-Aminocamptothecin in Aqueous Solutions

The present manuscript provides a detailed physicochemical and thermodynamic characterization of 9-aminocamptothecin (9AC) which can be used as a tool to develop novel formulation strategies for optimum pharmacological activity. The pKa of 9AC was determined to be 2.43 at 37°C, while the basicity of quinoline nitrogen of 9AC was found to decrease with increasing temperature due to a positive enthalpy of deprotonation of 10.36 kJ mol(-1). The equilibrium solubility as well as the intrinsic solubility of the drug was found to increase with increasing temperature and decreasing pH. The enthalpies of solution of unionized and ionized forms of 9AC obtained from isothermal and iso-pH equilibrium solubility measurements were found to be 36.01 and 24.72 kJ mol(-1), respectively. Equilibrium hydrolysis studies revealed the hydrolytic susceptibility of 9AC with only 14% of active lactone species remaining at physiological pH 7.4. The intrinsic partition coefficient log P of the free base, 9AC-lactone, was estimated to be 1.28 (a characteristic of molecules suitable for oral absorption). The estimated pKa and log P values of 9AC, combined with its increased solubility at lower pH, are features that can be utilized to develop novel drug delivery systems to optimize the antitumor activity of 9AC.

First Experimental Evidence of Dopamine Interactions with Negatively Charged Model Biomembranes

Dopamine is essential for receptor-related signal transduction in mammalian central and peripheral nervous systems. Weak interactions between the neurotransmitter and neuronal membranes have been suggested to modulate synaptic transmission; however, binding forces between dopamine and neuronal membranes have not yet been quantitatively described. Herein, for the first time, we have explained the nature of dopamine interactions with model lipid membranes assembled from neutral 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG), and the mixture of these two lipids using isothermal titration calorimetry and differential scanning calorimetry. Dopamine binding to anionic membranes is a thermodynamically favored process with negative enthalpy and positive entropy, quantitatively described by the mole ratio partition coefficient, K. K increases with membrane charge to reach its maximal value, 705.4 ± 60.4 M(-1), for membrane composed from pure DMPG. The contribution of hydrophobic effects to the binding process is expressed by the intrinsic partition coefficient, K(0). The value of K(0) = 74.7 ± 6.4 M(-1) for dopamine/DMPG interactions clearly indicates that hydrophobic effects are 10 times weaker than electrostatic forces in this system. The presence of dopamine decreases the main transition temperature of DMPG, but no similar effect has been observed for DMPC. Basing on these results, we propose a simple electrostatic model of dopamine interactions with anionic membranes with the hydrophobic contribution expressed by K(0). We suggest that dopamine interacts superficially with phospholipid membranes without penetrating into the bilayer hydrocarbon core. The model is physiologically important, since neuronal membranes contain a large (even 20%) fraction of anionic lipids.

Kinetics and Thermodynamics of Chlorpromazine Interaction with Lipid Bilayers: Effect of Charge and Cholesterol

Passive transport across cell membranes is the major route for the permeation of xenobiotics through tight endothelia such as the blood–brain barrier. The rate of passive permeation through lipid bilayers for a given drug is therefore a critical step in the prediction of its pharmacodynamics. We describe a detailed study on the kinetics and thermodynamics for the interaction of chlorpromazine (CPZ), an antipsychotic drug used in the treatment of schizophrenia, with neutral and negatively charged lipid bilayers. Isothermal titration calorimetry was used to study the partition and translocation of CPZ in lipid membranes composed of pure POPC, POPC:POPS (9:1), and POPC:Chol:POPS (6:3:1). The membrane charge due to the presence of POPS as well as the additional charge resulting from the introduction of CPZ in the membrane were taken into account, allowing the calculation of the intrinsic partition coefficients (K(P)) and the enthalpy change (ΔH) associated with the process. The enthalpy change upon partition to all lipid bilayers studied is negative, but a significant entropy contribution was also observed for partition to the neutral membrane. Because of the positive charge of CPZ, the presence of negatively charged lipids in the bilayer increases both the observed amount of CPZ that partitions to the membrane (KP(obs)) and the magnitude of ΔH. However, when the electrostatic effects are discounted, the intrinsic partition coefficient was smaller, indicating that the hydrophobic contribution was less significant for the negatively charged membrane. The presence of cholesterol strongly decreases the affinity of CPZ for the bilayer in terms of both the amount of CPZ that associates with the membrane and the interaction enthalpy. A quantitative characterization of the rate of CPZ translocation through membranes composed of pure POPC and POPC:POPS (9:1) was also performed using an innovative methodology developed in this work based on the kinetics of the heat evolved due to the interaction of CPZ with the membranes.

Lipophilicity of morphine microspecies and their contribution to the lipophilicity profile

The complete set of experimental microscopic partition coefficients of morphine was determined for the first time for any compound. The acid–base microequilibria were characterized by combining pH-potentiometry and deductive methods using auxiliary compounds of reduced complexity. The results show around three times as many non-charged than zwitterionic microspecies in aqueous solution. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were determined and introduced. Thus the intrinsic partition coefficients of all the microspecies could be quantitated, including the non-charged and the zwitterionic ones. The non-charged microspecies is 1070 times as lipophilic as its zwitterionic protonation isomer. Their contribution ratio to the overall lipophilicity is 3090. The lipophilicity profile of morphine was expressed, calculated and depicted in terms of species-specific lipophilicities over the entire pH range.

Lipophilicity of zwitterions and related species: A new insight

The experimental determination of microscopic partition coefficients for protonation isomers is elaborated for the first time, and applied for niflumic acid, an ampholytic, mainly zwitterionic drug for pains in joints and muscles. The acid–base microequilibria of niflumic acid are also characterized by NMR-pH and deductive methods using auxiliary compounds of reduced complexity. The results show that 16 times as many zwitterionic than non-charged microspecies exist in aqueous solution. Partition of the individual microspecies was mimicked by model compounds of the closest possible similarity, then correction factors were also determined and introduced. Thus the long-awaited intrinsic partition coefficients of the non-charged vs. zwitterionic species could be calculated. The non-charged microspecies is 390 times as lipophilic as its zwitterionic protonation isomer. The microscopic partition coefficients are also in line with the experimentally determined distribution coefficients. These results make evident that contribution of the zwitterionic microspecies to the overall lipophilicity is not negligible, especially at the isoelectric pH region of the compound.

Thermodynamics of Chlorpromazine Association with Lipid Bilayers

Passive transport across cell membranes is the major route for the permeation of xenobiotics through tight epithelia, such as the vascular endothelium that constitutes the Blood Brain Barrier. The rate of passive permeation through lipid bilayers for a given drug is therefore a critical step in the prediction of its in vivo efficacy. This parameter is usually evaluated from the drug hydrophobicity with little consideration for the rate of interaction and/or translocation through the lipid bilayer. Our research group is developing a global model to quantitatively describe the rate of passive permeation through tight endothelia and one of the outcomes is that in most cases the rate of the interaction (rather then the equilibrium partition) is the most relevant parameter.In this work we present a detailed study on the kinetics and thermodynamics for the interaction of chlorpromazine (CPZ) with neutral and negatively charged lipid bilayers. CPZ is an antipsychotic drug used in the treatment of schizophrenia and is an ideal candidate for studies of passive permeation of the BBB by active drugs.The partition and translocation of CPZ in lipid membranes was studied by Isothermal Titration Calorimetry (ITC) and the lipid bilayers were composed of pure POPC, POPC:POPS (9:1) and POPC:Chol:POPS (6:3:1). The charge imposed by CPZ in the membrane was taken into account allowing the calculation of the intrinsic partition coefficients (KP) and the enthalpy change (ΔH) associated with this process. The relative rate of the partition and translocation processes was obtained following the uptake and release protocol [1]. A quantitative evaluation of the rate of translocation is also given for some systems using an innovative methodology.[1] Tsamaloukas, A. D., Keller, S. and Heerklotz, H. (2007) Nat. Prot. 2, 695-704

Colloids as a sink for certain pharmaceuticals in the aquatic environment

The occurrence and fate of pharmaceuticals in the aquatic environment is recognized as one of the emerging issues in environmental chemistry and as a matter of public concern. Existing data tend to focus on the concentrations of pharmaceuticals in the aqueous phase, with limited studies on their concentrations in particulate phase such as sediments. Furthermore, current water quality monitoring does not differentiate between soluble and colloidal phases in water samples, hindering our understanding of the bioavailability and bioaccumulation of pharmaceuticals in aquatic organisms. In this study, an investigation was conducted into the concentrations and phase association (soluble, colloidal, suspended particulate matter or SPM) of selected pharmaceuticals (propranolol, sulfamethoxazole, meberverine, thioridazine, carbamazepine, tamoxifen, indomethacine, diclofenac, and meclofenamic acid) in river water, effluents from sewage treatment works (STW), and groundwater in the UK. The occurrence and phase association of selected pharmaceuticals propranolol, sulfamethoxazole, meberverine, thioridazine, carbamazepine, tamoxifen, indomethacine, diclofenac, and meclofenamic acid in contrasting aquatic environments (river, sewage effluent, and groundwater) were studied. Colloids were isolated by cross-flow ultrafiltration (CFUF). Water samples were extracted by solid-phase extraction (SPE), while SPM was extracted by microwave. All sample extracts were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the multiple reaction monitoring. Five compounds propranolol, sulfamethoxazole, carbamazepine, indomethacine, and diclofenac were detected in all samples, with carbamazepine showing the highest concentrations in all phases. The highest concentrations of these compounds were detected in STW effluents, confirming STW as a key source of these compounds in the aquatic environments. The calculation of partition coefficients of pharmaceuticals between SPM and filtrate (observed partition coefficients, Kobsp, Kobsoc), between SPM and soluble phase (intrinsic partition coefficients, Kintp, Kintoc), and between colloids and soluble phase (Kcoc) showed that intrinsic partition coefficients (Kintp, Kintoc) are between 25% and 96%, and between 18% and 82% higher than relevant observed partition coefficients values, and are much less variable. Secondly, Kcoc values are 3-4 orders of magnitude greater than Kintoc values, indicating that aquatic colloids are substantially more powerful sorbents for accumulating pharmaceuticals than sediments. Furthermore, mass balance calculations of pharmaceutical concentrations demonstrate that between 23% and 70% of propranolol, 17-62% of sulfamethoxazole, 7-58% of carbamazepine, 19-84% of indomethacine, and 9-74% of diclofenac are present in the colloidal phase. The results provide direct evidence that sorption to colloids provides an important sink for the pharmaceuticals in the aquatic environment. Such strong pharmaceutical/colloid interactions may provide a long-term storage of pharmaceuticals, hence, increasing their persistence while reducing their bioavailability in the environment. Pharmaceutical compounds have been detected not only in the aqueous phase but also in suspended particles; it is important, therefore, to have a holistic approach in future environmental fate investigation of pharmaceuticals. For example, more research is needed to assess the storage and long-term record of pharmaceutical residues in aquatic sediments by which benthic organisms will be most affected. Aquatic colloids have been shown to account for the accumulation of major fractions of total pharmaceutical concentrations in the aquatic environment, demonstrating unequivocally the importance of aquatic colloids as a sink for such residues in the aquatic systems. As aquatic colloids are abundant, ubiquitous, and highly powerful sorbents, they are expected to influence the bioavailability and bioaccumulation of such chemicals by aquatic organisms. It is therefore critical for colloids to be incorporated into water quality models for prediction and risk assessment purposes.

Physicochemical Characterization and Membrane Binding Properties of Camptothecin

The intrinsic solubility of the CPT-lactone free base in acidic pH was determined to be 3.44 and 5.11 microM at 22 and 37 degrees C, respectively. The equilibrium solubility of the drug was found to increase with increasing temperature and decreasing pH. The enhanced solubility of the drug at very low pH is attributed to the protonation of the nitrogen atom in the ring B and the increased solvency of the highly concentrated acidic media. The logarithmic value of the intrinsic partition coefficient P of the free base CPT-lactone form was estimated to be 1.65, characteristic of a molecule suitable for absorption. Association constants K(f) of the drug for bilayers composed of the zwitterionic (DOPC) and the negatively charged (DOPG) were determined at acidic pH by fluorescence anisotropy to be 35.4 +/- 4.5 M(-1) and 93.1 +/- 11.0 M(-1), respectively, indicative of the CPT tendency to preferentially bind to negatively charged membranes. The results indicate that at highly acidic media, CPT is positively charged and exists at its stable lactone form of increased solubility and capacity to bind to negatively charged membranes. These features could be used to invent novel formulation strategies to optimize the antitumor activity of CPT.

Octanol/water partition coefficients of ionic liquids

AbstractBACKGROUND: Room temperature ionic liquids (ILs) are attractive alternatives to environmentally unfriendly volatile organic solvents. Partitioning is one of the most important and fundamental properties of a chemical, and the octanol/water partition coefficient is widely used to measure the tendency of a chemical to cross biological membranes. However, there is very limited information on the concentration dependence of the partition coefficients of ILs. This study investigated the octanol/water partitioning of 1‐butyl‐3‐methylimidazolium ([bmim]) ILs containing either hexafluorophosphate ([PF6]) or bis[(trifluoromethyl)sulfonyl]amide ([Tf2N]) over a wide range of IL concentrations of three to five orders of magnitude.RESULTS: It was found that the apparent partition coefficients of the ILs increased with increasing IL concentration. A model based on the ionic nature of ILs was proposed to explain this behaviour, and the results showed a good fit with the experimental data. The intrinsic partition coefficients and dissociation constants of the ILs were determined using the equations from the proposed model. The differences in the intrinsic partition parameter values between the two ILs showed a good correlation with other physicochemical properties.CONCLUSIONS: The present study clearly shows that the octanol/water partition coefficients of ILs increase with increasing IL concentration owing to the formation of ion pairs. By using the proposed partition model, it was possible to determine the intrinsic partition coefficients of ILs, and it was found that the apparent partition coefficients of ILs converge to the intrinsic partition coefficients of the ionic species and ion pairs of ILs with decreasing and increasing IL concentration respectively. Copyright © 2008 Society of Chemical Industry

Evaluation of the Interaction of Propranolol with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) Liposomes: The Langmuir Model

The interaction of the amine containing beta-receptor blocking agent propranolol (Ppn) with dimyristoylphosphatidylcholine (DMPC) vesicles was studied. Using a centrifugation assay, the protonated as well as unprotonated amount of the drug sorbed was verified, whereas the binding of the protonated Ppn was deduced from the surface charge density of the vesicles as calculated from electrophoretic mobility measurements. Assuming a 1:1 binding, a Langmuir model with only two parameters was found to be sufficient to fit all experimental data. Sensitivity analysis revealed that the estimated values of these parameters were reliable and independent from each other. These parameters were truly intrinsic, as electrostatic interactions were accounted for in the model. It was found that the pKa of Ppn shifted from 9.24, when dissolved in water, downward by 1.34 units upon sorption, indicating that the intrinsic partition coefficient of the unprotonated Ppn was about 22 times higher than that of the protonated analog. In addition, a significant increase in the affinity of both Ppn analogs with increasing salt concentration was found. Theoretical analysis revealed that the Langmuir sorption model may be considered as a partitioning model with decreasing partition coefficient as the sorbed amount increases. Thus, the Langmuir model provides a better fit than a simple partition model at conditions that induce a substantial amount of propranolol sorbed, such as high pH and high propranolol concentrations.

Cyclodextrins and the liquid-liquid phase distribution of progesterone, estrone and prednicarbate

The purpose of the present work was to investigate the interaction of drugs and octanol with hydroxypropyl β- (HPβCD) and γ- (HPγCD) cyclodextrin, sulfobutyl ether β-cyclodextrin (SBEβCD) and randomly methylated-β-cycoldextrin (RMβCD) and to describe the interaction by theoretical models. The poorly soluble steroid drugs progesterone, estrone and prednicarbate were used as model compounds in this study. Hexane and chloroform were also investigated in combination with HPβCD. Octanol formed a complex with all cyclodextrins and the saturation of the aqueous solution with this solvent therefore had a significant effect on the solubilization and extraction potential of cyclodextrins. Hexane had less affinity for cyclodextrins, but the drugs were poorly soluble in this solvent and it could therefore not be used in phase-distribution investigations. Previously we have derived equations that can be used to account for the competitive interaction between two guest compounds that compete for space in the cyclodextrin cavity. These equations were rearranged to calculate the complexation efficacy from phase-solubility data. An equation was derived that obtains intrinsic solubility (S 0) and intrinsic partition coefficient (P) from the slopes of the phase-solubility and phase-distribution profiles. Investigation of the data showed that the results could not be sufficiently explained by the “classical” drug/cyclodextrin complex model that recognizes the possibility of competitive interactions but ignores any contribution from higher order complexes or aggregation of the cyclodextrin complexes. Relative difference in solubilization potential of different cyclodextrins cannot be translated to relative differences in extraction efficacy. Thus, for these three steroid compounds, RMβCD and SBEβCD gave the best solubilization potential whereas the best extraction efficacy was observed with HPγCD.

Evaluation of the Interaction of Propranolol with 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) Liposomes: The Partitioning Model

The sorption behavior of the amine containing beta-receptor blocking agent propranolol (Ppn) in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) vesicles was investigated. Both protonated and unprotonated Ppn were measured in the continuous phase after removal of the vesicles containing sorbed Ppn by centrifugation. In contrast, by analyzing the surface charge density, deduced from electrophoretic mobility measurements, only the sorbed protonated Ppn was determined. A partitioning model was used to describe the sorption behavior. Sensitivity analysis revealed that sufficiently reliable and independent parameters were obtained. The partition coefficient of the unprotonated Ppn was about 22 times higher than that of the protonated analogue. Statistical analysis revealed a significant increase in the intrinsic partition coefficients of both Ppn analogues with an increase in the salt concentration.

Fusion Peptide of Influenza Hemagglutinin Requires a Fixed Angle Boomerang Structure for Activity

The fusion peptide of influenza hemagglutinin is crucial for cell entry of this virus. Previous studies showed that this peptide adopts a boomerang-shaped structure in lipid model membranes at the pH of membrane fusion. To examine the role of the boomerang in fusion, we changed several residues proposed to stabilize the kink in this structure and measured fusion. Among these, mutants E11A and W14A expressed hemagglutinins with hemifusion and no fusion activities, and F9A and N12A had no effect on fusion, respectively. Binding enthalpies and free energies of mutant peptides to model membranes and their ability to perturb lipid bilayer structures correlated well with the fusion activities of the parent full-length molecules. The structure of W14A determined by NMR and site-directed spin labeling features a flexible kink that points out of the membrane, in sharp contrast to the more ordered boomerang of the wild-type, which points into the membrane. A specific fixed angle boomerang structure is thus required to support membrane fusion.

Sorption and Remobilization Behavior of 4-tert-Octylphenol in Aquatic Systems

The sorption and desorption of 4-tert-octylphenol in aquatic systems were studied to unravel the underlying controls. The sorption process was relatively slow, reaching a final sorption equilibrium in 10 d. The sorption process was interpreted as consisting of two stages: an initial rapid adsorption on particle surface followed by a slow intraparticle diffusion. The key parameter affecting the sorption of 4-tert-octylphenol by sediment is the occurrence of colloids, which in turn explains the so-called sediment concentration (SC) effect. This was confirmed by the increasing amount of colloids with increasing SC, and the relative constancy of intrinsic partition coefficient of 4-tert-octylphenol between sediment and water (K(p)) and between colloids and water (K(c)). Further evidence was from the nonoccurrence of SC effect from the addition of the same amount of colloids in different SC. The adsorption equilibrium is best described by the Freundlich model at low equilibrium concentrations. The adsorption of 4-tert-octylphenol was enhanced in the presence of salts, due to the salting out effect, and a salting constant of 1.3 L/mol was obtained. Desorption experiments showed that the release of 4-tert-octylphenol from contaminated sediments was highly dependent on the "age" of sediments, with kinetics of desorption being much faster in fresh sediments than in "aged" sediments.