Estimation of Aqueous Solubility (-lgS_w) of All Polychlorinated Biphenyl (PCB) Congeners by Density Functional Theory and Position of Cl Substitution (NPCS) Method

Optimization calculations of 209 polychlorinated biphenyls （PCBs） were carried out at the B3LYP/6-31G^＊ level. It was found that there is significant correlation between the Cl substitution position and some structural parameters. Consequently, Cl substitution positions were taken as theoretical descriptors to establish a novel QSPR model for predicting –lgSw of all PCB congeners. The model achieved in this work contains four variables, of which r^2 = 0.9527, q^2 = 0.9490 and SD = 0.25 with large t values. In addition, the variation inflation factors （VIFs） of variables in this model are all less than 5.0, suggesting high accuracy of the –lgSw predicting model. And the results of cross-validation test and method validation also show that the model exhibits optimum stability and better predictive capability than that from the AM1 method.

Estimation of n-Octanol/water Partition Coeffi-cients(lgK_(ow)) and the Aqueous Solubility(-lg_(Sw)) of all PCDF Congeners by Density Functional Theory

Optimized calculation of dibenzofuran （DF） and 135 polychlorinated dibenzofurans （PCDFs） was carried out at the B3LYP/6-31G＊ level in GAUSSIAN 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel quantitative structureproperty relationship （QSPR） model for predicting n-octanol/water partition coefficients （lgKow） of PCDFs. The new model of lgKow achieved in this work contains three variables： energy of the highest occupied molecular orbital （EHOMO）, the most negative atomic partial charge （q^-） and average molecular polarizability （a）, of which R^2= 0.9011 and SD = 0,17 with larger t values. In addition, the variation inflation factors （VIF） of variables in the present model are all less than 5.5, suggesting high accuracy of the lgKow model. And the results of cross-validation test （q^2 = 0.8688） and method validation also show this model exhibits optimum stability and better predictive power than semi-empirical method. At the same time, it is found that the aqueous solubility （-lgSw） has high relative correlation with constant volume molar heat capacity （Cv^0）, of which R^2 = 0.9777 and SD = 0.22. Moreover, lgKow and -lgSw values of all PCDF congeners were predicted respectively.

Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone(PVP)-polyethylene glycol(PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formulation and its constituents were characterized using powder X-ray diffraction(PXRD), differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and Fourier transform infrared spectroscopy(FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dissolution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000(0.25/1.5/1.5, w/w/w) furnished the highest solubility(24.3972.95 mg/mL) and an excellent dissolution profile( $100% in 40 min). The solubility enhancement with this formulation was $ 1150-fold as compared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

DFT and Position of Cl Substitution (PCS) Methods Studies on n-Octanol/water Partition Coefficients (lgK_(ow)) and Aqueous Solubility (–lgS_w) of All PCDD Congeners

Optimized calculations of 75 PCDDs and their parent DD were carded out at the B3LYP/6-31G＊ level by density functional theory （DFT） method. The structural parameters were obtained and significant correlation between the C1 substitution position and some structural parameters was found. Consequently, the number of C1 substitution positions was taken as theoretical descriptors to establish two novel QSPR models for predicting lgKow and -lgSw of all PCDD congeners. The two models achieved in this work contain two variables （Na and Nβ）, of which r = 0.9312, 0.9965 and SD = 0.27, 0.12 respectively, and t values are all large. The variation inflation factors （VIF） of variables in the two models herein are both less than 5.0, suggesting high accuracy of the lgKow and -lgSw predicting models, and the results of cross-validation test also show that the two models exhibit optimum stability and good predictive power. By comparison, the correlation and predictive ability of the present work are more advantageous than those obtained using semi-empirical AM1 and GC-RI methods.

Prediction of Aqueous Solubility for 209 Polychlorinated Diphenyl Ethers from Molecular Structural Parameters by DFT Method

Optimized calculations of 209 polychlorinated diphenyl ethers （PCDEs） and diphenyl ethers were carried out at the B3LYP/6-31G^＊ level with the Gaussian 98 program. Based on the theoretical linear solvation energy relationship （TLSER） model, the obtained structural parameters were taken as theoretical descriptors to establish the novel QSPR model for predicting aqueous solubility （-lgSw） of PCDEs. The model obtained in this work contains two variables： mean molecular polarizability （a） and the most positive partial charge on a hydrogen atom （qH^＋）, of which RE = 0.9606 and SD = 0.32. And the results of cross-validation test also show that the model exhibits optimum stability and better predictive power. Moreover, the predictive power of the new model is better than that of MCIs method.

AQUEOUS PHASE RHODIUM HYDROFORMYLATION OF DODECENE－1 WITH SURFACE ACTIVE WATER－SOLUBLE PHOSPHINE

The surface active water-soluble phosphine, P[p-C6H4O(CH2CH2O)nH]3, n=4, is used to generate an squeous rhoditun catalyst for the hydroformylation of dodecene-1. Under I00℃, 5.0 MPa (CO/H2=1∶1 ), pH=6.5, and reachon time 4h, the conversion of dodecene-1 was 96.0%, the yield for aldehyde was 84.0%. and n/i =1.8. The catalyst can be reused for more than four times without any appreciable loss in activity and selechvity.

Enhancing effect of choline chloride-based deep eutectic solvents with polyols on the aqueous solubility of curcumin–insight from experiment and theoretical calculation

The development of green solvents for enhancing aqueous solubility of drug curcumin remains a challenge. This study explores the enhancing effect of deep eutectic solvents(DESs) on the aqueous solubility of curcumin(CUR) via experiment and theoretical calculation. Choline chloride-based DESs with polyols 1,2-propanediol(1,2-PDO), 1,3-propanediol, ethylene glycol, and glycerol as hydrogen bond donors were prepared and used as co-solvents. The CUR aqueous solubility increased with increasing the DESs content at temperature of 303.15-318.15 K, especially in aqueous ChCl/1,2-PDO(mole ratio 1:4) solutions. The positive apparent molar volume values and reduced density gradient analysis confirmed the existence of strong interactions between CUR and solvent. The van der Waals interactions and hydrogen bonding coexisted in DESs monomer retained the stability of DESs structure after introducing CUR. Moreover,the lower interaction energy of DESs…CUR system than that of the counterpart DESs further proved the strong interaction between CUR and DESs. The lowest interaction energy of ChCl/1,2-PDO…CUR system indicated that this system was the most stable and ChCl/1,2-PDO was promising for CUR dissolution.This work provides efficient solvents for utilizing curcumin, contributing to a deep insight into the interactions between DES and CUR at the molecular level, and the role of DESs on enhancing drugs solubility.

Prediction of aqueous solubility of PCBs based on molecular structure

The thermodynamic relationships among aqueous solubility and molar volume (MV) , total molecular surface area (TSA) and molecular connectivity index (MCI) for highly hydrophobic chemicals. PCBs are established and discussed, respectively. Good linear relationships exist among In Cs and MV, TSA or MCI.

Aqueous Solubility Enhancement of Mirtazapine: Effect of Cosolvent and Surfactant

The poor aqueous solubility of drugs is a challenging problem faced by pharmaceutical scientists in drug formulation. Cosolvency and micellization techniques have been severally used to enhance the solubility of poorly aqueous soluble drugs. Mirtazapine, a tetracyclic antidepressant used for the treatment of moderate to severe depression and anxiety, has very poor aqueous solubility. The objective of the study was to investigate the effect of solubilizing agents (cosolvents and surfactants) on the aqueous solubility of mirtazapine while envisaging that any significant improvement in its aqueous solubility could contribute towards alleviating the withdrawal symptoms often associated with the drug. The solubility of mirtazapine was determined at room temperature in aqueous mixtures of cosolvents (propylene glycol and polyethylene glycol 400) and surfactants (polysorbate 20, polysorbate 80 and sodium lauryl sulfate). An exponential increase in mirtazapine solubility was observed when total drug solubility in water-cosolvent system was plotted against cosolvent fraction volume. Polyethylene glycol 400 gave larger solubilization capacity (σ) when compared to propylene glycol. With the surfactants, linear relationship between the total solubility of the drug in water-surfactant mixtures and surfactant concentration was noted. Sodium lauryl sulfate showed the largest solubilization power (k) when compared to the nonionic surfactants (polysorbate 20 and polysorbate 80 respectively). A linear relationship between standard free energy and partition coefficient was also observed. The result of the study shows that aqueous solubility of mirtazapine is significantly improved by cosolvency and micellization and therefore there exists the possibility of improving the withdrawal symptoms often experienced with the drug. It also suggests that large free energy is required for drugs with high partition coefficients to permeate the biological membrane.

Absorption Spectroscopic Determination of Solubility of Alloxazine in Aqueous Solutions

The solubility of alloxazine in aqueous solution at pH 4 (10–4 molar HCl) and pH 10 (10–4 molar NaOH) at room temperature is determined by absorption spectroscopic characterization. Knowledge of the solubility is needed for sample preparation and quantitative spectroscopic solution characterization. Samples of different in-weight concentration were prepared and absorption spectra were measured versus storage time. The solubility limit concentration Csol was determined by the crossing point of the linearized absorption coefficient dependences on in-weight preparation concentration below and above the solubility limit. Values of Csol= 9.05 ± 1 μM and 14.5 ± 1 μM were determined for alloxazine in aqueous solution at pH 4 and pH 10, respectively.

Study of the Relationship Between New Ionic Interaction Parameters and Salt Solubility in Electrolyte Solutions Based on Molecular Dynamics Simulation

Studying the relationship between ionic interactions and salt solubility in seawater has implications for seawater desalination and mineral extraction.In this paper,a new method of expressing ion-to-ion interaction is proposed by using molecular dynamics simulation,and the relationship between ion-to-ion interaction and salt solubility in a simulated seawater water-salt system is investigated.By analyzing the variation of distance and contact time between ions in an electrolyte solution,from both spatial and temporal perspectives,new parameters were proposed to describe the interaction between ions:interaction distance(ID),and interaction time ratio(ITR).The best correlation between characteristic time ratio and solubility was found for a molar ratio of salt-to-water of 10:100 with a correlation coefficient of 0.96.For the same salt,a positive correlation was found between CTR and the molar ratio of salt and water.For type 1-1,type 2-1,type 1-2,and type 2-2 salts,the correlation coefficients between CTR and solubility were 0.93,0.96,0.92,and 0.98 for a salt-to-water molar ratio of 10:100,respectively.The solubility of multiple salts was predicted by simulations and compared with experimental values,yielding an average relative deviation of 12.4%.The new ion-interaction parameters offer significant advantages in describing strongly correlated and strongly hydrated electrolyte solutions.

Measurement and Correlation of Equilibrium Data for Aqueous Two-phase System Ethanol+Water+ K_2HPO_4

The isothermal solubility data of aqueous two-phase system ethanol+water+K 2HPO 4 were determined with the turbidity titration method at 303.2 K. The binodal curves were described by using the Mistry equation very well. An experimental procedure for measuring the liquid-liquid equilibrium data of the aqueous two-phase system was proposed, in which the concentrations of the coexisting phases were determined with the corresponding densities of the solution. The tie lines were satisfactorily described by using the Othmer-Tobias and Bancroft equations.

Prediction of the Aqueous Solubilities of Polychlorinated Biphenyls

Using the molecular electronegativity distance vector descriptors derived directly from the molecular topological structures, the aqueous solubilities of polychlorinated biphenyls (PCBs) were predicted. A three-variable regression equation with correlation coefficient of 0.9739 and the root mean square errors of 0.26 was developed. The descriptors included in the equation represent three interactions between three pairs of atomic types, i.e., atom -C= and >C=, -C= and -Cl, and -Cl and -Cl. It has been proved that the aqueous solubilities of 137 PCB congeners can be accurately predicted as long as there are more than 65 calibration compounds.

Evaluation of Albuminated Curcumin as Soluble Drug Form to Control Growth of Cancer Cells <i>in Vitro</i>

Curcumin (Curc) is well known for its anticancer activity, but its poor solubility in aqueous medium is a major concern for little therapeutic outcome. Therefore, the effort to improve its bioavailability is a major research interest. The current study aimed at conjugation of Curc to serum albumin (Alb) to increase aqueous solubility of the former without affecting its drug action on cancer cell lines and primary cells in culture. Conditions for preparation of albumin-curcumin (Alb-Curc) conjugate were standardized to obtain pure and stable drug. The product was obtained in sufficient quantity to test its effect on cells in culture at different doses. Briefly, the conjugate was prepared by mixing Curc dissolved in DMSO with the Alb dissolved in phosphate buffered saline;conjugate was purified by gel filtration chromatography and was analyzed using UV-Vis spectroscopy for characteristic peaks of both molecules. The conjugate was added to culture medium to identify the effect of conjugate on cell cycling and apoptosis. Albuminated curcumin that showed 100-fold higher solubility than free Curc was stable and inhibitory to proliferation, induced cell cycle arrest and apoptosis. The conjugate showed apoptotic effects on endothelial cells indicating its anti angiogenic property. Primary fibroblast growth was also inhibited but at the higher dose. The in vitro results suggest that Alb-Curc which is free of insoluble native drug may find application in cancer therapy after appropriate in vivo evaluations.

Utilizing the Alterable Solubility of Chitosan in Aqueous Solution to Synthesize Nanosized Sulfur for High Performance Li-S Batteries

Summary of main observation and conclusion We demonstrate the synthesis of cathode material with nanosized sulfur by a precipitation method making use of the alterable solubility of chitosan (CTS) in aqueous solution.Mesoporous Ketjen Black (KB) and carbon nanotube (CNT) are added as conductive agents to provide the three-dimensional electric channels.This method can reduce the size of the sulfur particles,thus the nanosized sulfur obtained can fully contact with the conductive agent,which could increase the utilization of sulfur and improve the capacity of Li-S batteries.Moreover,CTS with abundant hydroxyl and amine groups has strong interaction with polysulfides,which can improve the stability of Li-S batteries.As a result,the obtained CTS/C-S cathode containing 76 wt% sulfur delivers an impressively initial discharge specific capacity of 1141.6 mA.h.g^-1 at 0.5 C and maintains a capacity of 842.3 mA·h·g-1 after 300 cycles.Our finding paves a way for the rational design of high-performance sulfur cathodes for advanced Li-S batteries.

DFT Study on Dissolvability-structure Relationship of Halogeno-benzene

Structural parameters of 36 fluorobenzene, chlorobenzene and bromobenzene compounds were computed at the B3LYP/6-31G^＊ level with DFT method. Based on the experimental data of aqueous solubility （–lgSw） and n-octanol/water partition coefficient （lgKow）, using the modified theoretical linear solvation energy relation （MTLSER） model, correlation equations that can predict –lgSw and lgKow were developed using structural parameters as theoretical descriptors. The correlation coefficients （r） of these equations are 0.9728 and 0.9967, respectively. These equations were further validated by variance inflation factors （VIF） and t-test methods and then used to predict –lgSw and lgKow values. By comparison, the correlation and predictive ability of our work are more advantageous than those calculated from valence molecular connectivity indices method and molecular topology index method.

Taking into Account Density Fluctuations in a Solvent in a Model of Dissolution

Earlier it was shown by different authors that there are cavities (vacancies, holes) in any liquid. The cavities should play a prominent role in dissolution processes. Nevertheless this fact was ignored in previous model of dissolution. The sizes of the cavities in different solvents containing benzene molecules were determined using solvent induced spectral shift method. The measurements of S1←S0 benzene transition spectral shifts permit to conclude that 1) macroscopic excess volumes play an almost negligible role in processes of benzene dissolution in very different solvents and 2) the minimal size of the cavity in water able to accommodate benzene molecule coincides with the solute size. Generalization of this conclusion to other nonpolar aromatics leads to evaluation contraction of the solutes under aqueous solvent influence permits to predict the solubility values of other aromatics in water and to evaluate effect of enhancement hydrate cell around these molecules on solubility.

Variability of SO_2 in an intensive fog in North China Plain:Evidence of high solubility of SO_2

A field experiment was conducted in an intensive fog event between November 5 and November 8, 2009, in a heavily SO2-polluted area in North China Plain （NCP）, to measure SO2 and other air pollutants, liquid water content （LWC） of fog droplets, and other basic meteorological parameters. During the fog period, the concentrations of SO2 showed large variability, which was closely related to the LWC in the fog droplets. The averaged concentration of SO2 during non-fog periods was about 25 ppbv, while during the fog period, it rapidly reduced to about 4-7 ppbv. Such large reduction of SO2 suggested that a majority of SO2 （about 70%-80%） had reverted from gas to aqueous phase on account of the high solubility of SO2 in water in the fog droplets. However, the calculated gas to aqueous phase conversion was largely underestimated by merely using the Henry＇s Law constant of SO2, thus suggesting that aqueous reaction of SO2 in fog droplets might play some important role in enhancing the solubility of SO2. To simplify the phenomenon, an ＂effective solubility coefficient＂ is proposed in this study. This variability of SO2 measurement during the extensive fog event provides direct evidence of oxidation of SO2 in fog droplets, thus providing important implications for better understanding of the acidity in clouds, precipitation, and fogs in NCP, now a central environmental focus in China due to its rapid economic development.

Effects of Autoclaving and Mercuric Chloride Sterilization on PAHs Dissipation in a Two-Liquid-Phase Soil Slurry

A two-liquid-phase （TLP） soil slurry system was employed to quantify the efficiencies of autoclaving and mercuric chloride sterilization in the dissipation of polycyclic aromatic hydrocaxbons （PAHs）. The fates of 11 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benzo（a）anthracene, benzo（a）pyrene, benzo（b）fluoranthene, benzo（k）fluoranthene, dibenzo（a, h）anthracene） were recorded over 113 days of incubation. No microorganisms were detected in the HgC12-sterilized soil slurries during the whole incubation period, indicating very effective sterilization. However, about 2% 36% losses of PAHs were observed in the HgCl2- sterilized slurry. In contrast to the HgCl2-sterilized soil slurry, some microorganisms survived in the autoclaved soil slurries. Moreover, significant biodegradiation of 6 PAHs （naphthalene, fluorene, phenanthrene, anthracene, fluoranthene and pyrene） was observed in the autoclaved soil slurries. This indicated that biodegradation results of PAHs in the soil slurries, calculated on basis of the autoclaved control, would be underestimated. It could be concluded that the sterilization efficiency and effectiveness of HgCl2 on soil slurry was much higher than those of autoclaving at 121 ℃ for 45 rain.

Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes（ICs） with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal（DIF） as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly（ethylene glycol）（PEG） and poly（s-caprolactone）（PCL）.The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.