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Intermolecular interactions of drug molecules can lead to aggregation, which has a significant impact on their application. This problem might escape the attention when studying their solubility as small aggregates might behave almost as single molecules. We studied the aggregation behaviour of doxorubicin (DOX) molecules through density functional (DFT) methods and molecular dynamics (MD) simulations in water, dimethylformamide (DMF), ethanol (EtOH), and dimethyl sulfoxide (DMSO). We described the degree of aggregation by MD-calculated radial distribution function, combined radial/angular distribution functions, autocorrelation functions, and the number of hydrogen bonds of individual DOX and solvent atoms. MD-calculated diffusion coefficients for DOX decrease along the series water > DMF > EtOH > DMSO (0.101 × 10−9, 0.047 × 10−9, 0.025 × 10−9, and 0.007 × 10−9 m2 s−1, respectively) consistent with increasing aggregation found in the MD simulations. These aggregates have different characters, depending on the DOX⋯solvent interactions, and include hydrogen bonding and π-stacking. Even though the solvation energy of a single DOX molecule in DMSO (−24.8 kcal mol−1) is higher than in other solvents, the formation of larger aggregates in this solvent prevents proper solvation. Further, the orientation of doxorubicin molecules at octanol/water and dipalmitoylphosphatidylcholine (DPPC)/water interfaces was studied with two different orientations from the bivariate maps. In the case of the DPPC/water interface, the anthracycline part points toward the aqueous phase, while this part is oriented almost parallel to the octanol/water interface in DMSO. [ABSTRACT FROM AUTHOR]

The behavior of aqueous solutions of mixtures of ionic liquids (ILs) is of special interest because of their amphiphilic character, from both a fundamental and application viewpoint. In this work, we conducted molecular dynamics (MD) simulations and density functional theory (DFT) calculations to understand the effect of water on the intermolecular interactions in three IL binary mixtures [C4mim]/[Cl]/[BF4], [C4mim]/[Cl]/[PF6] and [C4mim]/[BF4]/[PF6] containing the well-characterized cation, 1-n-butyl-3-methylimidazolium [C4mim]+ and the anions chloride [Cl]−, tetrafluoroborate [BF4]−, and hexafluorophosphate [PF6]−. The perturbation of the structures in the binary IL mixture by water molecules was analyzed in the bulk and at the liquid/vacuum interface using distribution functions, hydrogen-bond statistics, and density profiles. Interactions between anions and cations change drastically when the IL mixtures are dissolved in water. In particular, anion–water interactions are stronger than anion–cation interactions. H-Bonds are the dominant interactions. They are prevalently electrostatic and strong for the two [Cl]-containing systems in both the water-free and the water-containing systems. The very hydrophobic [C4mim]/[BF4]/[PF6] system gains stability from dispersive interactions and consequently segregates water markedly when admixed. The most probable orientations of IL cations in the bulk and at the vicinity of the interface were examined using bivariate distribution calculations and show [PF6]− segregating to the surface in keeping with its highly hydrophobic nature. DFT calculated structures, energies, dipole moments, global hardness and solvation energies using model ion pairs [C4mim][X] or complexes [C4mim]2[X][Y], with [X/Y]− = [Cl]−, [BF4]−, or [PF6]− are completely consistent with the findings for the bulk. [ABSTRACT FROM AUTHOR]

To obtain a better understanding of TiO2 nanotube (TiO2-NT) synthesis in different ethylene glycol (EG)-based electrolyte solutions by electrochemical anodization, the primary steps of TiO2-NT formation were studied by experimental techniques. In this regard, three different EG-based electrolyte solutions were used for anodic oxidation of titanium foil. The first electrolyte solution contains conventional ammonium fluoride (NH4F) dissolved in EG/water (98 : 2 v/v). In the second one, Ti foil anodization is performed in an electrolyte solution containing the 1-butyl-3-methyl-imidazolium tetrafluoroborate (Bmim-BF4) ionic liquid. Finally, the fluorine-containing species was replaced by the 1-butyl-3-methyl-imidazolium chloride (Bmim-Cl) ionic liquid. The results indicate that the TiO2-NTs did not form by anodization in the EG/H2O/Bmim-Cl electrolyte solution at 60 V. Interestingly, this electrolyte solution is less viscous than the fluorine-containing electrolyte solutions. In addition, we report a detailed study on the structural arrangement of electrolyte solution components near the solid surfaces using molecular dynamics (MD) simulation methods to reveal the factors governing the difference of the ionic species distribution. The MD results elucidate the role of the ionic constituents in the length of the nanotube arrays at a certain anodization condition. Furthermore, as reported herein for the first time, the lifetimes of ion–ion contacts and the interactions of ionic species with TiO2 walls have a substantial effect on the resulting nanotubes. These characteristics are analyzed by using radial distribution functions, density profiles, distance analysis, time correlation functions, and mean-square-displacements, complemented by DFT calculations. [ABSTRACT FROM AUTHOR]

Drug delivery systems sensitive to pH have been investigated recently as a responsive strategy for tumour targeting in view of the slightly acidic pH environment of most solid tumours. Herein, we report Zn capped Al2O3 and TiO2 nanoporous arrays for pH sensitive drug release. The nanostructures were fabricated through electrochemical anodisation. Vitamin C as a model drug was loaded into the nanopores; some were then capped using elemental Zn. The release rates of vitamin C were investigated in water or lactic acid using high performance liquid chromatography (HPLC). The amount of drug loaded into the nanostructures was about 7 times higher for TiO2 compared with Al2O3 and the release was faster from TiO2. Zn capping proved to be quite efficient at preventing release at high pH (7) and not largely hindering the release at low pH (5), making both systems suitable for pH-triggered release. Molecular dynamics (MD) simulations showed that the diffusion of vitamin C molecules through the model nanopores is faster for TiO2 than for Al2O3, consistent with the experimental results. The tremendously stronger H bonding interactions observed for vitamin C molecules and water molecules with the TiO2 walls compared with Al2O3 are responsible for the observed differences in the calculated number density profiles and radial distribution functions. [ABSTRACT FROM AUTHOR]

Bulk and surface properties of the ionic liquids 1-alkyl-3-methyl-imidazolium iodides ([Cnmim]I) were simulated by classical molecular dynamics using all atom non-polarizable force field (n = 4, butyl; 6, hexyl; 8, octyl). The structure of ionic liquids were initially optimized by density functional theory and atomic charges obtained by CHELPG method. Reduction of partial atomic charges (by 20% for simulation of density and surface tension, and by 10% for viscosity) found to improve the accuracy, while a non-polarizable force field was applied. Additionally, the simulation ensembles approach the equilibrium faster when the charge reduction is applied. By these refined force field parameters, simulated surface tensions in the range of 323-393 k are quite in agreement with the experiments. Simulation of temperature dependent surface tension of [C4mim]I well beyond room temperature (up to 700 K) permits prediction of the critical temperature in agreement with that predicted from experimental surface tension data. Simulated densities in the range of 298-450 K for the three ionic liquids are within 0.8% of the experimental data. Structural properties for [C4mim]I were found to be in agreement with the results of Car-Parrinello molecular dynamics simulation we performed, which indicates a rather well-structured cation-anion interaction and occurs essentially through the imidazolium ring cation. Diffusion coefficient changes with alkyl chain length in the order of [C8mim]I > [C6mim]I > [C4mim]I for the cation and the anion. Formation of a dense domain in subsurface region is quite evident, and progressively becomes denser as the alkyl chain length increases. Bivariate orientational analysis was used to determine the average orientation of molecule in ionic liquids surface, subsurface, and bulk regions. Dynamic bisector-wise and side-wise movement of the imodazolium ring cation in the surface region can be deduced from the bivariate maps. Atom-atom density profile and bivariate analysis indicate that the imidazolium cation takes a spoon like configuration in the surface region and the tilt of alkyl group is a function length of alkyl chain exposing as linear as possible to the vapor phase. [ABSTRACT FROM AUTHOR]

In this paper, molecular dynamics simulation was performed to investigate the liquid/vapor interfacial structure of neat polar liquids. Large-scale ensembles of liquid pyridine and its alkyl derivatives, 4-methylpyridine and 4-ethylpyridine, were simulated by classical molecular dynamics at 298 K. For the liquid system of low polarity, the surface density profile of the atoms meet exactly at the middle of interfacial region, and atoms of hydrophobic nature can be hardly discriminated from hydrophilic ones in either vapor or liquid sides. For a liquid system of high polarity, the density profile of atoms with different nature is highly discriminated all over the interfacial region, and as the polarity increases, a dense region of atomic density is clearly developed in the subsurface region. The recognized bivariate method was also used to study the molecular orientational distribution quantitatively. Orientational analysis of the three liquid systems indicates that the pyridine ring plane in the outmost surface tends to be vertical. Its tendency in the innermost interfacial region is parallel. The orientational states available to 4-ethylpyridine and pyridine are discriminated by predicting the possibility of a bisector-wise tumbling for the ring plane in pyridine and a side-wise tumbling in 4-ethylpyridine. The orientational distribution maps explain the trend of experimental surface tension and surface entropy. As the dipole moment of these liquids increases with the alkyl chain length, the surface structural profile changes from a regular definite one to a surface of complex atomic structure involving a dense phase near the interface. The development of dense region in alkyl derivatives is the result of segregation of molecules due to the alkyl group, which is captured and discriminated by molecular dynamics simulation even when the length of a short alkyl chain is increased by one carbon atom. [ABSTRACT FROM AUTHOR]

All-atom molecular dynamics (MD) simulations were performed to systematically analyse the distribution and agglomeration of a series of small neuroprotective N-(3-anilinopropyl)-9H-carbazole based molecules at octanol/water interfaces along with a detailed assessment of their structural and dynamical properties, such as density profiles, distribution functions, average orientations, hydrogen bonding (H-bonding), and mean-square displacements. Our simulations show that the biologically active neuroprotective molecules easily migrate from the water phase to the octanol phase during the simulation trajectories. However, biologically inactive derivatives agglomerated in the water phase. Calculated radial distribution functions (RDFs) clearly underpin the necessity of the two 3,6-dibromo substituents on the carbazole core for a sufficient hydrophobic character. Furthermore, we could show that H-bonding from F, or OH groups located on the propyl unit with octanol or water molecules are decisive structural requirements for their distribution between the two liquid phases. [ABSTRACT FROM AUTHOR]

Recent studies have shown that the aggregation of the amyloid-beta peptide (Aβ) in the brain cell membrane is responsible for the emergence of Alzheimer's disease (AD); the exploration of effective factors involved in the extension of the aggregation process and alternatively the examination of an effective inhibitor via theoretical and experimental tools are among the main research topics in the field of AD treatment. Therefore, in this study, we used all-atom molecular dynamics (MD) simulations to clarify the impact of cell membrane cholesterol on the interaction of Aβ with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) as a membrane model. Moreover, the effect of the P7C3-S243 molecule on the abovementioned process was investigated. The simulation results disclosed the neuroprotective property of the P7C3-S243 molecule. The MD simulation results indicate that the interaction of cholesterol molecules with the Aβ oligomer is negligible and cannot enhance membrane rupture. However, strong hydrogen bonding between the POPC molecules and the oligomers led to membrane perturbation. According to our modellings, the P7C3-S243 molecular layer can protect the cell membrane by inhibiting the direct interaction between the bilayer and Aβ. In addition, free-energy calculations were conducted to determine the possible penetration of Aβ fibrils into the cholesterol-enriched membrane. [ABSTRACT FROM AUTHOR]

Electrostatic potential in the vicinity of the surface is induced when aqueous mixtures of hydrophobic and hydrophilic ionic liquids (ILs) are confined between a slit nanopore of amorphous but not crystalline TiO2 semiconductors. According to our molecular dynamics (MD) simulations, the extent of ion-pairing lifetime under such nanoscale confinement is substantially lower than its value in the bulk. It becomes still lower when aqueous mixtures of ionic liquid electrolytes are used. Ion–ion correlation is broken completely in the confined dilute aqueous electrolyte systems. The anions and cations of the ILs migrate and accumulate at the opposite amorphous TiO2 electrodes that are separated by 10 nm to arrange a nanosize pore. In contrast, we have shown that the electrostatic interactions between the IL ions are dominant when the electrolyte is confined between anatase (101) TiO2. A similar trend is observed for the inorganic electrolyte system. These findings shed light on the design of new cells for electrochemical applications. [ABSTRACT FROM AUTHOR]

Abstract: A series of high quality 1-alkyl-3-methylimidazolium-based ionic liquids are synthesized and used for studying their surface tension. The capillary rise method is used for measuring the surface tension of I−, Cl−, PF6 −, and BF4 − salts in the temperature range 298–393K. The capillary apparatus is evacuated and sealed under vacuum. The experimental results show that surface tension of these compounds depend systematically on temperature. For ionic liquids containing a butyl alkyl chain, the contribution of the anion to the surface tension is found to be in the order of I− >Cl− >PF6 − >BF4 −. As the chain length of the alkyl group is increased, the surface tension decreases and approaches the surface tension of alkyl fluids of the same chain length. The surface entropy decreases smoothly as the chain length increases while the surface energy decreases rather sharply. This resembles the behavior of normal liquids, molten salts, and molten metals. Comparison with literature suggests that the complete removal of water and dissolved atmospheric gases as well as sufficient thermal equilibrium would produce a highly correlated and thus accurate surface tension of ionic liquids. [Copyright &y& Elsevier]

The pyridine-2,6-carboxylic esters pydicR2 with R = Me or Ph form the unprecedented mononuclear CuII complexes [Cu(pydicR2)Cl3]− in one-pot reactions starting from pyridine-2,6-carboxychloride pydicCl2, CuII chloride, and NEt3 in MeOH or PhOH solution under non-aqueous conditions. The triethylammonium salts (HNEt3)[Cu(pydicR2)Cl3] were isolated. The methyl derivative could be crystallized to allow a XRD structure determination. Both structures were optimized using DFT calculations in various surroundings ranging from gas phase and the non-coordinating solvent CH2Cl2 to the weakly coordinating acetone and well-coordinating solvents acetonitrile (MeCN) or dimethylformamide (DMF), while detailed calculation showed the charge distribution, dipole moments, and HOMO–LUMO gap energies changing upon solvation. According to these calculations, the ion pairs and the anionic CuII complexes were stable, which shows only Cu–Cl bond elongation and weakening of the charge transfer between the anionic complex and the cation as solvents become polar. Synthesis attempts in the presence of water yielded the CuII complexes [Cu(pydic)(OH2)2]n and [Cu(OH2)6][{Cu(pydic)}2(µ-Cl)2], which results from pydicCl2 hydrolysis. Alternatively, the new pydic(IPh)2 (IPh = 2-iodo-phenyl) ester ligand was synthesized and reacted with anhydrous CuCl2, which yields the new binuclear complex [{Cu(pydic(IPh)2)Cl}2(µ-Cl)2]. EPR spectroscopy of the solid compounds reveals typical axial spectra in line with the observed and DFT calculated geometries. Cyclic voltammetry and UV–vis absorption spectroscopy in solution are in line with un-dissociated complex species [Cu(pydicR2)Cl3]−. [ABSTRACT FROM AUTHOR]

A simple and reliable colorimetric method for the quantitative determination of citalopram (CIT) enantiomers in aqueous solution using gold nanoparticles as a colorimetric probe was presented. S-citalopram induced aggregation of citrate capped AuNPs resulted in a decrease in the plasmon absorption at 520 nm and the formation of a broadened surface plasmon band around 600–700 nm. The results show that the colorimetric system possesses a very well selectivity toward S-citalopram compare to the R-citalopram as evidenced by the fact that there is the same color change from S-citalopram and (RS)-citalopram, and significant UV–vis spectral shift. The experimental conditions were optimized and the results show that S-citalopram can be determined in a linear range 2.5 × 10 −6 –6.0 × 10 −4 M with correlation coefficients of 0.9963 and limit of detection 2.1 × 10 −6 M. [ABSTRACT FROM AUTHOR]

In this paper, properties of binary mixture of polar portions of the crude oil are studied by classical molecular dynamics simulation. Particularly, the bulk and the interface of pyridine (and its alkyl derivatives) mixture with n -octane are studied, including density and structure in bulk as well as their molecular orientations at the liquid–vapor interface. Initial simulations of density profile and interfacial properties are to validate the force field applied. Additionally, the structure of solution of pyridine derivatives in bulk and at the interface is studied. As a result, the derivatives with long alky chain (of low surface tension) approaches to the surface while those with short chain (of high surface tension) aggregate in the solution and avoid approaching the surface. Finally, the molecular orientations of pyridine and alkyl derivatives are investigated in the bulk and at interface by the intrinsic bivariate orientational maps. [ABSTRACT FROM AUTHOR]

Abstract: Viscosities of ionic liquids were correlated with two linear relations. The first one presents the temperature dependence of imidazolium-, pyridinium-, pyrrolidinium-, quaternary ammonium-, and nicotinium-based ionic liquids with high accuracy. The second one is a linear relation between logarithm of surface tension and fluidity involving the characteristic exponent ϕ, and fits the ionic liquids uniquely with ϕ =0.30. Our previously measured surface tension data of ionic liquids and literature''s were used in this study. The dependence of surface tension–fluidity relation of the imidazolium-based ionic liquids on the anion type is likely disappeared as alkyl chain length increases. [Copyright &y& Elsevier]

To find an alternative way for improving the efficacy of deep eutectic solvents (DESs) to dissolve carbon dioxide, a computational study of DES systems comprising choline chloride and different hydrogen-bond donors (ethylene glycol and glycerol) immobilized on hydrophobic (graphite) and hydrophilic (titanium dioxide) solid surfaces was performed. This research provides quantitative molecular understanding of the role of the DES thickness and also the type of solid support in CO 2 sorption and diffusion using molecular dynamics simulations. In general, the proposed model based on supported DESs immobilized on different supports was developed to correlate the solubility of CO 2 in DESs based on choline chloride. The simulated systems illustrate that CO 2 molecules mainly accumulate at the gas/DES interface in short times, whereas diffusion of CO 2 to the bulk DESs is slower as the thickness of the immobilized DES increases. In addition, the CO 2 absorption capacity of both DESs coated on the TiO 2 surface is larger than that on the graphite surface. Structural and dynamic characteristics were determined using density profiles, distribution functions, orientational analysis, and mean-square displacements. We further demonstrate the effective interaction parameters associated with CO 2 capture by DESs via density functional theory.

Titanium dioxide (TiO 2 ) nanotubes are attractive materials for drug-delivery systems because of their biocompatibility, chemical stability, and simple preparation. In this study, we loaded TiO 2 nanotubes with anticancer drug doxorubicin (DOX) experimentally and in all-atom molecular dynamics (MD) simulations. The release of doxorubicin from the nanotubes was studied by high-performance liquid chromatography (HPLC) and confocal Raman spectroscopy, and drug-release profiles were evaluated under various conditions. The polyethylene glycol (PEG) coating and capping of the nanotubes led to a marked increase in the water contact angles from about 16 to 33° in keeping with reduced wettability. The capping retarded the release rate without decreasing the overall release amount. The MD simulations further show that the DOX molecule diffusion coefficients ( D i ) are in the order of 10 -10 m 2 /s. The DOX molecules show a plethora of short- and long-range H-bonding interactions with TiO 2 nanotube walls and water. Calculated radial distribution functions (RDFs) and combined radial/angular distribution functions (CDFs) allowed gauging the strength of these hydrogen bonds. The strength does not fully correlate with the pKa values of DOX atoms which we assign to the confinement of DOX and water in the tubes. The lifetimes of hydrogen bonds between the DOX atoms and water molecules are shorter than that of the DOX ... TiO 2 interactions, and DOX ... DOX aggregation does not play an important role. These results suggest TiO 2 nanotubes as promising candidates for controllable drug-delivery systems for DOX or similar antiproliferative molecules.

To obtain a better understanding of TiO2 nanotube (TiO2-NT) synthesis in different ethylene glycol (EG)-based electrolyte solutions by electrochemical anodization, the primary steps of TiO2-NT formation were studied by experimental techniques. In this regard, three different EG-based electrolyte solutions were used for anodic oxidation of titanium foil. The first electrolyte solution contains conventional ammonium fluoride (NH4F) dissolved in EG/water (98 : 2 v/v). In the second one, Ti foil anodization is performed in an electrolyte solution containing the 1-butyl-3-methyl-imidazolium tetrafluoroborate (Bmim-BF4) ionic liquid. Finally, the fluorine-containing species was replaced by the 1-butyl-3-methyl-imidazolium chloride (Bmim-Cl) ionic liquid. The results indicate that the TiO2-NTs did not form by anodization in the EG/H2O/Bmim-Cl electrolyte solution at 60 V. Interestingly, this electrolyte solution is less viscous than the fluorine-containing electrolyte solutions. In addition, we report a detailed study on the structural arrangement of electrolyte solution components near the solid surfaces using molecular dynamics (MD) simulation methods to reveal the factors governing the difference of the ionic species distribution. The MD results elucidate the role of the ionic constituents in the length of the nanotube arrays at a certain anodization condition. Furthermore, as reported herein for the first time, the lifetimes of ion-ion contacts and the interactions of ionic species with TiO2 walls have a substantial effect on the resulting nanotubes. These characteristics are analyzed by using radial distribution functions, density profiles, distance analysis, time correlation functions, and mean-square-displacements, complemented by DFT calculations.

Electrostatic potential in the vicinity of the surface is induced when aqueous mixtures of hydrophobic and hydrophilic ionic liquids (ILs) are confined between a slit nanopore of amorphous but not crystalline TiO2 semiconductors. According to our molecular dynamics (MD) simulations, the extent of ion-pairing lifetime under such nanoscale confinement is substantially lower than its value in the bulk. It becomes still lower when aqueous mixtures of ionic liquid electrolytes are used. Ion-ion correlation is broken completely in the confined dilute aqueous electrolyte systems. The anions and cations of the ILs migrate and accumulate at the opposite amorphous TiO2 electrodes that are separated by 10 nm to arrange a nanosize pore. In contrast, we have shown that the electrostatic interactions between the IL ions are dominant when the electrolyte is confined between anatase (101) TiO2. A similar trend is observed for the inorganic electrolyte system. These findings shed light on the design of new cells for electrochemical applications.