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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]

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]