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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]

[Display omitted] • This study marks the molecular investigation of metallodrugs aggregation in water. • Examining cisplatin solvation in water by molecular dynamics simulation. • As the concentration of cisplatin in water solutions increases, drug aggregation intensifies, significantly. Cisplatin (CPT), recognized as a widely used metallodrug, is a prevalent therapeutic agent for the treatment of various cancers. Given the diverse biological conditions in humans, as well as the hydrated environment within cells and the toxicity associated with CPT in cancer treatment, it is imperative to assess and optimize the solvation of CPT under various conditions. In this study, the influence of CPT on the structure of water is explored. In this regard, a systematic molecular dynamics (MD) simulation is employed to investigate the structure and dynamics of CPT in aqueous media, encompassing a range of concentrations from much diluted (0.05 M) to concentrated (5 M). The disruption of water structure by CPT molecules is determined using radial distribution function (RDF), mean-squared displacement (MSD), and combined radial/angular distribution function (CDF). Notably, the CPT aggregates exhibit an impact on the average number of water-water hydrogen bonds. Through calculations of apparent and partial molal volumes of CPT at various concentrations, we observed a sudden and dramatic change in the solution structures up to the critical aggregation concentration of CPT (0.5 molal), a finding corroborated by the calculations of diffusion coefficients. In summary, the self-aggregation of CPT molecules commences at 0.5 molal, leading to increased apparent and partial molal volumes with rising concentration. However, beyond 0.5 molal, the change in volumes becomes less significant, suggesting that while the number of CPT aggregates continues to increase, their size remains relatively constant above this concentration. [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]

[Display omitted] • Combined experimental/theoretical study using a novel nanomaterial namely Nickel Molybdate (NiMoO 4) as electrode in fabrication of DSSCs is reported. • The influence of this nanomaterial on the photovoltaic performance of DSSCs was systematically explored. • Insight into the molecular interactions at the interface of electrolyte solution and the NiMoO 4 electrode by molecular dynamics simulations is provided. This study explores both computational and experimental aspects of third-generation solar cells, specifically dye-sensitized solar cells (DSSCs) using Nickel Molybdate (NiMoO 4) as both a new alternative electron transport layer (working electrode, WE) and counter electrode (CE). The synthesized NiMoO 4 nanoparticles have an average size of 800 nm with crystalline size of 24.12 nm using Scanning electron microscopy (SEM) and X-ray diffraction (XRD) spectroscopy. The results indicate that the DSSCs based on NiMoO 4 exhibit low photovoltaic performance due to poor photocurrent production. However, when NiMoO 4 is employed as the WE (with platinum serving as the CE); it yields a better short circuit current (J sc = 20.04 μA/cm2) and overall photovoltaic performance compared to TiO 2 WE (with NiMoO 4 serving as the CE) (J sc = 0.23 μA/cm2). Interestingly, the DSSCs with NiMoO 4 as WE featured the lowest performance degradation (90 % efficiencies has been maintained after 250 h). Additionally, this study investigates the distribution of electrolyte between NiMoO 4 /Pt and TiO 2 /NiMoO 4 slabs using molecular dynamics (MD) simulations, highlighting its effective contribution to ionic conductivity (Λ), ultimately leading to an increase in photocurrent for the NiMoO 4 /Pt system (Λ of 27.51 10−4 S.m2/mol) compared to the TiO 2 /NiMoO 4 (Λ of 13.45 10−4 S.m2/mol). Interestingly, the iodide ions interact more tightly with the TiO 2 semiconductor (at a distance of 0.32 nm) than with NiMoO 4. [ABSTRACT FROM AUTHOR]

In this work, various atomic charge schemes including natural bond orbital (NBO), electrostatic potential based (CHELPG), and σ -hole model charges were applied in the OPLS-AA force field to investigate their effects on the thermophysical and structural properties of iodobenzene and its derivatives. Molecular dynamics simulations presented in this work show that the studied structural and thermophysical properties are in good agreement with experiments when the CHELPG charge was coupled with the OPLS-AA force field. Also, the arrangement of iodobenzene derivatives in the liquid phase was investigated via combined radial/angular distribution functions (CDFs) analyses and halogen-bonding theory. The most probable orientation of iodobenzene derivatives at the liquid/vacuum interface was assigned by atom density profile and bivariate orientational distribution maps. For all studied iodobenzene derivatives, benzene rings are oriented such that the iodine atoms tend toward the vacuum phase. [Display omitted] • The effect of different partial atomic charges of iodobenzene derivatives is investigated by MD simulation.. • Structure of liquid iodobenzene derivatives is predicted using halogen-bonding theory. • Most probable orientation of iodobenzene derivatives at liquid/vacuum interface is determined. [ABSTRACT FROM AUTHOR]

Drug absorption at an acceptable dose depends on the pair of solubility and permeability. There are many potent therapeutics that are not active in vivo, presumably due to the lack of capability to cross the cell membrane. Molecular dynamics simulation of radicicol, diol-radicicol, cyclopropane-radicicol and 17-DMAG were performed at water/octanol interface to suggest interfacial activity as a physico-chemical characteristic of these heat shock protein 90 (HSP90) inhibitors. We have observed that orally active HSP90 inhibitors form aggregates at the water/octanol and DPPC-lipid/water interfaces by starting from an initial configuration with HSP90 inhibitors embedded in the water matrix. [ABSTRACT FROM AUTHOR]

The self-assembly of dibromocarbazole based small molecule (P7C3) and its analogues is studied at the octane/water interface by using molecular dynamics simulations. P7C3 protects newborn neurons from apoptotic cell death and enhances neurogenesis. The bromines on the carbazole appear particularly important, as the derivatives with dichloro and parent carbazole did not appear active at the concentrations tested. We are mainly focused on the question that why is dibromocarbazole derivative an effective neuroprotective drug, but not dichlorocarbazole or parent carbazole? It was found that P7C3 and P7C3-Cl were concentrated in the interfacial region, whereas the parent carbazole derivative were distributed throughout the water phase. The diffusion of P7C3 molecules in the interfacial region are higher than P7C3-Cl. This approach could use by experimentalist to evaluate the permeability of drug candidates prior to their synthesis. [ABSTRACT FROM AUTHOR]

Partial atomic charges using various quantum mechanical calculations for [C n mim]Cl ( n = 1, 4) ionic liquids (ILs) are obtained and used for development of molecular dynamics simulation (MD) force fields. The isolated ion pairs are optimized using HF, B3LYP, and MP2 methods for electronic structure with 6-311++G(d,p) basis set. Partial atomic charges are assigned to the atomic center with CHELPG and NBO methods. The effect of these sets of partial charges on the static and dynamic properties of ILs is evaluated by performing a series of MD simulations and comparing the essential thermodynamic properties with the available experimental data and available molecular dynamics simulation results. In contrast to the general trends reported for ionic liquids with BF 4 , PF 6 , and iodide anions (in which restrained electrostatic potential (RESP) charges are preferred), partial charges derived by B3LYP-NBO method are relatively good in prediction of the structural, dynamical, and thermodynamic energetic properties of the chloride based ILs. [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: Using classical molecular dynamics simulation, liquid density and isobaric expansion coefficient of n-butyl formate were studied in the temperature range 298.15 to 623.15K. Fluctuations in ensemble volume and energy were used to determine the isothermal compressibility and heat capacities, hence the internal pressure. In addition, self-diffusion coefficient and viscosity were determined from dynamic properties of the ensemble. The low viscosity of the ester, which is of considerable interest as a solvent in extraction processes, was substantiated by results of the simulation. The structural properties were studied by atom–atom pair correlation function, and the results are discussed. From the structural analysis, it was found that the formate head group could form a specific hydrogen bonding extended only at short range. [Copyright &y& Elsevier]

The molecular basis of Alzheimer’s disease (AD) is a critical aspect for understanding the role of A β fibrils in neurotoxicity and for designing therapeutic strategies against AD. Molecular insight into the prevention of A β peptide aggregates in the presence of P7C3, a derivative of dibromocarbazole, molecule is presented for the first time. P7C3 protects newborn neurons from apoptotic cell death, but mechanistic details are lacking. The ability of P7C3 to prevent the onset or to slow the progression of the Alzheimer’s disease was studied by using molecular dynamics (MD) simulations. Two different mechanisms were considered: the disruption of A β aggregation by direct binding of P7C3 to A β and alterations in amyloid precursor protein processing through the inhibition of β -secretase. The results indicate that P7C3 molecule can efficiently bind to the β -secretase active site. The direct interactions of P7C3 with A β peptide are also important but in a lesser extent. [ABSTRACT FROM AUTHOR]