Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs) can solubilize hydrophobic drugs ...in water enhancing their bioavailability. In this theoretical study based on molecular mechanics and molecular dynamics methods, the interactions between β-cyclodextrin and piroxicam, an important nonsteroidal anti-inflammatory drug, were investigated. At first, both host-guest complexes with native β-CD in the 1:1 and in 2:1 stoichiometry were considered without assuming any initial a priori inclusion: the resulting inclusion complexes were in good agreement with literature NMR data. The interaction between piroxicam and a β-CD nanosponge (NS) was then modeled at different concentrations. Two inclusion mechanisms were found. Moreover, piroxicam can interact with the external NS surface or with its crosslinkers, also forming one nanopore. At larger concentration, a nucleation process of drug aggregation induced by the first layer of adsorbed piroxicam molecules is observed. The flexibility of crosslinked β-CDs, which may be swollen or quite compact, changing the surface area accessible to drug molecules, and the dimension of the aggregate nucleated on the NS surface are important factors possibly affecting the kinetics of release, which shall be theoretically studied in more detail at specific concentrations.
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Carbon nanomaterials are receiving an increasingly large interest in a variety of fields, including also nanomedicine. In this area, much attention is devoted to investigating and modeling the ...behavior of these nanomaterials when they interact with biological fluids and with biological macromolecules, in particular proteins and oligopeptides. The interaction with these molecules is in fact crucial to understand and predict the efficacy of nanomaterials as drug carriers or therapeutic agents as well as their potential toxicity when they occupy the active site of a protein or severely affect the secondary and tertiary structure, or even the local dynamics, thus inhibiting their biological function. In this review, therefore, we describe the most recent work carried out in the last few years to model the interaction between carbon nanomaterials, either pristine or functionalized, and proteins or oligopeptides using classical atomistic methods, mainly molecular dynamics simulations. The attention is focused on 0-dimensional fullerenes, mainly C60, on 1-dimensional carbon nanotubes, mostly the single-walled armchair and some chiral ones, and on 2-dimensional graphene and graphyne, the latter containing also sp hybridized atoms in addition to the sp2 ones common to the other carbon nanomaterials.
•Atomistic computer simulations can provide important information about protein adsorption on nanostructured materials.•Charged residues such as lysine, and in particular arginine, may interact very efficiently with hydrophobic carbon nanomaterials, even more than aromatic residues.•Nanomaterials can interact with proteins by occupying their active sites, by changing their secondary or tertiary structure or by affecting their intramolecular dynamics.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We report a molecular dynamics (MD) simulation study of protein adsorption on the surface of nanosized carbon allotropes, namely single-walled carbon nanotubes (SWNT) considering both the convex ...outer surface and the concave inner surface, together with a graphene sheet for comparison. These systems are chosen to investigate the effect of the surface curvature on protein adsorption at the same surface chemistry, given by sp2 carbon atoms in all cases. The simulations show that proteins do favorably interact with these hydrophobic surfaces, as previously found on graphite which has the same chemical nature. However, the main finding of the present study is that the adsorption strength does depend on the surface topography: in particular, it is slightly weaker on the outer convex surfaces of SWNT and is conversely enhanced on the inner concave SWNT surface, being therefore intermediate for flat graphene. We additionally find that oligopeptides may enter the cavity of common SWNT, provided their size is small enough and the tube diameter is large enough for both entropic and energetic reasons. Therefore, we suggest that proteins can effectively be used to solubilize in water single-walled (and by analogy also multiwalled) carbon nanotubes through adsorption on the outer surface, as indeed experimentally found, and to functionalize them after insertion of oligopeptides within the cavity of nanotubes of appropriate size.
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Adsorption of human lysozyme on hydrophobic graphite is investigated through atomistic computer simulations with molecular mechanics (MM) and molecular dynamics (MD) techniques. The chosen strategy ...follows a simulation protocol proposed by the authors to model the initial and the final adsorption stage on a bare surface. Adopting an implicit solvent and considering 10 starting molecular orientations so that all the main sides of the protein can face the surface, we first carry out an energy minimization to investigate the initial adsorption stage, and then long MD runs of selected arrangements to follow the surface spreading of the protein maximizing its adsorption strength. The results are discussed in terms of the kinetics of surface spreading, the interaction energy, and the molecular size, considering both the footprint and the final thickness of the adsorbed protein. The structural implications of the final adsorption geometry for surface aggregation and nanoscale structural organization are also pointed out. Further MD runs are carried out in explicit water for the native structure and the most stable adsorption state to assess the local stability of the geometry obtained in implicit solvent, and to calculate the statistical distribution of the water molecules around the whole lysozyme and its backbone.
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Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into ...cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes (γ-CD)2/C70 are investigated analyzing the differences with the analogous C60 complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy. The inclusion complex of γ-CD and C70 has a 2:1 stoichiometry, the same as C60, but is significantly less stable and displays an unlike arrangement. In vacuo, mimicking an apolar solvent, the complex is compact, whereas in water the two γ-CDs encapsulate C70 forming a relatively stable complex by interacting through their primary rims, however exposing part of C70 to the solvent. Other higher-energy complexes with the γ-CDs facing different rims can form in water, but in all cases part of the hydrophobic C70 surface remains exposed to water. The stability and arrangement of these peculiar amphiphilic inclusion complexes having non-covalent interactions in water can be an important key for cancer therapy to enhance both the solubilization and the fullerene insertion into liposomes or cell membranes.
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Biomaterial-based drug delivery systems for a controlled drug release are drawing increasing attention thanks to their possible pharmaceutical and biomedical applications. It is important to control ...the local administration of drugs, especially when the drug exhibits problems diffusing across biological barriers. Thus, in an appropriate concentration, it would be released in situ, reducing side effects due to interactions with the biological environment after implantation. A theoretical study based on Molecular Mechanics and Molecular Dynamics methods is performed to investigate possible surface interactions between the amorphous SiO
surface and the ketoprofen molecules, an anti-inflammatory drug, considering the role of drug concentration. These theoretical results are compared with experimental data obtained by analyzing, through Fourier transform infrared spectroscopy (FT-IR), the interaction between the SiO
amorphous surface and two percentages of the ketoprofen drug entrapped in a silica matrix obtained via the sol-gel method and dried materials. The loaded drug in these amorphous bioactive material forms hydrogen bonds with the silica surface, as found in this theoretical study. The surface interactions are essential to have a new generation of biomaterials not only important for biocompatibility, with specific structural and functional properties, but also able to incorporate anti-inflammatory agents for release into the human body.
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Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of ...hydrophobic drugs. The complexation of 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits the solubilization of this poorly soluble anticancer drug. In this theoretical work, the complexes between β-CD and 5-FU are investigated using molecular mechanics (MM) and molecular dynamics (MD) simulations in water. The inclusion complexes are formed thanks to the favorable intermolecular interactions between β-CD and 5-FU. Both 1:1 and 1:2 β-CD/5-FU stoichiometries are investigated, providing insight into their interaction geometries and stability over time in water. In the 1:2 β-CD/5-FU complexes, the intermolecular interactions affect the drug’s mobility, suggesting a two-step release mechanism: a fast release for the more exposed and hydrated drug molecule, with greater freedom of movement near the β-CD rims, and a slow one for the less-hydrated and well-encapsulated and confined drug. MD simulations study the intermolecular interactions between drugs and specific carriers at the atomistic level, suggesting a possible release mechanism and highlighting the role of the impact of the drug concentration on the kinetics process in water. A comparison with experimental data in the literature provides further insights.
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The adsorption of organic molecules on graphene surfaces is a crucial process in many different research areas. Nano-sized carbon allotropes, such as graphene and carbon nanotubes, have shown promise ...as fillers due to their exceptional properties, including their large surface area, thermal and electrical conductivity, and potential for weight reduction. Surface modification methods, such as the “pyrrole methodology”, have been explored to tailor the properties of carbon allotropes. In this theoretical work, an ab initio study based on Density Functional Theory is performed to investigate the adsorption process of small volatile organic molecules (such as pyrrole derivatives) on graphene surface. The effects of substituents, and different molecular species are examined to determine the influence of the aromatic ring or the substituent of pyrrole’s aromatic ring on the adsorption energy. The number of atoms and presence of π electrons significantly influence the corresponding adsorption energy. Interestingly, pyrroles and cyclopentadienes are 10 kJ mol−1 more stable than the corresponding unsaturated ones. Pyrrole oxidized derivatives display more favorable supramolecular interactions with graphene surface. Intermolecular interactions affect the first step of the adsorption process and are important to better understand possible surface modifications for carbon allotropes and to design novel nanofillers in polymer composites.
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The theoretical study of dendrimers is reviewed, considering both analytical approaches and molecular simulation methods. We discuss the effect of molecular symmetry on the degeneracy of the ...relaxation times, and then the calculation of observable quantities, in particular the intrinsic viscosity, and then the viscoelastic complex modulus and the dynamic structure factor, in comparison with the available experimental data. In particular, the maximum intrinsic viscosity with increasing molar mass is analyzed in some detail. The approximations and/or assumptions of the adopted methods are also described in connection with analogous results for polymer of a different topology, in particular linear and star polymers.
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Helicenes are an extremely interesting class of conjugated molecules without asymmetric carbon atoms but with intrinsic chirality. These molecules can interact with double-stranded chiral B-DNA ...architecture, modifying after their adsorption the hydrophilicity exposed by DNA to the biological environment. They also form ordered structures due to self-aggregation processes with possible different light emissions. Following initial studies based on molecular mechanics (MM) and molecular dynamics (MD) simulations regarding the adsorption and self-aggregation process of 5-aza5helicenes on double-stranded B-DNA, this theoretical work investigates the interaction between (M)- and (P)-5-aza6helicenes with double-helix DNA. Initially, the interaction of the pure single enantiomer with DNA is studied. Possible preferential absorption in minor or major grooves can occur. Afterward, the interaction of enantiopure compounds (M)- and (P)-5-aza6helicenes, potentially occurring in a racemic mixture at different concentrations, was investigated, taking into consideration both competitive adsorption on DNA and the possible helicenes’ self-aggregation process. The structural selectivity of DNA binding and the role of helicene concentration in adsorption and the self-aggregation process are interesting. In addition, the ability to form ordered structures on DNA that follow its chiral architecture, thanks to favorable van der Waals intermolecular interactions, is curious.
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