176 research outputs found
64. Aristofane, Le Donne all'Assemblea, a cura di Massimo Vetta, traduzione di Dario Del Corno
No full textThiercy Pascal. 64. Aristofane, Le Donne all'Assemblea, a cura di Massimo Vetta, traduzione di Dario Del Corno. In: Revue des Études Grecques, tome 103, fascicule 490-491, Janvier-juin 1990. pp. 326-330
64. Aristofane, Le Donne all'Assemblea, a cura di Massimo Vetta, traduzione di Dario Del Corno
No full textThiercy Pascal. 64. Aristofane, Le Donne all'Assemblea, a cura di Massimo Vetta, traduzione di Dario Del Corno. In: Revue des Études Grecques, tome 103, fascicule 490-491, Janvier-juin 1990. pp. 326-330
Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations
No full textConfinement in mesoporous silica can greatly increase the solubility of pharmaceutical compounds. Propionic acid derivatives (a very popular class of drugs that include ibuprofen and ketoprofen) would greatly benefit from such technology, given their common apolar character. However, it is still debated whether, after confinement, these drugs are adsorbed on the pore walls as individual molecules or they keep the H-bonded dimeric structure that exists in their crystalline form. Their physical state inside the mesopores could have important consequences on the final performances of the drug delivery system. We employed accurate periodic density functional theory simulations, both static and dynamic, to investigate the issue. We simulated ibuprofen, as a model for all propionic acid derivatives, adsorbed both as a monomer and as a dimer inside a realistic model for the MCM-41 mesoporous silica. We found that adsorption is energetically favored in both cases, driven by both vdW and H-bond interactions. However, through ab initio molecular dynamics, we observed a continuous forming, breaking and reforming of these interactions. In the end, by comparing computed energetics, vibrational spectra and mobility, we were able to provide some important clues on the physical state of this class of drugs inside mesoporous silica, helping to define which drug family (monomer or dimer) is more probable after confinement
Does Dispersion Dominate over H-Bonds in Drug–Surface Interactions? The Case of Silica-Based Materials As Excipients and Drug-Delivery Agents
Get PDFAmorphous silica is widely employed in pharmaceutical formulations both as a tableting, anticaking agent and as a drug delivery system, whereas MCM-41 mesoporous silica has been recently proposed as an efficient support for the controlled release of drugs. Notwithstanding the relevance of this topic, the atomistic details about the specific interactions between the surfaces of the above materials and drugs and the energetic of adsorption are almost unknown. In this work, we resort to a computational ab initio approach, based on periodic Density Functional Theory (DFT), to study the adsorption behavior of two popular drugs (aspirin and ibuprofen) on two models of an amorphous silica surface characterized by different hydrophilic/hydrophobic properties due to different SiOH surface groups’ density. Particular effort was devoted to understand the role of dispersive (vdW) interactions in the adsorption mechanism and their interplay with H-bond interactions. On the hydrophilic silica surface, the H-bond pattern of the Si–OH groups rearranges to comply with the formation of new H-bond interactions triggered by the adsorbed drug. The interaction energy of ibuprofen with the hydrophilic model of the silica surface is computed to be very close to the sublimation energy of the ibuprofen molecular crystal, accounting for the experimental evidence of ibuprofen crystal amorphization induced by the contact with the mesoporous silica material. For both surface models, dispersion interactions play a crucial role in dictating the features of the drug/silica system, and they become dominant for the hydrophobic surface. It was proved that a competition may exist between directional H-bonds and nonspecific dispersion driven interactions, with important structural and energetic consequences for the adsorption. The results of this work emphasize the inadequacy of plain DFT methods to model adsorption processes involving inorganic surfaces and drugs of moderate size, due to the missing term accounting for London dispersion interactions
Drug delivery mediated by silica based support: does dispersion over H-bond interactions?
No full textAmorphous silica is widely employed in pharmaceutical formulations both as a tableting,
anti-caking agent and as a drug delivery system. Particularly, mesoporous silica materials, such as
MCM-41, have been recently proposed as efficient supports for the controlled release of drugs.
However, little information is known about the interactions between drugs and amorphous silica
surfaces, especially at the atomic level. In this work we have applied a computational ab initio
approach, exploiting the periodic Density Functional Theory (DFT), to study the adsorption behavior
of two popular drugs (aspirin and ibuprofen) on silica surfaces. The CRYSTAL09 1 code was used and
PBE level of theory with a triple-ζ polarized basis set was adopted as level of calculus. Two silica
surface models were adopted: one with 4.5 OH/nm 2 (hydrophilic character) and the other with 1.5
OH/nm 2 (hydrophobic). These two surface models are representative of two real surfaces treated at
low ( 600°C), respectively. Particular importance was given to the
study of the role of dispersive interactions (depending on 1/R 6 term) in the adsorption mechanism
by including the correction proposed by Grimme 2 . All calculations have revealed that adsorption of
the considered drugs on silica surfaces is an exothermic process. In all considered cases dispersion
interactions play a crucial role in dictating the features of the drug/silica system, and they are the
dominant factor for the highly dehydroxylated surface (see Figure). We have concluded that a
subtle balance may exist between specific and directional interactions like H-bonds and non-specific
dispersion interactions, with important structural and energetic consequences. From the
methodological point of view, this work has shown that pure DFT methods are in serious error
when dealing with adsorption processes due to the missing dispersive term.
Case A – without dispersive contributions. Case B – with dispersive contributions.
Figure Ibuprofen in interaction with the 1.5 OH/nm 2 highly dehydroxylated amorphous silica surface.
1 R. Dovesi, R. Orlando, B. Civalleri, C. Roetti, V. R. Saunders, C. M. Zicovich-Wilson, Z. Kristallogr.,
2005, 220, 571-573
2 S. Grimme, J. Comput. Chem., 2006, 7(15), 1787-179
Models for biomedical interfaces: A computational study of quinone-functionalized amorphous silica surface features
No full textA density functional theory (PBE functional) investigation is carried out, in which a model of an amorphous silica surface is functionalized by ortho- benzoquinone. Surface functionalization with catechol and quinone- based compounds is relevant in biomedical fields, from prosthetic implants to dentistry, to develop multifunctional coatings with antimicrobial properties. The present study provides atomistic information on the specific interactions between the functionalizing agent and the silanol groups at the silica surface. The distinct configurations of the functional groups, the hydrogen bond pattern, the role of dispersion forces and the simulated IR spectra provide detailed insight into the features of this model surface coating. Ab initio molecular dynamics gives further insights into the mobility of the functionalizing groups. As a final step, we studied the condensation reaction with allylamine, via Schiff base formation, to ground subsequent simulations on condensation with model peptides of antimicrobial activity
Test Pattern Generation under Low Power Constraints
No full textA technique is proposed to reduce the peak power consumption of sequential circuits during test pattern application. High-speed computation intensive VLSI systems, as telecommunication systems, make power management during test a critical problem. A Genetic Algorithm computes a set of redundant test sequences, then a genetic optimization algorithm selects the optimal subset of sequences able to reduce the consumed power, without reducing the fault coverage. Experimental results gathered on benchmark circuits show that our approach decreases the peak power consumption by 20% on the average with respect to the original test sequence generated ignoring the power dissipation problem, without affecting the fault coverage
Silica-based materials as drug adsorbents: First principle investigation on the role of water microsolvation on ibuprofen adsorption
Get PDFSilica-based materials find applications as excipients and, particularly for those of mesoporous nature, as drug delivery agents for pharmaceutical formulations. Their performance can be crucially affected by water moisture, as it can modify the behavior of these formulations, by limiting their shelf life. Here we describe the role of water microsolvation on the features of ibuprofen adsorbed on a model of amorphous silica surface by means of density functional theory (DFT) simulations. Starting from the results of the simulation of ibuprofen in interaction with a dry hydrophobic amorphous silica surface, a limited number of water molecules has been added to study the configurational landscape of the microsolvated system. Structural and energetics properties, as well as the role of dispersive forces, have been investigated. Our simulations have revealed that the silica surface exhibits a higher affinity for water than for ibuprofen, even if several structures coexist at room temperature, with an active competition of ibuprofen and water for the exposed surface silanols. Dispersive interactions play a key role in this system, as pure DFT fails to correctly describe its potential energy surface. Indeed, van der Waals forces are the leading contribution to adsorption, independently of whether the drug is hydrogen-bonded directly to the surface or via water molecules
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