Large-Scale B3LYP Simulations of Ibuprofen Adsorbed in MCM-41 Mesoporous Silica as Drug Delivery System

Abstract

The atomistic details of the interaction between ibuprofen (one of the most common nonsteroidal anti-inflammatory drugs) and a realistic model of MCM-41 (one of the most studied mesoporous silica materials for drug delivery) were elucidated by quantum mechanical modeling inclusive of London forces. Calculations are based on periodic density functional theory adopting all-electron Gaussian-type basis functions of polarized double-ζ quality and the B3LYP hybrid functional. By docking the drug on different sites of the MCM-41 pore walls, we have sampled different local features of the potential energy surface of the drug–silica system, both for low and high loadings (one and seven drug molecules per unit cell, respectively). For all cases, ibuprofen adsorption in MCM-41 is exothermic (average ΔH = −99 kJ·mol–1) and exergonic (average ΔG = −33 kJ·mol–1), exclusively when London interactions are taken into account due to their dominant role in dictating all features of this system. The comparison between simulated IR and NMR spectra suggests that static disorder of the adsorbed ibuprofen due to surface sites heterogeneity can also be invoked together with the current interpretation based on a dynamic behavior of the adsorbed ibuprofen to interpret the spectral features. Analysis of H-bond patterns exhibited by the drug interacting with the MCM-41 surface silanol (SiOH) groups revealed the importance of cooperativity in the H-bond strength. The present work shows that large-scale all-electron full quantum mechanical simulations employing accurate hybrid functionals can soon become competitive over modeling studies based on molecular mechanics methods, both in terms of superior accuracy and absence of the problematic parametrization, due to organic/inorganic interface

Molecular Picture of the Adsorption of Ibuprofen and Benzoic Acid on Hydrated Amorphous Silica through DFT-D Calculations Combined with Solid-State NMR Experiments

“…The shielding tensor is computed using the GIPAW 34 approach which permits the reproduction of the results of a fully converged all-electron calculation. Absolute shielding tensors are obtained and the 13 C scale was fixed so that experimental 35 and calculated chemical shifts of all carbon sites in bulk ibuprofen 36 coincide.…”

“…A very complete study by the group of Ugliengo [13][14] , presented a new realistic model for MCM-41, introducing hybrid functionals corrected for dispersion forces. They showed that electronic dispersion contributions to the interaction are critical for the correct description of the interactions.…”

Experimental and first-principles IR characterization of quercetin adsorbed on a silica surface

“…The surface is represented by a realistic model of hydroxylated amorphous silica layers as designed by Ugliengo et al [14] exhibiting a surface OH density of 4.5 nm −2 , a thickness of 7.2 Å and a surface area per unit cell of 161.8 Å 2 [15]. All the calculations reported in the manuscript are performed with the public version of the program Crystal [12,16] for ab initio quantum chemistry of solid state.…”

“…It seems evident that the driving force, promoting the anchor on the surface despite the sensitive strain on both the molecule and the surface adsorption layer, is the possibility to form strong and cooperative hydrogen bonds. Such opportunity is maximized in the case of the configuration 1 which results the most thermodynamically stable also at room temperature, as shown in the last column of Table 1, where differences in the standard Gibbs free energies, thus including the zero point energy and the temperature-dependent vibrational contributions to both energy and entropy, are reported [15]. Then, to model a more diluted coverage as representative of the correct experimental situation, a 2 × 2 supercell (with a surface area of 647.2 Å 2 ) was designed starting from aggregate 1.…”

Propionic acid derivatives confined in mesoporous silica: monomers or dimers? The case of ibuprofen investigated by static and dynamic ab initio simulations

“…Quantum-mechanical simulations can give some insight on the issue, by providing geometries of adsorption, energetics and by predicting experimental observables (e.g., infrared spectra). In the past years, we have extensively investigated the interaction between ibuprofen, as a model of all propionic acid derivatives, and silica, using both surface models [12] and a realistic model for the MCM-41 mesoporous material [13], also simulating the effect of air humidity on the system [14].…”