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

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-?? 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 ??H = ???99 kJ·mol???1) and exergonic (average ??G = ???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.