Mapping of Guest Localization in Mesoporous Silica Particles by Solid-State NMR and Ab Initio Modeling: New Insights into Benzoic Acid and p-Fluorobenzoic Acid Embedded in MCM-41 via Ball Milling

Abstract

We present a novel strategy for mapping the localization of guest molecules (GMs) in mesoporous materials by combining mechanochemistry with solid-state nuclear magnetic resonance (ssNMR) spectroscopy. To this end, we consider model guest–host systems of benzoic acid (BA) and para-fluorobenzoic acid (4-FBA) embedded in mesoporous MCM-41 material and examine the recently proposed loading (MeLo) procedure for efficient encapsulation of molecular species. Application of high-resolution NMR experiments (1H and 19F NMR) has allowed detection of a multimodal distribution of the spectral signals ascribed to embedded GMs. This peculiarity reflects the presence of distinct molecular ensembles subjected to intrinsically different local environments and exhibiting different dynamical behavior. Furthermore, a considerable fraction of an amorphous phase has been found as a byproduct of the ball-milling. The stability of the phase mixture was further checked by subjecting the samples to chemical and physical stimuli, and a detailed interpretation of the NMR data was corroborated by theoretical calculations. To this end, we have undertaken a challenge to predict the NMR spectra of the GMs@MCM-41 using advanced ab initio molecular dynamics (AIMD) simulations, providing an accurate and exhaustive analysis of the NMR spectra. On the basis of the ab initio modeling validated against the experimental results, we find that the multimodal signal distribution reflects the level of the pore filling, and can be ascribed to the presence of both interface and fluid molecular species trapped inside the pores. This has been confirmed for both BA@MCM-41 and 4-FBA@MCM-41 systems. The presence of the third, amorphous fraction can be linked to interstitial space between randomly ordered crystallites, pointing at the importance of the external surface in further stabilization of encapsulated materials. Altogether, a consistent experimental and theoretical methodology has been presented, paving the way for a more accurate analysis of complex nanoconfined systems.

Mesoporous Silica Particles as Drug Delivery Systems—The State of the Art in Loading Methods and the Recent Progress in Analytical Techniques for Monitoring These Processes

“…The maximum capacity of loading was over 50% at a 1:1 ratio. Moreover, it has been proven that using this technique, guest molecules are located in different zones of MCM-41 particles (Figure 4) [122]. Hedous et al demonstrated that the co-milling of SBA-15 with ibuprofen made it possible to load the drug into the porous matrix, enhancing thereby the filling degree to almost 40 wt% [59].…”

“…Co-milling is a commonly used technique to produce sub micrometric particles [120] as well as for solid-state amorphization [121]. Recent studies have shown that milling using a planetary ball mill is an effective solvent-free method for introducing organic compounds such as benzoic acid and 4-fluoro benzoic acid into the pores of MCM-41 [122]. This study also appeared that the guest-loading process is fully controlled and dependent on the ratio of the loaded substance and silica.…”

“…The external surface gives rise to interstitial space (right) formed between the randomly ordered crystallites (see the horizontal arrows). Adapted with permission from [122], Copyright 2021 American Chemical Society.…”

Confinement of molecular materials using a solid-state loading method: a route for exploring new physical states and their subsequent transformation highlighted by caffeine confined to SBA-15 pores

“…This paper shows that the innovative MAL method, developed by the authors, is a very efficient and unique solid-state method for loading molecular materials within mesoporous silica matrices, as recently confirmed in a very recent study performed by another group. 26 It is now recognized as an alternative to solvent-based drug loading methods, and considered as very useful for pharmaceutical applications. 27,28 We show that using this solid-state method makes possible to confine the selected crystalline form of a polymorphic system.…”

The Journal of Physical Chemistry C Virtual Special Issue on Advanced Characterization by Solid-State NMR and In Situ Technology and in Recognition of Michael Hunger’s 65th Birthday

“…The Buntkowsky group used 1D and 2D multinuclear magic-angle spinning (MAS) NMR to monitor the synthesis of the novel Wilkinson’s type silica supported polymer catalysts . The guest localization in mesoporous silica particles was mapped by 1 H and 19 F MAS NMR by the Potrzebowski group . The Sun group investigated the structure–property relationship of chitosan-based biopolymers .…”