¹⁹F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials

Abstract

The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, (19) F NMR spectroscopy can be viewed as a useful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using (19) F magic-angle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in a confined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of a molecular-liquid-like layer besides crystalline confined FFA form I.

Combined solid-state NMR, FT-IR and computational studies on layered and porous materials

“…About 25 % of all marketed drugs are fluorinated molecules and developing novel nano-confined pharmaceutical formulations as drug delivery systems can have day-to-day applications. Nartowski et al 363 Azaïs et al have applied DFT calculations and ssNMR spectroscopy to determine the origin and the strength of the interactions at the molecular level for Ibuprofen and benzoic acid, encapsulated in hydrated MCM-41 modified with organic moieties. 364 They have observed both by calculations and experimental methods that micro-solvated silica surface was found to adsorb better Ibuprofen and benzoic acid than the bare silica surface at 300 K. The water layer acted as an adhesive between the organic molecules and the silica surface, where rapid reorientation of the molecules inside the mesoporous silica occur due to adsorption/desorption induced by the interactions.…”

Hydrogen‐Bonded Liquid Crystals in Confined Spaces—Toward Photonic Hybrid Materials

“…Nuclear magnetic resonance is one of few useful techniques to directly probe the molecular order and structure of constituent molecules in liquid crystals . Recently, Nartowski et al demonstrated that 19 F NMR is a powerful tool to investigate the order of molecular guests confined inside of mesoporous silica materials . To get insight into the dynamics of the alignment of the liquid crystalline HBAs inside the mesoporous materials, variable‐temperature solid‐state 19 F NMR studies of the composites were performed.…”

Crystallisation Behaviour of Pharmaceutical Compounds Confined within Mesoporous Silicon

“…Change in scattering contrast was witnessed between unloaded and loaded samples, with the principal peak within the loaded diffraction pattern displaying a broader nature with a lower intensity [39]. In a study by Nartowski and collaborators, 19 F solid-state NMR together with terahertz spectroscopy was used to detect the presence of confined molecules of flufenamic acid (FFA) in different environments and motional regimes [40]. This enabled the authors to gain in situ mechanistic insight into the molecular self-assembly at different length scales by taking advantage of the higher sensitivity of 19 F nuclei to changes in the local environments of molecules confined in the porous hosts.…”