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,w ith more than 40 new drugs entering the market in the last 15 years.I nt his context, 19 FNMR spectroscopyc an be viewed as au seful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems.A lthough the interest in confined crystallization, nanosized devices,a nd porous catalysts is gradually increasing,u nderstanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using 19 Fm agicangle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in ac onfined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of amolecularliquid-like layer besides crystalline confined FFAform I.

Manipulating the physical states of confined ibuprofen in SBA-15 based drug delivery systems obtained by solid-state loading: Impact of the loading degree

“…However, there is clearly a lack of systematic information about the loading/filling degree influence on the physical states of encapsulated systems. In a recent paper, Nartowski et al 21 performed detailed 19 F solid-state NMR investigations of flufenamic acid (FFA) in mesoporous silica matrices with different pore diameters (3.2 to 29 nm) and a large range of loading degrees. For fulfilled pores (loading up to 30 wt.%), FFA was found as a disordered amorphous phase along with a liquid-like surface layer, in the 3.2 nm (MCM-41) and 7.1 nm (SBA-15) pore diameters (< 10 ).…”

Fast Magic‐Angle Spinning 19F NMR Spectroscopy of HIV‐1 Capsid Protein Assemblies

“…Fluorine is absent from any naturally occurring biological molecule, yet it can be readily and selectively incorporated into proteins, largely without causing major structural perturbations . 19 F NMR spectroscopy, both solution and solid‐state, has therefore emerged as an essential method with broad applications in pharmaceutical chemistry (∼30 % of all drugs at present in the clinic contain fluorine), chemical biology, biochemistry, and materials science . 19 F NMR spectroscopy has been used to investigate proteins, lipids, nucleic acids, and synthetic small‐molecule ligands, as well as their complexes, both in solution and in the solid state .…”

“…[18] 19 F NMR, both solution and solid-state, has therefore emerged as an essential method with broad applications in pharmaceutical chemistry (as ~30% of all drugs at present in the clinic contain fluorine), [19] chemical biology, [20] biochemistry, [16, 21–24] and materials science. [25] 19 F NMR has been applied to investigate proteins, lipids, nucleic acids, synthetic small-molecule ligands, as well as their complexes, both in solution [16, 21] and in the solid state. [22–24] 19 F MAS NMR of biological systems remains underutilized, due to challenges associated with inherently broad lines due to strong homonuclear 19 F- 19 F and heteronuclear 19 F- 1 H dipolar couplings, particularly at traditionally used MAS frequencies below 25 kHz.…”

Structure and Mobility of Lactose in Lactose/Sodium Montmorillonite Nanocomposites

“…62 It is known that nanoconfined/surface molecules demonstrate increased mobility that may lead to loss 23 of CP signal. 22,[63][64][65][66] Furthermore, the decreased signal intensity in the CP/MAS experiment can be related partially to the paramagnetic impurities present in the naturally sourced clay, that is, 2.9 wt% of the Fe(III) ions. 67 The substantial decrease in the longitudinal (T1) relaxation times due to contribution from electron-nuclear spin relaxation mechanism led to an overall decrease of the signal intensity.…”