New Development in Understanding Drug-Polymer Interactions in Pharmaceutical Amorphous Solid Dispersions from Solid-State Nuclear Magnetic Resonance.

Pharmaceutical amorphous solid dispersions (ASDs) represent a widely used technology to increase the bioavailability of active pharmaceutical ingredients (APIs). ASDs are based on an amorphous API dispersed in a polymer, and their stability is driven by the presence of strong intermolecular interactions between these two species (e.g., hydrogen bond, electrostatic interactions, etc.). The understanding of these interactions at the atomic level is therefore crucial, and solid-state nuclear magnetic resonance (NMR) has demonstrated itself as a very powerful technique for probing API-polymer interactions. Other reviews have also reported exciting approaches to study the structures and dynamic properties of ASDs and largely focused on the study of API-polymer miscibility and on the identification of API-polymer interactions. Considering the increased use of NMR in the field, the aim of this Review is to specifically highlight recent experimental strategies used to identify API-polymer interactions and report promising recent examples using one-dimensional (1D) and two-dimensional (2D) experiments by exploiting the following emerging approaches of very-high magnetic field and ultrafast magic angle spinning (MAS). A range of different ASDs spanning APIs and polymers with varied structural motifs is targeted to illustrate new ways to understand the mechanism of stability of ASDs to enable the design of new dispersions

Coherence transfer between spy nuclei and nitrogen-14 in solids

Coherence transfer from ‘spy nuclei’ such as 1H or 13C (S = 1/2) was used to excite single- or double-quantum coherences of 14N nuclei (I = 1) while the S spins were aligned along the static field, in the manner of heteronuclear single-quantum correlation (HSQC) spectroscopy. For samples spinning at the magic angle, coherence transfer can be achieved through a combination of scalar couplings J(I, S) and second-order quadrupole–dipole cross-terms, also known as residual dipolar splittings (RDS). The second-order quadrupolar powder patterns in the two-dimensional spectra allow one to determine the quadrupolar parameters of 14N in amino acids

Evidence for Dynamics on a 100 ns Time Scale from Single- and Double-Quantum Nitrogen-14 NMR in Solid Peptides

The indirect detection of 14N spectra via protons in the manner of heteronuclear multiple-quantum correlation (HMQC) allows one to obtain single- (SQ) and double-quantum (DQ) 14N spectra in solids. A comparison of the SQ and DQ line widths as a function of temperature with simulations reveals motions in the tripeptide AAG with rates on the order of 107 s−1 at 49 °C

¹H MAS NMR Study of Cysteine-Coated Gold Nanoparticles

¹H MAS NMR experiments were performed on gold nanoparticles coated with l-cysteine. The experiments show that l-cysteine molecules are zwitterions and support a structural model of cysteine forming two layers. The inner layer is composed of cysteine molecules chemisorbed to the gold surface via the sulfur atom. The outer layer interacts with the chemisorbed layer. The ¹H NMR suggests that the cysteine in the outer layer exhibits large amplitude motion about specific carbon–carbon bonds

¹H MAS NMR Study of Cysteine-Coated Gold Nanoparticles

¹H MAS NMR experiments were performed on gold nanoparticles coated with l-cysteine. The experiments show that l-cysteine molecules are zwitterions and support a structural model of cysteine forming two layers. The inner layer is composed of cysteine molecules chemisorbed to the gold surface via the sulfur atom. The outer layer interacts with the chemisorbed layer. The ¹H NMR suggests that the cysteine in the outer layer exhibits large amplitude motion about specific carbon–carbon bonds

¹H MAS NMR Study of Cysteine-Coated Gold Nanoparticles

¹H MAS NMR experiments were performed on gold nanoparticles coated with l-cysteine. The experiments show that l-cysteine molecules are zwitterions and support a structural model of cysteine forming two layers. The inner layer is composed of cysteine molecules chemisorbed to the gold surface via the sulfur atom. The outer layer interacts with the chemisorbed layer. The ¹H NMR suggests that the cysteine in the outer layer exhibits large amplitude motion about specific carbon–carbon bonds

An Under-Appreciated Source of Reproducibility Issues in Cross-Coupling: Solid-State Decomposition of Primary Sodium Alkoxides in Air

The decomposition of primary sodium alkoxide salts under ambient storage conditions and the effects of this phenomenon on commonly employed transition-metal-catalyzed cross-coupling reactions are described. By utilizing NMR, IR, and Raman spectroscopy, along with a modified Karl Fischer analysis, the main inorganic degradants were characterized, and CO2 in the air was found to be a critical reactant within the decomposition process. The effects of storage conditions on decomposition were evaluated, and the preliminary experiments to understand the kinetics of this process were performed

l‑Cysteine Interaction with Au₅₅ Nanoparticle

Simulations of l-cysteine molecules attaching on Au nanoparticles provide insight on how larger biomolecules (such as proteins and peptides) can interact with Au nanoparticles. The attaching mode is still in debate and of strong impact on the fundamental research in biosensors and biomedicine. We used a density functional theory (DFT) approach to calculate the interactions between l-cysteine molecules and the quantum sized Au nanoparticle Au₅₅. Our results support the attaching mode recognized in solid-state NMR studies, which indicate that a double layer of l-cysteine molecules is the likely configuration. A strong electronic interaction between gold and sulfur atoms establishes a strong-bonding inner layer, while a hydrogen-bond network between zwitterion-structured cysteine molecules stabilizes the existence of a second layer with thiol (−SH) groups oriented outward. Such a structure has high potential for further biofunctionalization