Hydrogen bonding networks in gabapentin protic pharmaceutical salts: NMR and in silico studies.

Hydrogen bonds (HBs) play a key role in the supramolecular arrangement of crystalline solids and, although they have been extensively studied, the influence of their strength and geometry on crystal packing remains poorly understood. Here we describe the crystal structures of two novel protic gabapentin (GBP) pharmaceutical salts prepared with the coformers methanesulfonic acid (GBP:METHA) and ethanesulfonic acid (GBP:ETHA). This study encompasses experimental and computational electronic structure analyses of 1 H NMR chemical shifts (CSs), upon in silico HB cleavage. GBP:METHA and GBP:ETHA crystal packing comprise two main structural domains: an ionic layer (characterized by the presence of charge-assisted + NHGBP ⋯O-METHA/ETHA HB interactions) and a neutral layer generated in a different way for each salt, mainly due to the presence of bifurcated HB interactions. A comprehensive study of HB networks is presented for GBP:METHA, by isolating molecular fragments involved in distinct HB types (NH⋯O, OH⋯O, and CH⋯O) obtained from in silico disassembling of an optimized three-dimensional packing structure. Formation of HB leads to calculated 1 H NMR CS changes from 0.4 to ~5.8 ppm. This study further attempts to assess how 1 H NMR CS of protons engaged in certain HB are affected when other nearby HB, involving bifurcated or geminal/vicinal hydrogen atoms, are removed.

Detecting Proton Transfer in CO2 Species Chemisorbed on Amine-Modified Mesoporous Silicas by Using 13 C†NMR Chemical Shift Anisotropy and Smart Control of Amine Surface Density.

The wealth of site-selective structural information on CO2 speciation, obtained by spectroscopic techniques, is often hampered by the lack of easy-to-control synthetic routes. Herein, an alternative experimental protocol that relies on the high sensitivity of 13 C chemical shift anisotropy (CSA) tensors to proton transfer, is presented to unambiguously distinguish between ionic/charged and neutral CO2 species, formed upon adsorption of 13 CO2 in amine-modified porous materials. Control of the surface amine spacing was achieved through the use of amine protecting groups during functionalisation prior to CO2 adsorption. This approach enabled the formation of either "isolated" or "paired" carbamate/carbamic acid species, providing a first experimental NMR proof towards the identification of both aggregation states. Computer modelling of surface CO2 -amine adducts assisted the solid-state NMR assignments and validated various hydrogen-bond arrangements occurring upon formation of isolated/aggregated carbamic acid and alkylammonium carbamate ion species. This work extends the understanding of chemisorbed CO2 structures formed at pore surfaces and reveals structural insight about the protonation source responsible for the proton-transfer mechanism in such aggregates.

Structure of Chemisorbed CO(2) Species in Amine-Functionalized Mesoporous Silicas Studied by Solid-State NMR and Computer Modeling.

Two-dimensional (2D) solid-state nuclear magnetic resonance (SSNMR) experiments on samples loaded with 13C-labeled CO2, "under controlled partial pressures", have been performed in this work, revealing unprecedented structural details about the formation of CO2 adducts from its reaction with various amine-functionalized SBA-15 containing amines having distinct steric hindrances (e.g., primary, secondary) and similar loadings. Three chemisorbed CO2 species were identified by NMR from distinct carbonyl environments resonating at δC ≈ 153, 160, and 164 ppm. The newly reported chemisorbed CO2 species at δC ≈ 153 ppm was found to be extremely moisture dependent. A comprehensive 1H-based SSNMR study [1D 1H and 2D 1H-X heteronuclear correlation (HETCOR, X = 13C, 29Si) experiments] was performed on samples subjected to different treatments. It was found that all chemisorbed CO2 species are involved in hydrogen bonds (HBs) with either surface silanols or neighboring alkylamines. 1H chemical shifts up to 11.8 ppm revealed that certain chemisorbed CO2 species are engaged in very strong HBs. We effectively demonstrate that NMR may help in discriminating among free and hydrogen-bonded functional groups. 13C{14N} dipolar-recoupling NMR showed that the formation of carbonate or bicarbonate is excluded. Density functional theory calculations on models of alkylamines grafted into the silica surface assisted the 1H/13C assignments and validated various HB arrangements that may occur upon formation of carbamic acid. This work extends the understanding of the chemisorbed CO2 structures that are formed upon bonding of CO2 with surface amines and readily released from the surface by pressure swing.

New Insight into Sorption Cycling Stability of Three Al-Based MOF Materials in Water Vapour.

Three porous aluminium benzene-1,3,5-tricarboxylates MIL-96(Al), MIL-100(Al) and MIL-110(Al) materials were studied for their hydrothermal stability. The 40-cycles water vapour sorption experiments for the three samples were performed by varying the temperature between 40 and 140 °C at 75% relative humidity to simulate working conditions for materials used in water sorption-based low-T heat storage and reallocation applications. The materials were characterized by powder X-ray diffraction, N2 physisorption, and Nuclear Magnetic Resonance and Infrared spectroscopies before and after the cycling tests. The results showed that the structure of MIL-110(Al) lost its crystallinity and porosity under the tested conditions, while MIL-96(Al) and MIL-100(Al) exhibited excellent hydrothermal stability. The selection of structures, which comprise the same type of metal and ligand, enabled us to attribute the differences in stability primarily to the known variances in secondary building units and the shielding of potential water coordination sites due to the differences in pore accessibility for water molecules. Additionally, our results revealed that water adsorption and desorption at tested conditions (T, RH) is very slow for all three materials, being most pronounced for the MIL-100(Al) structure.

The boundary lipid around DMPC-spanning influenza A M2 transmembrane domain channels: Its structure and potential for drug accommodation.

We have investigated the perturbation of influenza A M2TM in DMPC bilayers. We have shown that (a) DSC and SAXS detect changes in membrane organization caused by small changes (micromolar) in M2TM or aminoadamantane concentration and aminoadamantane structure, by comparison of amantadine and spiro[pyrrolidine-2,2'-adamantane] (AK13), (b) that WAXS and MD can suggest details of ligand topology. DSC and SAXS show that at a low M2TM micromolar concentration in DPMC bilayers, two lipid domains are observed, which likely correspond to M2TM boundary lipids and bulk-like lipids. At higher M2TM concentrations, one domain only is identified, which constitutes essentially all of the lipid molecules behaving as boundary lipids. According to SAXS, WAXS, and DSC in the absence of M2TM, both aminoadamantane drugs exert a similar perturbing effect on the bilayer at low concentrations. At the same concentrations of the drug when M2TM is present, amantadine and, to a lesser extent, AK13 cause, according to WAXS, a significant disordering of chain-stacking, which also leads to the formation of two lipid domains. This effect is likely due, according to MD simulations, to the preference of the more lipophilic AK13 to locate closer to the lateral surfaces of M2TM when compared to amantadine, which forms stronger ionic interactions with phosphate groups. The preference of AK13 to concentrate inside the lipid bilayer close to the exterior of the hydrophobic M2TM helices may contribute to its higher binding affinity compared to amantadine.