Chiral Discrimination Mechanisms by Silylated-Acetylated Cyclodextrins: Superficial Interactions vs. Inclusion.

Cyclodextrin derivatives constitute a powerful class of auxiliary agents for the discrimination of apolar chiral substrates. Both host-guest inclusion phenomena and interactions with the derivatizing groups located on the surface of the macrocycle could drive the enantiodiscrimination; thus, it is important to understand the role that these processes play in the rational design of new chiral selectors. The purpose of this study is to compare via nuclear magnetic resonance (NMR) spectroscopy the efficiency of silylated-acetylated α-, ß-, and γ-cyclodextrins in the chiral discrimination of 1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane (compound B) and methyl 2-chloropropionate (MCP). NMR DOSY (Diffusion Ordered SpectroscopY) experiments were conducted for the determination of the bound molar fractions and the association constants, whereas ROESY (Rotating-frame Overhauser Enhancement SpectroscopY) measurements provided information on the hosts' conformation and on the interaction phenomena with the guests. Compound B, endowed with fluorinated moieties, is not deeply included due to attractive Si-F interactions occurring at the external surface of the cyclodextrins. Therefore, a low selectivity toward the size of cyclodextrin cavity is found. By contrast, enantiodiscrimination of MCP relies on the optimal fitting between the size of the guest and that of the cyclodextrin cavity.

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside the intensive care unit.

AIM: We aimed to characterise a large population of coronavirus disease 2019 (COVID-19) patients with moderate-to-severe hypoxaemic acute respiratory failure (ARF) receiving continuous positive airway pressure (CPAP) outside the intensive care unit (ICU), and to ascertain whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. METHODS: In this retrospective, multicentre cohort study, we included adult COVID-19 patients, treated with CPAP outside ICU for hypoxaemic ARF from 1 March to 15 April, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay and 60-day in-hospital mortality. RESULTS: The study included 537 patients with a median (interquartile range (IQR) age of 69 (60-76) years. 391 (73%) were male. According to the pre-defined CPAP therapeutic goal, 397 (74%) patients were included in the full treatment subgroup, and 140 (26%) in the do not intubate (DNI) subgroup. Median (IQR) CPAP duration was 4 (1-8) days, while hospital length of stay was 16 (9-27) days. 60-day in-hospital mortality was 34% (95% CI 0.304-0.384%) overall, and 21% (95% CI 0.169-0.249%) and 73% (95% CI 0.648-0.787%) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95% CI 0.345-0.488%) for 180 (45%) CPAP failures requiring intubation, and 2% (95% CI 0.008-0.035%) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality (hazard ratio 1.093, 95% CI 1.010-1.184). CONCLUSIONS: We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures.

Diagnosis and management of right colonic diverticular disease: A review. / Diagnóstico y tratamiento de la enfermedad diverticular del colon derecho: revisión de conjunto.

The aim of this narrative review is to define the clinical-pathological characteristics and to clarify the management of right colonic diverticular disease. It is rare in Europe, USA and Australia and more common in Asia. In the recent years its incidence has increased in the West, with various distributions among populations. Many studies have reported that it is difficult to differentiate the presenting symptoms of this disease from those of appendicitis before surgery, because the signs and symptoms are similar, so misdiagnosis is not infrequent. With accurate imaging studies it is possible to reach a precise preoperative diagnosis, in order to assess an accurate treatment strategy. Currently the management of this disease is not well defined, no clear guidelines have been proposed and it is not known whether the guidelines for left colonic diverticular disease can also be applied for it. Several authors have stated that conservative management is the best approach, even in case of recurrence, and surgery should be indicated in selected cases.

Hydrolytic inhibition of α-chymotrypsin by 2,8,14,20-tetrakis(D-leucyl-D-valinamido)resorc[4]arenecarboxylic acid: a spectroscopic NMR and computational combined approach.

The stereochemical features of 2,8,14,20-tetrakis(D-leucyl-D-valinamido)resorc[4]arenecarboxylic acid and the N-succinyl-L-alanyl-L-alanyl-L-prolyl-L-phenylalanine-4-nitroanilide polypeptide substrate were investigated by nuclear magnetic resonance spectroscopy. Proton selective relaxation parameters gave the basis for the inhibitory activity of resorcin[4]arene in the hydrolysis of the polypeptide substrate by α-chymotrypsin. Results showed that an interaction between the resorcin[4]arene and α-chymotrypsin does occur, and involves the hydrophobic moiety of the macrocycle. This interaction is further reinforced by polar groups located on the side chains of the resorcin[4]arene, whereas the macrocycle-polypeptide substrate interaction is negligible. Conformational analysis and interaction studies carried out by molecular modeling are in good agreement with the NMR data, thus providing an additional support to the rationalization of the inhibitory potential of resorcin[4]arenes on the α-chymotrypsin activity.

Synergistic effects of trace amounts of water in the enantiodiscrimination processes by lipodex E: a spectroscopic and computational investigation.

Nuclear magnetic resonance (NMR) investigations on mixtures containing octakis(3-O-butanoyl-2,6-di-O-pentyl)-γ-cyclodextrin (Lipodex E) and each enantiomer of methyl-2-chloropropionate (MCP) ascertained the role of trace amounts of water in the enantiodiscrimination processes. Water is deeply included into the cyclodextrin and favors the formation of the inclusion complex with (S)-MCP, whereas (R)-MCP is only slightly affected, thus causing a significant increase of NMR differentiation. Molecular dynamics simulations were performed to shed light on the possible behavior of Lipodex E in different conditions (i.e., solvent, inclusion complexes), providing energetic and atomistic details that are in agreement with NMR observations.

Mucoadhesive properties of tamarind-seed polysaccharide/hyaluronic acid mixtures: A nuclear magnetic resonance spectroscopy investigation.

Mixtures of tamarind-seed polysaccharide (TSP) and hyaluronic acid (HA), which are employed as artificial tears for ophthalmic applications in the eye dry syndrome, were investigated by NMR spectroscopy by analyzing the effect of TSP/HA ratio and total concentration on their capability to form stable aggregates with enhanced mucoadhesive properties over those of the separate polysaccharides. The effect of TSP, HA or TSP/HA mixtures on the affinity of diclofenac sodium salt (DS) to mucin (BSM) was ascertained by means of proton selective relaxation rate measurements and assumed as the basis to compare polysaccharides mucoadhesive properties. The NMR relaxation parameters of pure DS (2mM), binary DS/BSM (5mg/mL or 10mg/mL) and ternary DS/BSM/polysaccharide systems (polysaccharide=TSP, HA or variable ratios TSP/HA mixtures) were compared in aqueous medium. The experimental data demonstrate that the minimum concentration of 1.5mg/mL of each polysaccharide is needed to have formation of a stable TSP/HA aggregate endowed with NMR detectable mucoadhesive properties and inside which reciprocal synergistic interaction occurs.

Water soluble heptakis(6-deoxy-6-thio)cyclomaltoheptaose capped gold nanoparticles via metal vapour synthesis: NMR structural characterization and complexation properties.

The complexation of heptakis(6-deoxy-6-thio)cyclomaltoheptaose to gold nanoparticles prepared by using the Metal Vapour Synthesis (MVS) led to water soluble gold nanoaggregates, thermally stable at 25°C. The role of gold concentration in the MVS-derived starting solution as well as of the cyclodextrin to gold molar ratio on the size of cyclodextrin-capped gold nanoparticles were investigated. The ability of cyclodextrin bonded to gold nanoparticles to include deoxycytidine was also probed in comparison with that of 1-thio-ß-D-glucose sodium salt.

NMR enantiodiscrimination by pentafluorophenylcarbamoyl derivatives of quinine: C10 versus C9 derivatization.

9-O-(Pentafluorophenylcarbamoyl)quinine and 10-(pentafluorophenylcarbamoyloxy)-6'-methoxy-11-norcinchonan-9-ol, obtained by derivatization of alkaloid double bond, were compared in NMR enantiodiscrimination experiments of selected chiral substrates.

Nuclear magnetic resonance approaches to the rationalization of chromatographic enantiorecognition processes.

NMR spectroscopy represents a valuable tool for obtaining information about structure and dynamics at a molecular level on the diastereoisomeric complexes formed by enantiomeric substrates and chromatographic chiral selectors or modifiers. Some examples collected from the literature show the potentialities of solution NMR spectroscopy in the rationalization of chromatographic enantiorecognition processes and the different NMR approaches needed according to the chiral selector features.