The Effect of Ligands and Transducers on the Neurotensin Recep-tor 1 (NTS1) Conformational Ensemble

Using a discrete, intracellular 19F-NMR probe on Neurotensin receptor 1 (NTS1) transmembrane helix (TM) 6, we aim to understand how ligands and transducers modulate the receptors structural ensemble in solution. For apo NTS1, 19F-NMR spectra reveal an ensemble of at least three states (one inactive and two active-like) in equilibrium that exchange on the ms-s timescale. Dynamic NMR experiments reveal that these substates follow a linear three-site exchange process that is both thermodynamically and kinetically remodeled by orthosteric ligands. As previously observed in other GPCRs, the full agonist is insufficient to completely stabilize the active state. Receptor coupling to b-arrestin-1 or the C-terminal helix of Gaq, which comprises >60% of the GPCR/G protein interface surface area, abolishes the inactive substate. But whereas b-arrestin-1 selects for preexisting active-like substates, the Gaq peptide induces two new substates. Both transducer molecules promote substantial line-broadening of active states suggesting contributions from additional us-ms exchange processes. Together, our study suggests i) the NTS1 allosteric activation mechanism is alternatively dominated by induced fit or conformational selection depending on the coupled transducer, and ii) the available static structures do not represent the entire conformational ensemble observed in solution.

Применение политетрафторэтилена для дозиметрического контроля по данным ЯМР 19F

The 13C, 19F NMR spectra of the initial and irradiated polytetrafluoroethylene samples were studied in the range of gamma radiation doses up to 50 kGy. In this range, the 19F NMR spectrum width increases linearly with an increase in the absorbed dose. It is concluded that it is possible to control technological doses by the NMR method using polytetrafluoroethylene as a detector.

π‑Extended Boron Difluoride [NՈNBF2] Complex, Crystal Structure, Liquid NMR, Spectral, XRD/HSA Interactions: A DFT and TD-DFT Study

The novel tetrahedral 10-(4-carboxyphenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl- 5H-di-pyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide [NՈNBF2] BODIPY complex was prepared in a very good yield and via one-pot synthesis. The desired [NՈNBF2] has been used as a model complex for XRD/HSA interactions and DFT/B3LYP/6-311G(d,p) computations. The tetrahedral geometry around the boron center was demonstrated by DFT optimization and XRD-crystallography. The 1H, 11B, and 19F-NMR spectra were used also to support the high symmetrical BODIPY via π‑extended phenomena. Moreover, the values of the DFT-calculated structural bond lengths/angles and DFT-IR were matched to the corresponding experimental XRD and IR parameters, respectively. The crystal lattice interactions were correlated to Hirshfeld surface analysis (HSA) calculations. Calculations of the Mulliken Atomic Charge (MAC), Natural Population Analysis (NPA), Global reactivity descriptors (GRD), and Molecular Electrostatic Potential (MEP) quantum parameters were performed to support the XRD/HSA interactions result. Analysis of the predicted Density of States (DOS), molecular orbital, and time-dependent density functional theory (TD-DFT) calculations have been combined to explain the experimental UV-vis spectra and electron transfer behavior in [NՈNBF2] complex using MeOH and other four solvents.

Synthesis and Evaluation of Thymol-Based Synthetic Derivatives as Dual-Action Inhibitors against Different Strains of H. pylori and AGS Cell Line

Following a similar approach on carvacrol-based derivatives, we investigated the synthesis and the microbiological screening against eight strains of H. pylori, and the cytotoxic activity against human gastric adenocarcinoma (AGS) cells of a new series of ether compounds based on the structure of thymol. Structural analysis comprehended elemental analysis and 1H/13C/19F NMR spectra. The analysis of structure–activity relationships within this molecular library of 38 structurally-related compounds reported that some chemical modifications of the OH group of thymol led to broad-spectrum growth inhibition on all isolates. Preferred substitutions were benzyl groups compared to alkyl chains, and the specific presence of functional groups at para position of the benzyl moiety such as 4-CN and 4-Ph endowed the most anti-H. pylori activity toward all the strains with minimum inhibitory concentration (MIC) values up to 4 µg/mL. Poly-substitution on the benzyl ring was not essential. Moreover, several compounds characterized by the lowest minimum inhibitory concentration/minimum bactericidal concentration (MIC/MBC) values against H. pylori were also tested in order to verify a cytotoxic effect against AGS cells with respect to 5-fluorouracil and carvacrol. Three derivatives can be considered as new lead compounds alternative to current therapy to manage H. pylori infection, preventing the occurrence of severe gastric diseases. The present work confirms the possibility to use natural compounds as templates for the medicinal semi-synthesis.

Synthesis of π-Conjugated Polymers Containing Benzotriazole Units via Palladium-Catalyzed Direct C-H Cross-Coupling Polycondensation for OLEDs Applications

Four D-π-A conjugated polymers, namely P1–P4, which contain benzotriazole building blocks in their backbone as acceptor, are synthesized via palladium-catalyzed direct C-H cross-coupling polycondensation of 5,6-difluorobenzotriazole with different thiophene derivatives, including 3-octylthiophene, 2,2’-bithiophene, thieno[3,4-b][1,4]dioxine, and 4,4-dioctyl-4H-silolo-[3,2-b:4,5-b’]dithiophene as donor units, respectively. Taking the polymer P1 as an example, the chemical structure of the polymer is demonstrated by 1H and 19F NMR spectra. The optical, electrochemical, and thermal properties of these polymers are assessed by UV–vis absorption and fluorescence spectroscopy, cyclic voltammetry (CV), and thermal gravimetric analysis (TGA), respectively. DFT simulations of all polymers are also performed to understand their physicochemical properties. Furthermore, P1 and P2, which have relatively higher molecular weights and better fluorescent quantum efficiency than those of P3 and P4, are utilized as lighting emitters for organic light-emitting diodes (OLEDs), affording promising green and red luminescence with 0.07% and 0.14% of maximum external quantum efficiency, respectively, based on a device with an architecture of ITO/PEDOT:PSS/PTAA/the polymer emitting layer/TPBi/LiF/Al.

Enhanced Ca2+ Influx in Mechanically Distorted Erythrocytes: Measurements with 19F Nuclear Magnetic Resonance Spectroscopy

We present the first direct nuclear magnetic resonance (NMR) evidence of enhanced entry of Ca2+ ions into human erythrocytes (red blood cells; RBCs) when these cells are mechanically distorted. For this we loaded the RBCs with the fluorinated Ca2+ chelator, 1,2-bis(2-amino-5fluorophenoxy)ethane-N,N,N ′ ,N ′ -tetraacetic acid (5FBAPTA), and recorded 19F NMR spectra. The RBCs were suspended in gelatin gel in a special stretching/compression apparatus. The 5FBAPTA was loaded into the cells as the tetraacetoxymethyl ester; and 13C NMR spectroscopy with [1,6-13C]D-glucose as substrate showed active glycolysis albeit at a reduced rate in cell suspensions and gels. The enhancement of Ca2+ influx is concluded to be via the mechanosensitive cation channel Piezo1. The increased rate of influx brought about by the activator of Piezo1, 2-[5-[[(2,6-dichlorophenyl)methyl]thio]-1,3,4-thiadiazol-2-yl]-pyrazine (Yoda1) supported this conclusion; while the specificity of the cation-sensing by 5FBAPTA was confirmed by using the Ca2+ ionophore, A23187.

Synthesis and Biological Evaluation of Carvacrol-Based Derivatives as Dual Inhibitors of H. pylori Strains and AGS Cell Proliferation

This study reports on the synthesis, structural assessment, microbiological screening against several strains of H. pylori and antiproliferative activity against human gastric adenocarcinoma (AGS) cells of a large series of carvacrol-based compounds. Structural analyses consisted of elemental analysis, 1H/13C/19F NMR spectra and crystallographic studies. The structure-activity relationships evidenced that among ether derivatives the substitution with specific electron-withdrawing groups (CF3 and NO2) especially in the para position of the benzyl ring led to an improvement of the antimicrobial activity, whereas electron-donating groups on the benzyl ring and ethereal alkyl chains were not tolerated with respect to the parent compound (MIC/MBC = 64/64 µg/mL). Ester derivatives (coumarin-carvacrol hybrids) displayed a slight enhancement of the inhibitory activity up to MIC values of 8–16 µg/mL. The most interesting compounds exhibiting the lowest MIC/MBC activity against H. pylori (among others, compounds 16 and 39 endowed with MIC/MBC values ranging between 2/2 to 32/32 µg/mL against all the evaluated strains) were also assayed for their ability to reduce AGS cell growth with respect to 5-Fluorouracil. Some derivatives can be regarded as new lead compounds able to reduce H. pylori growth and to counteract the proliferation of AGS cells, both contributing to the occurrence of gastric cancer.

Formulation Composition and Process Affect Counterion for CSP7 Peptide

Counterions commonly remain with peptides in salt form after peptide purification. In animal and human studies, acetate counterions are a safer and more acceptable choice for peptides than others (e.g., trifluoroacetate counterions). Various salt forms of caveolin-1 scaffolding domain (CSP7) affect counterion volatilization. The development of lyophilized formulations containing volatile compounds is a challenge because these compounds sublimate away during the process. This work aims to investigate the effect of excipients and lyophilization parameters on the preservation of volatile compounds after lyophilization. The peak areas obtained from 1H and 19F NMR spectra were used to calculate the molar ratio of counterions to CSP7. We found that the pH modifier excipient had the greatest impact on the loss of counterions. By optimizing the molar ratio of bulking agent to CSP7, volatile compounds can be preserved after lyophilization. Higher chamber pressure during lyophilization can lower the sublimation rate of volatile compounds. Moreover, the loss of volatile compounds affects the stability of CSP7 due to the pH shift of reconstituted solutions, thereby causing peptide aggregation. The optimization of the formulation and processing helps preserve volatile compounds, thus minimizing the pH change of reconstituted solutions and maintaining the stability of peptide.

Physical chemistry CeF4 complexes in organic solvents

The first complexes of cerium tetrafluoride in solutions were investigated by 19F NMR and IR spectroscopy. The temperature dependence of the 19F NMR spectra was, studied and it was concluded that mobile equilibrium exists between the molecular adduct and singly charged ionic forms, including geometric isomers. The static probability of stereoisomer formation [CeF4(dmso)4] was calculated using the square antiprism configuration and, based on the relative intensity of the 19F NMR resonance signals, they were assigned to possible stereoisomers. Quantum-chemical calculations of the structure of the isomer [CeF4(dmso)4], the isomer [CeF3(dmso)5]+ and [CeF5(dmso)3]-, showing their thermodynamic stability, were performed.