Solution NMR Spectra Research Articles

Novel Thiourea Ligands—Synthesis, Characterization and Preliminary Study on Their Coordination Abilities

Two series of polydentate N,O,S-ligands containing thiourea fragments attached to a p-cresol scaffold, unsymmetrical mono-acylated bis-amines and symmetrical bis-thioureas, are obtained by common experiments. It is observed that the reaction output is strongly dependent on both bis-amine and thiocarbamic chloride substituents. The products are characterized by 1D and 2D NMR spectra in solution and by single crystal XRD. A preliminary study on the coordination abilities of selected products is performed by ITC at around neutral media.

The Liebeskind-Srogl Cross-Coupling Reaction as a Crucial Step in the Synthesis of New Squaramide-Based Antituberculosis Agents.

The synthesis of an extensive series of new squaramides with high potential in treating drug-resistant tuberculosis employing the Liebeskind-Srogl cross-coupling reaction is presented. Using the protocol given and various substrates, we assessed the scope and limitations of our methodology and prepared an extensive range of desired compounds. Moreover, 1H NMR spectra in solution show the presence of two rotational conformers (rotamers) in special cases. The results of antimycobacterial activity demonstrate the highly selective substrate specificity of the tested squaramides, requiring an efficient and widely applicable synthetic approach needed for the discovery of lead compounds. Our synthetic strategy confirms the versatility of squaramides that can be easily transformed into diverse functionalized molecules.

Explorations of the chemical constitution and aqueous solution status of caries-arresting silver(I)-diammine fluoride and silver(I)-fluoride products using high-resolution 19F NMR analysis. Spectroscopic and SEM investigations of their interactions with human saliva: evidence for the in vivo salivary-catalysed autoconstruction of Ag/AgCl-based nanoparticles (IV-SCAN)-part I.

Silver(I)-diammine fluoride (SDF) and silver(I)-fluoride (SF) complexes have been successfully employed for the arrest of dental caries for many years. However, to date there are very few studies available reporting on the molecular structural compositional and solution status of these agents [typically applied as highly-concentrated 38% (w/v) solutions]. Here, we explored the solution status and chemical constitution of commercially-available SDF and SF products, and secondly investigated the multicomponent interplay of these products with biomolecules present in intact human whole-mouth salivary supernatants (WMSSs) in vitro. High-resolution 19F NMR analysis was employed to explore SDF and SF product solutions, and to determine WMSS fluoride (F-) concentrations, whereas ammonia (NH3) release form SDF was tracked by 1H NMR spectroscopy. SEM and thin-film FTIR-ATR analyses were employed to explore the atomic and molecular compositions of sequentially-generated AgCl deposits and chromophoric Ag/AgCl nanoparticles (CSNPs); the time-dependent generation of the latter was followed spectrophotometrically. 19F NMR spectra of aqueous SF solutions contained a very broad F- signal (Δv1/2 70 Hz), demonstrating that much of its solvated F- content was rapidly exchanging with Ag(I) on the NMR timescale, but those of SDF had a much sharper resonance, similar to that of "free" F- (4 Hz). Moreover, further NMR results revealed that a popular SDF product contained high molar excesses of both F- and NH3. Treatment of WMSSs with SDF and SF generated an off-white precipitate, which slowly developed into CSNPs at 23°C; SEM demonstrated high contents of both silver and chloride in this material (ca.1:1 atomic content ratio). FTIR-ATR analysis found that the CSNPs formed contained a range of salivary biomolecules, which appear to encapsulate the Ag/AgCl core (significant thiocyanate contents were also found). In conclusion, NMR results acquired demonstrated that SF, but not SDF, product solutions feature rapidly-exchanging F - between its "free" and Ag(I)-bound forms, and that SDF contains large excesses of both F- and its NH3 ligands. Characterised AgCl deposits and CSNPs were sequentially produced from the interactions of these complexes with WMSS biomolecules. In view of their well-known microbicidal and cariostatic properties, the observed autobioconstruction of CSNPs involving salivary catalysis is of much therapeutic significance.

Functionalization of 2-Mercapto-5-methyl-1,3,4-thiadiazole: 2-(ω-Haloalkylthio) Thiadiazoles vs. Symmetrical Bis-Thiadiazoles.

A study on the functionalisation of 2-mercapto-5-methyl-1,3,4-thiadiazole has been conducted, yielding two series of products: 2-(ω-haloalkylthio)thiadiazoles and symmetrical bis-thiadiazoles, with variable chain lengths. The experimental conditions were optimised for each class of compounds by altering the base used and the reagents' proportions, leading to the development of separate protocols tailored to their specific reactivity and purification needs. The target halogenide reagents and bis-thiadiazole ligands were obtained either as single products or as mixtures easily separable by chromatography. Characterisation of the products was performed using 1D and 2D NMR spectra in solution, complemented by single crystal X-ray diffraction (XRD) for selected samples, to elucidate their structural properties.

REACTION OF 1-ANTIPYRYL-4-AROYL-5-METHOXYCARBONYL-1H-PYRROLE-2,3-DIONES WITH ARYLAMINES

In this work, we investigated the reaction of 1-antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with aromatic amines, which resulted in the production of 1-antipyryl-5-arylamino-4-aroyl-3-hydroxy-5-methoxycarbonyl-1H-pyrrol-2-ones. The reactivity of previously synthesized antipyryl-substituted monocyclic 1H-pyrrole-2,3-diones was studied using the example of reactions with NH-mononucleophilic reagents such as aniline, p-toluidine and 1-naphthylamine. The studied 1-antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones are generated by boiling 1-antipyryl-4-aroyl-3-hydroxy-5-chloro -1,5-dihydro-1H-pyrrol-2-ones in an absolute toluene environment for 20-30 min, followed by distillation of part of the solvent and hydrogen chloride. Arylamines were added to the resulting concentrated hot solution in a 1:1 ratio. The resulting adduct is a light yellow crystalline substance. Apparently, the reaction of 1-antipyryl-4-aroyl-5-methoxycarbonyl-1H-pyrrole-2,3-diones with aromatic amines occurs through a nucleophilic attack by the amino group at the most electron-deficient position of the pyrrole ring. For all synthesized compounds, physical properties are given, such as solubility, melting points. The elemental composition was determined, and the structure of the molecules is established using NMR and IR spectroscopy. The 1H NMR spectra of solutions of the obtained compounds contain two singlets of the protons of the methyl groups of the antipyryl fragment in the region of 2.17-2.18 ppm. and 3.17-3.19 ppm, singlet of protons of the methoxycarbonyl group in the region of 3.69-3.71 ppm, singlet of protons of the amino group in the region of 6.53-6.68 ppm (1H, NH). The IR spectra of the products contain stretching vibrations of the ketone group in the region of 1653-1658 cm-1, the ester carbonyl group in the region of 1716-1718 cm-1, as well as a signal in the region of 3375-3388 cm-1 (NH). The described interaction proceeds quickly and with high yields. The reaction is a convenient preparative method for the synthesis of 1-antipyryl-5-arylamino-4-aroyl-3-hydroxy-5-methoxycarbonyl-1H-pyrrol-2-ones, which are of interest for further study of various types of biological activities, such as antimicrobial, anti-inflammatory, analgesic and others.

Polydentate N,O-Ligands Possessing Unsymmetrical Urea Fragments Attached to a p-Cresol Scaffold.

In this study, three series of polydentate N,O-ligands possessing unsymmetrical urea fragments attached to a p-cresol scaffold are obtained, namely mono- and bi-substituted open-chain aromatics, synthesised using a common experiment, as well as fused aryloxazinones. Separate protocols for the preparation of each series are developed. It is found that in the case of open-chain compounds, the reaction output is strongly dependent on both bis-amine and carbamoyl chloride substituents, while oxazinones can be effectively obtained via a common protocol. The products are characterized via 1D and 2D NMR spectra in solution and using single-crystal XRD. A preliminary study on the coordination abilities of the products performed via ITC shows that there are no substantial interactions in the pH range of 5.0-8.5 in general.

Spectroscopic, X-ray crystallographic and preliminary biological screening study of unsymmetrical diphosphinoamine (PNP’) and monodentate aminophosphine (PNH) ligands coordinated to Pt(II)

An efficient and simple synthetic route to a new class of unsymmetrical diphosphinoamine {PNP'=(o-Tol)2P'N(R1)P(R2)2} and monophosphinoamine {(o-Tol)2P(R1)NH} ligands are presented, which allowed the manipulation of the R1 substituents on the amine as well as the cyclic R2 substituents on the phosphorus atom. The unsymmetrical (o-Tol)2P'N(R1)P(R2)2 ligands {R1 = p-MePh (A), o-MePh (B), p-ClPh (C) or p-FPh (D)} and their coordination to a Pt(II) metal center as [Pt{κ2-(P,P')(PNP')}Cl2] (3N; N = A, C, D) type of complexes are presented. In addition, monophosphinoamine ligands {(o-Tol)2P(R1)NH} are described, yielding the cisplatin analogue cis-[Pt((o-Tol)2P(p-MePh)NH)2Cl2] (2A), and trans-[Pt((o-Tol)2P(o-MePh)NH)2Cl2] (2B). Five single crystal X-ray studies are reported (2A, 2B, 3A, 3C, 3D), together with a detailed 31P NMR spectroscopy study. The electrostatic and steric repulsions on the ortho-CH3 on these types of ligands induces restricted rotation as seen by solution NMR spectra of all free ligands. The presence of two stable conformers (syn,syn,anti) and (syn,syn,syn) for the free PNP' ligands is illustrated, both in solution and solid state (31P MAS NMR). Moreover, in the synthesis, a scrambling/disproportionation of the unsymmetrical PNP' ligand is observed, yielding some 20% of the corresponding symmetrical PNP nucleophiles. However, the (syn,syn,anti)-conformer disappear upon coordination to the Pt(II), as required by the cis-[Pt(PNP')Cl2] complexes. The two Pt-PN complexes cis-[Pt((o-Tol)2P(p-MePh)NH)2Cl2] (2A) and trans-[Pt((o-Tol)2P(o-MePh)NH)2Cl2] (2B) were evaluated for biological activity to ascertain whether the stereo chemistry on these would show more activity as analogous cisplatin and derivatives. Additionally, 2A and 2B were also screened for antimicrobial activity. Significant microbial inhibition against Gram-positive Staphylococcus aureus and two Fungi Cryptococcus neoformans and Candida albicans was found for complex trans-[Pt(p-MePh-PNH)2Cl2] (2A), while the cytotoxicity evaluation of 2A against HEK293 human embryonic kidney cells displayed a moderate activity CC50 of 18.1 μM.

Solution NMR of Battery Electrolytes: Assessing and Mitigating Spectral Broadening Caused by Transition Metal Dissolution.

NMR spectroscopy is a powerful tool that is commonly used to assess the degradation of lithium-ion battery electrolyte solutions. However, dissolution of paramagnetic Ni2+ and Mn2+ ions from cathode materials may affect the NMR spectra of the electrolyte solution, with the unpaired electron spins in these paramagnetic solutes inducing rapid nuclear relaxation and spectral broadening (and often peak shifts). This work establishes how dissolved Ni2+ and Mn2+ in LiPF6 electrolyte solutions affect 1H, 19F, and 31P NMR spectra of pristine and degraded electrolyte solutions, including whether the peaks from degradation species are at risk of being lost and whether the spectral broadening can be mitigated. Mn2+ is shown to cause far greater peak broadening than Ni2+, with the effect of Mn2+ observable at just 10 μM. Generally, 19F peaks from PF6 - degradation species are most affected by the presence of the paramagnetic metals, followed by 31P and 1H peaks. Surprisingly, when NMR solvents are added to acquire the spectra, the degree of broadening is heavily solvent-dependent, following the trend of solvent donor number (increased broadening with lower solvent donicity). Severe spectral broadening is shown to occur whether Mn is introduced via the salt Mn(TFSI)2 or is dissolved from LiMn2O4. We show that the weak 19F and 31P peaks in spectra of electrolyte samples containing micromolar levels of dissolved Mn2+ are broadened to an extent that they are no longer visible, but this broadening can be minimized by diluting electrolyte samples with a suitably coordinating NMR solvent. Li3PO4 addition to the sample is also shown to return 19F and 31P spectral resolution by precipitating Mn2+ out of electrolyte samples, although this method consumes any HF in the electrolyte solution.

Determining the oxidation states of dissolved transition metals in battery electrolytes from solution NMR spectra.

Dissolved transition metal ions can induce peak shifts in the NMR spectra of degraded battery electrolytes. Here, we exploit this staightforward, accessible method to calculate magnetic moments for dissolved Ni2+, Mn2+, Co2+, and Cu2+; subsequent analysis of dissolution from LiMn2O4, LiNiO2, and LiNi0.5Mn1.5O4 shows that the dissolved metals are exclusively divalent.

Glucose exchange parameters in a subset of physiological conditions.

The chemical exchange of labile protons of the hydroxyl groups can be exploited in a variety of magnetic resonance experiments to gain information about the groups and their physicochemical environment. The exchangeable -OH protons provide important contributions to the T2 of water signals thus contributing to the T2-weighted contrast of MRI images. This exchange can be exploited more specifically and sensitively in chemical exchange saturation transfer (CEST) or longitudinal rotating frame relaxation (T1,ρ) experiments. Since glucose is omnipresent in living organisms, it may be seen as a rather universal probe. Even though the potential was first recognized many years ago, practical use has remained scarce due to numerous challenges. The major limitation is the rather low glucose concentration in most tissues. The other obstacles are related to multiple dependencies of the exchange parameters, such as temperature, pH, and concentration of various ions that are not known in sufficient detail for glucose. Thus, we embarked on evaluating the exchange parameters of a model that included every relevant chemical site for all -OH protons in both dominant enantiomers of glucose. We have (1) obtained conventional one-dimensional proton NMR spectra of glucose solutions in suitable temperature ranges, (2) we have iterated through several exchange models with various degrees of freedom determined by the number of distinguishable -OH proton sites and compared their performance, (3) we extrapolated the parameters of the best model of physiological temperature and (4) we demonstrated the use of the parameters in virtual experiments. As the main results, (1) we have obtained the temperature dependence of exchange parameters with reliable confidence intervals in three different pH values, with two of them reaching physiological temperature, and (2) we show how the parameters can be used in virtual experiments, helping to develop new applications for glucose as an NMR/MRI probe.

Rapid prediction of full spin systems using uncertainty-aware machine learning.

Accurate simulation of solution NMR spectra requires knowledge of all chemical shift and scalar coupling parameters, traditionally accomplished by heuristic-based techniques or ab initio computational chemistry methods. Here we present a novel machine learning technique which combines uncertainty-aware deep learning with rapid estimates of conformational geometries to generate Full Spin System Predictions with UnCertainty (FullSSPrUCe). We improve on previous state of the art in accuracy on chemical shift values, predicting protons to within 0.209 ppm and carbons to within 1.213 ppm. Further, we are able to predict all scalar coupling values, unlike previous GNN models, achieving 3JHH accuracies between 0.838 Hz and 1.392 Hz on small experimental datasets. Our uncertainty quantification shows a strong, useful correlation with accuracy, with the most confident predictions having significantly reduced error, including our top-80% most confident proton shift predictions having an average error of only 0.140 ppm. We also properly handle stereoisomerism and intelligently augment experimental data with ab initio data through disagreement regularization to account for deficiencies in training data.

The Effect of Terminal Bromoalkoxy Substituents on the Photochromism of Functionalized 2H‐Chromenes

AbstractA series of 2,2‐diphenyl‐2H‐chromene derivatives bearing electron‐donating groups at the benzopyran ring have been synthesized. A significant effect of the bromoalkoxy chain length and the concentration of chromenes on the conversion of closed (CF) into open forms under UV irradiation and the equilibrium between TC (transoid‐cis) and TT (transoid‐trans) isomers in the photostationary state was found. For chromene derivatives, a sequential (CF→TC→TT) or parallel (CF→TC; CF→TT) mechanism of transformation of the closed form into an open one is possible. A high solution concentration contributes to a significant shift of the photochromic equilibrium towards the TT isomer. The proposed scheme of the ring‐opening reaction was confirmed by the analysis of the NMR spectra of acetonitrile solutions of chromene derivatives obtained by gradual irradiation. The results obtained are important for a deeper understanding of the nature of photochromic reactions.

Rheo-NMR Spectroscopy for Cryogenic-Probe-Equipped NMR Instruments to Monitor Protein Aggregation.

Cryogenic-probe-based Rheo-NMR spectroscopy is a recently developed methodology to obtain solution NMR spectra of protein samples in situ under external shear. It is applicable to atomic-resolution monitoring of protein aggregation in situ, thereby aiding understanding of the transient structural changes and state conversion of amyloidogenic proteins, which are strongly associated with the both the onset and the progression of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Here, we present detailed experimental procedures for the instrumental setup and practical tips for preparation of NMR measurement to analyze protein aggregation by this technique. This protocol will thus aid future Rheo-NMR spectroscopic studies not only of protein aggregation but also of other phenomena related to shear stress, such as shear-induced viscosity increase and shear-enhanced crystallization. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Setup of a Rheo-NMR Instrument Basic Protocol 2: Adjustment of the Vertical and Horizontal Positions of the Glass Stick Basic Protocol 3: Monitoring Protein Aggregation by Rheo-NMR Spectroscopy.

NMR Crystallographic Approach to Study the Variation of the Dynamics of Quinine and Its Quasienantiomer Quinidine

The structure and dynamics of quinine and its quasienantiomer quinidine were studied at the atomic resolution by measuring the chemical shift anisotropy (CSA) tensor and site-specific spin–lattice relaxation time. For quinine, there are three crystallographically independent molecules “a”, “b”, and “c” in an asymmetric unit since its 13C CP-MAS SSNMR spectrum features three distinct resonance peaks for certain carbon nuclei. The 13C assignments are fulfilled by DFT calculations. The experimental 13C isotropic chemical shifts well match the calculated values. These variations of isotropic chemical shift for three independent molecules are also observed by two-dimensional 13C–1H heteronuclear correlation spectroscopy (HETCOR) of quinine. The spin–lattice relaxation time, and the principal components of CSA parameters are also varied substantially for certain carbon nuclei of “a”, “b”, and “c” molecules. For quinidine, its 13C CP-MAS SSNMR spectrum is remarkably different from that of quinine despite, their almost identical solution NMR spectra. Furthermore, the remarkable change in the structure and dynamics of quasienantiomers are also observed including the steric effect of the substituent vinyl group, the variation of helical motifs, and the variation of the strength of the intermolecular hydrogen bonds. The variation of the structure and dynamics of quasienantiomers are thoroughly studied by solid-state NMR measurements. These types of studies will enrich the field of NMR crystallography.

SsPINE: Probabilistic Algorithm for Automated Chemical Shift Assignment of Solid-State NMR Data from Complex Protein Systems.

The heightened dipolar interactions in solids render solid-state NMR (ssNMR) spectra more difficult to interpret than solution NMR spectra. On the other hand, ssNMR does not suffer from severe molecular weight limitations like solution NMR. In recent years, ssNMR has undergone rapid technological developments that have enabled structure–function studies of increasingly larger biomolecules, including membrane proteins. Current methodology includes stable isotope labeling schemes, non-uniform sampling with spectral reconstruction, faster magic angle spinning, and innovative pulse sequences that capture different types of interactions among spins. However, computational tools for the analysis of complex ssNMR data from membrane proteins and other challenging protein systems have lagged behind those for solution NMR. Before a structure can be determined, thousands of signals from individual types of multidimensional ssNMR spectra of samples, which may have differing isotopic composition, must be recognized, correlated, categorized, and eventually assigned to atoms in the chemical structure. To address these tedious steps, we have developed an automated algorithm for ssNMR spectra called “ssPINE”. The ssPINE software accepts the sequence of the protein plus peak lists from a variety of ssNMR experiments as inputs and offers automated backbone and side-chain assignments. The alpha version of ssPINE, which we describe here, is freely available through a web submission form.

A new tripodal 8-hydroxyquinoline as a high sensitivity fluorescence sensor for Zn(II) in ethanol and its two morphology in solid

New tripodal ligand form two different dinuclear Zn 2+ complex in solid, but identical in solution. The strong chelate significantly increased fluorescence sensitivity toward Zn 2+ in ethanol solution. • New tripodal ligands (HL) were synthesized from 8-hydroxyquinoline and bis(pyridin-2-ylmethyl)amine. • HL forms stable Zn(II) complexes which has very strong fluorescence in ethanol. The LOD for Zn(II) fluorescence is 2.3 nM. • Symmetric/asymmetric dinuclear Zn(II) complexes with identical formulae can be isolated from CH 3 CN solution, but they are identical in solution. A new tripodal chelate HL was synthesized from tridentate chelate bis(pyridin-2-ylmethyl)amine (BPA) and 8-hydroxyquinoline (8-HQ) to increase interaction between HL and Zn 2+ and improve fluorescence sensitivity. Asymmetric and symmetric dinuclear Zn(II) complex in rod and block shape were formed in CH 3 CN with identical formula, 1 H NMR and fluorescence spectra in solution, but different IR, TG, and PXRD in solid. The fluorescence quantum yields are 0.0145 and 0.602 for HL and [ZnL] 2 2+ in ethanol respectively. LOD reached 2.3 nM Zn 2+ , which is the highest sensitivity. The 7-position functionalization of 8-HQ is critical to the strong coordination and high fluorescence sensitivity.

Crystallochemical Characterizations, Raman Spectroscopy and Studies Nuclear Magnetic Resonance (NMR) of Cu<sub>2</sub>Zn(Sn, Si)S<sub>4 </sub> Compounds for Photovoltaic Applications

In this study, Si-doped Cu2ZnSnS4 compounds (Cu2ZnSn1-xSixS4, 0 ≤ x ≤ 1) were prepared by solid state reaction method for use of materials for photovoltaic cells. The structural and spectroscopic properties of the as-prepared compounds were studied by X-ray diffraction (XRD), 119Sn, 29Si and 65Cu Magic Angle Spinning nuclear magnetic resonance (MAS NMR) and Raman spectroscopy. The Si-substitution in the Sn-site induces three different types of XRD patterns which depend largely on the Si content in the compound. For 0 ≤ x ≤ 0.5, XRD analysis reveals the presence of a pure tetragonal phase of solid solution with I-42m as a space group. Mixed tetragonal and orthorhombic phases were observed for 0.5 1 at high content of Si (x ≥ 0.8). 119Sn MAS NMR spectra show the presence of Sn/Si disorder as a function of the Si content. The 65Cu MAS NMR spectra of the quadratic solid solution confirm the presence of the two copper sites (Cu-2a and Cu-2c) at 780 ppm while in the case of the orthorhombic solid solution samples, a very broad band is observed. The optical properties were investigated of all compounds by UV-Vis diffuse reflectance and the obtained optical band gap values (1.31 to 2.43 eV) confirm a semiconductor character.

Helic[6]arene‐Based Chiral Pseudo[1]rotaxanes and [1]Rotaxanes

Chiral pseudo[1]rotaxanes and [1]rotaxanes constructed from macrocyclic arenes still remain a big challenge mainly owing to the lack of such chiral macrocycles. In this work, a new system of chiral pseudo[1]rotaxanes formed by self-inclusion of helic[6]arene containing amide linked with the terminal tertiary amines was first discovered. Based on an atom-economic stopping strategy, a pair of chiral [1]rotaxanes were conveniently obtained in almost quantitative yields by blocking the pseudo[1]rotaxanes with monobenzyl bromide of tetraphenylethene. The structures of pseudo[1]rotaxanes and [1]rotaxanes were characterized by 2D NMR spectra in solution, combined with DFT calculations. The photophysical properties further revealed the efficient chirality transfer of helic[6]arene to the tetraphenylethene moiety, compared to their unthreaded chiral isomers. The discovery of the chiral pseudo[1]rotaxanes allows for a wide and available synthesis of chiral [1]rotaxanes, and also opening a new avenue to the design of chiral supramolecular materials.

Effect of Dihydropyridine Enrichment in the Microstructure of the Palisade Layer on the Stability of Fat Nano-emulsions.

Relationship between the stability of fat nano-emulsions and the incorporated drug at the molecular level are rarely known. Herein, fat nano-emulsions containing dihydropyridine drugs were prepared and the microstructure of their palisade layers were investigated.The prepared 1.0mg/mL nimodipine nano-emulsion was found to contain 65.50% drug in the palisade layer. The increasing drug concentration led to a decrease-increase-decrease trend in centrifugal stability constant, particle size and proton nuclear magnetic resonance (1H NMR) signal intensity of the lecithin trimethyl ammonium group in the nimodipine and felodipine nano-emulsions. The 1H NMR spectra of test solutions including nano-emulsions suggest that increasing drugs penetrated into the palisade layer, resulting in the lecithin arrangement from loose to tight, and then from monolayer to bilayer. Nimodipine and felodipine nano-emulsions showed two valley values at concentrations of 0.15 and 0.75mg/mL, and 0.30 and 0.90mg/mL respectively, which indicated that the nano-emulsion has two more stable states corresponding to the tightly arranged mono- and bi-palisade layer. These two concentrations are positively correlated with lipophilicity of nimodipine and felodipine. Further, nimodipine liposomes were prepared to validate the effect of drugs on the arrangement of lecithin in the palisade layer. 1H NMR characterizations of the liposomes showed a similar profile to that of nano-emulsions. These results demonstrated that the increasing drug concentration could cause a rearrangement of lecithin in the palisade layer, thus affecting emulsion stability.

1H NMR spectra of triethylamine binary aqueous solutions as functions of concentration and temperature. The triethylamine rich phase

Triethylamine (Et3N) aqueous solutions with different weight contents of dissolved molecules (9, 18, 25, 30, and 42 wt% of Et3N) were studied for the first time by the 1H NMR method in the region of the liquid–liquid phase transition. After an interface between two phases was formed, anomalous inhomogeneous broadening of 1H NMR lines of Et3N molecules was discovered in the Et3N rich phase. The inhomogeneous character of broadening depends on the weight content of dissolved molecules and is observed up to 313 K. It is concluded that the studied systems exist in the transition region between critical and classical states.