Helicity is expressed differently in ortho- and para-fused acenes-helicenes and twistacenes, respectively. While the extent of helicity is constant in helicenes, it can be tuned in twistacenes, and the handedness of flexible twistacenes is often determined by more rigid helicenes. Here, we combine helicenes with rigid twistacenes consisting of a tunable degree of twisting, forming helitwistacenes. While the X-ray structures reveal that the connection does not affect the helicity of each moiety, their electronic circular dichroism (ECD) and circularly polarized luminescence (CPL) spectra are strongly affected by the helicity of the twistacene unit, resulting in solvent-induced sign inversion. ROESY NMR and TD-DFT calculations support this observation, which is explained by differences in the relative orientation of the helicene and twistacene moieties.

We present a comprehensive study on the conformational behavior of diversely substituted 4-fluorotetrahydrothiopyran derivatives. Through quantum chemical simulations including DFT as well as NBO and NPA analysis, we elucidate the pivotal role of electrostatic interactions, occasionally complemented by hyperconjugative interactions, in stabilizing axial fluorine conformers. Less polar conformers were occasionally obtained, attributed to the interplay of electrostatic and hyperconjugative interactions. Experimental validation through NMR spectroscopy aligns with the computational analysis, thus providing a coherent understanding of the structural dynamics of these compounds. Electrostatic interactions played a significant role in stabilizing the axial fluorine orientation of fluorinated tetrahydrothiopyran, occasionally supported by stereoelectronic interactions. These combined forces were observed to stabilize less polar conformers of fluorinated tetrahydrothiopyrans even in polar solutions. Both experimental and computational investigations were thoroughly conducted on a variety of fluorinated tetrahydrothiopyran derivatives. image

The coordination chemistry of sulfonium cations, dormant since the early eighties, was recently revived when we reported the synthesis and characterization of the first Rh(I) and Pt(II) pincer sulfonium complexes. With the Pt(II) complexes, we had noticed the hemilability of our sulfonium pincer ligands, further explored here. This hemilability led to mononuclear bidentate complexes with both the aromatic and aliphatic sulfonium ligands. With the latter, due to its flexibility, dimeric structures of two different kinds were also allowed. The more rigid aromatic backbone adopted only a mononuclear bidentate mode, leading to a dynamic equilibrium between two asymmetric geometries. Computational study of this process predicted a local energy minimum for a pincer sulfonium-PtCl complex. However, the activation energy of its formation, as a possible intermediate, was found to be too high and indeed was not observed experimentally. Nevertheless, such PtCl complex was prepared and characterized by XRD. Although its S-Pt bond was significantly shorter than in its PtMe analog, the former was easily dissociated in coordinating solvents. It seems that lowering the dz2 orbital in this complex by strong π-back donation, renders the Pt(II) nucleus more susceptible to nucleophilic attacks. This comprehensive study should lay the ground for future applications of pincer sulfonium-Pt(II) complexes in π-acid catalysis.

Most routine 1H NMR spectroscopy references the chemical shift of TMS to zero. However, its chemical shift varies with solvent and environmental conditions. Chemical shifts and magnetic susceptibilities of TMS and several NMR solvents are accurately measured over a range of temperatures. Methods for improving the measurements of chemical shifts and magnetic susceptibilities are developed and demonstrated. This makes it possible to compare chemical shifts of compounds between solvents, improving the accuracy of solvent effect measurements. The effects of polarizability and aromaticity on the chemical shift of TMS are shown. The molar magnetic susceptibilities of the deuterated solvents are similar to those of the regular protiated solvents.

The C-13 signals of adamantane are used as a chemical shift standard for solid-state NMR. Its chemical shifts are measured to greater accuracy than previously reported and over a temperature range from-2 to 70 degrees C. Combining the chemical shifts of adamantane's two NMR signals gives an accurate chemical shift over the whole temperature range without need for measuring the temperature directly. The difference between the chemical shifts gives the approximate temperature. The chemical shift of the adamantane CH signal at 25 degrees C is 37.777, sigma = 0.003 ppm. (C) 2022 Elsevier Inc. All rights reserved.

Final program, abstracts, and information about the 61st annual meeting of the Rocky Mountain Conference on Magnetic Resonance, co-endorsed by the Colorado Section of the American Chemical Society and the Society for Applied Spectroscopy. Held in Copper Mountain, Colorado, July 25-29, 2022.

Thallium chemical shifts are very sensitive to chemical and physical conditions. This makes accurate chemical shift referencing difficult. Therefore, chemical shifts are usually referenced to the H-1 reference multiplied by a standard factor. However, past papers are referenced to TlNO3 solution in water at infinite dilution. The chemical shift of TlNO3 at infinite dilution is measured accurately and found to be -22.16 and 0.75 ppm for Tl-203 and Tl-205, respectively relative to the standard frequency ratios to proton. The behavior of thallium chemical-shift with concentration and temperature are determined and discussed in relation to the degree of ionic association. (C) 2021 Elsevier Inc. All rights reserved.

Titanium(IV) complexes of diaminobis(phenolato)-bis(alkoxo) ligands are promising anticancer drugs, showing marked in-vivo efficacy with no toxic side-effects in mice, hence, it is of interest to elucidate their mechanism of action. Herein, we employed a fluoro-substituted derivative, FenolaTi, for mechanistic analysis of the active species and its cellular target by quantitative 19F NMR detection to reveal its biodistribution and reactivity in extracellular and intracellular matrices. Upon administration to the serum-containing medium, FenolaTi interacted with bovine serum albumin. 20 h post administration, the cellular accumulation of FenolaTi derivatives was estimated as 37% of the administered compound, in a concentration three orders-of-magnitude higher than the administered dose, implying that active membrane transportation facilitates cellular penetration. An additional 19% of the administered dose that was detected in the extracellular environment had originated from post-apoptotic cells. In the cell, interaction with cellular proteins was detected. Although some intact Ti(IV) complex localized in the nucleus, no signals for isolated DNA fractions were detected and no reactivity with nuclear proteins was observed. Interestingly, higher accumulation of FenolaTi-derived compounds in the endoplasmic reticulum (ER) and interaction with proteins therein were detected, supporting the role of the ER as a possible target for cytotoxic bis(phenolato)-bis(alkoxo) Ti(IV) complexes.

Usually a dedicated susceptometer is needed to measure diamagnetism accurately. An NMR spectrometer is more readily available in most chemistry departments but till now has been inaccurate for measuring diamagnetism. An improved NMR method is introduced to measure the magnetic susceptibility, or diamagnetism with similar absolute accuracy as other methods. This is achieved by accurate modelling of the NMR sample shape and response profile of the probe. The new method is validated by comparing the measured diamagnetism of water against the literature standard to within 0.05%. As a first example of its application, the diamagnetism of CDCl3 was measured over a range of temperatures and used to reanalyze earlier measurements of the variation of the chemical shift of tetramethylsilane in CDCl3 against 3He gas. This improved on the accuracy and reliability of the result and will allow, for the first time, accurate studies of the absolute effect of temperature on chemical shift.

The accurate dissection of binding energies into their microscopic components is challenging, especially in solution. Here we study the binding of noble gases (He-Xe) with the macrocyclic receptor cucurbit[5]uril in water by displacement of methane and ethane as 1H NMR probes. We dissect the hydration free energies of the noble gases into an attractive dispersive component and a repulsive one for formation of a cavity in water. This allows us to identify the contributions to host-guest binding and to conclude that the binding process is driven by differential cavitation energies rather than dispersion interactions. The free energy required to create a cavity to accept the noble gas inside the cucurbit[5]uril is much lower than that to create a similarly sized cavity in bulk water. The recovery of the latter cavitation energy drives the overall process, which has implications for the refinement of gas-storage materials and the understanding of biological receptors.

Omega fatty acids, mainly the triglyceride of docosahexaenoic acid (TG-DHA), are considered important nutraceuticals. These compounds are water-insoluble and their transport across membranes depends on their carriers. Dendrimers are known as drug carriers across cell membranes and also as permeation enhancers. The solubilization of TG-DHA and dendrimer into a microemulsion (ME) system serving as a carrier could be used for a targeted delivery in the future. The interactions between TG-DHA and second generation poly(propyleneimine) dendrimers (PPI-G2) and their effect on structural transitions of ME were explored along the water dilution line using electron paramagnetic resonance and pulsed-gradient spin-echo NMR along with other analytical techniques. The microviscosity, order parameter, and micropolarity of all studied systems decrease upon water dilution. Incorporation of TG-DHA reduces the microviscosity, order, and micropolarity, whereas PPI-G2 leads to an increase in these parameters. The effect of PPI-G2 is more pronounced at relative high contents (1 and 5wt%) where PPI-G2 interacts with the hydrophilic headgroups of the surfactants. In the macroscale, the effects of TG-DHA and PPI-G2 differ mostly in the bicontinuous region, where macroviscosity increases upon TG-DHA incorporation and decreases upon solubilization of 5wt% PPI-G2. From DSC measurements it was concluded that in the presence of TG-DHA the PPI-G2 is intercalated easily at the interface.

NMR chromatography is a promising and superior alternative to NMR spectroscopy for analyzing mixtures since it simultaneously separates the spectra of the compounds and supplies information about their structure. This implies that there is no need for extraction, purification or synthesis of standards, that are expensive, time consuming and usually impractical. The main aim of NMR chromatography is to increase the differences in the diffusivities of different analytes in a mixture, allowing them to be more easily and reliably identified.The selection of surfactants and other components of microemulsions for the best performance as NMR chromatographic media was studied. Attention was focused on the selection of the proper cosolvent in three types of water-dilutable microemulsions: two anionic (deuterated ionic and the previously published fluorinated ionic) and one nonionic (undeuterated Tween-based). The diffusivities of several analytes are compared. The study also examines the effect of dilution and determines the best compositions for the NMR chromatography performance.For the anionic microemulsions, 1-butanol was found to be the most promising cosurfactant in the deuterated system 1-butanol-d(10):toluene-d(8):SDS-d(25) in a 6:3:1 weight-ratio diluted by D2O. This composition, diluted with a 85 wt% D2O, formed a microemulsion that was even stable at relatively elevated temperatures (70 degrees C) and can serve as good medium for chromatographic NMR. Another possibility that was studied consists of nonionic-based microemulsions of isopropyl alcohol (IPA) in IPA:toluene:Tween 20 that could also be easily diluted indefinitely with water. IPA was found to be a very efficient cosurfactant at resolving diffusivities of all the components. However, the lack of availability of deuterated Tween makes it impractical for use as an NMR chromatography formulation. (C) 2016 Elsevier B.V. All rights reserved.

In our previous report we suggested a new analytical tool, high accuracy NMR chemical shift corrected for bulk magnetization as a supplementary tool to study structural transitions and droplet size and shape of dilutable microemulsions. The aim of this study was to show the generality of this technique and to demonstrate that in almost any type of microemulsion this technique provides additional valuable structural information. The analysis made by the technique adds to the elucidation of some structural aspects that could not be clearly determined by other classical techniques. Therefore, in this part we are extending the study to three additional systems differing in the type of oil phase (toluene and cyclohexane), the nature of the surfactants (anionic and nonionic), and other microemulsion characteristics. We studied sodium dodecyl sulfate (SDS)-based anionic microemulsions with different oils and a nonionic microemulsion based on Tween 20 as the surfactant and toluene as the oil phase. All the microemulsions were fully dilutable with water. We found that the change in the slope of chemical shift against dilution reflects phase transition points of the microemulsion (O/W, bicontinuous, W/O). Chemical shift changes were clearly observed with the transition between spherical and non-spherical (wormlike, etc.) droplet shapes. We compared the interaction of cyclohexane and toluene and used the anisotropic effect of toluene's ring current to determine its preferred orientation relative to SDS. Chemical shifts of the microemulsion components are therefore a useful addition to the arsenal of techniques for characterizing microemulsions.

In microemulsions, changes in droplet size and shape and possible transformations occur under various conditions. They are difficult to characterize by most analytical tools because of their nano-sized structure and dynamic nature. Several methods are usually combined to obtain reliable information, guiding the scientist in understanding their physical behavior. We felt that there is a need for a technique that complements those in use today in order to provide more information on the microemulsion behavior, mainly as a function of dilution with water. The improvement of NMR chemical shift measurements independent of bulk magnetization effects makes it possible to study the very weak intermolecular chemical shift effects. In the present study, we used NMR high resolution magic angle spinning to measure the chemical shift very accurately, free of bulk magnetization effects. The chemical shift of microemulsion components is measured as a function of the water content in order to validate the method in an interesting and promising, U-type dilutable microemulsion, which had been previously studied by a variety of techniques. Phase transition points of the microemulsion (O/W, bicontinuous, W/O) and changes in droplet shape were successfully detected using high-accuracy chemical shift measurements. We analyzed the results and found them to be compatible with the previous studies, paving the way for high-accuracy chemical shifts to be used for the study of other microemulsion systems. We detected two transition points along the water dilution line of the concentrate (reverse micelles) corresponding to the transition from swollen W/O nano-droplets to bicontinuous to the O/W droplets along with the changes in the droplets' sizes and shapes. The method seems to be in excellent agreement with other previously studied techniques and shows the advantage of this easy and valid technique.

The NMR chromatography method is applied to a class of molecules with similar physical properties. We correlate the separation ability of microemulsions to the physical properties of the analyzed molecules. Flavor and aroma compounds are very widespread. Compositional analysis is in many cases tedious. Any new method of analysis is always useful and challenging. Here we show a new application to a class of fragrance molecules, with only a moderate variation in their chemical and physical characteristics. Up to 11 selected compounds in one mixture are resolved in one spectrum by NMR chromatography, despite the similarity of the compounds. The differences between O/W and W/O microemulsions and their resolution mechanism as applied to fragrance molecules are explained in terms of hydrophilicity and lipophilicity and effective critical packing parameters of the microemulsions. The observed diffusion rates are shown to correlate with solvation parameters. These results can be used to estimate the diffusion rates of molecules to be separated, allowing selection of the microemulsion or NMR chromatography solvent appropriate for each specific application.

NMR spectroscopy is an excellent tool for structural analysis of pure compounds. However, for mixtures, it performs poorly because of overlapping signals. Diffusion ordered NMR. spectroscopy (DOSY) can be used to separate the spectra of compounds with widely differing molecular weights, but the separation is usually insufficient. NMR "chromatographic" methods have been developed to increase the diffusion separation but these usually introduced solids into the NMR sample that reduce resolution. Using nanostructured dispersed media, such as microemulsions, eliminates the need for suspensions of solids and brings NMR chromatography into the mainstream of NMR analytical techniques. DOSY was used in this study to resolve spectra of mixtures with no increase in line-width as compared to regular solutions. Components of a mixture are differentially dissolved into the separate phases of the microemulsions. Several examples of previously reported microemulsions and those specifically developed for this purpose were used here. These include a fully dilutable microemulsion, a fluorinated microemulsion, and a fully deuterated microemulsion. Log(diffusion) difference enhancements of up to 1.7 orders of magnitude were observed for compounds that have similar diffusion rates in conventional solvents. Examples of commercial pharmaceutical drugs were also analyzed via this new technique, and the spectra of up to six components were resolved from one sample.

Nanoparticles of novaluron, a water-insoluble insecticide, were prepared by a novel method, based on a direct conversion of O/W microemulsions containing pesticide and volatile solvents, into powders. The conversion of nanoparticles into powder was achieved by rapid evaporation of all the liquids in the microemulsion by spray drying. The microemulsions were evaluated by SAXS, self diffusion NMR, conductivity, and viscosity. The droplet size was approximately 6nm, and the novaluron particle size, after redispersion and evaluation by DLS, was 200±50nm. These particles consisted of aggregates of nanoparticles (30–100nm), as viewed by Cryo-TEM. Electron diffraction and XRD showed that the nanoparticles were amorphous indicating a possible improved bioactivity. The stability of the dispersed nanoparticles was evaluated by following particle size by DLS for a period of time, revealing a slight increase in particle size despite the high value of zeta potential. In vivo experiments carried out with Egyptian cotton leafworm Spodoptera littoralis larvae indicated that the toxicity of nanoparticles of novaluron resembled that of the commercial formulation.

Silica is used as an important component for NMR "chromatography". In this study the effect of the binding strength to silica of a variety of compounds on their diffusion rate is measured for the first time. Over two orders of magnitude of diffusion difference enhancement was obtained in the presence of silica for some compounds. An explanation of the enhancement is given that also allows one to predict the "chromatographic" behavior of new compounds or mixtures. The binding strength is divided into categories of weakly bound, singly bound and multiply bound. Carboxylates, sulfonates, and diols are found to be particularly strongly bound and to diffuse up to 2½ orders of magnitude more slowly in the presence of silica.