The Conformational Behaviour of Fluorinated Tetrahydrothiopyran.

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.

Helitwistacenes-Combining Lateral and Longitudinal Helicity Results in Solvent-Induced Inversion of Circularly Polarized Light.

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.

Deaths From Unintentional Injury, Homicide, and Suicide During or Within 1 Year of Pregnancy in Philadelphia.

OBJECTIVES: To understand the effect of unintentional injuries (e.g., drug overdose), suicide, and homicide on pregnancy-associated death (death during or within 1 year of pregnancy). METHODS: We analyzed all cases of pregnancy-associated death among Philadelphia, Pennsylvania, residents from 2010 to 2014, examining cause of death, contributing factors, and history of health care use. RESULTS: Approximately half (49%; 42 of 85) of pregnancy-associated deaths were from unintentional injuries (n = 31), homicide (n = 8), or suicide (n = 3); drug overdose was the leading cause (n = 18). Substance use was noted during or around events leading to death in 46% (31 of 67) of nonoverdose deaths. A history of serious mental illness was noted in 39% (32 of 82) of nonsuicide deaths. History of intimate partner violence (IPV) was documented in 19% (15 of 77) of nonhomicide deaths. Regardless of cause of death, approximately half of all decedents had an unscheduled hospital visit documented within a month of death. CONCLUSIONS: Unintentional injury, homicide, and suicide contribute to many deaths among pregnant and recently pregnant women. Interventions focused on substance use, mental health, and IPV may reduce pregnancy-associated and pregnancy-related deaths.

Solid-state chemical-shift referencing with adamantane.

The 13C 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 °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 °C is 37.777, σ = 0.003 ppm.

Magnetic susceptibility measurement by NMR: 2. The magnetic susceptibility of NMR solvents and their chemical shifts.

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.

NMR chromatography using microemulsion systems.

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.

Thallium chemical shift referencing.

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 1H 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 203Tl and 205Tl, 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.

From medium to endoplasmic reticulum: Tracing anticancer phenolato titanium(IV) complex by 19F NMR detection.

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.

NMR spectroscopic study of the Murex trunculus dyeing process.

It is widely accepted that indigo dyes derived from Murex trunculus were used to produce the biblical dyes tekhelet and argaman. We describe a method of following the debromination of natural leucoindigos and their binding to wool using NMR spectroscopy. Debromination is observed prior to reaction with the wool and prior to oxidation. Binding to the wool is shown to occur prior to oxidation. NMR allows the dyeing process to be followed. This, in principle, could be used to correct problems during dyeing that would increase the reliability of the process.

Magnetic susceptibility measurement by NMR: 1. The temperature dependence of TMS.

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.

Further conventions for NMR shielding and chemical shifts (IUPAC Recommendations 2008).

IUPAC has published a number of recommendations regarding the reporting of nuclear magnetic resonance (NMR) data, especially chemical shifts. The most recent publication [Pure Appl. Chem. 73, 1795 (2001)] recommended that tetramethylsilane (TMS) serve as a universal reference for reporting the shifts of all nuclides, but it deferred recommendations for several aspects of this subject. This document first examines the extent to which the (1)H shielding in TMS itself is subject to change by variation in temperature, concentration, and solvent. On the basis of recently published results, it has been established that the shielding of TMS in solution [along with that of sodium-3-(trimethylsilyl)propanesulfonate, DSS, often used as a reference for aqueous solutions] varies only slightly with temperature but is subject to solvent perturbations of a few tenths of a part per million (ppm). Recommendations are given for reporting chemical shifts under most routine experimental conditions and for quantifying effects of temperature and solvent variation, including the use of magnetic susceptibility corrections and of magic-angle spinning (MAS). This document provides the first IUPAC recommendations for referencing and reporting chemical shifts in solids, based on high-resolution MAS studies. Procedures are given for relating (13)C NMR chemical shifts in solids to the scales used for high-resolution studies in the liquid phase. The notation and terminology used for describing chemical shift and shielding tensors in solids are reviewed in some detail, and recommendations are given for best practice.

Cavitation energies can outperform dispersion interactions.

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.

Measurement of magnetic susceptibility and calculation of shape factor of NMR samples.

A method for accurate measurement of magnetic susceptibility and determination of the shape factor in an NMR tube is shown. The combination of accurate shape factor determination with susceptibility measurement leads to improved accuracy when measuring chemical shift. This is important for comparing samples in different solvents or under different conditions, such as temperature, solvent, and pH.

High accuracy NMR chemical shift corrected for bulk magnetization as a tool for structural elucidation of dilutable microemulsions. Part 1 - Proof of concept.

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.

High accuracy NMR chemical shift corrected for bulk magnetization as a tool for structural elucidation of microemulsions. Part 2 - Anionic and nonionic dilutable microemulsions.

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.

Docosahexaenoic acid triglyceride-based microemulsions with an added dendrimer - Structural considerations.

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.

Posthumously Assessing a Homeless Population: Services Use and Characteristics.

OBJECTIVE: Data on services use, characteristics, and geographic distribution of homeless individuals who died in Philadelphia from 2009 to 2011 provided perspective on assessments of the homeless population that rely on conventional counts and surveys. METHODS: Data from the City of Philadelphia Medical Examiner's Office were used to parse homeless decedents into three groups on the basis of use of homelessness services (known users, occasional users, and nonusers), and differences among the groups were assessed by using descriptive and multivariate methods. RESULTS: Of 141 adult decedents, 49% made substantial use of the homelessness services system (known users), 27% made occasional use of these services (occasional users), and 24% had no record of use of homelessness services (nonusers). Compared with known users, nonusers and occasional users were less likely to have had a severe mental illness diagnosis or to have received either disability benefits or Medicaid coverage and were more likely to be white. Nonusers and occasional users were also more likely than known users to have died in outlying parts of the city. CONCLUSIONS: More conventional homeless surveys and enumerations miss a substantial portion of the homeless population. Including these "hidden homeless" persons would alter perceptions about the composition of Philadelphia's homeless population, lowering estimates of the incidence of psychiatric disability and increasing estimates of racial diversity.

Temperature dependence of the 1H chemical shift of tetramethylsilane in chloroform, methanol, and dimethylsulfoxide.

The chemical shift of tetramethylsilane (TMS) is usually taken to be zero. However, it does vary slightly with temperature, having obvious implications for studies of temperature effects on chemical shifts. In this work, we measure the variation in the chemical shift of TMS with temperature in three solvents, CDCl3, CD3OD, and DMSO-d6, relative to the resonant frequency of 3He gas, which can be reasonably assumed to be temperature independent. In all three solvents, the average temperature coefficient over a wide temperature range is about -6 x 10(-4) ppm/degrees C, a factor of five smaller than that previously reported in the literature. Data are included for 3He resonance frequencies over a temperature range of -110 to +180 degrees C, along with new measurements of volume magnetic susceptibilities of the three solvents and estimates of their temperature dependence. A novel method is used to provide temperature measurement via 2H resonances of methanol and ethylene glycol samples, which can concurrently be used for field/frequency locking.

Variations on the chemical shift of TMS.

The chemical shift of TMS is commonly assumed to be zero. However, it varies by over 1 ppm for 1H and 4 ppm for 13C and shows a correlation with the physical properties of the solvent. Using the commonly accepted convention that TMS always resonates at zero leads to significant errors when comparing chemical shifts in different solvents. A new method for measuring absolute chemical shift with a conventional NMR spectrometer is demonstrated. The observed chemical shift is corrected by measuring and correcting for susceptibility and shape factor. Practical suggestions are made for modifying the current chemical shift standard while maintaining compatibility with earlier literature.

Food-grade microemulsions based on nonionic emulsifiers: media to enhance lycopene solubilization.

Water-dilutable food-grade microemulsions consisting of ethoxylated sorbitan esters, and in some cases blended with other emulsifiers, water, (R)-(+)-limonene, ethanol, and propylene glycol, have been prepared. These microemulsions are of growing interest to the food industry as vehicles for delivering and enhancing solubilization of natural food supplements with nutritional and health benefits. Lycopene, an active natural lipophilic antioxidant from tomato, has solubilized in water-in-oil, bicontinuous, and oil-in-water types of microemulsions up to 10 times the oil [(R)-(+)-limonene] dissolution capacity. The effects of aqueous-phase dilution, nature of surfactant (hydrophilic-lypophilic balance), and mixed surfactant on solubilization capacity and solubilization efficiency were studied. Structural aspects studied by self-diffusion NMR were correlated to the solubilization capacity, and transformational structural changes were identified.