Metabolic composition and authenticity evaluation of bergamot essential oil assessed by nuclear magnetic resonance spectroscopy.

In this work, a sample of pure and certified bergamot essential oil (BEO) was extensively studied for the first time directly by NMR spectroscopy with the aim of investigating its metabolic composition, quantifying the main components of this complex natural matrix and simultaneously assessing whether the NMR technique is able to highlight possible frauds to which this high-cost product may be subjected. Eleven low molecular weight compounds have been identified by using 1D 1H and 13C-{1H} NMR experiments, 2D homo- and heteronuclear correlation NMR spectra, and 2D 1H DOSY experiments; the most abundant of them, i.e., about 90% of the sample analyzed, has been quantified by employing benzoic acid as an internal standard by 1H NMR spectrum. Moreover, since the commercial fraud of this precious oil is often due to the addition of less expensive oils, we have simulated a possible adulteration through the preparation of BEO samples to which different percentages of orange essential oil (OEO) were added. The results, obtained by combining the 1H NMR spectra collected on the adulterated samples and on pure BEO, with chemometric analysis, principal component analysis (PCA), indicate that it is possible to distinguish the sample of pure BEO from the adulterated ones and also, among them, to differentiate between the degrees of adulteration.

Phase behavior of hard C_{2h}-symmetric particle systems.

Using Monte Carlo numerical simulation, this work sketches the phase diagram of systems of certain hard C_{2h}-symmetric particles, formed by gluing two aligned and displaced hard spherocylinders with a cylindrical-length-to-diameter ratio realistically, if viewed not only from the lyotropic colloidal liquid-crystal side but also from the thermotropic low-molecular-mass liquid-crystal side, equal to 5, as a function of the displacement. Several distinctive phases are observed, such as a nonperiodic smectic-B-like phase, a nonperiodic smectic-H-like phase, a smectic-C phase, and a short-layer-spacing uniaxial smectic-A phase but no biaxial nematic phase.

A combined LX-NMR and molecular dynamics investigation of the bulk and local structure of ionic liquid crystals.

The unique power of NMR spectroscopy in anisotropic media (LX-NMR) as a tool to obtain local and bulk structural information, combined with the effectiveness of molecular dynamics simulations at the atomistic level, shows very attractive potentialities for the study of interesting, even though still poorly understood, materials such as Ionic Liquid Crystals (ILCs). In this work, we focused our attention, in particular, on the orientational ordering of two mesophases: 1-dodecyl-3-methylimidazolium chloride, [C12C1im]Cl, and 1-dodecyl-3-methylimidazolium tetrafluoroborate, [C12C1im][BF4]. Both ILCs were studied by a 2H NMR direct investigation of the molecules forming the phases, suitably deuterated, and by 1H NMR spectroscopy, using the small rigid probe-solutes 1,4-dichlorobenzene (DCB), dissolved in [C12C1im][BF4] and [C12C1im]Cl, and 1,4-dibromobenzene (DBB) dissolved in [C12C1im][BF4], to probe the local, internal structure and organization of the mesophases. The experimental results were then compared with the predictions, by atomistic MD simulations, of the structure of the smectic phase of the two salts, at two selected temperatures, containing a single DCB molecule as a probe. The MD simulations show that the DCB solute is distributed only within the hydrophobic layers of the ILC. Orientational order parameters of the imidazolium cations and of the DCB molecule were obtained and compared with the experiments, showing a general good agreement and allowing a deeper understanding of the microscopic structure of the systems.

Assessing the stable conformations of ibuprofen in solution by means of Residual Dipolar Couplings.

Detailing the conformational equilibria between global and local minimum energy structures of anti-inflammatory α-arylpropionic acids directly in solution is of the utmost importance for a better understanding of the structure-activity relationships, hence providing valuable clues for rational structure-based drug design studies. Here the conformational preferences of the widely used pharmaceutical ibuprofen were investigated in solution by NMR spectroscopy in weakly ordering phases. A thorough theoretical treatment of the anisotropic interactions that are relevant for NMR spectra led to a conformational model characterized by six pairs of symmetry-related conformers, in particular four couples of gauche structures, with a total probability of 93%, and 2 couples of trans structures, counting for the remaining 7%.

Doped ionic liquid crystals as effective weakly alignment media for polar solutes.

The ionic liquid crystal 1-dodecyl-3-methylimidazolium tetrafluoroborate slightly doped with water is presented as a promising NMR alignment medium for the measurement of residual dipolar couplings for polar molecules dissolved therein.

Detection of Significant Aprotic Solvent Effects on the Conformational Distribution of Methyl 4-Nitrophenyl Sulfoxide: From Gas-Phase Rotational to Liquid-Crystal NMR Spectroscopy.

The conformational equilibrium of methyl 4-nitrophenyl sulfoxide (MNPSO) was experimentally investigated in the gas phase by using microwave spectroscopy and in isotropic and nematic liquid-crystal solutions, in which the solvents are nonaqueous and aprotic, by using NMR spectroscopy; moreover, it was theoretically studied in vacuo and in solution at different levels of theory. The overall set of results indicates a significant dependence of the solute conformational distribution on the solvent dielectric permittivity constant: when dissolved in low-polarity media, the most stable conformation of MNPSO proved to be strongly twisted with respect to that in more polar solvents, in which the conformational distribution maximum essentially coincides with that obtained in the gas phase. We discuss a possible explanation of this behavior, which rests on electrostatic solute-solvent interactions and is supported by calculations of the solute electric dipole moment as a function of the torsional angle. This function shows that the least polar conformation of MNPSO is located at a twist angle close to that of the conformational distribution maximum found in less-polar solvents. This fact, associated with a relatively flat torsional potential, can justify the stabilization of the twisted conformation by the less-polar solvents.

Conformational investigation in solution of a fluorinated anti-inflammatory drug by NMR spectroscopy in weakly ordering media.

The structural and conformational elucidation of flexible bioactive molecules in solution is currently a crucial goal for the scientific community, but it is rarely achievable by available techniques. The anti-inflammatory drug diflunisal is presented here as a model case for supporting the efficiency of NMR spectroscopy combined with the use of weakly ordering media as a promising methodology for the conformational investigation of small bioactive molecules. Starting from NMR anisotropic data (40 independent dipolar couplings), a quite accurate description of its torsional distribution around the inter-ring C-C bond was found, characterized by a pair of two couples of conformers. According to the relative configuration of the carboxylic group and the fluorine atom in the ortho position to the inter-ring C-C bond, the more stable couple of conformers are defined as "trans" type conformers (F opposite to the carboxylic group) whereas the less stable couple are "cis" type conformers (F and carboxylic group on the same side). In order to study the influence of fluorine nuclei on the structure and conformational distribution, the same analytical strategy has been applied to investigate the phenylsalicylic acid, its nonfluorinated analogue.

Order and conformation of biphenyl in cyanobiphenyl liquid crystals: a combined atomistic molecular dynamics and 1H NMR study.

The alignment of biphenyl (2P) in the liquid-crystal phases of 4-n-pentyl-4'-cyanobiphenyl (5CB) and 4-n-octyl-4'-cyanobiphenyl (8CB) is investigated by using a combination of predictive atomistic molecular dynamics (MD) simulations and (1)H liquid-crystal nuclear magnetic resonance (LXNMR) residual dipolar coupling measurements. A detailed comparison and validation of the MD results with LXNMR is provided, showing a good agreement between the simulated and experimental dipolar couplings at the same reduced temperature. MD is then used to examine the location of 2P in the smectic phase, which is unavailable to LXNMR, and 2P is found to be rather uniformly distributed. The combination of MD and NMR spectroscopy provides detailed information about the order, interconnection between orientation and conformation, local positional order, and interactions with the liquid-crystalline solvent.

Smectic order parameters via liquid crystal NMR spectroscopy: Application to a partial bilayer smectic A phase.

Solute molecules were dissolved in the liquid crystal 4-cyano-4'-n-octyloxybiphenyl (8OCB), known to form a partial bilayer smectic-A phase. Through measurement of solutes' and solvent's orientational order parameters via nuclear magnetic resonance spectroscopy, and their analysis via a statistical thermodynamic density functional theory, values of the solvent's positional order parameters and solutes' positional-orientational distribution functions were obtained. Near to the transition to the nematic phase, the main positional order parameter of the smectic liquid crystal turned out to be comprised in the interval 0.4-0.6, though the quality of the fittings assuming the phase as nematic all across the temperature range investigated was only slightly worse. This may be ascribed to the looseness of the partial bilayer smectic structure. Solutes were found to preferentially lie in those regions where liquid crystal molecule terminal chains are located.

Conformational distribution of trans-stilbene in solution investigated by liquid crystal NMR spectroscopy and compared with in vacuo theoretical predictions.

The basic question about the structure and the conformational distribution of a π-conjugated, flexible organic molecule (interesting in itself, in relation to the balance of forces determining its torsional equilibrium) becomes a really intriguing problem in the case of trans-stilbene (t-St), a "fundamental" molecule from a chemical point of view, as well as the prototype fragment of a series of derivatives endowed with several important biological and technological properties. As a matter of fact, the problem of t-St planarity when the molecule is isolated or in solution is a particularly debated question. In the present paper we studied the conformational distribution of t-St in solution, by resorting to the powerful technique of liquid crystal NMR spectroscopy (LXNMR), and we compared the obtained experimental results with accurate theoretical calculations carried out in vacuo, by using the MP2/6-31G** method (allowing for bond lengths and angles relaxation every 3° torsional steps). Our theoretical and experimental outcomes agree in indicating the nonplanarity of the molecule which, on the contrary, exhibits the coexistence of four stable rotamers, two by two symmetry related. In particular, we have found a couple of global minima corresponding to propeller-like C(2) symmetry conformations, where both the rings are "disrotated", with respect to the vinyl group, of about 17° in solution and of 27° in vacuo (theoretical value). Besides this, the presence of a couple of C(i) local minima, with both the rings "conrotated" of 17° (fluid phase) or of 27° (MP2/6-31G** calculations for the isolated molecule) has been determined.

Experimental assessment of the vibration-reorientation contribution to liquid crystal NMR dipolar couplings: the case of tetramethylallene dissolved in a nematic mesophase.

In the present paper, the peculiar orientational behavior, studied by liquid crystal NMR (LXNMR) spectroscopy, of the D(2d) symmetry quasi-spherical molecule of tetramethylallene (TMA) dissolved in the nematic solvent I52 is exploited to attempt a quantitative experimental assessment of the correlation between molecular vibrations and overall rotations in weakly oriented molecules. The analysis of the very small D(HH) and (1)D((13)C-H) dipolar couplings, available from the natural abundance LXNMR spectra of TMA at different temperatures, allows for a derivation leading (by making a few approximations) to the quantification of the vibration-reorientation (also called nonrigid) contribution affecting the observed direct (1)D((13)C-H) dipolar coupling. The obtained results show that, under the particular conditions of the studied system (very weak orientational ordering of a highly symmetric molecule), this contribution is particularly important, in order to reproduce the whole value of the "observed" dipolar coupling. This issue is discussed and commented on at length in the work, also, by making reference to the analogy with perfectly symmetric molecules (such as methane and analogues) dissolved in liquid crystalline phases.

Rigid probe solutes in a smectic-A liquid crystal: an unconventional route to the latter's positional order parameters.

Biphenylene and pyrene were dissolved in the nematic and smectic-A phases of the liquid crystal 4,4'-di-n-heptyl-azoxybenzene and the orientational order parameters of both solutes and solvent measured via proton and deuteron nuclear-magnetic-resonance spectroscopy. This new data set was then merged with the one previously obtained, formed by 4,4'-di-chloro-benzene and naphthalene as solutes in the same solvent, and the resulting overall data set analyzed with a statistical thermodynamic density-functional theory to provide positional-orientational distribution functions of the various solutes along with the smectic solvent's positional order parameters.

Orientational mechanisms in liquid crystalline systems. 2. The contribution to solute ordering from the reaction field interaction between the solute electric quadrupole moment and the solvent electric field gradient.

In the previous paper of this issue, [Celebre, G.; Ionescu, A. J. Phys. Chem. B doi: 10.1021/jp907310g], following a generalized reaction field approach in the linear response approximation, we were successful in obtaining an analytical compact expression for the mean-field anisotropic orientational potential U(Q-EFG) theoretically experienced by a highly idealized nonionic and apolar solute, considered as a point quadrupole immersed in a uniaxial polarizable continuum medium (model of a nematic solvent comprised of dipolar mesogenic molecules). The term U(Q-EFG) describes the electrostatic interaction between the electric quadrupole of the solute and the electric field gradient induced at the solute by the surrounding medium polarized by the distribution of electric charges representing the quadrupolar solute itself. In the present paper, the obtained potential has been considered as an additional orientational interaction contributing to the solute ordering, besides the well-recognized and very effective "short-range" (size-and-shape-dictated) mechanisms. Since in our theory the solvent is characterized by its dielectric tensor, the model has been widely tested by taking as references the experimental order parameters of several uniaxial and biaxial different small rigid probe molecules (H(2), N(2), acetylene, allene, propyne, benzene, hexafluorobenzene, 1,4-difluorobenzene, and norbornadiene) dissolved in the nematic solvents ZLI1132 (Deltaepsilon >> 0) and EBBA (Deltaepsilon < 0); moreover, the order parameters of the same solutes in the so-called nematic "magic mixture" (45 wt % EBBA + 55 wt % ZLI1132), where the short-range orientational effects are commonly believed to be very dominant, have been conventionally assumed as reference of the absence of electrostatic orientational effects. The experimental order parameters of the treated solutes, obtained in the past by liquid crystal NMR and available from literature, have been then compared with those theoretically predicted by our theoretical approach in order to obtain useful hints about two basic points, (a) the real physical nature of the interactions (other than the "size-and-shape") involved in the orientational mechanisms and (b) the conceptual effectiveness of the suggested mean-field approach in describing this kind of phenomena. Successes and failures of the approach in the predictions are discussed at length, along with their possible reasons and implications.

Orientational mechanisms in liquid crystalline systems. 1. A reaction field analytical description of the interaction between the electric quadrupole moment of a probe solute and the electric field gradient of a nematic solvent.

In the present paper, the fundamental problem of calculating the electric field gradient (EFG) experienced by a highly idealized solute, represented by a general point quadrupole immersed in an anisotropic uniaxial medium, has been tackled. Following a generalized reaction field approach (based upon the original ideas and the "mean-field philosophy" due to Kirkwood and Onsager) in the linear response approximation, a closed analytical expression of the EFG has been derived (to the best of our knowledge, for the first time). The obtained expression is particularly simple and elegant, also thanks to the oversimplifying approximation that the virtual cavity containing the solute is assumed to be perfectly spherical. This compact and manageable formula, obtained by a rigorous mathematical derivation (unlike other mean-field phenomenological models previously suggested in literature) can be useful to investigate and better understand a likely orientational mechanism, partly responsible for the ordering of small solutes dissolved in nematic mesophases, based on the interaction between the electric quadrupole of the solute and the electric field gradient of the anisotropic uniaxial medium (in the next paper of this issue, the formulation obtained in this work is widely tested on a variety of uniaxial and biaxial solutes dissolved in different nematic solvents).

Solvent smectic order parameters from solute nematic order parameters.

In liquid crystals, while the second and fourth rank orientational order parameters characterizing a nematic phase can be experimentally determined via several techniques, there is no straightforward experiment rendering the positional order parameters characterizing a smectic A phase. This work illustrates a novel method to estimate the positional order parameters of a smectogenic liquid crystal solvent from knowledge of the orientational order parameters of a number of solutes dissolved therein. The latter order parameters can be experimentally determined via liquid crystal NMR spectroscopy. These data can be then analyzed with a statistical-thermodynamic density functional theory, whose basic ingredient is a model for solute-solvent intermolecular interactions. Its parametrization and the subsequent fitting procedure eventually permit one to obtain the positional order parameters of the solvent besides the positional-orientational distribution function of the solutes. The method is applied to the smectogen 4,4(')-di-n-heptyl-azoxybenzene, in which the solutes 1,4-dichlorobenzene and naphthalene have been dissolved. With the help of this exploratory practical example, pros and cons of the method are pointed out and further developments prospected.

Multitechnique investigation of conformational features of small molecules: the case of methyl phenyl sulfoxide.

The conformational distribution of methyl phenyl sulfoxide (a molecule representative of a very important class of reagents widely used in asymmetric synthesis) has been studied in two different phases of matter (gas phase and solution) by a comprehensive approach including theoretical calculations, microwave spectroscopy, liquid crystal NMR experiments, and atomistic molecular dynamics computer simulations. The aim was to investigate the combined action of intra- and intermolecular interactions in determining the molecule's conformational equilibrium, upon which important physicochemical properties (inter alia, the chemoselectivity) significantly depend. Basically, the results converge in describing the tendency of the molecule to favor stable conformations governed by intramolecular interactions (in particular, the expected optimization between steric repulsion and conjugation of pi systems). However, significant solvent effects (whose "absolute" magnitude is actually difficult to assess, due to a certain "method-dependence" of the results) have been also detected.

An explicit relationship between the dielectric anisotropy and the average electric field gradient in nematic solvents.

Nowadays, the interaction between the electric quadrupole moment of a probe-solute and the so-called average electric field gradient (EFG) of the nematic medium is commonly suggested as an important long-range mechanism contributing to the ordering of small molecules dissolved in nematic solvents. Anyway, an explicit relationship between the solvent's EFG and some macroscopic property of the medium has never been established explicitly. In this work, a derivation is carried out leading to a simple formula that shows that the EFG of a nematic solvent is directly related to the dielectric permittivity of the medium (in particular, to its dielectric anisotropy, Deltaepsilon) and to the quadrupole moment of the solute. The obtained expression (a) allows for immediate considerations about the sign and the value of EFG (and could be very useful in designing proper nematic mixtures with null EFG) and (b) reconciles two existing conceptual ways of describing long-range orientational interactions, revealing they are only seemingly different.

Intrinsic information content of NMR dipolar couplings: a conformational investigation of 1,3-butadiene in a nematic phase.

The conformational equilibrium of 1,3-butadiene in a condensed fluid phase is investigated by liquid-crystal NMR spectroscopy. The full set of D(HH) and D(CH) dipolar couplings is determined from the analysis of the (1)H spectra of the three 1,3-butadiene most-abundant isotopomers (i.e. the all (12)C and the two single-labeled (13)C isotopomers) for a total of 21 independent dipolar couplings. A very good starting set of spectral parameters for the analysis of the (1)H spectrum is determined in a semiautomated way by the analysis of the (N-1) (specifically, N=6, the number of 1/2 spin nuclei in the spin system) quantum refocused (5QR), and not (5Q), spectra. As an alternative approach, a Monte Carlo (MC) numerical simulation, capable of predicting the solute ordering, is tested to simulate the 5QR spectrum. The set of D(ij) couplings is very good, proving that the MC method can represent a novel, valid alternative to the existing spectral simplification procedures. The experimentally determined dipolar-coupling data set is fully compatible with the 1,3-butadiene conformational distribution reported in the literature for isolated molecules, indicating the presence of about 99 % of s-trans conformer. With regards to the remaining 1 %, in spite of the direct and very strong dependence of the observables on the molecular structure, it was not possible to discriminate between the planar s-cis and s-gauche forms, both of which produce a very good fit of the dipolar couplings. Vibrational corrections, up to the anharmonic term, were applied; the calculated geometrical parameters are in good- although not exact-agreement with those reported in the literature from experimental and theoretical investigations. This result can be considered as supporting the methodology used for obtaining the structure and conformational distribution of a flexible molecule in a liquid phase.

On the analysis of Liquid Crystal NMR dipolar coupling data via mixed a priori-maximum entropy methods.

In this Letter, a general expression is derived for the conformational distribution function of a molecule dissolved in an anisotropic condensed fluid medium by combining an a priori model with the maximum entropy principle applied to treatment of liquid crystalline-NMR data. The recently proposed additive potential maximum entropy (APME) method is recovered as a special case, when the AP is chosen as the a priori model and the orientational order is low.

Orientational ordering of solutes in confined nematic solvents: a possible way to probe director distributions.

We propose a method to study the director distribution in a nematic liquid crystal confined in a slab geometry. It is based on the measurement, by NMR spectroscopy, of the Saupe ordering matrices of a collection of biaxial solute molecules dissolved in the confined nematic liquid crystal of interest. Due to the combined action of the surface anchoring and magnetic field interactions, the director is generally not uniformly aligned within the cell. Consequently, the resulting Saupe ordering matrices may be considered as weighted sums of the corresponding Saupe ordering matrices measured in the bulk nematic phase, and modulated by the director distribution. The determined Saupe ordering matrices may then be taken as the set of data in a fitting process where the fitting function, whose form is deduced from molecular mean field and continuum theories, is dependent on the director distribution; the angle that the director forms with the plain surfaces and the corresponding derivative at the surfaces are taken as fitting parameters. The methodology is preliminarily tested on the virtual nematic phase formed by the Lebwohl-Lasher lattice model, confined between two plain surfaces favoring planar anchoring, and where a number of model cuboidal solutes has been dissolved. We comment on the implemention of the method when applied to real experimental systems.