Determinazione dei tensori di "shielding" del 13C e del 19F da spettri NMR in solventi liquido cristallini e da calcoli quanto meccanici

I cristalli liquidi suscitano attualmente un grande interesse. Tale interesse, legato soprattutto al loro utilizzo nelle moderne applicazioni tecnologiche, è sostanzialmente dovuto al fatto che le proprietà macroscopiche di queste fasi possono essere variate per mezzo di perturbazioni esterne. Per esempio, gli effetti di allineamento del direttore di una fase liquido-cristallina ad opera di campi elettrici sono ampiamente sfruttati nella fabbricazione di display LCD. La spettroscopia NMR è un ottimo strumento di indagine delle proprietà dei cristalli liquidi legate all’ordine molecolare. Questa spettroscopia, infatti, è estremamente sensibile al grado medio di ordine molecolare rispetto al campo magnetico. Nel corso di questa tesi sono stati osservati i nuclei 13C e 19F in abbondanza naturale. L’uso del 13C per lo studio di fasi liquido-cristalline si è sviluppato da quando sono disponibili strumentazioni e tecniche adeguate, soprattutto per quanto riguarda l’efficacia del disaccoppiamento da 1H. In questa tesi particolare attenzione è stata riservata al nucleo 19F, il quale è di grande attualità perché la fluorurazione sembra conferire ai cristalli liquidi proprietà interessanti, che li distinguono dagli analoghi non florurati e che li rendono migliori per alcune applicazioni tecnologiche. I composti florurati dai quali prende spunto questo lavoro di tesi sono costituiti da un anello aromatico variamente sostituito con atomi di fluoro, a cui si lega un sostituente allungato ma flessibile di diversa natura, struttura questa che porta alla costituzione della molecola mesogena. Due di questi composti sono stati oggetto di uno studio recente, volto a determinare il grado d’ordine molecolare nelle loro fasi liquido cristalline mediante varie tecniche, fra cui la spettroscopia NMR del 13C. L’analisi dei dati spettrali del 13C (anisotropie del chemical shift e accoppiamenti dipolari) ha messo in luce quale utilità potrebbe avere la conoscenza dei tensori di chemical shift per un vasto numero di carboni (così come avviene per i corrispondenti dati isotropi). Attualmente vari metodi di calcolo permettono di determinare ab initio questi tensori, come molte altre proprietà molecolari; solo saltuariamente, però, è stato affrontato il confronto puntuale fra valori calcolati e quantità sperimentali. Questo lavoro di tesi si inserisce dunque in un progetto di ricerca che si propone di studiare, mediante spettroscopia NMR, le molecole di tolueni diversamente fluorurati (piccoli modelli essenziali dei mesogeni citati) disciolte in fasi liquido cristalline, per convalidare con dati sperimentali alcune quantità, in particolare i tensori di chemical shift dei nuclei di 13C e 19F,calcolate con vari metodi quantomeccanici. I valori, di cui venisse confermata l’attendibilità e definita la trasferibilità, potrebbero trovare applicazione nello studio di altre molecole florurate. Saranno qui prese in esame le molecole di parafluorotoluene e metafluorotoluene disciolte in una fase nematica

Study of organic molecules in their crystalline phases by Solid State NMR: dynamics and related aspects

The study of molecular motions of small organic molecules in the solid state has a considerable interest, not only for the intrinsic value of such a deep knowledge of a chemical system, but also because molecular motions can be intimately connected with physical properties, such as stability, intermolecular interactions and chemical reactivity. In this PhD thesis, the various tools offered by SSNMR have been intensively exploited in order to characterize in detail some peculiar aspects of the dynamic properties of small organic molecules in crystalline phases. The nuclei observed, 1H and 13C, present different characteristics of the two nuclear species often al- lowed us to get complementary dynamic information. A wide variety of nuclear observables has been investigated, ranging from isotropic and anisotropic chemical shifts, scalar and dipolar couplings, to different kinds of relaxation properties, by using many advanced SSNMR pulse sequences. The work is also characterized by the extension of the measurements over an unconventional range of temperatures, in particular some 13C CP-MAS spectra have been acquired at temperatures down to 20 K. Moreover the combination of measurements at different experimental frequencies was exploited in many cases. A last important feature of the thesis work is the use of many mathematical models for the data analysis. In particular the use of motional models for relaxation time analyses, like BBP and Cole-Cole models for spectral densities, the Mc Connell equations for modeling exchange motions, in some cases integrated with other models for the description of interference phenomena; finally the extension of a model firstly proposed by Wittebort et al. for the quantitative analysis of the effect of small-amplitude motions, such as vibrations and librations, on chemical shielding tensors. In all the cases studied the aid of DFT calculations resulted to be very important and in some cases crucial. The developed approaches were applied to four small organic molecules in crystalline phases, chosen for some similar chemical characteristics and for their pharmacological interest, since they are widely used non-steroidal anti-inflammatory drugs. The systems chosen are Ibuprofen, Sodium Ibuprofen, Naproxen and Sodium Naproxen, all of them in their stable crystalline phases

Solid State NMR Study of the Mixing Degree Between Ginkgo Biloba Extract and a Soy-Lecithin-Phosphatidylserine in a Composite Prepared by the Phytosome® Method

Leaves extract of Ginkgo biloba, known in China since the most ancient times, has been widely used in the area of senile dementia thanks to its improving effects on cognitive function. A promising formulation of this botanical ingredient consists in a Ginkgo biloba-soy-lecithin-phosphatidylserine association obtained by the Phytosome® process. The precise assess- ment of the mixing degree between Ginkgo biloba and soy-lecithin-phosphatidylserine in this formulation is an important piece of information for understanding the reasons of its final performances. To this aim in the present study we carried out for the first time a Solid State Nuclear Magnetic Resonance investigation on Ginkgo biloba-soy-lecithin-phosphatidylserine association, on its constituents and on a mechanical mixture. The analysis of different observables highlighted a very intimate mixing (domains of single components not larger than 60 nm) of Ginkgo biloba and soy-lecithin-phosphatidylserine in their association obtained by Phytosome® process, together with a slight modification of their molecular dynamics, not observed in the case of the mechanical mixture

Anisotropy and NMR spectroscopy

Abstract In this paper, different aspects concerning anisotropy in Nuclear Magnetic Resonance (NMR) spectroscopy have been reviewed. In particular, the relevant theory has been presented, showing how anisotropy stems from the dependence of internal nuclear spin interactions on the molecular orientation with respect to the external magnetic field direction. The consequences of anisotropy in the use of NMR spectroscopy have been critically discussed: on one side, the availability of very detailed structural and dynamic information, and on the other side, the loss of spectral resolution. The experiments used to measure the anisotropic properties in solid and soft materials, where, in contrast to liquids, such properties are not averaged out by the molecular tumbling, have been described. Such experiments can be based either on static low-resolution techniques or on one- and two-dimensional pulse sequences exploiting Magic Angle Spinning (MAS). Examples of applications of NMR spectroscopy have been shown, which exploit anisotropy to obtain important physico-chemical information on several categories of systems, including pharmaceuticals, inorganic materials, polymers, liquid crystals, and self-assembling amphiphiles in water. Solid-state NMR spectroscopy can be considered, nowadays, one of the most powerful characterization techniques for all kinds of solid, either amorphous or crystalline, and semi-solid systems for the obtainment of both structural and dynamic properties on a molecular and supra-molecular scale. Graphic abstrac

Solid-State Nuclear Magnetic Resonance of Triple-Cation Mixed-Halide Perovskites

Mixed-cation lead mixed-halide perovskites are the best candidates for perovskite-based photovoltaics, thanks to their higher efficiency and stability compared to the single-cation single-halide parent compounds. TripleMix (Cs0.05MA0.14FA0.81PbI2.55Br0.45 with FA = formamidinium and MA = methylammonium) is one of the most efficient and stable mixed perovskites for single-junction solar cells. The microscopic reasons why triplecation perovskites perform so well are still under debate. In this work, we investigated the structure and dynamics of TripleMix by exploiting multinuclear solid-state nuclear magnetic resonance (SSNMR), which can provide this information at a level of detail not accessible by other techniques. 133Cs, 13C, 1 H, and 207Pb SSNMR spectra confirmed the inclusion of all ions in the perovskite, without phase segregation. Complementary measurements showed a peculiar longitudinal relaxation behavior for the 1 H and 207Pb nuclei in TripleMix with respect to single-cation single-halide perovskites, suggesting slower dynamics of both organic cations and halide anions, possibly related to the high photovoltaic performances

Nuclear spin conversion of water inside fullerene cages detected by low-temperature nuclear magnetic resonance

The water-endofullerene H2O@C60 provides a unique chemical system in which freely rotating water molecules are confined inside homogeneous and symmetrical carbon cages. The spin conversion between the ortho and para species of the endohedral H2O was studied in the solid phase by low-temperature nuclear magnetic resonance. The experimental data are consistent with a second-order kinetics, indicating a bimolecular spin conversion process. Numerical simulations suggest the simultaneous presence of a spin di↵usion process allowing neighbouring ortho and para molecules to exchange their angular momenta. Cross-polarization experiments found no evidence that the spin conversion of the endohedral H2O molecules is catalysed by 13C nuclei present in the cages

Dynamics by Solid-State NMR: Detailed Study of Ibuprofen Na Salt and Comparison with Ibuprofen

The various internal rotations and interconfor- mational jumps of the Na-salt form of ibuprofen in the solid state were characterized in detail by means of the simultaneous analysis of a variety of low- and high-resolution NMR experi- ments aimed at measuring several 13C and 1H spectral and relaxation properties at different temperatures and frequencies. The results were first qualitatively analyzed to identify the motions of the different molecular fragments and to assign them to specific frequency regimes (slow, 106 Hz). Subsequently, a simultaneous fit of the experimental data sets most sensitive to each frequency range was performed by using suitable motional models, thus obtaining, for each motion, correlation times and activation energies. The motions so characterized were: the rotations of the three methyl groups and of the isobutyl group, occurring in the fast regime, and the π-flip of the phenyl ring, belonging to the intermediate motional regime. The results obtained for the Na-salt form were compared with those of the acidic form of ibuprofen, previously obtained from a similar solid-state NMR approach: despite the very similar chemical structure of the two compounds, their dynamic properties in the solid state are noticeably different

Dynamics of Clay-Intercalated Ibuprofen Studied by Solid State Nuclear Magnetic Resonance

In designing drug delivery systems with improved release properties and bioavailability, the dynamic features of the active pharmaceutical ingredient can be crucial for the final product properties. In this work, we aimed at obtaining the first characterization of the molecular dynamic properties of one of the most common nonsteroidal anti-inflammatory drug, ibuprofen, intercalated in hydrotalcite, an interesting inorganic carrier. By exploiting a variety of solid state NMR techniques, including 1H and 13C MAS spectra and T1 relaxation measurements, performed at variable temperature and carrying out a synergic analysis of all results, it has been possible to ascertain that the mobility of ibuprofen within the carrier is remarkably increased. In particular, strong indications have been obtained that ibuprofen molecules, in addition to internal interconformational dynamics, experience an overall molecular motion. Also considering that ibuprofen is "anchored" to the charged surface of the hydrotalcite layers through its carboxylate moiety, such motion could be a wobbling-in-a-cone. Activation energies and correlation times of all the motions of intercalated ibuprofen have been determined

Direct observation of the effects of small-amplitude motions on 13C nuclear shielding tensors by means of low-temperature 2D MAS NMR spectroscopy

Fast small-amplitude motions, such as vibrations or librations, do affect NMR properties of molecules in the solid state. The quantification of these effects is very important for structural studies exploiting Solid State NMR and computational methods, particularly in the field of NMR crystallography. In this work 2D MAS NMR experiments were carried out over a wide range of low temperatures (129–295 K) on a non-standard high-resolution Solid State NMR equipment to obtain the first experimental determination of the effects of small-amplitude motions on 13C Chemical Shift Tensors of a multi-carbon molecule (ibuprofen)

Magic-Angle Spinning NMR of Cold Samples

M agic-angle-spinning solid-state NMR provides site-resolved structural and chemical information about molecules that complements many other physical techniques. Recent technical advances have made it possible to perform magic-angle-spinning NMR experiments at low temperatures, allowing researchers to trap reaction intermediates and to perform site-resolved studies of low-temperature physical phenomena such as quantum rotations, quantum tunneling, ortho-para conversion between spin isomers, and super- conductivity. In examining biological molecules, the improved sensitivity provided by cryogenic NMR facilitates the study of protein assembly or membrane proteins. The combination of low-temperatures with dynamic nuclear polarization has the potential to boost sensitivity even further. Many research groups, including ours, have addressed the technical challenges and developed hardware for magic-angle-spinning of samples cooled down to a few tens of degrees Kelvin. In this Account, we briefly describe these hardware developments and review several recent activities of our group which involve low-temperature magic-angle-spinning NMR. Low-temperature operation allows us to trap intermediates that cannot be studied under ambient conditions by NMR because of their short lifetime. We have used low-temperature NMR to study the electronic structure of bathorhodopsin, the primary photoproduct of the light-sensitive membrane protein, rhodopsin. This project used a custom-built NMR probe that allows low-temperature NMR in the presence of illumination (the image shows the illuminated spinner module). We have also used this technique to study the behavior of molecules within a restricted environment. Small-molecule endofullerenes are interesting molecular systems in which molecular rotors are confined to a well-insulated, well-defined, and highly symmetric environment. We discuss how cryogenic solid state NMR can give information on the dynamics of ortho-water confined in a fullerene cage. Molecular motions are often connected with fundamental chemical properties; therefore, an understanding of molecular dynamics can be important in fields ranging from material science to biochemistry. We present the case of ibuprofen sodium salt which exhibits different degrees of conformational freedom in different parts of the same molecule, leading to a range of line broadening and line narrowing phenomena as a function of temperature