Influence of the Thiophene Ring on the Molecular Order of Structurally Simple π-Conjugated Smectogens: 13 C NMR Study.

Structurally simple rod-like π-conjugated mesogens with thiophene directly connected to phenyl, biphenyl, and fluorenone rings with terminal chains are synthesized respectively. The occurrence of smectic A/smectic C phases is concurred by a hot-stage optical polarising microscope (HOPM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). The static 1D and 2D 13 C nuclear magnetic resonance (NMR) studies in the liquid crystalline phase are carried out to find the alignment-induced chemical shifts (AIS) and 13 C-1 H dipolar couplings. The orientational order parameters of the mesogens determined from 13 C-1 H dipolar couplings disclose that the long axis is not only collinear to the C3-C4 bond of the thiophene ring but also for the local axes of phenyl and biphenyl rings. For fluorenone-based mesogen, the molecular biaxiality is found to be high owing to the increased breadth of the molecule. The study unveils that the orientation of thiophene and the phenyl rings is similar in the current mesogens in stark contrast to mesogens, where thiophene is connected to phenyl rings through linking groups.

Molecular Conformations of Shape Anisometrically Variant Mesogens in Liquid Crystalline Phase Studied by 13 C NMR Spectroscopy.

Mesogens that vary in shape anisometry have been investigated by 13 C solid-state NMR in the liquid crystalline phase to inspect the conformations. The molecules examined comprise of (i) rod-like mesogen with three-phenyl ring core and terminal hexyloxy chains, (ii) three-ring core linked to the fourth phenyl ring via a spacer, and (iii) trimesic acid connected to three side arms core units through a spacer. The order parameter (Szz ) values for the phenyl rings of the rod-like mesogen are 0.65-0.68, while the mesogen with a three-ring core linked to a phenyl ring via spacer showed dissimilarity. Consequently, for the core unit phenyl rings, Szz is ~0.70, and the terminal phenyl ring showed a low value of 0.12. For the trimesic acid based mesogen, the Szz value for the side arm phenyl rings is ~0.53, and for the central phenyl ring, a very low value of 0.11 is witnessed. By considering the ordering of the rod-like mesogen as a yardstick and employing the ratios of Szz values of the phenyl rings, the average conformations of other mesogens are arrived. Accordingly, for the trimesic acid based mesogen, a tripod-like conformation instead of λ shape is proposed in the liquid crystalline phase.

13C Nuclear Magnetic Resonance Investigations of Molecular Mesogens with a Terminal Phenyl Ring Linked via a Spacer: Odd-Even Effect.

A set of mesogens considered as model molecules to the technologically important twist-bend (NTB) nematogens are investigated. They consist of a three-ring core connected to a phenyl ring via a flexible spacer and displayed enantiotropic nematic and smectic C mesophases. In such systems, odd or even number of atoms present in the spacer could influence the orientation of the terminal phenyl ring and thus have a bearing on designing the NTB phase, considered as intermediate between the nematic and the cholesteric phases. One-dimensional (1D) and two-dimensional (2D) 13C NMR spectra have been recorded in the liquid crystalline phases and the alignment-induced chemical shifts (AIS) and the 13C-1H dipolar couplings obtained. The order parameters of the phenyl rings reveal features relatable to the odd/even number of atoms of the flexible spacer and the type of linkage. The AIS plots of the phenyl rings of the even spacer-based mesogen showed the usual behavior for all of the phenyl rings with a decrease in AIS with increasing temperature. However, for the odd-spacer mesogens, unusual behaviors are noted for the terminal phenyl ring. Thus, two of the mesogens showed an increase of AIS in the smectic C phase that continued till the middle of the nematic phase temperature range, followed by a decrease. The other two odd-spacer mesogens also showed different behaviors. These observations indicate that the terminal phenyl ring is oriented at an angle with respect to the long molecular axis for the odd-spacer mesogens that changes as a function of temperature. The angles have been found to depend on the nature of the atom/group connecting the spacer to the terminal ring and the spacer length. Thus, the present study provides critical information on the design of the odd dimers that are recognized to generate fascinating NTB mesophases.

Molecular Order of Topologically Variant Flexible Mesogens by 13C Nuclear Magnetic Resonance.

13C nuclear magnetic resonance investigations in the nematic phase of mesogens comprising a rod-like core with three phenyl rings connected to a fourth phenyl ring via a flexible spacer are reported. The molecules are abbreviated as monomer, dimer, and trimer as they comprised one, two, and three pairs of core and spacer combinations linked to ring IV, respectively. Hot-stage optical polarizing microscopy and differential scanning calorimetry studies confirmed that all of them exhibit an enantiotropic nematic phase with additional monotropic or enantiotropic smectic mesophases. Large values of 13C-1H dipolar couplings of the order of 11 kHz are observed for all the cases for the terminal carbon C1 of the core unit. These high values indicated that the corresponding CH vector is collinear with the long axis of the molecule, which itself is aligned parallel to the magnetic field. In contrast, the terminal carbon of the ring IV (C19/C17) exhibits a relatively smaller value in the range of 2.0-2.5 kHz, reflecting the divergent local dynamics at different sections of the mesogens. The orientational order parameters of the phenyl rings computed from the 13C-1H dipolar couplings have been used to obtain the conformation of the mesogens in the nematic phase. It is concluded that the dimer and trimer exhibit C2 and C3 symmetry with the ring IV connected by spacers tilted away from the symmetry axis by 35.9 and 90° for the two cases, respectively. This leads to the interesting tripod-like molecular shape for the trimer in the nematic phase rather than the planar representation of the λ shape.

Measurement of Large Dipolar Couplings of a Liquid Crystal with Terminal Phenyl Rings and Estimation of the Order Parameters.

NMR spectroscopy is a powerful means of studying liquid-crystalline systems at atomic resolutions. Of the many parameters that can provide information on the dynamics and order of the systems, (1) H-(13) C dipolar couplings are an important means of obtaining such information. Depending on the details of the molecular structure and the magnitude of the order parameters, the dipolar couplings can vary over a wide range of values. Thus the method employed to estimate the dipolar couplings should be capable of estimating both large and small dipolar couplings at the same time. For this purpose, we consider here a two-dimensional NMR experiment that works similar to the insensitive nuclei enhanced by polarization transfer (INEPT) experiment in solution. With the incorporation of a modification proposed earlier for experiments with low radio frequency power, the scheme is observed to enable a wide range of dipolar couplings to be estimated at the same time. We utilized this approach to obtain dipolar couplings in a liquid crystal with phenyl rings attached to either end of the molecule, and estimated its local order parameters.

Effortless Extraction of Structural and Orientational Information from 13C-1H Dipolar Couplings for Thiophene Mesogens.

Five molecular mesogens containing phenyl rings and thiophene are subjected to a detailed 13C NMR investigation. The first mesogen contains only phenyl rings, while the other four have thiophene with substitution at position 2 or 3. Two of these also have a spacer inserted between the thiophene and the rest of the core unit. The mesophase properties evaluated by complementary techniques reveal an enantiotropic nematic phase for all the cases and smectic C as well as Crystal J for a few mesogens. In addition to solution 13C NMR, the samples were studied using 1D and 2D solid-state 13C NMR experiments in the liquid crystalline phase. The chemical shifts and 13C-1H dipolar couplings obtained in the mesophase provided cutting-edge information about the molecular structure and orientation of the thiophene mesogens. Accordingly, dramatic differences in these parameters are noted for the mesogens, and consequently, the identification of 2- and 3-substituted thiophene mesogens is accomplished by a simple visual examination of the 2D spectra. Furthermore, for mesogens with a spacer between thiophene and the rest of the core, 13C chemical shifts and 13C-1H dipolar couplings showed remarkable variation, which was directly reflected in the order parameters. For instance, the order parameter (Szz) of thiophene in 2- and 3-substituted mesogens in which the spacer is absent is ∼0.63 whereas for those with spacer, it is reduced to ∼0.14-0.18. In comparison, the mesogen in which the core unit is made up of phenyl rings alone that is used to benchmark the characteristics of thiophene ordering showed an order parameter of ∼0.85. The study unambiguously demonstrates the supremacy of 13C NMR in extracting the structural and orientational information on mesogens in which thiophene is a constituent of the core unit.

Imaging and Intervention in Internal Carotid Artery Pseudoaneurysm Secondary to Retropharyngeal Abscess.

Vascular complications secondary to retropharyngeal abscess are rarely encountered in the post antibiotic era and include compression of internal carotid artery (ICA), infective arteritis and pseudoaneurysm formation. Post infectious ICA pseudoaneurysm formation is reported predominantly in the paediatric age group and rare in adults. We report a case of retropharyngeal abscess complicated by ICA pseudoaneurysm in an adult successfully managed by endovascular approach.

Igg4 Related Disease of Skull Base-A Diagnostic Challenge.

IgG4 related disease (IgG4-RD) is a fibro-inflammatory disease, with tendency to affect any organ of the body. However, few cases affecting the skull base have been reported in literature. We report one such case in an elderly male, who presented us with a mass lesion in the skull base that mimicked nasopharyngeal malignancy. On thorough clinical history, examination, and investigations, IgG4 Related disease was diagnosed and treatment was started for it. The patient responded well to the treatment and is on follow up.

Conformational investigation of peptides using solid-state NMR spectroscopy-A study of polymorphism of ß-turn peptides containing diprolines.

The construction of complex protein folds relies on the precise conversion of a linear polypeptide chain into a compact 3-dimensional structure. In this context, study of isolated secondary structural modules containing short stretches of amino acids assumes significance. Additionally, peptides, both natural and synthetic, play a major role as potential drugs. With a view to understand the local conformations adopted by peptides in the solid state, we propose a multinuclear NMR approach utilizing spectra of nuclei in their natural isotopic abundance. Various solid-state NMR experiments have been utilized for assignment of the spectra. Additionally, the gauge-including projector augmented-wave (GIPAW) calculations were used to confirm the assignments. Particularly, the utility of the double-quantum-single-quantum correlation experiments is highlighted for the purpose of assignment and for inferring the conformation across the peptide bond. The methodology is illustrated for the case of designed peptides containing diproline residues occurring at the ß-turns for identifying their cis-trans conformational polymorphism. The proposed method promises to be of use in the study of conformations of small- to medium-sized peptides such as antimicrobial peptides and in the study of polymorphism leading to applications in drug development protocols.

Experimental Insights into the Electronic Nature, Spectral Features, and Role of Entropy in Short CH3···CH3 Hydrophobic Interactions.

Hydrophobic interactions are often explored in solution-state aggregation of molecules. However, an experimental electron density description about these interactions is still lacking. Here, we report a systematic study on the electronic nature of methyl···methyl hydrophobic interactions in a series of multicomponent crystals of biologically active molecules. Charge density models based on high-resolution X-ray diffraction allow the visualization of subtle details of electron density features in the interaction region. Our study classifies these interactions as atypical group···group interactions in contrast to σ-hole interactions, which are stabilized by the minimized electrostatic repulsion and maximized dispersion forces. For the first time, we quantified the solid-state entropic contribution from the torsional mode of the methyl groups in stabilizing these interactions by thermal motion analysis based on neutron diffraction as well as variable-temperature crystallography. The carbon atoms in methyl···methyl interactions show a unique upfield chemical shift in the 13C solid-state NMR signal.

Does aluminium bind to histidine? An NMR investigation of amyloid ß12 and amyloid ß16 fragments.

Aluminium and zinc are known to be the major triggering agents for aggregation of amyloid peptides leading to plaque formation in Alzheimer's disease. While zinc binding to histidine in Aß (amyloid ß) fragments has been implicated as responsible for aggregation, not much information is available on the interaction of aluminium with histidine. In the NMR study of the N-terminal Aß fragments, DAEFRHDSGYEV (Aß12) and DAEFRHDSGYEVHHQK (Aß16) presented here, the interactions of the fragments with aluminium have been investigated. Significant chemical shifts were observed for few residues near the C-terminus when aluminium chloride was titrated with Aß12 and Aß16 peptides. Surprisingly, it is nonhistidine residues which seem to be involved in aluminium binding. Based on NMR constrained structure obtained by molecular modelling, aluminium-binding pockets in Aß12 were around charged residues such as Asp, Glu. The results are discussed in terms of native structure propagation, and the relevance of histidine residues in the sequences for metal-binding interactions. We expect that the study of such short amyloid peptide fragments will not only provide clues for plaque formation in aggregated conditions but also facilitate design of potential drugs for these targets.

Sensitivity Enhancement in Solid-State Separated Local Field NMR Experiments by the Use of Adiabatic Cross-Polarization.

Measurement of dipolar couplings using separated local field (SLF) NMR experiment is a powerful tool for structural and dynamics studies of oriented molecules such as liquid crystals and membrane proteins in aligned lipid bilayers. Enhancing the sensitivity of such SLF techniques is of significant importance in present-day solid-state NMR methodology. The present study considers the use of adiabatic cross-polarization for this purpose, which is applied for the first time to one of the well-known SLF techniques, namely, polarization inversion spin exchange at the magic angle (PISEMA). The experiments have been carried out on a single crystal of a model peptide, and a dramatic enhancement in signal-to-noise up to 90% has been demonstrated.

Single-file diffusion of confined water inside SWNTs: an NMR study.

We report a nuclear magnetic resonance (NMR) study of confined water inside approximately 1.4 nm diameter single-walled carbon nanotubes (SWNTs). We show that the confined water does not freeze even up to 223 K. A pulse field gradient (PFG) NMR method is used to determine the mean squared displacement (MSD) of the water molecules inside the nanotubes at temperatures below 273 K, where the bulk water outside the nanotubes freezes and hence does not contribute to the proton NMR signal. We show that the mean squared displacement varies as the square root of time, predicted for single-file diffusion in a one-dimensional channel. We propose a qualitative understanding of our results based on available molecular dynamics simulations.

Electron spin-spin exchange coupling mediated by the porphyrin pi system.

The syntheses and electron paramagnetic resonance (EPR) spectral characterizations of porphyrins (1-3) substituted with two radical groups bound to trans-meso positions are described. One of these compounds, 3, has been studied by variable-temperature magnetic susceptibility and has been structurally characterized. Biradical porphyrin 3 is monoclinic, space group P2(1)/n, with a = 12.239(2) A, b = 17.819(3) A, c = 34.445(7) A, alpha = 90 degrees , beta = 97.466(3) degrees , gamma = 90 degrees , and Z = 2. The bis(nitroxide) porphyrins 1 and 2 exhibit fluid solution EPR spectra consistent with |J| >> |a|. No evidence was observed for conformational modulation of J by rotation about single bonds as shown by the lack of change of the EPR spectra as a function of temperature. The bis(semiquinone) porphyrin 3 exhibits frozen-solution EPR spectra with zero-field splitting and a Deltam(s) = 2 transition characteristic of a triplet state. The intensity of the Deltam(s) = 2 transition of 3 was measured as a function of temperature, and the data fit according to a singlet-triplet model to yield J(3,solution) = -75 cm(-1) (H = - 2Js1.s2). Polycrystalline samples of porphryin 3 were examined by variable-temperature magnetometry. The paramagnetic susceptibility data were fit using a modified Bleaney-Bowers equation to give J(3,solid) = -29 cm(-1) (H = - 2Js(1).s(2)). The antiferromagnetic J values are consistent with the pi topology of the porphyrin ring.