Discotic Star Mesogen with Thymine Nucleobases Exhibiting a Rare Gyroid Cubic Mesophase with 3D Conductivity.

A unique gyroid cubic phase has been discovered for a discotic star mesogen with three covalently attached DNA bases. In this cubic I a 3 ‾ d ${Ia\bar{3}d}$ phase, the conjugated core of the mesogens and the thymine pseudo guests self-assemble in mirror image continuous networks, representing a semiconducting material with three-dimensional transport pathways. The hole carrier mobilities are found to be in the typical range of poly(phenylenevinylene) scaffolds. This structure is stabilized by a weak hydrogen bonding between the thymine bases and can be switched to a columnar liquid crystal - thermally and by the addition of complementary adenine guests.

An Enzyme-Linked Immunosorbent Assay (ELISA) for Quantification of Circulating Pi*Z Alpha1-Antitrypsin Polymers.

Enzyme-linked immunosorbent assay (ELISA) is a sensitive immunoassay based on specific antigen-antibody reaction that is used for quantitative/qualitative analysis of various analytes in serum, plasma, saliva, cell and tissue lysates, and urine. ELISAs are typically performed in multi-well plates and depending on the design require coating antibody/antigen, analyte, detection antibodies, buffer, wash solution, and substrate/chromogen. Here we describe highly specific monoclonal antibody-based ELISA that detects circulating polymers formed by Pi*Z variant of human alpha-1-antitrypsin (Z-AAT). The circulating Z-AAT polymers are present in all individuals with inherited Pi*Z AAT deficiency. Thus, our assay provides a useful tool to examine the clinical significance and utility of Z-AAT polymers.

A Photomechanical Film in which Liquid Crystal Design Shifts the Absorption into the Visible Light Range.

Liquid crystalline polymer networks (LCN) with azobenzene monomers bend reversibly under UV-light irradiation, combining photomechanical and photothermal effects. However, the harmful nature of UV-light limits their use in biology and soft robotics. Although visible light-absorbing tetra-ortho-fluoro-substituted azobenzenes exist, liquid crystalline monomers have never been prepared. Previously, such azobenzenes were added as photoactive additives (up to 10%) to otherwise passive liquid crystalline polymer networks. In this work, a molecular design of a liquid crystalline, polymerizable azobenzene switchable by visible light is presented. The monomer assembles in a highly fluid nematic phase, but polymerizes in a layered smectic C phase. The films are produced solely from the monomer without additional liquid crystalline components and are actuated with visible light. Bending experiments in air and under water differentiate photomechanical and photothermal effects. Remarkably, a 60 µm splay aligned film maintains its deformation for hours, slowly reverting over days. Monomer liquid crystallinity is characterized using differential scanning calorimetry (DSC), wide-angle X-ray scattering (WAXS), and polarized optical microscopy (POM); polymer films are analyzed using WAXS and DSC on a homogeneously aligned film. The synthetic procedure is high yielding and polymer film fabrication is scalable, which enables the use of safe and efficient photomechanical LCNs in soft robotics, engineering and biology.

Skin hyperpigmentation index in melasma: A complementary method to classic scoring systems.

BACKGROUND: Due to relapsing nature of melasma with significant impact on quality of life, an objective measurement score is warranted, especially to follow-up the patients with melasma and their therapy response in a quantitative and precise manner. AIMS: To prove concordance of skin hyperpigmentation index (SHI) with well-established scores in melasma and demonstrate its superiority regarding inter-rater reliability. Development of SHI mapping for its integration in common scores. METHODS: Calculation of SHI and common melasma scores by five dermatologists. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) and concordance by Kendall correlation coefficient. RESULTS: Strong concordance of SHI with melasma area and severity index (MASI)-Darkness (0.48; 95% CI: 0.32, 0.63), melasma severity index (MSI)-Pigmentation (0.45; 95% CI: 0.26, 0.61), and melasma severity scale (MSS) (0.6; 95% CI: 0.42, 0.74). Using step function for mapping SHI into pigmentation scores showed an improvement of inter-rater reliability with a difference in (ICC of 0.22 for MASI-Darkness and 0.19 for MSI-Pigmentation), leading to an excellent agreement. CONCLUSION: Skin hyperpigmentation index could be an important additional cost-and time-conserving assessment method, to follow-up the patients with melasma undergoing brightening therapies in clinical studies, as well as in routine clinical practice. It is in strong concordance with well-established scores but superior regarding inter-rater reliability.

Atropisomerism in a polyglutamate-based thermoresponsive alignment medium.

Structure elucidation via residual dipolar couplings (RDCs) relies on alignment media. We report on lyotropic liquid crystals (LLCs) of poly-γ-p-biphenyl(2'-methoxy-2-methyl)methyl-L-glutamate (PBPM3LG). Temperature dependent atropisomerism within the biphenyl group enables the acquisition of multiple RDC-datasets within one sample.

Joint Venture of Metal Cluster and Amphiphilic Cationic Minidendron Resulting in Near Infrared Emissive Lamellar Ionic Liquid Crystals.

Inorganic red-NIR emissive materials are particularly relevant in many fields like optoelectronic, bioimaging or solar cells. Benefiting from their emission in devices implies their integration in easy-to-handle materials like liquid crystals, whose long-range ordering and self-healing abilities could be exploited and influence emission. Herein, we present red-NIR emissive hybrid materials obtained with phosphorescent octahedral molybdenum cluster anions electrostatically associated with amphiphilic guanidinium minidendrons. Polarized optical microscopy and X-ray analysis show that while the minidendron chloride salts self-organize into columnar phases, their association with the dianionic metal cluster leads to layered phases. Steady-state and time-resolved emission investigations demonstrate the influence of the minidendron alkyl chain length on the phosphorescence of the metal cluster core.

Investigations of the Alignment Process of PBPMLG: 2 H NMR Analysis Reveals a Thermoresponsive 90° Flip of the Polymer.

The application of anisotropic parameters in NMR-spectroscopy enables the acquisition of spatial and angular information, complementary to those from conventional isotropic NMR-measurements. The use of alignment media is a well-established method for inducing anisotropy. PBPMLG is a recently discovered polyglutamate-based alignment medium, exhibiting thermoresponsive behavior in the lyotropic liquid crystalline (LLC) phase, thus offering potential for deeper understanding of the alignment process. We present one approach for investigating the thermoresponsive behavior by synthesizing specifically deuterated PBPMLG-isotopologues and their subsequent analyses using 2 H NMR-spectroscopy. It was possible to relate the observed thermoresponsive behavior to a flip of the polymer with respect to the external magnetic field-an effect never observed before in glutamate-based polymeric alignment media. Furthermore, a solvent-induced temperature dependent gelation was verified in THF, which might provide yet another opportunity to manipulate the properties of this alignment medium in the future.

Polymerization of misfolded Z alpha-1 antitrypsin protein lowers CX3CR1 expression in human PBMCs.

Expression levels of CX3CR1 (C-X3-C motif chemokine receptor 1) on immune cells have significant importance in maintaining tissue homeostasis under physiological and pathological conditions. The factors implicated in the regulation of CX3CR1 and its specific ligand CX3CL1 (fractalkine) expression remain largely unknown. Recent studies provide evidence that host's misfolded proteins occurring in the forms of polymers or amyloid fibrils can regulate CX3CR1 expression. Herein, a novel example demonstrates that polymers of human ZZ alpha-1 antitrypsin (Z-AAT) protein, resulting from its conformational misfolding due to the Z (Glu342Lys) mutation in SERPINA1 gene, strongly lower CX3CR1 mRNA expression in human peripheral blood mononuclear cells (PBMCs). This parallels with increase of intracellular levels of CX3CR1 and Z-AAT proteins. Presented data indicate the involvement of the CX3CR1 pathway in the Z-AAT-related disorders and further support the role of misfolded proteins in CX3CR1 regulation.

Proteins can lose their structure and form polymers because of mutations or changes in their immediate environment which can lead to cell damage and disease. Interestingly, polymers formed by a variety of proteins can reduce the levels of CX3C chemokine receptor 1 (CX3CR1 for short) that controls the behaviour of immune cells and is implicated in a range of illnesses. Inherited ZZ alpha-1 antitrypsin deficiency is a rare genetic condition that highly increases the risk of liver and lung diseases. This disorder is characterised by mutant alpha-1 antitrypsin proteins (AAT for short) reacting together to form polymers; yet it remains unclear how the polymers affect different cells or organs, and lead to diseases. To investigate this question, Tumpara et al. examined whether polymers of mutant AAT influence the level of the CX3CR1 protein in specific classes of immune cells. Experiments revealed that in people with AAT deficiency, certain blood immune cells express lower levels of CX3CR1. Regardless of age, clinical diagnosis, or treatment regimen, all individuals with ZZ alpha-1 antitrypsin deficiency had AAT polymers circulating in their blood: the higher the levels of polymers measured, the lower the expression of CX3CR1 recorded in the specific immune cells. When Tumpara et al. added polymers of mutant AAT to the immune cells of healthy donors, the expression of CX3CR1 dropped in a manner dependent on the polymer concentration. According to microscopy data, AAT polymers occurred inside cells alongside the CX3CR1 protein, suggesting that the two molecular actors interact. In the future, new drugs that remove these polymers, either from inside cells or as they circulate in the body, could help patients suffering from conditions associated with this abnormal protein aggregation.

Impact of Substitution Pattern and Chain Length on the Thermotropic Properties of Alkoxy-Substituted Triphenyl-Tristriazolotriazines.

Tristriazolotriazines (TTTs) with a threefold alkoxyphenyl substitution were prepared and studied by DSC, polarized optical microscopy (POM) and X-ray scattering. Six pentyloxy chains are sufficient to induce liquid-crystalline behavior in these star-shaped compounds. Thermotropic properties of TTTs with varying substitution patterns and a periphery of linear chains of different lengths, branching in the chain and swallow-tails, are compared. Generally, these disks display broad and stable thermotropic mesophases, with the tangential TTT being superior to the radial isomer. The structure-property relationships of the number of alkyl chains, their position, length and structure were studied.

Controlling Supramolecular Structures of Drugs by Light.

Controlling physicochemical properties of light-unresponsive drugs, by light, prima facie, a paradox approach. We expanded light control by ion pairing light-unresponsive salicylate or ibuprofen to photoswitchable azobenzene counterions, thereby reversibly controlling supramolecular structures, hence the drugs' physicochemical and kinetic properties. The resulting ion pairs photoliquefied into room-temperature ionic liquids under ultraviolet light. Aqueous solutions showed trans-cis-dependent supramolecular structures under a light with wormlike aggregates decomposing into small micelles and vice versa. Light control allowed for permeation through membranes of cis-ibuprofen ion pairs within 12 h in contrast to the trans ion pairs requiring 72 h. In conclusion, azobenzene ion-pairing expands light control of physicochemical and kinetic properties to otherwise light-unresponsive drugs.

Unfolding multi-stranded perylene bisimide LC columns - a mesogen design for efficient nanoscale multilayer self-assembly.

A mesogen tethered, twofold bay-substituted perylene bisimide (PBI) is found to generate a columnar phase, which unfolds and gradually transforms to a completely nanosegregated multilayer columnar-lamellar liquid crystal. The structure is based on the formation of bundles of H-bonded PBI strands in the central layer. This design opens the way to new complex multifunctional materials.

Metal Phthalocyanine-Fullerene Dyads: Promising Lamellar Columnar Donor-Acceptor Liquid Crystal Phases.

Liquid crystal (LC) shape-amphiphiles with a disc tethered to a fullerene have been intensely studied for the application in photovoltaics, and helical nanosegregation of C60 has been claimed around the π-stacking disks based on X-ray results. The most promising materials reported to date have been resynthesized and studied comprehensively by XRS, density measurements, modelling, and electron density reconstruction. In contrast to previous reports, the results indicate that metal phthalocyanine-fullerene mesogens pack in lamellar columnar phases with p2gm symmetry. Fullerenes assemble in layers and are flanked by phthalocyanine columns, thus explaining the balanced charge carrier mobility of electrons and holes. Such variable donor-acceptor structures are promising for organic electronic applications.

Columnar Liquid Crystals from Star-Shaped Conjugated Mesogens as Nano-Reservoirs for Small Acceptors.

Shape-persistent conjugated mesogens with oligothiophene arms of different lengths have been synthesized. Such mesogens possess free intrinsic space between their conjugated arms. They form columnar liquid-crystalline phases, in which the void is filled by dense helical packing in the neat phase similar to an oligo(phenylene vinylene) derivative of equal size. The void can also be compensated by the inclusion of the small acceptor molecule 2,4,7-trinitrofluorenone. In solution, the acceptor interacts with the core as the largest π-surface, while in the solid material, it is incorporated between the arms and sandwiched by the star-shaped neighbours along the columnar assemblies. The TNF acceptors are not nanosegregated from the star-shaped donors, thus the liquid crystal structure converts to a nano-reservoir for TNF (endo-receptor). These host-guest arrangements are confirmed by comprehensive X-ray scattering experiments and solid-state NMR spectroscopy. This results in ordered columnar hexagonal phases at high temperatures, which change to helical columnar mesophases or to columnar soft crystals at room temperature.

Self-Sorting Supramolecular Polymerization: Helical and Lamellar Aggregates of Tetra-Bay-Acyloxy Perylene Bisimide.

A new perylene bisimide (PBI), with a fluorescence quantum yield up to unity, self-assembles into two polymorphic supramolecular polymers. This PBI bears four solubilizing acyloxy substituents at the bay positions and is unsubstituted at the imide position, thereby allowing hydrogen-bond-directed self-assembly in nonpolar solvents. The formation of the polymorphs is controlled by the cooling rate of hot monomer solutions. They show distinctive absorption profiles and morphologies and can be isolated in different polymorphic liquid-crystalline states. The interchromophoric arrangement causing the spectral features was elucidated, revealing the formation of columnar and lamellar phases, which are formed by either homo- or heterochiral self-assembly, respectively, of the atropoenantiomeric PBIs. Kinetic studies reveal a narcissistic self-sorting process upon fast cooling, and that the transformation into the heterochiral (racemic) sheetlike self-assemblies proceeds by dissociation via the monomeric state.

From molecular biaxiality of real board-shaped mesogens to phase biaxiality? On the hunt for the holy grail of liquid crystal science.

In the search of the predicted biaxial nematic phase, a series of shape-persistent board-shaped mesogens with maximum molecular biaxiality and a dipole along the minor molecular axis were designed to form nematic (N) mesophases. One compound exhibits a wide nematic temperature range, which can be supercooled to room temperature. A comprehensive variable temperature X-ray study on aligned samples reveals patterns being dominated by the form factor of very small aggregates, from which the aspect ratio of the lead compound with length (L) : breadth (B) : width (W) of 10.73 : 3.16 : 1.23 could be obtained. The ratio is close to the predicted optimum molecular biaxiality by Straley's hard particle model. Hence variable temperature proton relaxation studies on this mesogen were carried out over a wide frequency range. The global fit of the frequency dispersions at five temperatures with a motional model requires in addition to the usual rotation/reorientation contribution, two independent director fluctuations contributions: one for the conventional nematic order director (n) fluctuations and the other for the minor director (m) fluctuations (normal to n). The correlation length of the minor directors determined by NMR could extend to 5-8 molecules in the W direction, but only to the nearest neighbour in the B direction, as found by X-ray diffraction. Both X-ray and NMR studies indicate that these new types of lead structure are extremely promising to find the long sought-after biaxial N mesophase.

Synthesis, Thermal, and Optical Properties of Tris(5-aryl-1,3,4-oxadiazol-2-yl)-1,3,5-triazines, New Star-Shaped Fluorescent Discotic Liquid Crystals.

The synthesis of tris(aryloxadiazolyl)triazines (TOTs), C3 -symmetrical star-shaped mesogenes with a 1,3,5-triazine center, 5-phenyl-1,3,4-oxadiazole arms, and various peripheral alkoxy side chains is reported. Threefold Huisgen reaction on a central triazine tricarboxylic acid and suitable aryltetrazoles yields the title compounds. Selected analogues with a benzene center are included in this study and allow for an evaluation of the impact of the central unit on the physical properties. Thermal (differential scanning calorimetry, DSC; polarization optical microscopy, POM), optical (UV/Vis, fluorescence), electric (time of flight, TOF), and structural (single crystal; wide-angle X-ray scattering, WAXS) properties of these compounds were investigated. The modification of alkoxy chain length and substitution pattern allows for a tuning of the physical properties. TOTs emit blue to yellow light, depending on conjugation length, donor-acceptor substitution, and solvent polarity, whereas concentration quenches and aggregation enhances the emission. The width of the mesophases is typically around ΔT=100-150 K but can even exceed 220 K. Polarization optical microscopy and X-ray diffraction on oriented filaments reveal that TOTs are highly ordered liquid crystals (LCs) with long-range hexagonal columnar structure.

Photoconductive Core-Shell Liquid-Crystals of a Perylene Bisimide J-Aggregate Donor-Acceptor Dyad.

A novel core-shell structured columnar liquid crystal composed of a donor-acceptor dyad of tetraphenoxy perylene bisimide (PBI), decorated with four bithiophene units on the periphery, was synthesized. This molecule self-assembles in solution into helical J-aggregates guided by π-π interactions and hydrogen bonds which organize into a liquid-crystalline (LC) columnar hexagonal domain in the solid state. Donor and acceptor moieties exhibit contrasting exciton coupling behavior with the PBIs' (J-type) transition dipole moment parallel and the bithiophene side arms' (H-type) perpendicular to the columnar axis. The dyad shows efficient energy and electron transfer in solution as well as in the solid state. The synergy of photoinduced electron transfer (PET) and charge transport along the narcissistically self-assembled core-shell structure enables the implementation of the dye in two-contact photoconductivity devices giving rise to a 20-fold increased photoresponse compared to a reference dye without bithiophene donor moieties.

Free Space in Liquid Crystals-Molecular Design, Generation, and Usage.

In the last 50 years, an important aim of molecular and materials design has been the generation of space for the uptake of guest molecules in macrocycles and cryptands, in dendrimers as monomolecular containers, and recently in porous networks like metal-organic and covalent organic frameworks. Such molecular, oligomeric, and polymeric materials can be applied for sensing, separation, catalysis, drug delivery, and gas storage, among others. The common goal is the recognition of molecules and their uptake into and release from an appropriate space. Typically, completely empty space is unfavorable in crystalline materials. Therefore, the elimination of molecules from the cavities is often accompanied by the collapse of the cavities, that is, by a change in the molecular conformation. In contrast to this solid matter, in which the cavities are rationally designed by covalent or coordinative bonds, liquid crystals (LCs) are fluid materials with high molecular mobility. Thus, the proposal of empty space in LCs is certainly a scientific provocation. However, various recent publications on columnar mesophases claim the existence of pores with low electron density or even completely empty space on the basis of X-ray and solid-state NMR studies. Although the latter may be debated, there are many examples in which LCs take up dopants such as polymerizable monomers in disclination lines, perdeuterated chains in the interstices between columns, or electron acceptors to fill mesogens with incommensurate building blocks, which eventually stabilize the LC phases. It seems that in LC science the generation and usage of free space has been studied only occasionally and were lucky discoveries rather than investigations based on rational design. This Account summarizes the research on the formal generation of void in LCs and highlights that rational design of molecules can lead to unconventional mesophases by efficient filling of the provided space, as was shown with shuttlecock mesogens and discotic mesogens related to the concept of complementary polytopic interactions. The topic was recently further developed by the investigation of shape-persistent star mesogens. Despite the formally empty space between their arms, they all form columnar liquid crystals. Such shape-persistent oligo(phenylenevinylene) molecules fill the void and efficiently nanosegregate by helical packing in columns and deformation of the molecular scaffold at the expense of the torsional energy. This inspired us to fill the intrinsic free space by guest molecules either via supramolecular or covalent bonds or just by physical mixing in order to avoid the increase in torsional energy and to stabilize the structure. This strategy led to complex filled liquid-crystalline matter with high structural control and may in the future be used for the design of organic electronic materials that are easily alignable for device applications.

Fullerene-Filled Stilbene Stars: The Balance between Isolated C60 Helices and 3D Networks in Liquid-Crystal Self-Assemblies.

A series of shape-persistent star-shaped oligo(phenylene vinylene) liquid crystals and derivatives with fullerene tethered through spacers of different lengths to one arm were successfully synthesized. Solution studies by NMR, UV/Vis and fluorescence spectroscopy revealed the preferential location of the C60 acceptor in the vicinity of the peripheral donor unit, which affects the quenching of the emission of the conjugated stilbenoid scaffold in the donor-acceptor dyad. The fluorescence was completely absent in the liquid crystal phase due to the extraordinary hierarchical self-assembly. In this family of mesogens, the intrinsic free space has to be filled either by an extremely tight packing of the stars or by the fullerenes as guests. The spacer lengths control the nanosegregation of the C60 units in the cavities of the stars in either independent triple helices or unprecedented 3D networks, in which fullerenes are positioned at the interface of neighboring columns. Eventually, the clearing temperature of such large complex donor-acceptor systems can be tuned by an entropy effect defined by the length of the spacer. The accessibility of the isotropic phase without decomposition is an important prerequisite for future alignment studies associated with potential material applications in organic electronics.

Fullerene-Filled Liquid-Crystal Stars: A Supramolecular Click Mechanism for the Generation of Tailored Donor-Acceptor Assemblies.

Two shape-persistent star mesogens with oligo(phenylene ethenylene) arms and a phthalocyanine core-one providing free space (2) and one sterically encumbered by four fullerenes attached through spacers (3)-have been successfully synthesized. In contrast to the smaller discotic derivative 1, mesogen 2 forms a columnar liquid crystal (LC), which can only be partially aligned without π-stacking, while 3 is not an LC. Exceptionally, the 1:1 mixture of 2 and 3 forms an alignable columnar LC with strong π-stacking and quadruply helically organized fullerenes by an unprecedented click process that is similar to a ball detent mechanism. The C60 units also interconnect different columns. This is driven by nanosegregation and space-filling of the voids with fullerenes. Photophysical studies confirm the presence of a light-collecting system that generates charge-separated states in solution and in the solid state, which makes such highly organized materials attractive for the study of future photovoltaic devices.