The Influence of Methyl Groups on the Formation of the Ferroelectric Nematic Phase.

The synthesis and characterization of 12 ferroelectric nematogens based on the RM734 structural template are reported in the form of two series named ECMe and ECMeF. Within both series, the position of the methyl groups present was varied and all 12 of these compounds exhibited the ferroelectric nematic phase. In general, when modifications were made that decreased the shape anisotropy of the molecule, the value of decreased in line with the literature.

A key region of Tau that is able to drive assembly and modulate inhibition by Hydromethylthionine.

Tau (dGAE) forms paired helical filaments in vitro that resemble those deposited in Alzheimer's disease brain tissue. We have previously shown that hydromethylthionine (HMT) has the ability to inhibit dGAE self-assembly at sub-stoichiometric ratios. Here, we examined two regions of tau within the core filament-forming region that possess high self-assembly propensity sequences and have explored their ability to form filaments and whether their self-assembly can be inhibited by HMT.

Sulfur-linked cyanoterphenyl-based liquid crystal dimers and the twist-bend nematic phase.

The synthesis and characterisation of two series of cyanoterphenyl-based liquid crystal dimers containing sulfur links between the spacer and mesogenic units, the 3-{ω-[(4'-cyano-[1,1'-biphenyl]-4-yl)thio]alkyl}-[1,2:2,3-terphenyl]-1-carbonitriles (CBSCT), and the 3-({ω-[(4'-cyano-[1,1'-biphenyl]-4-yl)thio]alkyl}oxy)-[1,2:2,3-terphenyl]-1-carbonitriles (CBSOCT) are described. The odd members of both series show twist-bend nematic and nematic phases, whereas the even members exhibit only the nematic phase. This is consistent with the widely held view that molecular curvature is a prerequisite for the observation of the twist-bend nematic phase.

Twist-bend liquid crystal phases and molecular structure: the role of methoxybiphenyl.

The synthesis and characterisation of the 4-[{[4-({6-[4-(4-methoxyphenyl)phenyl]hexyl}oxy)phenyl]methylidene}amino]phenyl 4-alkyloxybenzoates is reported. These are referred to using the acronym MeOB6OIBeO in which denotes the number of carbon atoms in the terminal alkyloxy chain and is varied from one to ten. All ten members exhibit an enantiotropic conventional nematic (N) phase.

LETC inhibits α-Syn aggregation and ameliorates motor deficiencies in the L62 mouse model of synucleinopathy.

Alpha-Synuclein (α-Syn) aggregation is a pathological feature of synucleinopathies, neurodegenerative disorders that include Parkinson's disease (PD). Here, we explored the efficacy of N,N,N',N'-tetraethyl-10H-phenothiazine-3,7-diamine dihydrochloride (LETC), a protein aggregation inhibitor, on α-Syn aggregation. In both cellular models and transgenic mice, α-Syn aggregation was achieved by the overexpression of full-length human α-Syn fused with a signal sequence peptide.

Liquid Crystal Dimers and the Twist-Bend Phases: Non-Symmetric Dimers Consisting of Mesogenic Units of Differing Lengths.

The syntheses and characterisation of the 4-[{[4-({n-[4-(4-cyanophenyl)phenyl]-n-yl}oxy)phenyl]-methylidene}amino]phenyl-4-alkoxybenzoates (CBnOIBeOm) are reported with n=8 and 10 and m=1-10. The two series display fascinating liquid crystal polymorphism. All twenty reported homologues display an enantiotropic nematic (N) phase at high temperature.

To Be or Not To Be Polar: The Ferroelectric and Antiferroelectric Nematic Phases.

We report two new series of compounds that show the ferroelectric nematic, N, phase in which the terminal chain length is varied. The longer the terminal chain, the weaker the dipole-dipole interactions of the molecules are along the director and thus the lower the temperature at which the axially polar N phase is formed. For homologues of intermediate chain lengths, between the non-polar and ferroelectric nematic phases, a wide temperature range nematic phase emerges with antiferroelectric character.

Ferroelectric Nematic-Isotropic Liquid Critical End Point.

A critical end point above which an isotropic phase continuously evolves into a polar (ferroelectric) nematic phase with an increasing electric field is found in a ferroelectric nematic liquid crystalline material. The critical end point is approximately 30 K above the zero-field transition temperature from the isotropic to nematic phase and at an electric field of the order of 10  V/μm. Such systems are interesting from the application point of view because a strong birefringence can be induced in a broad temperature range in an optically isotropic phase.

Intrinsically Chiral Twist-Bend Nematogens: Interplay of Molecular and Structural Chirality in the N Phase.

The front cover artwork is provided by Dr Rebecca Walker of the Liquid Crystals Group at the University of Aberdeen. The image is a cartoon depiction of the formation of the heliconical chiral twist-bend nematic phase (N* ) from its constituent bent molecules. The presence of a single enantiomer of the chiral, lactate-based liquid crystal dimers biases the formation of helices with only one handedness, unlike in the conventional N phase, observed for achiral molecules, for which the left- and right-handed helices are doubly degenerate.

Molecular Shape, Electronic Factors, and the Ferroelectric Nematic Phase: Investigating the Impact of Structural Modifications.

The synthesis and characterisation of two series of low molar mass mesogens, the (4-nitrophenyl) 2-alkoxy-4-(4-methoxybenzoyl)oxybenzoates (NT3.m) and the (3-fluoro-4-nitrophenyl) 2-alkoxy-4-(4-methoxybenzoyl)oxybenzoates (NT3F.m), are reported in order to investigate the effect of changing the position of a lateral alkoxy chain from the methoxy-substituted terminal ring to the central phenyl ring in these two series of materials based on RM734.

Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391).

Aggregation of the tau protein into fibrillar cross-β aggregates is a hallmark of Alzheimer's diseases (AD) and many other neurodegenerative tauopathies. Recently, several core structures of patient-derived tau paired helical filaments (PHFs) have been solved revealing a structural variability that often correlates with a specific tauopathy. To further characterize the dynamics of these fibril cores, to screen for strain-specific small molecules as potential biomarkers and therapeutics, and to develop strain-specific antibodies, recombinant in-vitro models of tau filaments are needed.

Using Lateral Substitution to Control Conformational Preference and Phase Behaviour of Benzanilide-based Liquid Crystal Dimers.

The inclusion of secondary and tertiary benzanilide-based mesogenic groups into liquid crystal dimers is reported as a means to develop new materials. Furthermore, substitution at the nitrogen atom is shown to introduce an additional synthetic 'handle' to modify the molecular structure of the tertiary materials. The design of these materials has proved challenging due to the strong preferences of 3° benzanilides for the E amide conformation.

Intrinsically Chiral Twist-Bend Nematogens: Interplay of Molecular and Structural Chirality in the N Phase.

Non-symmetric lactate-based chiral liquid crystal dimers containing an odd-membered spacer are shown to exhibit a chiral twist-bend nematic phase which is stable on cooling to room temperature. A comparison of racemic and optically pure materials reveals that the pitch length in the N* phase is not influenced by molecular chirality, whereas the nematic-twist-bend nematic transition temperature is increased.

The effect of a lateral alkyloxy chain on the ferroelectric nematic phase.

The synthesis and characterisation of two series of low molar mass liquid crystals, the 4-[(4-nitrophenoxy)carbonyl]phenyl 2-alkoxy-4-methoxybenzoates (series 5-) and the 4-[(3-fluoro-4-nitrophenoxy)carbonyl]phenyl 2-alkoxy-4-methoxybenzoates (series 6-) are reported in order to explore the effects of a lateral alkyloxy chain on the formation and stability of the recently discovered ferroelectric nematic phase. In both series , the number of carbon atoms in the lateral chain, is varied from one to nine. The two series differ by the addition of a fluorine substituent in the 6- series.

Novel Method of Analysis for the Determination of Residual Formaldehyde by High-Performance Liquid Chromatography.

Formaldehyde is commonly used as an alkylating agent in the pharmaceutical industry. Consequently, its residual level in drug substances and/or their intermediates needs to be accurately quantified. Formaldehyde is a small, volatile molecule with a weak chromophore (the carbonyl group), and its direct analysis by GC-FID and HPLC-UV is difficult.

New patterns of twist-bend liquid crystal phase behaviour: the synthesis and characterisation of the 1-(4-cyanobiphenyl-4'-yl)-10-(4-alkylaniline-benzylidene-4'-oxy)decanes (CB10O·).

The synthesis and characterisation of the 1-(4-cyanobiphenyl-4'-yl)-10-(4-alkylanilinebenzylidene-4'-oxy)decanes (CB10O·) are reported. This series shows a rich liquid crystal polymorphism including twist-bend nematic and smectic phases. All the homologues reported exhibit an enantiotropic conventional nematic phase.

HMTM-Mediated Enhancement of Brain Bioenergetics in a Mouse Tauopathy Model Is Blocked by Chronic Administration of Rivastigmine.

The tau protein aggregation inhibitor hydromethylthionine mesylate (HMTM) was shown recently to have concentration-dependent pharmacological activity in delaying cognitive decline and brain atrophy in phase 3 Alzheimer's disease (AD) clinical trials; the activity was reduced in patients receiving symptomatic therapies. The methylthionine (MT) moiety has been reported to increase the clearance of pathological tau and to enhance mitochondrial activity, which is impaired in AD patients. In line 1 (L1) mice (a model of AD), HMTM (5/15 mg/kg) was administered either as a monotherapy or as an add-on to a chronic administration with the cholinesterase inhibitor rivastigmine (0.

Flexoelectric Polarization in a Nematic Liquid Crystal Enhanced by Dopants with Different Molecular Shape Polarities.

Flexoelectricity may have an important impact on the switching properties of nematic and cholesteric liquid crystals due to the linear coupling between the flexoelectric polarization of the liquid crystal and the applied electric field. This coupling is the origin of the extraordinary electro-optic effect in cholesterics aligned in the uniform lying helix texture, resulting in fast switching and field control of both rise and fall times. Therefore, the flexoelectric properties of the liquid crystals have become an important issue when designing and synthesizing liquid crystal materials and/or preparing their mixtures with appropriate flexoelectric compounds (dopants).

Combined electric and photocontrol of selective light reflection at an oblique helicoidal cholesteric liquid crystal doped with azoxybenzene derivative.

An oblique helicoidal cholesteric liquid crystal Ch_{OH} represents a unique optical material with a single-harmonic periodic modulation of the refractive index and a pitch that can be tuned by an electric or magnetic field in a broad range from submicrometers to micrometers. In this work, we demonstrate that the oblique helicoidal cholesteric doped with azoxybenzene molecules can be tuned by both the electric field and light irradiation. The tuning mechanism is explained by the kinetics of trans-cis photoisomerization of the azoxybenzene molecules.

Multiple Polar and Non-polar Nematic Phases.

Liquid-crystal materials exhibiting up to three nematic phases are reported. Dielectric response measurements show that while the lower temperature nematic phase has ferroelectric order and the highest temperature nematic phase is apolar, the intermediate phase has local antiferroelectric order. The modification of the molecular structure by increasing the number of lateral fluorine substituents leads to one of the materials showing a direct isotropic-ferronematic phase transition.

Photonic Bandgap in Achiral Liquid Crystals-A Twist on a Twist.

Achiral mesogenic molecules are shown to be able to spontaneously assemble into liquid crystalline smectic phases having either simple or double-helical structures. At the transition between these phases, the double-helical structure unwinds. As a consequence, in some temperature range, the pitch of the helix becomes comparable to the wavelength of visible light and the selective reflection of light in the visible range is observed.

Understanding the remarkable difference in liquid crystal behaviour between secondary and tertiary amides: the synthesis and characterisation of new benzanilide-based liquid crystal dimers.

A number of liquid crystal dimers have been synthesised and characterised containing secondary or tertiary (N-methyl) benzanilide-based mesogenic groups. The secondary amides all form nematic phases, and we present the first example of an amide to show the twist-bend nematic (NTB) phase. Only two of the corresponding N-methylated dimers formed a nematic phase and with greatly reduced nematic-isotropic transition temperatures.

Concentration-Dependent Activity of Hydromethylthionine on Clinical Decline and Brain Atrophy in a Randomized Controlled Trial in Behavioral Variant Frontotemporal Dementia.

Background: Hydromethylthionine is a potent inhibitor of pathological aggregation of tau and TDP-43 proteins.

Objective: To compare hydromethylthionine treatment effects at two doses and to determine how drug exposure is related to treatment response in bvFTD.

Methods: We undertook a 52-week Phase III study in 220 bvFTD patients randomized to compare hydromethylthionine at 200 mg/day and 8 mg/day (intended as a control).

High-Contrast and Fast Photorheological Switching of a Twist-Bend Nematic Liquid Crystal.

Smart viscoelastic materials that respond to specific stimuli are one of the most attractive classes of materials important to future technologies, such as on-demand switchable adhesion technologies, actuators, molecular clutches, and nano-/microscopic mass transporters. Recently it was found that through a special solid-liquid transition, rheological properties can exhibit significant changes, thus providing suitable smart viscoelastic materials. However, designing materials with such a property is complex, and forward and backward switching times are usually long.