Search Results (18)

The objective of this work was to improve the solubility and discover a stable co-amorphous form of valsartan (VAL), a BCS class-II drug, by utilizing small molecule 2-Aminopyridine (2-AP) in varying molar ratios (2:1, 1:1, and 1:2), employing a solvent evaporation technique. Additionally, by way of a density functional theory (DFT)-based computational method with commercially available software, a new approach for determining the intermolecular connectivity of multi-molecular hydrogen bonding systems was proposed. The binary systems’ features were characterized by PXRD, DSC, FTIR, and Raman spectroscopy, while the equilibrium solubility and dissolution was determined in 0.1 N HCL and water conditions to investigate the dissolution advantage of the prepared co-amorphous systems. The results demonstrated that the co-amorphous system was successfully prepared in VAL/2-AP with a 1:2 molar ratio following solvent evaporation, whereby the hydrogen bonding sites of VAL were fully occupied. Physical stability studies were carried out under dry conditions at room temperature for 6 months. Furthermore, four possible ternary systems were constructed, and their vibrational modes were simulated by DFT calculations. The calculated infrared spectra of the four configurations varied widely, with trimer 1 showing the most resemblance to the experimental spectrum of the co-amorphous 1:2 system. Additionally, co-amorphous VAL/2-AP displayed significant improvement in the solubility and dissolution study. Notably, in the 1:2 ratio, there was almost a 4.5-fold and 15.6-fold increase in VAL’s solubility in 0.1 N HCL and water environments, respectively. In conclusion, our findings highlight the potential of co-amorphous systems as a feasible approach to improving the properties and bioavailabilities of insoluble drugs. The proposed simulation method provides valuable insights into determining the supramolecular structure of multi-molecular hydrogen bonding systems, offering a novel perspective for investigating such systems. Full article

Recently, the formation of chiral materials by the self-organization of achiral small molecules has attracted much attention. How can we obtain chirality without a chiral source? Interesting approaches, such as mechanical rotation, circularly polarized light, and asymmetric reaction fields, have been used. We describe recent research developments in supramolecular chirality in liquid crystals, focusing primarily on our group’s experimental results. We present the following concepts in this review. Spontaneous mirror symmetry breaking in self-assembled achiral trimers induces supramolecular chirality in the soft crystalline phase. Two kinds of domains with opposite handedness exist in non-equal populations. The dominant domain is amplified to produce a homochiral state. Chirality is transferred to a polymer film during the polymerization of achiral monomers by using the homochiral state as a template. Finally, we discuss how the concepts obtained from this liquid crystal research relate to the origin of homochirality in life. Full article

New sulfone 2-aminobenzimidazole derivatives were designed and synthesized. Their nickel(II), copper(II), zinc(II), cadmium(II) and mercury(II) compounds were obtained and fully characterized by spectroscopic and analytical techniques. Single crystal X-ray structural analysis was performed in order to study the relevant intra and inter non-covalent interactions, mainly H···π, lone pair···π, and π···π, highlighting the difference between the terminal ethyl and phenyl groups in such interactions. Dimeric and trimeric supramolecular syntons were found for some of these compounds. Additionally, their antiproliferative activity was investigated, finding that the copper(II) compounds with the sulfone phenyl derivative were the most active. Full article

Carbohydrate-derived molecular gelators have found many practical applications as soft materials. To better understand the structure and molecular gelation relationship and further explore the applications of sugar-based gelators, we designed and synthesized eight trimeric branched sugar triazole derivatives and studied their self-assembling properties. These included glucose, glucosamine, galactose, and maltose derivatives. Interestingly, the gelation properties of these compounds exhibited correlations with the peripheral sugar structures. The maltose derivative did not form gels in the tested solvents, but all other compounds exhibited gelation properties in at least one of the solvents. Glucose derivatives showed superior performance, followed by glucosamine derivatives. They typically formed gels in toluene and alcohols; some formed gels in ethanol-water mixtures or DMSO water mixtures. The glycoclusters 9 and 10 demonstrated rate acceleration for the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. These were further studied for their metallogels formation properties, and the copper metallogels from compound 9 were successfully utilized to catalyze click reactions. These metallogels were able to form a gel column, which was effective in converting the reactants into the triazole products in multiple cycles. Moreover, the same gel column was used to transform a second click reaction using different reactants. The synthesis and characterization of these compounds and their applications for catalytic reactions were discussed. Full article

A strategy for optimizing the rolling resistance, wet skid and cut resistance of reinforced rubber simultaneously using a supramolecular filler is demonstrated. A β-alanine trimer-grafted Styrene Butadiene Rubber (A₃-SBR) pristine polymer was designed and mechanically mixed with commercially available styrene butadiene rubber to help the dispersion of a β-alanine trimer (A₃) supramolecular filler in the rubber matrix. To increase the miscibility of A₃-SBR with other rubber components during mechanical mixing, the pristine polymer was saturated with ethanol before mixing. The mixture was vulcanized using a conventional rubber processing method. The morphology of the assembles of the A₃ supramolecular filler in the rubber matrix was studied by Differential Scanning Calorimetry (DSC) and Transmission Electron Microscopy (TEM). The Differential Scanning Calorimetry study showed that the melting temperature of β-sheet crystals in the vulcanizates was around 179 °C and was broad. The melting temperature was similar to that of the pristine polymer, and the broad melting peak likely suggests that the size of the crystals is not uniform. The Transmission Electron Microscopy study revealed that after mixing the pristine polymer with SBR, some β-sheet crystals were rod-like with several tens of nanometers and some β-sheet crystals were particulate with low aspect ratios. Tensile testing with pre-cut specimens showed that the vulcanizate containing A₃-SBR was more cut-resistant than the one that did not contain A₃-SBR, especially at a large cut size. The rolling resistance and wet skid were predicted by dynamic mechanical analysis (DMA). DMA tests showed that the vulcanizates containing A₃-SBR were significantly less hysteretic at 60 °C and more hysteretic at 0 °C based on loss factor. Overall, the “magic triangle” was expanded by optimizing the rolling resistance, wet-skid, and cut resistance simultaneously using a β-alanine trimer supramolecular filler. The Payne effect also became less severe after introducing the β-alanine trimer supramolecular filler into the system. Full article

Two new Ni(II) and Co(II) coordination compounds, viz., [Ni(H₂O)₅(DMAP)](IPhth)·2H₂O (1) and [Co(Hdmpz)₄(H₂O)₂]Cl₂ (2) (where DMAP = 4-dimethylaminopyridine, IPhth = Isophthalate, Hdmpz = 3,5-dimethylpyrazole),were synthesized and characterized using elemental analysis, TGA, spectroscopic (FTIR and electronic) and single-crystal X-ray diffraction techniques. Compound 1 crystallizes as a co-crystal hydrate of Ni(II), whereas compound 2 is a mononuclear compound of Co(II). The crystal structure analysis of compound 1 reveals the presence of various non-covalent interactions such as anion–π, π–π, C–H∙∙∙π, C–H∙∙∙C, etc., which stabilize the layered assembly of the compound. In compound 2, enclathration of counter chloride ions within the supramolecular trimeric host cavity plays a crucial role in the stabilization of the compound. The non-covalent interactions observed in the crystal structures were further studied theoretically, focusing on the cooperative π-stacking interactions between the DMAP and IPhth counter-ions in 1. To identify the non-covalent interactions of the compounds, Hirshfeld surfaces and their associated two-dimensional fingerprint regions were analyzed. Theoretical calculations confirm that H-bonding interactions combined with the π-stacking contacts are crucial synthons for the solid-state stability of compound 1. Full article

The four new complexes, [Cu(HL¹)(L²)Cl] (1), [Cu(HL¹)(L¹)]∙Cl∙2H₂O (2), [Co(L¹)₂]∙Cl (3) and [Cd(HL¹)I₂]∙dmso (4), have been prepared by one-pot reactions of the respective chloride or iodide metal salt with a non-aqueous solution of the polydentate Schiff base, HL¹, resulted from in situ condensation of benzhydrazide and 2-pyridinecarboxaldehyde, while a ligand HL², in case of 1, has been formed due to the oxidation of 2-pyridinecarboxaldehyde under reaction conditions. The crystallographic analysis revealed that the molecular building units in 1–4 are linked together into complex structures by hydrogen bonding, resulting in 1D, 2D and 3D supramolecular architectures for 1, 2 and 4, respectively, and the supramolecular trimer for 3. The electronic structures of 1–4 were investigated by the DFT theoretical calculations. The non-covalent interactions in the crystal structures of 1–4 were studied by means of the Hirshfeld surface analysis and the QTAIM theory with a special focus on the C–H⋯Cl bonding. From the DFT/DLPNO-CCSD(T) calculations, using a series of charged model {R₃C–H}⁰⋯Cl⁻ assemblies, we propose linear regressions for assessment of the interaction enthalpy (ΔH, kcal mol⁻¹) and the binding energy (BE, kcal mol⁻¹) between {R₃C–H}⁰ and Cl⁻ sites starting from the electron density at the bond critical point (ρ(r_BCP), a.u.): ΔH = −678 × ρ(r) + 3 and BE = −726 × ρ(r) + 4. It was also has been found that compounds 1, 3 and 4 during in vitro screening showed an antibacterial activity toward the nine bacteria species, comprising both Gram-positive and Gram-negative, with MIC values ranging from 156.2 to 625 mg/L. The best results have been obtained against Acinetobacter baumannii MβL. Full article

Reversible imine- and metal-coordination reactions are dynamic enough to produce complex libraries of macrocycles, cages, and supramolecular polymers in solution, from which amplification effects have been identified in solution or during crystallization in response to ligand- and metal-driven selection modes. Crystallization-driven selection can lead to the amplification of unexpected metallosupramolecular architectures. The addition of Ag⁺ triggered the change of the optimal components, so that the crystallization process showed different ligand preferences than in solution. The most packed constituents are amplified in the solid state, taking into account the optimal coordination of metal ions together with non-specific non-covalent interactions between the macrocycle packed in dimers or trimers in the solid state. Full article

Lectins, carbohydrate-binding proteins, are attractive biomolecules for medical and biotechnological applications. Many lectins have multiple carbohydrate recognition domains (CRDs) and strongly bind to specific glycans through multivalent binding effect. In our previous study, protein nano-building blocks (PN-blocks) were developed to construct self-assembling supramolecular nanostructures by linking two oligomeric proteins. A PN-block, WA20-foldon, constructed by fusing a dimeric four-helix bundle de novo protein WA20 to a trimeric foldon domain of T4 phage fibritin, self-assembled into several types of polyhedral nanoarchitectures in multiples of 6-mer. Another PN-block, the extender PN-block (ePN-block), constructed by tandemly joining two copies of WA20, self-assembled into cyclized and extended chain-type nanostructures. This study developed novel functional protein nano-building blocks (lectin nano-blocks) by fusing WA20 to a dimeric lectin, Agrocybe cylindracea galectin (ACG). The lectin nano-blocks self-assembled into various oligomers in multiples of 2-mer (dimer, tetramer, hexamer, octamer, etc.). The mass fractions of each oligomer were changed by the length of the linkers between WA20 and ACG. The binding avidity of the lectin nano-block oligomers to glycans was significantly increased through multivalent effects compared with that of the original ACG dimer. Lectin nano-blocks with high avidity will be useful for various applications, such as specific cell labeling. Full article

Membrane-scaffolding proteins (MSPs) derived from apolipoprotein A-1 have become a versatile tool in generating nano-sized discoidal membrane mimetics (nanodiscs) for membrane protein research. Recent efforts have aimed at exploiting their controlled lipid protein ratio and size distribution to arrange membrane proteins in regular supramolecular structures for diffraction studies. Thereby, direct membrane protein crystallization, which has remained the limiting factor in structure determination of membrane proteins, would be circumvented. We describe here the formation of multimers of membrane-scaffolding protein MSP1D1-bounded nanodiscs using the thiol reactivity of engineered cysteines. The mutated positions N42 and K163 in MSP1D1 were chosen to support chemical modification as evidenced by fluorescent labeling with pyrene. Minimal interference with the nanodisc formation and structure was demonstrated by circular dichroism spectroscopy, differential light scattering and size exclusion chromatography. The direct disulphide bond formation of nanodiscs formed by the MSP1D1_N42C variant led to dimers and trimers with low yield. In contrast, transmission electron microscopy revealed that the attachment of oligonucleotides to the engineered cysteines of MSP1D1 allowed the growth of submicron-sized tracts of stacked nanodiscs through the hybridization of nanodisc populations carrying complementary strands and a flexible spacer. Full article

We present a long-term follow-up in autosomal dominant gyrate atrophy-like choroidal dystrophy (adGALCD) and propose a possible genotype/phenotype correlation. Ophthalmic examination of six patients from two families revealed confluent areas of choroidal atrophy resembling gyrate atrophy, starting in the second decade of life. Progression continued centrally, reaching the fovea at about 60 years of age. Subretinal deposits, retinal pigmentation or choroidal neovascularization as seen in late-onset retinal degeneration (LORD) were not observed. Whole genome sequencing revealed a novel missense variant in the C1QTNF5 gene (p.(Q180E)) which was found in heterozygous state in all affected subjects. Haplotype analysis showed that this variant found in both families is identical by descent. Three-dimensional modeling of the possible supramolecular assemblies of C1QTNF5 revealed that the p.(Q180E) variant led to the destabilization of protein tertiary and quaternary structures, affecting both the stability of the single protomer and the entire globular head, thus exerting detrimental effects on the formation of C1QTNF5 trimeric globular domains and their interaction. In conclusion, we propose that the p.(Q180E) variant causes a specific phenotype, adGALCD, that differs in multiple clinical aspects from LORD. Disruption of optimal cell-adhesion mechanisms is expected when analyzing the effects of the point mutation at the protein level. Full article

Under acidic conditions and at high ionic strength, the zinc cation is removed from its metal complex with 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS₄) thus leading to the diacid free porphyrin, that subsequently self-organize into J-aggregates. The kinetics of the demetallation step and the successive supramolecular assembly formation have been investigated as a function of pH and ionic strength (controlled by adding ZnSO₄). The demetallation kinetics obey to a rate law that is first order in [ZnTPPS₄] and second order in [H⁺], according to literature, with k₂ = 5.5 ± 0.4 M⁻² s⁻¹ at 298 K (IS = 0.6 M, ZnSO₄). The aggregation process has been modeled according to an autocatalytic growth, where after the formation of a starting seed containing m porphyrin units, the rate evolves as a power of time. A complete analysis of the extinction time traces at various wavelengths allows extraction of the relevant kinetic parameters, showing that a trimer or tetramer should be involved in the rate-determining step of the aggregation. The extinction spectra of the J-aggregates evidence quite broad bands, suggesting an electronic coupling mechanism different to the usual Frenkel exciton coupling. Resonance light scattering intensity in the aggregated samples increases with increasing both [H⁺] and [ZnSO₄]. Symmetry breaking occurs in these samples and the J-aggregates show circular dichroism spectra with unusual bands. The asymmetry g-factor decreases in its absolute value with increasing the catalytic rate k_c, nulling and eventually switching the Cotton effect from negative to positive. Some inferences on the role exerted by zinc cations on the kinetics and structural features of these nanostructures have been discussed. Full article

Due to the nature of the carboxylic group, acetic acid can serve as both a donor and acceptor of a hydrogen bond. Gaseous acetic acid is known to form cyclic dimers with two strong hydrogen bonds. However, trimeric and various oligomeric structures have also been hypothesized to exist in both the gas and liquid phases of acetic acid. In this work, a combination of gas-phase NMR experiments and advanced computational approaches were employed in order to validate the basic dimerization model of gaseous acetic acid. The gas-phase experiments performed in a glass tube revealed interactions of acetic acid with the glass surface. On the other hand, variable-temperature and variable-pressure NMR parameters obtained for acetic acid in a polymer insert provided thermodynamic parameters that were in excellent agreement with the MP2 (the second order Møller–Plesset perturbation theory) and CCSD(T) (coupled cluster with single, double and perturbative triple excitation) calculations based on the basic dimerization model. A slight disparity between the theoretical dimerization model and the experimental data was revealed only at low temperatures. This observation might indicate the presence of other, entropically disfavored, supramolecular structures at low temperatures. Full article

Pillararenes trimer with particularly designed structural geometry and excellent capacity of recognizing guest molecules is a very efficient and attractive building block for the fabrication of advanced self-assembled materials. Pillararenes trimers could be prepared via both covalent and noncovalent bonds. The classic organic synthesis reactions such as click reaction, palladium-catalyzed coupling reaction, amidation, esterification, and aminolysis are employed to build covalent bonds and integrate three pieces of pillararenes subunits together into the “star-shaped” trimers and linear foldamers. Alternatively, pillararenes trimers could also be assembled in the form of host-guest inclusions and mechanically interlocked molecules via noncovalent interactions, and during those procedures, pillararenes units contribute the cavity for recognizing guest molecules and act as a “wheel” subunit, respectively. By fully utilizing the driving forces such as host-guest interactions, charge transfer, hydrophobic, hydrogen bonding, and C–H^…π and π–π stacking interactions, pillararenes trimers-based supramolecular self-assemblies provide a possibility in the construction of multi-dimensional materials such as vesicular and tubular aggregates, layered networks, as well as frameworks. Interestingly, those assembled materials exhibit interesting external stimuli responsiveness to e.g., variable concentrations, changed pH values, different temperature, as well as the addition/removal of competition guests and ions. Thus, they could further be used for diverse applications such as detection, sorption, and separation of significant multi-analytes including metal cations, anions, and amino acids. Full article

A selection of novel non-symmetric supramolecular liquid crystal dimers and trimers formed by hydrogen-bonding have been prepared and their phase behaviour characterised by polarised optical microscopy, X-ray diffraction and temperature-dependent Fourier-transform infrared spectroscopy. We mix the bent twist-bend nematogen 4-[6-(4’-cyanobiphenyl-4-yl) hexyloxy]-benzoic acid (CB6OBA) with a series of small stilbazole-based compounds 4-[(E)-2-(n-alkoxyphenyl)ethenyl]pyridines (nOS) of varying terminal chain length (n) to obtain the CB6OBA:nOS complexes. Complexes with n ≤ 7 exhibit nematic and twist-bend nematic behaviour, followed on cooling by a smectic C phase for n = 4–7, and finally, a hexatic-type smectic X phase for n = 3–7. Mixtures with n = 8–10 exhibit a smectic A phase below the conventional nematic phase, and on further cooling, a biaxial smectic A_b phase and the same hexatic-type SmX phase. Supramolecular trimers, CB6OBA:CB6OS and CB6OBA:1OB6OS, formed between CB6OBA and dimeric stilbazoles [(E)-2-(4-{[6-(4’-methoxy[1,1’-biphenyl]-4-yl)hexyl]oxy}phenyl)ethenyl]pyridine (1OB6OS) or 4-[(E)-4’-(6-{4-[(E)-2-(pyridin-4-yl)ethenyl]phenoxy}hexyl)[1,1’-biphenyl]-4- carbonitrile (CB6OS), exhibit nematic and twist-bend nematic phases, and are the first hydrogen-bonded trimers consisting of unlike donor and acceptor fragments to do so. Full article