Chiral supramolecular polymers.

As an active branch within the field of supramolecular polymers, chiral supramolecular polymers (SPs) are an excellent benchmark to generate helical structures that can clarify the origin of homochirality in Nature or help determine new exciting functionalities of organic materials. Herein, we highlight the most utilized strategies to build up chiral SPs by using chiral monomeric units or external stimuli. Selected examples of transfer of asymmetry, in which the point or axial chirality contained by the monomeric units is efficiently transferred to the supramolecular scaffold yielding enantioenriched helical structures, will be presented. The importance of the thermodynamics and kinetics associated with those processes is stressed, especially the influence that parameters such as the helix reversal and mismatch penalties exert on the achievement of amplification of asymmetry in co-assembled systems will also be considered. Remarkable examples of breaking symmetry, in which chiral supramolecular polymers can be attained from achiral self-assembling units by applying external stimuli like stirring, solvent or light, are highlighted. Finally, the specific and promising applications of chiral supramolecular polymers are presented with recent relevant examples.

Supramolecular Block Copolymers from Tricarboxamides. Biasing Co-assembly by the Incorporation of Pyridine Rings.

The synthesis of a series of triangular-shaped tricarboxamides endowed with three picoline or nicotine units (compounds 2 and 3, respectively) or just one nicotine unit (compound 4) is reported, and their self-assembling features investigated. The pyridine rings make compounds 2-4 electronically complementary with our previously reported oligo(phenylene ethynylene)tricarboxamides (OPE-TA) 1 to form supramolecular copolymers. C3 -symmetric tricarboxamide 2 forms highly stable intramolecular five-membered pseudocycles that impede its supramolecular polymerization into poly-2 and the co-assembly with 1 to yield copolymer poly-1-co-2. On the other hand, C3 -symmetric tricarboxamide 3 readily forms poly-3 with great stability but unable to form helical supramolecular polymers despite the presence of the peripheral chiral side chains. The copolymer poly-1-co-3 can only be obtained by a previous complete disassembly of the constitutive homopolymers in CHCl3 . Helical poly-1-co-3 arises in a process involving the transfer of the helicity from racemic poly-1 to poly-3, and the amplification of asymmetry from chiral poly-3 to poly-1. Importantly, C2v -symmetric 4, endowed with only one nicotinamide moiety and three chiral side chains, self-assembles into a P-type helical supramolecular polymer (poly-4) in a thermodynamically controlled cooperative process. The combination of poly-1 and poly-4 generates chiral supramolecular copolymer poly-1-co-4, whose blocky microstructure has been investigated by applying the previously reported supramolecular copolymerization model.

Exploring a Route to Cyclic Acenes by On-Surface Synthesis.

A route to generate cyclacenes by on-surface synthesis is explored. We started by synthesizing two tetraepoxycyclacenes by sequences of Diels-Alder cycloadditions. Subsequently, these molecules were deposited onto Cu(111) and scanning-tunneling-microscopy(STM)-based atom manipulation was employed to dissociate the oxygen atoms. Atomic force microscopy (AFM) with CO-functionalized tips enabled the detailed characterization of the reaction products and revealed that, at most, two oxygens per molecule could be removed. Importantly, our experimental results suggest that the generation of cyclacenes by the described route might be possible for larger epoxycyclacenes.

Decacene: On-Surface Generation.

Acenes are intriguing molecules with unique electronic properties. The difficulties in their preparation owing to low stability under ambient conditions are apparent because successful syntheses of long unsubstituted acenes are still scarce, in spite of the great attention they have attracted. Only unsubstituted acenes up to heptacene have been isolated in bulk, with nonacene being the largest acene detected to date. Herein we use on-surface assisted reduction of tetraepoxy decacene precursors on Au(111) as the key step to generate unprecedented decacene which is visualized and its electronic resonances studied by scanning tunneling microscopy (STM) and spectroscopy (STS).

4-Aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles: multitasking skeleton as a self-assembling unit.

The synthesis of a series of 4-aryl-3,5-bis(arylethynyl)aryl-4H-1,2,4-triazoles derivatives is reported and the influence exerted by peripheral substitution on the morphology of the aggregates generated from these 1,2,4-triazoles is investigated by SEM imaging. The presence of paraffinic side chains results in long fibrillar supramolecular structures, but unsubstituted triazoles self-assemble into thinner ribbons and needle-like aggregates. The crystals obtained from methoxy-substituted triazoles have been utilised to elaborate a model that helps to justify aggregation of the investigated 1,2,4-triazoles, in which the operation of arrays of C-H⋅⋅⋅π non-covalent interactions plays a significant role. The results presented herein demonstrate the ability of simple molecules to behave as multitasking scaffolds with different properties, depending on peripheral substitution. Thus, although 1,2,4-triazoles without long paraffinic side chains exhibit optical waveguiding behaviour, triazoles endowed with peripheral paraffinic side chains exhibit hexagonal columnar mesomorphism.

Two Novel Nanosized Radiolabeled Analogues of Somatostatin for Neuroendocrine Tumor Imaging.

The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. [Tyr3, Lys(Boc)5]-Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out by a direct method. 99mTc-Tyr3-Octreotide was conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in AR42J cancer cells. Biodistribution studies were accomplished in athymic mice with AR42J-induced tumors with blocked and unblocked receptors. Elemental analysis demonstrated that 26 Tyr3-Octreotide molecules were successfully conjugated to one molecule of PAMAM. RP for both nanosized conjugates was > 94% and showed recognition for SR in AR42J cells. The tissue distribution of radioactivity 2 h after 99mTc-PAMAM-Tyr3-Octreotide administration in mice showed specific tumor uptake (4.12 ± 0.57% of injected dose/g) and high accumulation in the pancreas (15.08 ± 3.11% of injected dose/g) which expresses SR. No significant difference in the tumor uptake was found between 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr3-Octreotide. However, the dendrimer-peptide conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target-specific agents for molecular imaging of tumors that overexpressed SR.

Tuning the self-assembly of rectangular amphiphilic cruciforms.

The self-assembly of a series of nonionic amphiphilic cruciforms based on the 1,2,4,5-tetrakis(phenylethynyl)benzene (TPEB) skeleton, in which the peripheral substituents have been modified to modulate the morphology of the supramolecular structures, is reported. The presence of linear paraffinic and hydrophilic chains in TPEBs 1 and 2 gives rise to two-dimensional structures of high aspect ratio. In contrast, the incorporation of dendronized hydrophilic chains results in the formation of twisted ribbons in amphiphile 3 and impedes the organized self-assembly of TPEB 4. Theoretical calculations show that the self-assembly of these amphiphiles might be initiated with the formation of π-stacked dimeric units. Compound 2, which self-assembles into different morphologies depending on the solvent, interacts by π-stacking and also by the interdigitation of the peripheral decyl tails to generate bidimensional supramolecular structures. The steric demand exerted by the dendronized polar wedges in 3 and 4 strongly conditions their supramolecular organization. This steric demand together with the interdigitation of the decyl chains results in the self-assembly of cruciform 3 into helical aggregates. However, the lack of the paraffinic chains in 4 impedes this helical organization, and the formation of amorphous material is visualized. The joint experimental and theoretical study presented herein provides relevant guidelines for the modulated self-assembly of nonionic amphiphilic molecules.

Electronically and geometrically complementary perylenediimides for kinetically controlled supramolecular copolymers.

The synthesis of 3,4,9,10-benzo[d,e]isoquinolino[1,8-g,h]quinoline-tetracarboxylic diimide (BQQDI) 1 endowed with peripheral trialkoxybenzamide fragments is reported and its self-assembling features investigated. The peripheral benzamide moieties generate metastable monomeric species that afford a kinetically controlled supramolecular polymerization. The electron-withdrawing character of 1 in comparison with previously reported PDIs 2, together with the similar geometry, makes this dye an optimal candidate to perform seeded supramolecular copolymerization yielding four different supramolecular block copolymers. Whilst heteropolymers poly-1-co-2a, poly-2a-co-1 and poly-1-co-2b present an H-type arrangement of the monomeric units, heteropolymer poly-2b-co-1, prepared by seeding the chiral, metastable monomers of 2b with achiral seeds of 1, produces chiral, J-type aggregates. Interestingly, the monosignated CD signal of pristine poly-2b changes to a bisignated CD signal most probably due to the formation of columnar domains around the seeds of 1 which implies the blocky nature of the supramolecular copolymers formed.

Impact of universal use of a hyperangulated videolaryngoscope as the first option for all intubations in the ICU: A prospective before-after study.

BACKGROUND: Tracheal intubation in ICU is associated with high incidence of difficult intubations. The study aimed to investigate whether the "universal" use of a hyperangulated videolaryngoscope would increase the frequency of "easy intubation" in ICU patients compared to direct laryngoscopy. METHODS: A prospective before-after study was conducted. The pre-interventional period (36 months) involved tracheal intubations using direct laryngoscopy as the first intubation option. In the interventional period (18 months) a hyperangulated videolaryngoscope was the first intubation option. The primary outcome was the percentage of patients with "easy intubation" defined as intubation on the first attempt and easy laryngoscopy (modified Cormack-Lehane glottic view of I-IIa). Secondary outcomes included difficult laryngoscopy, operator technical difficulty, and complications. RESULTS: We enrolled 407 patients, 273 in non-interventional period, and 134 in interventional period. Tracheal intubation in the interventional period was associated with higher incidence of "easy intubation" (92.5%) compared with the non-interventional period (75.8%); P < 0.001)). Glottic visualization improved in the interventional period, with a reduced incidence of difficult laryngoscopy (1.5% vs. 22.5%; P < 0.001). The proportion of first-success rate intubation was 92.5% in the interventional period, and 87.8% in the non-interventional period (P = 0.147). Moderate and severe technical difficulty of intubation reported decreased in the interventional period (6% vs. 17.6%; P < 0.001). There was no significant difference between both periods in the incidence of complications. CONCLUSION: "Universal" use of hyperangulated videolaryngoscopy for tracheal intubation in patients admitted in ICU improves the percentage of easy intubation compared to direct laryngoscopy.

Supramolecular polymerization of C3-symmetric organogelators: cooperativity, solvent, and gelation relationship.

A systematic study of the influence of solvent and the size of C(3)-symmetric discotics on their supramolecular polymerization mechanism is presented. The cooperativity of the self-assembly of the reported compounds is directly related to their gelation ability. The two series of C(3)-symmetric discotics investigated herein are based on benzene-1,3,5-tricarboxamides (BTAs) and oligo(phenylene ethynylene)-based tricarboxamides (OPETAs) that are peripherally decorated with achiral (1a and 2a) or chiral N-(2-aminoethyl)-3,4,5-trialkoxybenzamide units (1b and 2b). The supramolecular polymerization of compounds 1a,b and 2a,b has been exhaustively investigated in a number of solvents and by using various techniques: variable-temperature circular dichroism (VT-CD) spectroscopy, concentration-dependent (1)H NMR spectroscopy, and isothermal titration calorimetry (ITC). The supramolecular polymerization mechanism of compounds 2 is highly cooperative in solvents such as methylcyclohexane and toluene and is isodesmic in CHCl(3). Unexpectedly, chiral compound 1b is practically CD-silent, in contrast with previously reported BTAs. ITC measurements in CHCl(3) demonstrated that the supramolecular polymerization of BTA 1a is isodesmic. These results confirm the strong influence of the π-surface of the central aromatic core of the studied discotic and the branched nature of the peripheral side chains on the supramolecular polymerization. The gelation ability of these organogelators is negated in CHCl(3), in which the supramolecular polymerization mechanism is isodesmic.

A bis(triazole)benzamide receptor for the complexation of halide anions and neutral carboxylic acid guests. Guest-controlled topicity and self-assembly.

Bis(triazole)benzamide 1 has been readily synthesized by means of Cu-catalyzed 1,3-dipolar cycloaddition and its ability to bind halide anions and neutral gallic acid derivative 12GA has been theoretically and experimentally investigated. The cavity defined by the N-H amide group and the vicinal aromatic hydrogens is suitable to form H-bonding arrays with halide guests. The stability of complexes 1·Cl(-) and 1·Br(-) is very similar, as DFT calculations predict and (1)H NMR titration experiments confirm. The zigzag "anti" conformation of the molecule generates two regions with complementary positive and negative potentials that favor the statistical complexation of two molecules of the neutral carboxylic acid 12GA. This guest-controlled topicity demonstrates the versatility of this class of receptor to bind species of different nature. The amide group determines the complexation of both anionic and neutral species by primary acid-base interactions.

Silver nanoparticles and silver ions indistinguishably decrease sperm motility in Pacific oysters (Magallana gigas) after short-term direct exposure.

The present study aimed to evaluate the reprotoxicity of environmental (0.25 µg.L-1) and supra-environmental (25 µg.L-1 and 250 µg.L-1) levels of silver nanoparticles (Ag NP) on the Pacific oyster (Magallana gigas), by determining sperm quality. For that, we evaluated sperm motility, mitochondrial function and oxidative stress. To determine whether the Ag toxicity was related to the NP or its dissociation into Ag ions (Ag+), we tested the same concentrations of Ag+. We observed no dose-dependent responses for Ag NP and Ag+, and both impaired sperm motility indistinctly without affecting mitochondrial function or inducing membrane damage. We hypothesize that the toxicity of Ag NP is mainly due to adhesion to the sperm membrane. Blockade of membrane ion channels may also be a mechanism by which Ag NP and Ag+ induce toxicity. The presence of Ag in the marine ecosystem is of environmental concern as it may affect reproduction in oysters.

Structural rules for the chiral supramolecular organization of OPE-based discotics: induction of helicity and amplification of chirality.

A systematic study on the structural rules that regulate the chiral supramolecular organization of oligo(phenylene ethynylene) (OPE)-based discotics is presented. This study is based on the chirooptical properties of two different series of triangular shape OPEs. The first of them is composed by OPE-based trisamides with a variable number of chiral side chains (compounds 1) that self-assemble following a cooperative mechanism. The CD experiments carried out with these desymmetrized trisamides demonstrate that only one stereogenic center is sufficient to achieve a helical organization with a preferred handedness. However, the ability to amplify the chirality decreases upon decreasing the number of stereocenters at the peripheral side chains. The second series is constituted by triangular shape OPEs with a variable number of ether and amide functional groups and constant absolute configuration of the stereogenic centers at all of the peripheral chains (compounds 2). These compounds do not self-assemble into helical aggregates as demonstrated by the corresponding CD studies. The amplification of chirality observed in the mixtures of some of the components of both series has been investigated. The combination of chiral trisamide 1d with chiral but nonhelical 2b or 2c does not produce an amplification of chirality most probably due to the mismatch between the stereogenic centers of both components. However, the combination of achiral trisamide 1a with chiral but nonhelical bisamide 2c generates, in a cooperative manner, helical structures with a preferred handedness in a process involving the transfer of helicity from 1a to 2c and the transfer of chirality from 2c to 1a. The structural features of the OPE discotics also exert a strong influence on the columnar aggregates. Thus, while achiral 1a bundles into thick filaments to form an organogel, the gelation ability of these triangular OPEs decreases upon increasing the number of stereogenic centers, being totally canceled for compounds 2 in which the amide functionalities are replaced by ether linkages. Finally, we have also registered AFM images of the helical aggregates obtained from the mixture of 1a+2c, which implies an efficient transfer of the chiral objects from solution to surfaces. The study presented herein increases the understanding of the structural rules that regulate the chiral supramolecular organization of discrete molecules in general and, more specifically, those based on π-conjugated oligomers.

Effects from the Freezing of Either Whole or Crushed Grapes on the Volatile Compounds Contents in Muscat Wines.

The transfer of aromatic compounds from the grape skins to the musts has been studied using a process involving freezing whole bunches or crushed grapes for winemaking the Muscat of Alexandria variety (white wine). Subsequently, a prefermentative maceration has been applied to some of the samples. The aromatic profiles of the final wines have been determined using gas chromatography coupled to mass spectrophotometry (GC-MS). The results revealed that, in the trials in which whole grapes were frozen, the final wines had a higher aromatic concentration compared to that of wines obtained by either freezing crushed grapes or obtained with traditional winemaking techniques. Thus, the wines produced from frozen whole grapes were found to exhibit different characteristics from the rest of the wines. The compounds affected by the freezing either of the whole bunches or the crushed grapes were terpenes, acids, and esters. Lower differences were found for wines produced applying prefermentative maceration after the freezing process.

Mirror helices and helicity switch at surfaces based on chiral triangular-shape oligo(phenylene ethynylenes).

The self-assembly of triangular-shaped oligo(phenylene ethynylenes) (OPEs), peripherally decorated with chiral and linear paraffinic chains, is investigated in bulk, onto surfaces and in solution. Whilst the X-ray diffraction data for the chiral studied systems display a broad reflection centered at 2θ ∼20° (λ=Cu(Kα)), the higher crystallinity of OPE 3, endowed with three linear decyl chains, results in a diffractrogram with a number of well-resolved reflections that can be accurately indexed as a columnar packing arranged in 2D oblique cells. Compounds (S)-1 a and (R)-1 b-endowed with (S)- and (R)-3,7-dimethyloctyloxy chains-transfer their chirality to the supramolecular structures formed upon their self-assembly, and give rise to helical nanostructures of opposite handedness. A helicity switch is noticeable for the case of chiral (S)-2 decorated with (S)-2-methylnonyloxy chains which forms right-handed helices despite it possesses the same stereoconfiguration for their stereogenic carbons as (S)-1 a that self-assembles into left-handed helices. The stability and the mechanism of the supramolecular polymerization in solution have been investigated by UV/Vis experiments in methylcyclohexane. These studies demonstrate that the larger the distance between the stereogenic carbon and the aromatic framework is, the more stable the aggregate is. Additionally, the self-assembly mechanism is conditioned by the peripheral substituents: whereas compounds (S)-1 a and (R)-1 b self-assemble in a cooperative manner with a low degree of cooperativity, the aggregation of (S)-2 and 3 is well described by an isodesmic model. Therefore, the interaction between the chiral coil chains conditions the handedness of the helical pitch, the stability of the supramolecular structure and the supramolecular polymerization mechanism of the studied OPEs.

Supramolecular ribbons from amphiphilic trisamides self-assembly.

Two amphiphilic C(3)-symmetric OPE-based trisamides have been synthesized and their self-assembling features investigated in solution and on surface. Variable-temperature UV-vis experiments demonstrate the cooperative supramolecular polymerization of these trisamides that self-assemble by the operation of triple C═O···H-N H-bonding arrays between the amide functional groups and π-π stacking between the aromatic units. The helical organization of the aggregates has been demonstrated by circular dichroism at a concentration as low as 1 × 10(-4) M in acetonitrile. In the reported trisamides, the large hydrophobic aromatic core acts as a solvophobic module impeding the interaction between the polar TEG chains and the amide H-bonds. This strategy makes unnecessary the separation of the amide functional groups to the polar tri(ethylene glycol) chains by paraffinic fragments. Achiral trisamide 1 self-assembles into flat ribbon-like structures that experience an amplification of chirality by the addition of a small amount of chiral 2 that generates twisted stripes.

Changes in the Aromatic Compounds Content in the Muscat Wines as a Result of the Application of Ultrasound during Pre-Fermentative Maceration.

This research focuses on the aromatic composition of Muscat of Alexandria wines after the application of ultrasound for 40 or 80 min during a 4 h pre-fermentative maceration process. Two methods of ultrasound application were compared in this study: probe ultrasound and bath ultrasound, for periods of 10-20 min per hour. Increases of more than 200% were obtained for some of the compounds from the skins, such as two of its terpenes, citronellol and nerol. On the other hand, increases in alcohol and ester values were registered with the application of ultrasound for 40 min. However, a significant decrease in these compounds was recorded when the ultrasound process was extended. In fact, when ultrasound was applied for 80 min, content values were even lower than those registered for the wine produced without the application of ultrasound. At the sensory level, the effect resulting from probe and bath ultrasound application for different times were compared, where most of the judges successfully discriminated the wines resulting from the application of ultrasound bath. According to data, the wines resulting from the application of ultrasound bath for 80 min presented the most significant differences, which affected the aromas of white fruit, tropical fruit, stone fruit, flowers and citrus.

From starphenes to non-benzenoid linear conjugated polymers by substrate templating.

Combining on-surface synthetic methods with the power of scanning tunneling microscopy to characterize novel materials at the single molecule level, we show how to steer the reactivity of one anthracene-based precursor towards different product nanostructures. Whereas using a Au(111) surface with three-fold symmetry results in the dominant formation of a starphene derivative, the two-fold symmetry of a reconstructed Au(110) surface allows the selective growth of non-benzenoid linear conjugated polymers. We further assess the electronic properties of each of the observed product structures via tunneling spectroscopy and DFT calculations, altogether advancing the synthesis and characterization of molecular structures of notable scientific interest that have been only scarcely investigated to date, as applies both to starphenes and to non-benzenoid conjugated polymers.

Dendronized triangular oligo(phenylene ethynylene) amphiphiles: nanofibrillar self-assembly and dye encapsulation.

Triangular-shaped oligo(phenylene ethynylene) amphiphiles 1a and 1b decorated in their periphery with two- and four-branched hydrophilic triethyleneglycol dendron wedges, have been synthesized and their self-assembling properties in solution and onto surfaces investigated. The steric demand produced by the dendritic substituents induces a face-to-face rotated pi stacking of the aromatic moieties. Studies on the concentration and temperature dependence confirm this mechanism and provide binding constants of 1.2 x 10(5) and 1.7 x 10(5) M(-1) in acetonitrile for 1a and 1b, respectively. Dynamic and static light scattering measurements complement the study of the self-assembly in solution and demonstrate the formation of rod-like supramolecular structures in aqueous solution. The nanofibers formed in solution can be efficiently transferred onto surfaces. Thus, TEM images reveal the presence of strands of various thickness, with the most common being several micrometers long and with diameters of around 70 nm. Some of these nanofibers present folded edges that are indicative of their ribbon-like nature. Interestingly, compound 1b can also form thick filaments with a rope-like appearance, which points to a chiral arrangement of the fibers. AFM images under highly diluted conditions also reveal long fibers with height profiles that fit well with the molecular dimensions calculated for both amphiphiles. Finally, we have demonstrated the intercalation of the hydrophobic dye Disperse Orange 3 within the filaments and its subsequent release upon increasing the temperature.