Diversity and Hierarchy in Supramolecular Assemblies of Triphenylalanine: From Laminated Helical Ribbons to Toroids.

Microstructures from small phenylalanine-based peptides have attracted great attention lately because these compounds are considered to be a new class of tunable materials. In spite of the extensive studies on uncapped diphenylalanine and tetraphenylalanine peptides, studies on the self-assembly of uncapped triphenylananine (FFF) are very scarce and nonsystematic. In this work, we demonstrate that FFF assemblies can organize in a wide number of well-defined supramolecular structures, which include laminated helical-ribbons, leaflike dendrimers, doughnut-, needle-, and flower-shapes. These organizations are produced by the attractive or repulsive interactions between already formed assemblies and therefore can be controlled through the choice of solvents used as the incubation medium. Thus, the formation of the desired supramolecular structures is regulated through the protonation/deprotonation of the terminal groups, the polarity of the incubation medium, which affects both peptide···solvent interactions and the cavity solvation energy (i.e., solvent···solvent interactions), and the steric interactions between own assemblies that act as building blocks. Finally, the ß-sheet disposition in the latter structural motifs has been examined using both theoretical calculations and Fourier transform infrared spectroscopy. Results indicate that FFF molecules can adopt both parallel and antiparallel ß-sheets. However, the former one is the most energetically favored because of the formation of π-π stacking interactions between the aromatic rings of hydrogen-bonded strands.

Paradigm Shift for Preparing Versatile M2+-Free Gels from Unmodified Sodium Alginate.

This manuscript describes a new route to prepare rapidly Ca2+-free hydrogels from unmodified sodium alginate by simply mixing with small organic molecules such as poly(carboxylic acid) compounds as cross-linker agents instead of classical divalent metal salts such as CaCl2. Dimethyl sulfoxide (DMSO) was also found to induce the rapid gelation of aqueous alginate solutions. The gelation process takes place at room temperature, and depending on the composition, gels with good thermal (90-100 °C) and mechanical properties compared to classical metal-containing analogs are obtained. DMSO-based gels showed remarkable self-supporting and thixotropic properties, which can be tuned by the biopolymer concentration. Furthermore, oxalic acid-based gels show superior elasticity than HCl, CaCl2 and DMSO-based gels. The possibility to prepare monoliths, beads, and films of these gels provide them with significant versatility. In particular, films made of alginate and oxalic acid show good potential as synergistic anticancer drug delivery carrier. Computational studies using both quantum mechanical and classical force-field methodologies reveal that hydrogen bonding networks between water and DMSO molecules located close to the alginate chains are responsible for the stability of DMSO-based gels. In contrast, the cohesion of oxalic acid-based gels is a consequence of the coexistence of multiple ionic associations involving oxalate, alginate, and Na+ counterions, which stabilize the system and keep all the interacting species grouped.

Distribution of dopant ions around poly(3,4-ethylenedioxythiophene) chains: a theoretical study.

The effect of counterions and multiple polymer chains on the properties and structure of poly(3,4-ethylenedioxythiophene) (PEDOT) doped with ClO4- has been examined using density functional theory (DFT) calculations with periodic boundary conditions (PBCs). Calculations on a one-dimensional periodic model with four explicit polymer repeat units and two ClO4- molecules indicate that the latter are separated as much as possible, with the salt structure and band gap obtained from such ClO4- distribution being in excellent agreement with those determined experimentally. On the other hand, DFT calculations on periodic models that include two chains indicate that neighboring PEDOT chains are shifted along the molecular axis by a half of the repeat unit length, with dopant ions intercalated between the polymer molecules acting as cement. In order to support these structural features, classical molecular dynamics (MD) simulations have been performed on a multiphasic system consisting of 69 explicit PEDOT chains anchored onto a steel surface, explicit ClO4- anions embedded in the polymer matrix, and an acetonitrile phase layer onto the polymer matrix. Analyses of the radial distribution functions indicate that the all-anti conformation, the relative disposition of adjacent PEDOT chains and the distribution of ClO4- dopant ions are fully consistent with periodic DFT predictions. The agreement between two such different methodologies allows reinforcing the microscopic understanding of the PEDOT film structure.

Measurement of Vibrations in Two Tower-Typed Assistant Personal Robot Implementations with and without a Passive Suspension System.

This paper presents the vibration pattern measurement of two tower-typed holonomic mobile robot prototypes: one based on a rigid mechanical structure, and the other including a passive suspension system. Specific to the tower-typed mobile robots is that the vibrations that originate in the lower part of the structure are transmitted and amplified to the higher areas of the tower, causing an unpleasant visual effect and mechanical stress. This paper assesses the use of a suspension system aimed at minimizing the generation and propagation of vibrations in the upper part of the tower-typed holonomic robots. The two robots analyzed were equipped with onboard accelerometers to register the acceleration over the X, Y, and Z axes in different locations and at different velocities. In all the experiments, the amplitude of the vibrations showed a typical Gaussian pattern which has been modeled with the value of the standard deviation. The results have shown that the measured vibrations in the head of the mobile robots, including a passive suspension system, were reduced by a factor of 16.

Dissolving Hydroxyolite: A DNA Molecule into Its Hydroxyapatite Mold.

In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such a process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi-step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. In addition, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca(2+) ions.

Self-assembled fibrillar networks of a multifaceted chiral squaramide: supramolecular multistimuli-responsive alcogels.

Chiral N,N'-disubstituted squaramide has been found to undergo self-assembly in a variety of alcoholic solvents at low concentrations leading to the formation of novel nanostructured supramolecular alcogels. The gels responded to thermal, mechanical, optical and chemical stimuli. Solubility studies, gelation ability tests and computer modeling of a series of structurally related squaramides proved the existence of a unique combination of non-covalent molecular interactions and favorable hydrophobic/hydrophilic balance in that drive the anisotropic growth of alcogel networks. The results have also revealed a remarkable effect of ultrasound on both the gelation kinetics and the properties of the alcogels.

Hierarchical self-assembly of di-, tri- and tetraphenylalanine peptides capped with two fluorenyl functionalities: from polymorphs to dendrites.

Homopeptides with 2, 3 and 4 phenylalanine (Phe) residues and capped with fluorenylmethoxycarbonyl and fluorenylmethyl esters at the N-terminus and C-terminus, respectively, have been synthesized to examine their self-assembly capabilities. Depending on the conditions, the di- and triphenylalanine derivatives self-organize into a wide variety of stable polymorphic structures, which have been characterized: stacked braids, doughnut-like shapes, bundled arrays of nanotubes, corkscrew-like shapes and spherulitic microstructures. These highly aromatic Phe-based peptides also form incipient branched dendritic microstructures, even though they are highly unstable, making their manipulation very difficult. Conversely, the tetraphenylalanine derivative spontaneously self-assembles into stable dendritic microarchitectures made of branches growing from nucleated primary frameworks. The fractal dimension of these microstructures is ∼1.70, which provides evidence for self-similarity and two-dimensional diffusion controlled growth. DFT calculations at the M06L/6-31G(d) level have been carried out on model ß-sheets since this is the most elementary building block of Phe-based peptide polymorphs. The results indicate that the antiparallel ß-sheet is more stable than the parallel one, with the difference between them growing with the number of Phe residues. Thus, the cooperative effects associated with the antiparallel disposition become more favorable when the number of Phe residues increases from 2 to 4, while those of the parallel disposition remained practically constant.

Design, Implementation and Validation of the Three-Wheel Holonomic Motion System of the Assistant Personal Robot (APR).

This paper presents the design, implementation and validation of the three-wheel holonomic motion system of a mobile robot designed to operate in homes. The holonomic motion system is described in terms of mechanical design and electronic control. The paper analyzes the kinematics of the motion system and validates the estimation of the trajectory comparing the displacement estimated with the internal odometry of the motors and the displacement estimated with a SLAM procedure based on LIDAR information. Results obtained in different experiments have shown a difference on less than 30 mm between the position estimated with the SLAM and odometry, and a difference in the angular orientation of the mobile robot lower than 5° in absolute displacements up to 1000 mm.

Self-Assembly of Tetraphenylalanine Peptides.

Three different tetraphenylalanine (FFFF) based peptides that differ at the N- and C-termini have been synthesized by using standard procedures to study their ability to form different nanoassemblies under a variety of conditions. The FFFF peptide assembles into nanotubes that show more structural imperfections at the surface than those formed by the diphenylalanine (FF) peptide under the same conditions. Periodic DFT calculations (M06L functional) were used to propose a model that consists of three FFFF molecules defining a ring through head-to-tail NH3(+)⋅⋅⋅(-)OOC interactions, which in turn stack to produce deformed channels with internal diameters between 12 and 16 Å. Depending on the experimental conditions used for the peptide incubation, N-fluorenylmethoxycarbonyl (Fmoc) protected FFFF self-assembles into a variety of polymorphs: ultra-thin nanoplates, fibrils, and star-like submicrometric aggregates. DFT calculations indicate that Fmoc-FFFF prefers a parallel rather than an antiparallel ß-sheet assembly. Finally, coexisting multiple assemblies (up to three) were observed for Fmoc-FFFF-OBzl (OBzl = benzyl ester), which incorporates aromatic protecting groups at the two peptide terminals. This unusual and noticeable feature is attributed to the fact that the assemblies obtained by combining the Fmoc and OBzl groups contained in the peptide are isoenergetic.

Synergistic approach to elucidate the incorporation of magnesium ions into hydroxyapatite.

Although the content of Mg(2+) in hard tissues is very low (typically ≤1.5 wt %), its incorporation into synthetic hydroxyapatite (HAp) particles and its role in the mineral's properties are still subject of intensive debate. A combined experimental-computational approach is used to answer many of the open questions. Mg(2+) -enriched HAp particles are prepared using different synthetic approaches and considering different concentrations of Mg(2+) in the reaction medium. The composition, morphology and structure of the resulting particles are investigated using X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, scanning and transmission electron microscopies, FTIR, and wide-angle X-ray diffraction. After this scrutiny, the role of the Mg(2+) in the first nucleation stages, before HAp formation, is investigated using atomistic molecular dynamics simulations. Saturated solutions are simulated with and without the presence of DNA, which has been recently used as a soft template in the biomineralization process. This synergistic investigation provides a complete picture of how Mg(2+) ions affect the mineralization from the first stages onwards.

A rational design for the selective detection of dopamine using conducting polymers.

Poly(N-methylpyrrole) (PNMPy), poly(N-cyanoethylpyrrole) (PNCPy) and poly(3,4-ethylenedioxythiophene) (PEDOT) films have been prepared using both single and two polymerization steps for the selective determination of low concentrations of dopamine, ascorbic acid and uric acid in tertiary mixtures. Analysis of the sensitivity and resolution parameters derived from the electrochemical response of such films indicates that PEDOT is the most appropriate for the unambiguous detection of the three species. Indeed, the performance of PEDOT is practically independent of the presence of both gold nanoparticles at the surface of the film and interphases inside the film, even though these two factors are known to improve the electroactivity of conducting polymers. Quantum mechanical calculations on model complexes have been used to examine the intermolecular interaction involved in complexes formed by PEDOT chains and oxidized dopamine, ascorbic acid and uric acid. Results show that such complexes are mainly stabilized by C-HO interactions rather than by conventional hydrogen bonds. In order to improve the sensitivity of PEDOT through the formation of specific hydrogen bonds, a derivative bearing a hydroxymethyl group attached to the dioxane ring of each repeat unit has been designed. Poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PHMeDOT) has been prepared and characterized by FTIR, UV-vis spectroscopy, cyclic voltammetry, scanning electron microscopy and atomic force microscopy. Finally, the performance of PHMeDOT and PEDOT for the selective detection of the species mentioned above has been compared.

Properties of poly(3-halidethiophene)s.

The influence of the halogen atom on the intrinsic properties of poly(3-halidethiophene)s has been investigated using experimental and theoretical methodologies. Specifically, the electrochemical, electrical, electronic and morphological properties of poly(3-bromothiophene) have been determined and compared with those recently reported for poly(3-chlorothiophene) [Aradilla et al., Polym. Chem., 2012, 3, 436.]. The electrochemical stability and porosity are smaller for poly(3-bromothiophene) than for poly(3-chlorothiophene) while the π-π* lowest transition energy is higher for the former than for the latter. Moreover, quantum mechanical calculations on model oligomers have evidenced that the conformational properties of poly(3-halidethiophene)s, where the halogen is fluorine, chloride or bromine, are dominated by steric interactions and, therefore, are significantly influenced by the size of the halogen atoms. Both the ionization potential and the π-π* lowest transition energy have been predicted to increase slightly when the π-donor character of the halogen atom decreases, in agreement with experimental observations.

Reviewing extrapolation procedures of the electronic properties on the π-conjugated polymer limit.

In this article, the extrapolation procedures of π-π* electronic transition energy on π-conjugated oligomers are reexamined. Different models, including the simplest coupled oscillator, the free electron, the Hückel approach, the molecular exciton model, and some specific fitting-functions, are compared using the transition energies derived from theoretical calculations on three thiophene-based oligomer series. Specifically, oligomers of up to 30 repeating units have been considered to include the saturation effects as a function of chain length. The coupled oscillator model of W. Kuhn and the fitting-function of Hirayama are the models that present the better suit on the transition energy interpolation as a function of chain length. Using only the first four oligomers of the series (n = 2 up to 8) yields an estimation of the transition energy on the polymer limit with an average error of ∼1.5%. The vertical and adiabatic ionization potential present a better fit with the Hückel model approach. Finally, implications of the environmental polarity on the electronic properties, molecular geometry, charge distribution, and aromaticity are shortly discussed.

Self-assembly pathways in a triphenylalanine peptide capped with aromatic groups.

Peptide derivatives and, most specifically, their self-assembled supramolecular structures are being considered in the design of novel biofunctional materials. Although the self-assembly of triphenylalanine homopeptides has been found to be more versatile than that of homopeptides containing an even number of residues (i.e. diphenylalanine and tetraphenylalanine), only uncapped triphenylalanine (FFF) and a highly aromatic analog blocked at both the N- and C-termini with fluorenyl-containing groups (Fmoc-FFF-OFm), have been deeply studied before. In this work, we have examined the self-assembly of a triphenylalanine derivative bearing 9-fluorenylmethyloxycarbonyl and benzyl ester end-capping groups at the N- and C-termini, respectively (Fmoc-FFF-OBzl). The antiparallel arrangement clearly dominates in ß-sheets formed by Fmoc-FFF-OBzl, whereas the parallel and antiparallel dispositions are almost isoenergetic in Fmoc-FFF-OFm ß-sheets and the parallel one is slightly favored for FFF. The effects of both the peptide concentration and the medium on the self-assembly process have been examined considering Fmoc-FFF-OBzl solutions in a wide variety of solvent:co-solvent mixtures. In addition, Fmoc-FFF-OBzl supramolecular structures have been compared to those obtained for FFF and Fmoc-FFF-OFm under identical experimental conditions. The strength of π-π stacking interactions involving the end-capping groups plays a crucial role in the nucleation and growth of supramolecular structures, which determines the resulting morphology. Finally, the influence of a non-invasive external stimulus, ultrasounds, on the nucleation and growth of supramolecular structures has been examined. Overall, FFF-based peptides provide a wide range of supramolecular structures that can be of interest in the biotechnological field.

Plasma-Functionalized Isotactic Polypropylene Assembled with Conducting Polymers for Bacterial Quantification by NADH Sensing.

Rapid detection of bacterial presence on implantable medical devices is essential to prevent biofilm formation, which consists of densely packed bacteria colonies able to withstand antibiotic-mediated killing. In this work, a smart approach is presented to integrate electrochemical sensors for detecting bacterial infections in biomedical implants made of isotactic polypropylene (i-PP) using chemical assembly. The electrochemical detection is based on the capacity of conducting polymers (CPs) to detect extracellular nicotinamide adenine dinucleotide (NADH) released from cellular respiration of bacteria, which allows distinguishing prokaryotic from eukaryotic cells. Oxygen plasma-functionalized free-standing i-PP, coated with a layer (≈1.1 µm in thickness) of CP nanoparticles obtained by oxidative polymerization, is used as working electrode for the anodic polymerization of a second CP layer (≈8.2 µm in thickness), which provides very high electrochemical activity and stability. The resulting layered material, i-PPf /CP2 , detects the electro-oxidation of NADH in physiological media with a sensitivity 417 µA cm-2 and a detection limit up to 0.14 × 10-3 m, which is below the concentration of extracellular NADH found for bacterial cultures of biofilm-positive and biofilm-negative strains.

Examining the planarity of poly(3,4-ethylenedioxythiophene): consideration of self-rigidification, electronic, and geometric effects.

The intramolecular interactions responsible for the planarity observed in poly(3,4-ethylenedioxythiophene) and small 3,4-ethylenedioxythiophene-containing oligomers have been investigated using quantum mechanical methods. Specifically, the relative influence of electron-donating effects, pi-conjugation, and geometric restrictions induced by the cyclic substituent and attractive S...O intramolecular noncovalent interactions, which were proposed to be the most relevant factor for such planarity on the self-rigidification observed in these compounds, have been examined considering a wide number of model compounds. Results evidenced that noncovalent S...O interactions, which were postulated on the basis that the nonbonded distances between sulfur and oxygen atoms belonging to neighboring repeating units are significantly shorter than the sum of the van der Waals radii of sulfur and oxygen, are slightly repulsive destabilizing the planar anti conformation. In contrast, the latter arrangement is favored by the pi-conjugation produced by both geometric restrictions imposed by the cyclic substituent and the electron-donating effects provided by the oxygen atoms attached to positions three and four of each tiophene ring. Therefore, these factors produce gain in aromaticity and favorable electrostatic interactions when the planarity is reached, compensating the Pauli repulsions between the shared electron pairs of the sulfur and oxygen atoms.

Heterochirality Restricts the Self-Assembly of Phenylalanine Dipeptides Capped with Highly Aromatic Groups.

The influence of stereochemistry on the self-assembly of phenylalanine (Phe) dipeptides bearing aromatic fluorenyl groups at both the N- and C-termini (Fmoc, OFm) has been investigated. For this purpose, Fmoc-d-Phe-l-Phe-OFm and Fmoc-l-Phe-l-Phe-OFm have been examined considering a wide variety of solvents, which differ in dielectric constant and volatility. Results reveal that replacement of l-Phe by d-Phe has a major impact on the self-assembly propensities, restricting drastically the structural diversity and polymorphism shown by the homochiral dipeptide. Thus, the analogous heterochiral dipeptide shows a great propensity to form micro/nanofibers, independently of the environmental conditions. Theoretical calculations revealed that the stability of antiparallel disposition is much higher (a factor of ca. 15) for Fmoc-d-Phe-l-Phe-OFm than that for Fmoc-l-Phe-l-Phe-OFm, which has been attributed to the hydrophobic core formed in the former. Overall, results suggest that control of the backbone chirality is a potent and versatile strategy to drive and finely tune the self-assembly propensities of highly aromatic peptides.

Sensing abilities of crown ether functionalized polythiophenes.

Tuning sensing abilities! The affinity of three different [15]crown-5 ether functionalized polythiophenes for alkali ions has been explored (see figure). Ab initio and DFT quantum mechanical calculations show that the binding energy between neutral conducting polymers and metallic ions, which interact attractively, decreases as the size of the ion increases. Oxidation of these polythiophene derivatives significantly reduces their affinity towards alkali ions, becoming low or even nonexistent.This work reports a theoretical study of the affinity of three different [15]crown-5 ether functionalized polythiophenes for alkali ions. Ab initio and DFT quantum mechanical calculations have evidenced that the binding energy between neutral conducting polymers and metallic ions, which interact attractively, decreases as the size of the ion increases. However, the preferences of these polythiophene derivatives have been found to be influenced by the entropic contribution, which favors binding with Na(+) in preference to Li(+). Molecular dynamics simulations have shown that this behavior can be accounted for on the basis of the large fluctuations that Li(+) undergoes when it is contained in the cavity of the [15]crown-5 ether macrocycle. In contrast, the fluctuations detected for complexes with Na(+) and K(+) were particularly low, even though only the former ion fits into the center of the macrocyclic cavity. Oxidation of these polythiophene derivatives produces a drastic change in their sensing abilities, their affinities towards alkali ions becoming low or even nonexistent. Moreover, calculations indicate that the presence of unsubstituted thiophene rings directly attached to a functionalized thiophene modulates the strength of the binding in the oxidized state by reducing the repulsive interaction between the metallic cation and the pi-conjugated system. On the other hand, the influence of alkali ions on the electronic properties, in particular, on the ionization potentials and the lowest pi-pi* transitions, of both the neutral and oxidized polythiophenes is discussed.

Protonation of the side group in beta- and gamma-aminated proline analogues: effects on the conformational preferences.

This work shows the influence of the side-chain protonation on the conformational properties, relative stabilities, and peptide bond isomerization of four aminoproline isomers. Thus, this research has been useful to define the rules that allow control the conformation of aminoproline with the pH. Comparison of the results obtained using density functional theory calculations for the N-acetyl-N'-methylamide derivatives of the protonated isomers, which differ in the beta- or gamma-position of the substituent and its cis or trans relative disposition, with those reported for the corresponding neutral analogues (J. Phys. Chem. B 2008, 112, 14045) has allowed us to reach the following conclusions: (i) protonation of the amino group produces a reduction of the backbone conformational flexibility and a destabilization of the cis configuration of the amide bond involving the pyrrolidine nitrogen; (ii) the planarity of the peptide bond is broken in some cases to form strong side chain...backbone interactions, which induce a very significant pyramidilization at the amide nitrogen atom; (iii) as was also detected for the neutral analogues, the formation of side chain...backbone intraresidue interactions favor the cis disposition of the substituent; and (iv) protonation of the amino side group increases the energy gaps that separate the different investigated isomers resulting in an enhancement of the destabilization of the dipeptides with the substituent attached in a trans position.

Thermodynamic control of the polymerizability of five-, six-, and seven-membered lactones.

The thermodynamics of polymerization of epsilon-caprolactone and 1,4-dioxan-2-one has been investigated theoretically and compared with that recently reported for delta-valerolactone and gamma-butyrolactone. Specifically, the ability of these monomers to polymerize has been related to the strain of the rings, the Gibbs free energy of simple models for ring-opening reactions of the cyclic lactones, and the conformational preferences of linear model compounds of the corresponding homopolyesters. The results are fully consistent with the lack of polymerizability of gamma-butyrolactone, while the ring openings of epsilon-caprolactone and delta-valerolactone have been found to be exergonic processes. Polymerizability of 1,4-dioxan-2-one has been found to be favored, even though less than that of epsilon-caprolactone and delta-valerolactone. Two factors explain these features: (i) the strain of the ester group in the lactones increases with the exergonic character of the ring-opening process, and (ii) the stability of coiled conformations in model compounds follows this order: poly-4-hydroxybutyrate > poly(1,4-dioxan-2-one) > poly-6-hydroxycaproate approximately poly-5-hydroxyvalerate. Finally, the influence of the environment on the polymerizability of the three cyclic lactones is discussed in detail.