Spectroscopic, morphological, and mechanistic investigation of the solvent-promoted aggregation of porphyrins modified in meso-positions by glucosylated steroids

Solvent-driven aggregation of a series of porphyrin derivatives was studied by UV/Vis and circular dichroism spectroscopy. The porphyrins are characterised by the presence in the meso positions of steroidal moieties further conjugated with glucosyl groups. The presence of these groups makes the investigated macrocycles amphiphilic and soluble in aqueous solvent, namely, dimethyl acetamide/water. Aggregation of the macrocycles is triggered by a change in bulk solvent composition leading to formation of large architectures that express supramolecular chirality, steered by the presence of the stereogenic centres on the periphery of the macrocycles. The aggregation behaviour and chiroptical features of the aggregates are strongly dependent on the number of moieties decorating the periphery of the porphyrin framework. In particular, experimental evidence indicates that the structure of the steroid linker dictates the overall chirality of the supramolecular architectures. Moreover, the porphyrin concentration strongly affects the aggregation mechanism and the CD intensities of the spectra. Notably, AFM investigations reveal strong differences in aggregate morphology that are dependent on the nature of the appended functional groups, and closely in line with the changes in aggregation mechanism. The suprastructures formed at lower concentration show a network of long fibrous structures spanning over tens of micrometres, whereas the aggregates formed at higher concentration have smaller rod-shaped structures that can be recognised as the result of coalescence of smaller globular structures. The fully steroid substituted derivative forms globular structures over the whole concentration range explored. Finally, a rationale for the aggregation phenomena was given by semiempirical calculations at the PM6 level.     

Metadynamics study of a β-hairpin stability in mixed solvents

Understanding the molecular mechanisms that allow some organisms to survive in extremely harsh conditions is an important achievement that might disclose a wide range of applications and that is constantly drawing the attention of many research fields. The high adaptability of these living creatures is related to the presence in their tissues of a high concentration of osmoprotectants, small organic, highly soluble molecules. Despite osmoprotectants having been known for a long time, a full disclosure of the machinery behind their activity is still lacking. Here we describe a computational approach that, taking advantage of the recently developed metadynamics technique, allows one to fully describe the free energy surface of a small β-hairpin peptide and how it is affected by an osmoprotectant, glycine betaine (GB) and for comparison by urea, a common denaturant. Simulations led to relevant thermodynamic information, including how the free energy difference of denaturation is affected by the two cosolvents; unlike urea, GB caused a considerable increase of the folded basin stability, which transposes into a higher melting temperature. NMR experiments confirmed the picture derived from the theoretical study. Further molecular dynamics simulations of selected conformations allowed investigation into deeper detail the role of GB in folded state protection. Simulations of the protein in GB solutions clearly showed an excess of osmoprotectant in the solvent bulk, rather than in the protein domain, confirming the exclusion from the protein surface, but also highlighted interesting features on its interactions, opening to new scenarios besides the classic "indirect mechanism" hypothesis.     

Chemical fingerprinting of Equisetum arvense L. using HPTLC densitometry and HPLC

Equisetum arvense L. is a herbaceous medicinal plant, commonly known as horsetail, whose extracts have been reported to possess diuretic and haemostatic properties. The aim of this study was to evaluate the use of fingerprint chromatographic methods on commercially available raw materials or preparations of E. arvense L. in order to ascertain their quality and identify possible adulterants using HPLC and HPTLC densitometry. Two chromatographic methods were used to determine the chemical fingerprints of E. arvense and other allied species. The first was based on HPTLC identification followed by densitometric measurement at 350?nm. The second was based on HPLC separation. The ease of sample preparation and the possibility of simultaneous analysis of several samples in a short time make HPTLC a method of choice for the comprehensive quality evaluation of herbal products.     

Deciding the existence of uniform interpolants over transitive models

We consider the problem of the existence of uniform interpolants in the modal logic K4. We first prove that all ${\square}$ -free formulas have uniform interpolants in this logic. In the general case, we shall prove that given a modal formula ${\phi}$ and a sublanguage L of the language of the formula, we can decide whether ${\phi}$ has a uniform interpolant with respect to L in K4. The ${\square}$ -free case is proved using a reduction to the G?del L?b Logic GL, while in the general case we prove that the question of whether a modal formula has uniform interpolants over transitive frames can be reduced to a decidable expressivity problem on the???-calculus.     

A successful chemical strategy to induce oligothiophene self-assembly into fibers with tunable shape and function

Functional supramolecular architectures for bottom-up organic nano- and microtechnology are a high priority research topic. We discovered a new recognition algorithm, resulting from the combination of thioalkyl substituents and head-to-head regiochemistry of substitution, to induce the spontaneous self-assembly of sulfur overrich octathiophenes into supramolecular crystalline fibers combining high charge mobility and intense fluorescence. The fibers were grown on various types of surfaces either as superhelices or straight rods depending on molecular structure. Helical fibers directly grown on a field effect transistor displayed efficient charge mobility and intrinsic 'memory effect'. Despite the fact that the oligomers did not have chirality centers, one type of hand-helicity was always predominant in helical fibers, due to the interplay of molecular atropisomerism and supramolecular helicity induced by terminal substituents. Finally, we found that the new sulfur overrich oligothiophenes can easily be prepared in high yields through ultrasound and microwave assistance in green conditions.     

Interaction of cationic liposomes with cell membrane models

The colloidal dispersion stability of nano-sized graphene sheets in supercritical fluid (SCF) media is very important for developing SCF-based exfoliation and dispersion technologies for stabilization and solubilization of graphenes. We carried out molecular dynamics simulations to elucidate the stability mechanism of graphene in supercritical CO(2) (scCO(2)). The potential of mean force (PMF) between two graphene nanosheets in scCO(2) was simulated, and the effect of scCO(2) density and temperature on the PMF behavior has been investigated. The simulation results demonstrate that there exists a free energy barrier between graphenes in the scCO(2) fluid, possibly obstructing the aggregation of graphenes. The single-layer confined CO(2) molecules between the graphene sheets can induce a dominating repulsion interaction between graphene sheets. At higher scCO(2) fluid density, there are more confined CO(2) molecules within the interplate regions, resulting in a stronger repulsive free energy barrier. The effect of temperature on the PMF is relatively minor. The scCO(2) solvent structure shows layered confined arrangement in the interfacial region near the graphene nanosheets, which is correlated well with the PMF profile curve.     

cis-Apa: a practical linker for the microwave-assisted preparation of cyclic pseudopeptides via RCM cyclative cleavage

A new linker cis-5-aminopent-3-enoic acid (cis-Apa) was prepared for the synthesis of cyclic pseudopeptides by cyclization-cleavage by using ring-closing methatesis (RCM). We developed a new synthetic pathway for the preparation of the cis-Apa linker that was tested in the cyclization-cleavage process of different RGD peptide sequences. Different macrocyclic peptidomimetics were prepared by using this integrated microwave-assisted method, showing that the readily available cis-Apa amino acid is well adapted as a linker in the cyclization-cleavage process.     

Interconversion study in 1,4-substituted six-membered cyclohexane-type rings. Structure and dynamics of trans-1,4-dibromo-1,4-dicyanocyclohexane

Cyclohexane is an extremely flexible molecule that oscillates, at room temperature, between two clearly distinct and extreme conformations that cannot be distinguished at room temperature; so much so that the NMR spectrum is a single line that includes all 12 protons be they axial or equatorial. This raises the interesting question as to what happens when there are equal substituents at the 1 and 4 carbon atoms of the ring. Therefore substitution in the 1,4-positions in the cyclohexane ring has been the subject of considerable interest because some form of interconversion between extreme conformations could lead to the existence of a rather unusual behavior. To study this problem, the interconversion in (di- or tetra-1,4)-substituted six-membered cyclohexane-type rings, trans-1,4-dibromo-1,4-dicyanocyclohexane, was found to be a particularly suitable candidate. Although X-ray diffraction studies on the crystalline solid found the molecule to be centrosymmetric, it still shows a significant dipole moment μ in solution, as determined with a procedure that leads to the vapor phase values of μ. Furthermore, the low magnetic field proton NMR spectrum at ambient temperature appears as a single line, a situation that changes with increasing field intensity and different solvents. Both these effects are attributed to dynamics, because small distortions can easily disrupt the exact cancellation of the individual dipoles (which are quite strong) associated with each end of the molecule. The molecule can exist in two forms, with both the bromines in an axial geometry or both in an equatorial position. Interconversion between these forms is observed, as in the parent cyclohexane. The single NMR line observed at low magnetic fields is due to fast exchange and requires that the two forms have roughly equal populations. Spectra obtained at low temperature confirm this, and variable-temperature studies allow measurement of the rates, leading to an enthalpy of activation of 62 kJ mol(-1). More details of the interconversion are provided by some new calculation methods. Even for a relatively small molecule like this, calculation of a full potential energy surface is prohibitive. However, methods are now available to follow the molecule along the reaction coordinate in quite an efficient way. The results of these calculations lead to an extremely detailed picture of chair-chair interconversion in a di- and tetrasubstituted six-membered ring of the cyclohexane family.     

Supramolecular chirality transfer to large random aggregates of porphyrins

Chirality is rapidly induced in a fractal aggregate of the porphyrin t-CuPagg by addition of α-helical poly-glutamate. These results demonstrate a facile transfer of chirality via noncovalent interactions to preformed supramolecular assemblies grown in the absence of a chiral template.