Sparkling Organic Phosphorescence from Fluorinated Tetrathia[7]helicenes: Synthesis and Photophysical, Electrochemical and Computational Studies.

Structure-property correlations in the thiahelicene family are often not trivial beacuse most of the functional groups present on the helical scaffold modify the conjugation size of the π-system. Selecting fluorine-containing groups to provide strong inductive effects without interacting with low-lying orbitals of the system could be the way to overcome the issue. Here we report a study on three fluorine-functionalized tetrathia[7]helicenes, highlighting interesting correlations between the position of the functional groups and the conjugated skeleton properties. Helicenes Heli-F2 and Heli-CF-F2 were prepared by photoinduced isomerization-electrocyclization (the Mallory photocyclization) of the corresponding fluorinated benzodithienyl-ethenes Alk-F2 and Alk-CF-F2, which were prepared in high yields through stereo-conservative Stille reaction. Notably these helicenes were found to display green phosphorescence around 530-550 nm, and the studies suggest an efficient spin-orbit coupling mechanism in these high-energy triplet nonplanar conjugated molecules. Both helicenes and their precursors were thoroughly characterized by means of optical and electrochemical measurements, while DFT calculations enable a rationale on their structure-property correlations to be defined.

(BO)2 -Doped Tetrathia[7]helicene: A Configurationally Stable Blue Emitter.

Helicenes combine two central themes in chemistry: extended π-conjugation and chirality. Hetero-atom doping preserves both characteristics and allows modulation of the electronic structure of a helicene. Herein, we report the (BO)2 -doped tetrathia[7]helicene 1, which was prepared from 2-methoxy-3,3'-bithiophene in four steps. 1 is formally derived by substituting two (Mes)B-O moieties in place of (H)C=C(H) fragments in two benzene rings of the parent tetrathia[7]helicene. X-ray crystallography revealed a dihedral angle of 50.26(9)° between the two terminal thiophene rings. The (P)-/(M)-1 enantiomers were separated by chiral HPLC and are configurationally stable at room temperature. The experimentally determined enantiomerization barrier of 27.4±0.1 kcal mol-1 is lower than that of tetrathia[7]helicene (39.4±0.1 kcal mol-1 ). The circular dichroism spectra of (P)- and (M)-1 show a perfect mirror-image relationship. 1 is a blue emitter (λem =411 nm) with a photoluminescence quantum efficiency of ΦPL =6 % (cf. tetrathia[7]helicene: λem ≈405 nm, ΦPL =5 %).

Enantioselective Synthesis of Dithia[5]helicenes and their Postsynthetic Functionalization to Access Dithia[9]helicenes.

A highly enantioselective synthesis of 5,13-disubstituted dibenzo[d,d']benzo[1,2-b:4,3-b']dithiophenes is reported. Key for the successful assembly of these helical architectures is the last two successive Au-catalyzed intramolecular alkyne hydroarylation events. Specifically, the second cyclization is the enantiodetermining step of the whole process and provides the desired helicenes with excellent ee values when a TADDOL-derived 1,2,3-(triazolium)phosphonite moiety (TADDOL: α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol) is employed as an ancillary ligand. The absolute stereochemistry of the newly prepared structures has been determined by X-ray crystallography to be P; the optical properties of these heterohelicenes are also reported. A three-step procedure was subsequently developed that allows the transformation of the initially obtained dithia[5]helicenes into dithia[9]helicenes without erosion of the enantiopurity.

An Approach for Magnetic Halloysite Nanocomposite with Selective Loading of Superparamagnetic Magnetite Nanoparticles in the Lumen.

We present for the first time a method for the preparation of magnetic halloysite nanotubes (HNT) by loading of preformed superparamagnetic magnetite nanoparticles (SPION) of diameter size ∼6 nm with a hydrodynamic diameter of ∼10 nm into HNT. We found that the most effective route to reach this goal relies on the modification of the inner lumen of HNT by tetradecylphosphonic acid (TDP) to give HNT-TDP, followed by the loading with preformed oleic acid (OA)-stabilized SPION. Transmission electron microscopy evidenced the presence of highly crystalline magnetic nanoparticles only in the lumen, partially ordered in chainlike structures. Conversely, attempts to obtain the same result by exploiting either the positive charge of the HNT inner lumen employing SPIONs covered with negatively charged capping agents or the in situ synthesis of SPION by thermal decomposition were not effective. HNT-TDP were characterized by infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), and ζ-potential, and all of the techniques confirmed the presence of TDP onto the HNT. Moreover, the inner localization of TDP was ascertained by the use of Nile Red, a molecule whose luminescence is very sensitive to the polarity of the environment. The free SPION@OA (as a colloidal suspension and as a powder) and SPION-in-HNT powder were magnetically characterized by measuring the ZFC-FC magnetization curves as well as the hysteresis cycles at 300 and 2.5 K, confirming that the super-paramagnetic behavior and the main magnetic properties of the free SPION were preserved once embedded in SPION-in-HNT.

Exploring miR-9 Involvement in Ciona intestinalis Neural Development Using Peptide Nucleic Acids.

The microRNAs are small RNAs that regulate gene expression at the post-transcriptional level and can be involved in the onset of neurodegenerative diseases and cancer. They are emerging as possible targets for antisense-based therapy, even though the in vivo stability of miRNA analogues is still questioned. We tested the ability of peptide nucleic acids, a novel class of nucleic acid mimics, to downregulate miR-9 in vivo in an invertebrate model organism, the ascidian Ciona intestinalis, by microinjection of antisense molecules in the eggs. It is known that miR-9 is a well-conserved microRNA in bilaterians and we found that it is expressed in epidermal sensory neurons of the tail in the larva of C. intestinalis. Larvae developed from injected eggs showed a reduced differentiation of tail neurons, confirming the possibility to use peptide nucleic acid PNA to downregulate miRNA in a whole organism. By identifying putative targets of miR-9, we discuss the role of this miRNA in the development of the peripheral nervous system of ascidians.

Unusual Through-Space Interactions between Oxygen Atoms that Mediate Inverse Morphochromism of an AIE Luminogen.

We have studied the photophysics of tetrafurylethene, an aggregation-induced emission luminogen with exceptionally short intramolecular O-O distances of 2.80 Šand a significant red-shifted morphochromism (27 nm) when going from the aggregate to the crystal. The short O-O distances, which are substantially smaller than the sum of the van der Waals radii (3.04 Å), are due to the fact that the oxygen atoms act as an electronic bridge connecting the furan rings on opposite ends of the central double bond, giving rise to a circular delocalization of the π-electron density across the rings. In the excited state the O-O distance is further reduced to 2.70 Å; the increased O-O interaction causes a narrowing of the HOMO-LUMO gap, resulting in the red morphochromism of the emission. Our results show the structural origin of the red-shifted emission lies in close O-O contacts, paving the way for understanding the clusteroluminescence of oxygen-rich non-conjugated systems that emit visible light.

miR-7 Knockdown by Peptide Nucleic Acids in the Ascidian Ciona intestinalis.

Peptide Nucleic Acids (PNAs) are synthetic mimics of natural oligonucleotides, which bind complementary DNA/RNA strands with high sequence specificity. They display numerous advantages, but in vivo applications are still rare. One of the main drawbacks of PNAs application is the poor cellular uptake that could be overcome by using experimental models, in which microinjection techniques allow direct delivery of molecules into eggs. Thus, in this communication, we investigated PNAs efficiency in miR-7 downregulation and compared its effects with those obtained with the commercially available antisense molecule, Antagomir (Dharmacon) in the ascidian Ciona intestinalis. Ascidians are marine invertebrates closely related to vertebrates, in which PNA techniques have not been applied yet. Our results suggested that anti-miR-7 PNAs were able to reach their specific targets in the developing ascidian embryos with high efficiency, as the same effects were obtained with both PNA and Antagomir. To the best of our knowledge, this is the first evidence that unmodified PNAs can be applied in in vivo knockdown strategies when directly injected into eggs.

Chiral thiahelicene-based alkyl phosphine-borane complexes: synthesis, X-ray characterization, and theoretical and experimental investigations of optical properties.

Chiral helical-based phosphanes are challenging and promising ligands, with a great potential for the generation of both organic and organometallic catalysts. We report here the preparation of novel chiral thiahelicene-based alkyl phosphanes, isolated and characterized as air-stable borane adducts, and the investigation of their experimental and theoretical (chir)optical properties. X-ray characterization of a mono- and a disubstituted derivative as a racemic mixture has been performed, which confirms the influence of the number and nature of substituents on the flexibility of the helix. In addition, the absolute configuration inferred from CD spectra of the two enantiomers of a diborane complex has been established from X-ray analysis. State-of-the-art quantum chemical calculations of vibrationally resolved spectra allow, for the first time, for an unambiguous assignment of the experimentally observed peaks in linear absorption and circular dichroism spectra to excited electronic states of this class of thiahelicene phosphorus derivatives.

Phosphathiahelicenes: synthesis and uses in enantioselective gold catalysis.

Enantiomerically pure thiahelicenes displaying a terminal phosphole unit and a stereogenic phosphorus center have been prepared by oxidative photocyclization of a diaryl-olefin precursor. Starting from one of these phosphathiahelicene oxides, the corresponding trivalent phosphine-Au(I) complex is obtained with complete diastereoselectivity. It affords a new, excellent precatalyst for the enantioselective cycloisomerization of N-tethered enynes (up to 96 % ee).

SPION-Smac mimetic nano-conjugates: putative pro-apoptotic agents in oncology.

Non-covalent (NP-1/3) and covalent (NP-A-1/3) pro-apoptotic SPION-Smac mimetic nano-conjugates antitumor agents are reported. The solution synthesis of key Smac mimetics, their support onto SPIONs through non-covalent adsorption (NP-1/3) or APTES-mediated covalent binding (NP-A-1/3), the analytical characterization of SPION-Smac mimetic conjugates, their target affinity in cell-free assays, and their cytotoxicity against tumor cells are thoroughly described.

Gold(I) complexes of tetrathiaheterohelicene phosphanes.

New tetrathia[7]helicene-based (7-TH-based) gold(I) complexes 6 and 7 have been readily prepared by reaction of the respective phosphine ligands 2 and 3 with Au(tht)Cl in a 1:1 and 1:2 molar ratio, respectively. These complexes have been fully characterized by analytical and spectroscopic techniques as well as quantum chemical calculations. The molecular structure of dinuclear complex 7 has been determined by single-crystal X-ray diffraction, showing a gold-gold interaction of 3.1825(3) Å and a significant contraction of the 7-TH total dihedral angle. Au(I) complex 7 displays luminescence emission at room and low temperature in diluted solution and in the solid state. Quantum chemical calculations show that the luminescence emission at room temperature is primarily due to slightly perturbed fluorescence emission from purely ππ* excited states of the conjugated helicene scaffold. At 77 K phosphorescence emission is displayed as well. Preliminary studies on the use of 6 and 7 as catalysts in typical Au(I)-catalyzed cycloisomerizations have demonstrated the reactivity of these systems in the intramolecular allene hydroarylations and the hydroxycarboxylation of allene-carboxylates.

Exploiting the interaction between halloysite and charged PNAs for their controlled release.

The design and development of nanomaterials that could be used in nanomedicine are of fundamental importance to obtain smart nanosystems for the treatment of several diseases. Halloysite, because of its interesting features, represents a suitable nanomaterial for the delivery of different biologically active species. Among them, peptide nucleic acids (PNAs) have attracted considerable attention in recent decades for their potential applications in both molecular antisense diagnosis and as therapeutic agents, although up to now, the actual clinical applications have been very limited. Herein we report a systematic study on the supramolecular interaction of three differently charged PNAs with halloysite. Understanding the interaction mode of charged molecules with the clay surfaces represents a key factor for the future design and development of halloysite based materials which could be used for the delivery and subsequent intracellular release of PNA molecules. Thus, three different PNA tetramers, chosen as models, were synthesized and loaded onto the clay. The obtained nanomaterials were characterized using spectroscopic studies and thermogravimetric analysis, and their morphologies were studied using high angle annular dark field transmission electron microscopy (HAADF/STEM) coupled with Energy Dispersive X-ray spectroscopy (EDX). The aqueous mobility of the three different nanomaterials was investigated by dynamic light scattering (DLS) and ζ-potential measurements. The release of PNA tetramers from the nanomaterials was investigated at two different pH values, mimicking physiological conditions. Finally, to better understand the stability of the synthesized PNAs and their interactions with HNTs, molecular modelling calculations were also performed. The obtained results showed that PNA tetramers interact in different ways with HNT surfaces according to their charge which influences their kinetic release in media mimicking physiological conditions.

(Dimesityl)boron Benzodithiophenes: Synthesis, Electrochemical, Photophysical and Theoretical Characterization.

Triarylboranes containing linear or angular benzodithiophene moieties and bearing one or two dimesitylboron units were synthesized. The electrochemical and optical features of these compounds were investigated by cyclic voltammetry, UV/Vis and fluorescence spectroscopy while DFT calculations were run to analyze the energetic landscape of these systems. For both linear and angular benzodithiophenes, symmetrical disubstitution leads to the highest photoluminescence yields. The linear benzodithiophene disubstituted with two dimesitylboron units proved to be the most interesting and promising molecule as an electron-transport material for organic electronics owing to its LUMO energy level of -2.84 eV which is close to those of commonly used electron transport materials like bathocuproine or bathophenantroline.

Nanocarrier based on halloysite and fluorescent probe for intracellular delivery of peptide nucleic acids.

The development of systems able to deliver genetic material into a target site is a challenge for modern medicine. Single-stranded peptide nucleic acids have attracted attention as promising therapeutic molecules for diagnostic and gene therapy. However, their poor cell membrane permeability represents a drawback for biomedical applications. Halloysite nanotubes (HNTs) are emerging materials in drug delivery applications both for their ability to penetrate cell membranes and for enhancing the solubility of drugs in biological media. Herein, we report the first example of the use of a nanocarrier based on halloysite labelled with fluorescent switchable halochromic oxazine molecules, to deliver a single-stranded peptide nucleic acids tetramer (PNAts) into living cells. The PNAts is covalently attached to halloysite (HNTs-PNA), whereas the fluorescent probe supramolecularly interacts with HNTs. The ability of the nanomaterial to bind complementary single-stranded DNA was assessed by resonance light scattering measurements. Finally, studies of cellular uptake were carried out by confocal laser scanning microscopy on normal and tumoral cell lines. This work highlights the usefulness of the covalent approach to generate HNTs-PNA nanomaterials for the potential targeting of future specific nucleic acids in living cells, which could open the doorway to novel possibilities for theranostic and gene therapy applications.

Acid-base and lipophilic properties of peptide nucleic acid derivatives.

The first combined experimental and theoretical study on the ionization and lipophilic properties of peptide nucleic acid (PNA) derivatives, including eleven PNA monomers and two PNA decamers, is described. The acidity constants (pKa) of individual acidic and basic centers of PNA monomers were measured by automated potentiometric pH titrations in water/methanol solution, and these values were found to be in agreement with those obtained by MoKa software. These results indicate that single nucleobases do not change their pKa values when included in PNA monomers and oligomers. In addition, immobilized artificial membrane chromatography was employed to evaluate the lipophilic properties of PNA monomers and oligomers, which showed the PNA derivatives had poor affinity towards membrane phospholipids, and confirmed their scarce cell penetrating ability. Overall, our study not only is of potential relevance to evaluate the pharmacokinetic properties of PNA, but also constitutes a reliable basis to properly modify PNA to obtain mimics with enhanced cell penetration properties.

Quantification of amino groups on halloysite surfaces using the Fmoc-method.

The functionalization of halloysite nanotube (HNT) surfaces with aminosilanes is an important strategy for their further decoration with organic molecules to obtain hybrid inorganic-organic nanoarchitectures to be used in catalysis and drug delivery. The exact quantification of amino groups on the surface is an important aspect in view of the obtainment of systems with a known number of loaded molecules. In the present study, we describe a simple and reliable method for the correct quantification of groups present on HNT surfaces after their reaction with aminopropyltriethoxysilane (APTES). This method, applied for the first time to HNT chemistry, was based on the use of Fmoc groups as probes covalently bound to APTES and quantified by UV-Vis after release from the HNT-APTES-Fmoc system. Interestingly, this method showed great accordance with the already employed quantitative thermogravimetric analysis (TGA), with some benefits such as simple and non-destructive procedure, besides the possibility to monitor the deprotection reaction.

Thiahelicene-based inherently chiral films for enantioselective electroanalysis.

Chiral electroanalysis could be regarded as the highest recognition degree in electrochemical sensing, implying the ability to discriminate between specular images of an electroactive molecule, particularly in terms of significant peak potential difference. A groundbreaking strategy was recently proposed, based on the use of "inherently chiral" molecular selectors, with chirality and key functional properties originating from the same structural element. Large differences in peak potentials have been observed for the enantiomers of different chiral molecules, also of applicative interest, using different selectors, all of them based on atropisomeric biheteroaromatic scaffolds of axial stereogenicity. However, helicene systems also provide inherently chiral building blocks with attractive features. In this paper the enantiodiscrimination performances of enantiopure inherently chiral films obtained by electrooxidation of a thiahelicene monomer with helicoidal stereogenicity are presented for the first time. The outstanding potentialities of this novel approach are evaluated towards chiral probes with different chemical nature and bulkiness, in comparison with a representative case of the so far exploited class of inherently chiral selectors with axial stereogenicity. It is also verified that the high enantiodiscrimination ability holds as well for electron spins, as for atropisomeric selectors.

Dirhenium Coordination Complex Endowed with an Intrinsically Chiral Helical-Shaped Diphosphine Oxide.

A one-pot, multicomponent strategy was used to synthesize the first example of the dirhenium carbonyl coordination complex 2, in which the two metal atoms are connected through a chiral helical-shaped diphosphine oxide. Thanks to the flexibility of the helix of helicene 1, complex 2 was isolated in quite a good yield as a stable compound. It was characterized by analytical and spectroscopic techniques as well as by single-crystal X-ray analysis, which confirmed the chemical structure and the peculiar architecture of 2. In addition, computational studies were in agreement with the transitions observed in the experimental UV-vis spectrum, revealing the presence of two bands with maxima at about 520 (metal-to-ligand charge transfer) and 400 nm (IL).

Helical push-pull systems for solar cells: Electrochemical, computational, photovoltaic and NMR data.

The data presented in this article are related to the research article entitled "An unconventional helical push-pull system for solar cells" (Dova et al., 2019). This article provides: a) the cyclic voltammogram plots in solution of helical push-pull sensitizers and the corresponding precursors; b) the visualization of the leading natural transition orbital (NTO) pairs obtained by theoretical calculation of frontiers orbitals; c) J/V curves of dye-sensitized solar cells (DSSC) sensitized by the dyes, without 3a,7a-dihydroxy-5b-cholic acid (CDCA) as co-adsorbent agent; d) 1H and 13C NMR spectra of dyes.

Oligonucleotide Determination via Peptide Nucleic Acid Macromolecular Imprinting in an Electropolymerized CG-Rich Artificial Oligomer Analogue.

We devised and fabricated a chemosensor for determination of the genetically relevant 5'-GCGGCGGC-3' (G = guanine; C = cytosine) oligonucleotide. For that, we simultaneously electrosynthesized and electrode-immobilized a sequence-defined octakis(2,2'-bithien-5-yl) DNA hybridizing probe using both a "macromolecular imprinting in polymer strategy" and a sequence-programmable peptide nucleic acid (PNA) template. With electrochemical impedance spectroscopy (EIS) and surface plasmon resonance (SPR) transductions under stagnant-solution and flow injection analysis (FIA) conditions, respectively, we determined the above oligonucleotide with 200-pM EIS limit of detection. With its EIS-determined apparent imprinting factor of ∼4.0, the chemosensor was discriminative to both mismatched oligonucleotides and Dulbecco's modified Eagle's medium sample interferences.