Supramolecular Polymerization of [5]Helicenes. Consequences of Self-Assembly on Configurational Stability

The supramolecular polymerization of [5]­helicenes <b>1</b> and <b>2</b> is investigated. The self-assembly of these helicenes proceeds by the operation of H-bonding interactions with a negligible participation of π-stacking. The enantiopurity of the sample has a dramatic effect on the supramolecular polymerization mechanism since it reverts the isodesmic mechanism for the racemic mixture to a cooperative one for the enantioenriched sample. Noticeably, the formation of supramolecular polymers efficiently increases the configurational stability of 1,14-unsubstituted [5]­helicenes

Heterofunctionalized Carbosilane Dendritic Systems: Bifunctionalized Dendrons as Building Blocks versus Statistically Decorated Dendrimers

“Click” chemistry based on thiol–ene synthetic protocols has been used to successfully bifunctionalize anionic carbosilane dendritic structures in two effective ways. The first consists of the formation of statistically heterofunctionalized dendrimers, the second being the synthesis of heterofunctionalized dendrons. Regarding the latter approach, a versatile and simple procedure has been developed for the synthesis of a library of anionic carbosilane dendrons. Taking into account the chemical diversity at the focal point for both neutral- and anionic-terminated dendrons, such as azide, alcohol, amine, bromine, carboxylic acid, and alkyne, these dendritic systems may act as building blocks to give more original dendritic architectures

Carbosilane Dendrimer 2G-NN16 Represses Tc17 Differentiation in Primary T CD8+ Lymphocytes

We studied changes in gene expression induced by the carbosilane dendrimer 2G-NN16 to evaluate their potential as a vehicle for gene therapy and as medication. Global gene expression profiles on CD8+ T lymphocytes reveal that ribosomal proteins are induced in the presence of 2G-NN16. IL17A and IL17F, the principal interleukins secreted by Tc17 cells, a subset of CD8+ T lymphocytes, were down-regulated when cultured in the presence of this dendrimer. Microarray results were confirmed by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). 2G-NN16 also showed a high potential for in vitro inhibition of Tc17 differentiation of CD8+ T lymphocytes in the presence of the Tc17 differentiation molecules IL6 and TGF-B1. These findings suggest that 2G-NN16 could facilitate drug delivery and may be used to treat inflammatory processes driven by Tc17 cells

Alteration of the HIF-1α/VEGF Signaling Pathway and Disruption of the Cell Cycle by Second Generation Carbosilan Dendrimers

Current therapies against prostate cancer (PCa) disease, such as surgery, radiotherapy, or in last term chemical castration by androgen deprivation, have led to significant reduction of the incidence of PCa throughout the world. Worse prognosis is found in those patients which exhibit castration resistance, relapsing into the disease with even greater aggressiveness. Hypoxia cancer cell adaption has been observed to be closely connected to fatal prognostic tumor features. Therefore, hypoxia adaptive mechanisms of cancer cells have attracted large interest as a relevant biological target for treatment-resistant patients. Dendrimers have been established as a promising nanotechnological tool owing to their beneficial physicochemical features such as multivalency and monodispersity. Herein, we have completed a thorough study to better understand the effect within the cell of the already published ruthenium(II)-N-heterocyclic carbene metallodendrimer (G2Ru) that was able to drastically reduce HIF-1α stabilization and exhibited antiproliferative capability against androgen-sensitive (LNCaP) and androgen-resistant prostate cancer cells (LNFLU) in vitro. G2Ru, as well as its cationic imidazolium precursor (G2P), displayed scavenging properties against intracellular and externally stimulated ROS levels, which would presumably hinder the stabilization of HIF-1α by prolyl hydroxylase (PHD) inhibition. Furthermore, these dendrimers have shown considerably beneficial properties against tumor progression capability in terms of apoptosis, cell cycle, CSCs expression, and epithelial phenotype promotion. Taken all together, in this study we could demonstrate the extraordinary anticancer properties of NHC-based carbosilane dendrimers against androgen-resistant prostate cancer cells in vitro

Thiol-Ene Synthesis of Cationic Carbosilane Dendrons: a New Family of Synthons

A variety of neutral and cationic carbosilane dendrons containing a wide range of active groups, such as −N₃, −OH, −NH₂, and −SH, at the focal points were synthesized from carbosilane vinyl dendrons BrG_<i>n</i>V_<i>m</i> from generations 1–3 by substitution of the bromine atom at the focal point and functionalization of the vinyl groups via thiol-ene click chemistry with HS­(CH₂)₂NMe₂·HCl. These dendritic wedges were characterized by NMR, MS, and elemental analysis

Synthesis of Cationic Carbosilane Dendrimers via Click Chemistry and Their Use as Effective Carriers for DNA Transfection into Cancerous Cells

New amine-terminated carbosilane dendrimers have been prepared by a Huisgen cycloaddition (“click chemistry” reaction) of azide-terminated carbosilane dendrimers with two different propargyl amines. The corresponding cationic derivatives with peripheral ammonium groups were obtained by subsequent addition of MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods, and have been studied as nonviral vectors for the transfection of DNA to cancer cells. In this study DNA-dendrimeric nanoparticles (dendriplexes) formulated with two different families of cationic carbosilane dendrimers (family 1 (G1, G2 and G3) and family 2 (G1, G2)) were characterized and evaluated for their ability to transfect cells <i>in vitro</i> and <i>in vivo</i>. Dendriplex derived from second generation dendrimer of family 1 (F1G2 5/1 (+/−)) increased the efficiency of plasmid-mediated gene transfer in HepG2 cells as compared to naked DNA and the commercial control dendrimer. Also, intravenously administered dendriplex F1G3 20/1 (+/−) is superior in terms of gene transfer efficiency <i>in vivo</i>

Improved Efficiency of Ibuprofen by Cationic Carbosilane Dendritic Conjugates

In order to improve the efficiency of the anti-inflammatory drug ibuprofen, cationic carbosilane dendrimers and dendrons with ibuprofen at their periphery or at their focal point, respectively, have been synthesized, and the release of the drug was studied using HPLC. Macrophages were used to evaluate the anti-inflammatory effect of the ibuprofen-conjugated dendritic systems and compared with mixtures of non-ibuprofen dendritic systems in the presence of the drug. The cationic ibuprofen-conjugated dendron was the compound that showed higher anti-inflammatory properties. It reduces the LPS-induced <i>COX-2</i> expression and decreases the release of several inflammatory cytokines such as TNFα, IL-1β, IL-6, and CCL3. These results open new perspectives in the use of these compounds as drug carriers

Extending Hexaazatriphenylene with Mono-/Bithiophenes in Acceptor–Donor Diads and Acceptor–Donor–Acceptor Triads

Three new hexaazatriphenylene (HAT)-based electron-accepting molecules with octupolar disc-like symmetry that combine the HAT core with six branches of electron-donor thiophenes in two modalities have been synthesized: (i) with six donor thiophenes and bithiophenes delineating a six-donor-to-one-acceptor (6–1) profile and (ii) with six donor–acceptor branches configuring a 6–6–1 acceptor–donor–acceptor triad. The 6-fold accumulation of donors and acceptors in the periphery of the HAT core is expected to tune the molecular electronic and optical properties. An exhaustive analysis of these properties as a function of the 6–1 and 6–6–1 stoichiometry of the molecules is described by combining a palette of experimental spectroscopic techniques such as electronic absorption (from the ground electronic and excited states), emission (fluorescence and phosphorescence), ultraviolet photoelectron spectroscopy, spectroelectrochemistry, and vibrational Raman have been implemented, all combined with electrochemistry and molecular theoretical modeling. A particular focus on the charged species and the charge distribution around the 6–1 and 6–6–1 patterns is conducted. Structure–property relationships have been outlined. The complete understanding of all these properties might help to design improved chromophores based on the HAT structure and to anticipate new properties