Dendritic hydrogels based on carbosilane crosslinkers are promising drug delivery systems, as their amphiphilic nature improves the compatibility with poorly water-soluble drugs. In this work, we explored the impact of the complementary polymer on the amphiphilic properties of the dendritic network. Different polymers were selected as precursors, from the highly lipophilic propylene glycol (PPG) to the hydrophilic polyethylene glycol (PEG), including amphiphilic Pluronics L31, L35 and L61. The dithiol polymers reacted with carbosilane crosslinkers through UV-initiated thiol-ene coupling (TEC), and the resultant materials were classified as non-swelling networks (for PPG, PLUL31 and PLUL61) and high-swelling hydrogels (for PEG and PLUL35). The hydrogels exhibited thermo-responsive properties, shrinking at higher temperatures, and exhibited an intriguing drug release pattern due to internal nanostructuring. Furthermore, we fine-tuned the dendritic crosslinker, including hydroxyl and azide pendant groups in the focal point, generating functional networks that can be modified through degradable (ester) and non-degradable (triazol) bonds. Overall, this work highlighted the crucial role of the amphiphilic balance in the design of dendritic hydrogels with thermo-responsive behavior and confirmed their potential as functional networks for biomedical applications.

Cationic dendritic amphiphiles were prepared through the linkage of interesting hydrophobic molecules such as cholesterol or vitamin E to the focal point of carbosilane dendrons. These new dendritic systems self-assembled in saline, producing micellar aggregates with hydrodynamic diameters ranging from 6.5 to 9.2 nm, and critical micelle concentrations of approximately 5 and 10 μM for second- and third-generation systems, respectively. The assemblies were able to encapsulate drugs of different charges (anionic, neutral, and cationic). Surprisingly, a 92% encapsulation efficiency for diclofenac was achieved in micelles prepared from second-generation dendrons. Toxicity measurements on peripheral blood mononuclear cells indicated different behavior depending on the generation, corresponding to the micellar regime. In contrast to the third-generation system, the second-generation system was non-toxic up to 20 μM, opening a window for its use in a micellar regimen, thereby operating as a drug delivery system for different biomedical applications.

Two families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified-GO and GO-dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses. In addition, the free dendrons and the dendrons grafted to GO were tested toward cancerous (HCT116) and non-cancerous (RPE1) cell lines.

Separation of PEGylated protein mixtures into individual species is a challenging procedure, and many efforts have been focused on creating novel chromatographic supports for this purpose. In this study, a new monolithic stationary phase with hyperbranched nanostructures was chemically synthesized. For this, monoliths with a support matrix of poly (glycidyl methacrylate-co-ethylene dimethacrylate) and ethylenediamine chemistry were modified with third-generation dendrons with butyl-end groups. The new monolith was analyzed by infrared spectroscopy, confirming the dendron with butyl ligands and exhibited low mass transfer resistance as observed by breakthrough frontal analysis. This support was able to separate mono-PEG ribonuclease A from the PEGylation mixture, indicated by a single band (∼30 kDa) in the electrophoretic analysis. Moreover, the separation of mono-PEGylated positional isomers was probably observed, as the protein with ∼30 kDa was found in two separate peaks. Interestingly, the dendronized monolith allowed the separation of the reaction mixture into individual PEGylated species when using high ammonium sulfate concentrations (2 M). A correlation between the PEGylation degree and the strength of the hydrophobic interactions on the monolith was observed. This chromatographic approach combines the natural branched architecture of dendrons and the higher capabilities of the monoliths enhancing the hydrophobic surface area, and therefore the interaction between the PEGylated proteins and ligands. Thus, the novel support represents a novel platform for the purification of PEGylated from non-PEGylated proteins with biotechnological applications.

DNA origami has emerged as a common technique to create custom two- (2D) and three-dimensional (3D) structures at the nanoscale. These DNA nanostructures have already proven useful in development of many biotechnological tools; however, there are still challenges that cast a shadow over the otherwise bright future of biomedical uses of these DNA objects. The rather obvious obstacles in harnessing DNA origami as drug-delivery vehicles and/or smart biodevices are related to their debatable stability in biologically relevant media, especially in physiological low-cation and endonuclease-rich conditions, relatively poor transfection rates, and, although biocompatible by nature, their unpredictable compatibility with the immune system. Here we demonstrate a technique for coating DNA origami with albumin proteins for enhancing their pharmacokinetic properties. To facilitate protective coating, a synthesized positively charged dendron was linked to bovine serum albumin (BSA) through a covalent maleimide-cysteine bonding, and then the purified dendron-protein conjugates were let to assemble on the negatively charged surface of DNA origami via electrostatic interaction. The resulted BSA-dendron conjugate-coated DNA origami showed improved transfection, high resistance against endonuclease digestion, and significantly enhanced immunocompatibility compared to bare DNA origami. Furthermore, our proposed coating strategy can be considered highly versatile as a maleimide-modified dendron serving as a synthetic DNA-binding domain can be linked to any protein with an available cysteine site.

The Staudinger reaction between a phosphine and an azide, applied to phosphorus azides, has been used for the synthesis of a large variety of dendritic structures, incorporating P=N-P=X moieties (X = mainly S, but also O and N-R). Conjugation of the P=N bond with the P=X bond greatly stabilizes the P=N bond. Highly branched structures such as dendrons, dendrimers, Janus dendrimers, layered dendrimers, surface-block dendrimers, and diverse other dendritic structures incorporating such linkage have been elaborated. Accelerated methods of synthesis of dendrimers are also based on the Staudinger reaction. A versatile reactivity was observed exclusively on the sulfur atom of P=N-P=S linkages, such as alkylation or complexation. Alkylation on S induces a weakening of the strength of the P=S bond, which can be easily cleaved to generate phosphines able to react in Staudinger reactions inside the structure of dendrimers, thus affording highly sophisticated dendritic structures.

Precision antisense antibacterial agents may be developed into novel antibiotics in the fight against multidrug-resistant Gram-negative bacteria. In this study, a series of diaminobutanoic acid (DAB) dendrons are presented as novel carriers for the delivery of antisense antibacterial peptide nucleic acids (PNAs). The dendron-PNA conjugates targeting the essential acpP gene exhibit specific antisense antimicrobial bactericidal activity against Escherichia coli and Klebsiella pneumoniae at one-digit micromolar concentrations, while showing low toxicity to human cells. One compound selected from a structure-activity relationship series showed high stability in mouse and human serum (t1/2 ≫ 24 h) as well as in vivo activity against a multidrug-resistant, extended spectrum beta-lactamase-producing E. coli in a murine peritonitis model. The compound was also well tolerated in mice upon i.v. administration up to a dose of 20 mg/kg, and in vivo fluorescence imaging indicated clearance via renal excretion with slight accumulation in the kidneys and liver. Thus, DAB-based dendrons constitute a promising new chemistry platform for development of effective delivery agents for antibacterial drugs with possible in vivo use.

Three new amino-s-triazine-based dendrons, 1a, 1b, and 1c, containing an aryl-CN moiety in the dendritic skeleton were prepared in 72-81% yields (1a: R1 = - N(n-C8H17)2, R2 = n-OC8H17, 1b: R1 = R2 = - N(n-C8H17)2, 1c: R1 = - N(n-C8H17)2, R2 = - N(n-C4H9)2). Dendrons 1a with N(n-C8H17)2 and n-OC8H17 peripheral substituents, surprisingly, did not show any mesogenic phase during the thermal process. However, non-mesogenic 1a can be converted to mesogenic 1b or 1c by eliminating the peripheral dipole arising from the alkoxy substituent; dendron 1b only comprising the same N(n-C8H17)2 peripheral groups showed a ~25 °C mesogenic range on heating and ~108 °C mesogenic range on cooling. In contrast, dendron 1c possessing different N(n-CmH2m+1)2 (m = 8 versus m = 4) peripheral units, having similar stacking as 1b, exhibited a columnar phase on thermal treatment, but its mesogenic range (~9 and ~66 °C on heating and cooling, respectively) was much narrower than that of 1b, attributed to 1c\'s less flexible alkyl chains in the peripheral part of dendron. Dendron 1a with the alkoxy substituent in the peripheral skeleton, creating additional dipole correspondingly, thus, leads to the dendritic molecules having a non-mesogenic stacking. Without the peripheral dipole for intermolecular side-by-side interaction, dendrons 1b and 1c exhibit a columnar phase on thermal treatment because of the vibration from the peripheral alkyl chain.

Carbon-carbon cross-coupling reactions are among the most important synthetic tools for the preparation of pharmaceuticals and bioactive compounds. However, these reactions are normally carried out using copper, phosphines, and/or amines, which are poisonous for pharmaceuticals. The use of nanocomposite catalysts holds promise for facilitating these reactions and making them more environmentally friendly. In the present work, the PEGylated (PEG stands for poly(ethylene glycol) pyridylphenylene dendrons immobilized on silica loaded with magnetic nanoparticles have been successfully employed for the stabilization of Pd2+ complexes and Pd nanoparticles. The catalyst developed showed excellent catalytic activity in copper-free Sonogashira and Heck cross-coupling reactions. The reactions proceeded smoothly in green solvents at low palladium loading, resulting in high yields of cross-coupling products (from 80% to 97%) within short reaction times. The presence of magnetic nanoparticles allows easy magnetic separation for repeated use without a noticeable decrease of catalytic activity due to the strong stabilization of Pd species by rigid and bulky dendritic ligands. The PEG dendron periphery makes the catalyst hydrophilic and better suited for green solvents. The minor drop in activity upon the catalyst reuse is explained by the formation of Pd nanoparticles from the Pd2+ species during the catalytic reaction. The magnetic separation and reuse of the nanocomposite catalyst reduces the cost of target products as well as energy and material consumption and diminishes residual contamination by the catalyst. These factors as well as the absence of copper in the catalyst makeup pave the way for future applications of such catalysts in cross-coupling reactions.

Functional supramolecular gel materials have potential applications in sensors, optical switches, artificial antennae, drug delivery and so on. In this paper, quinoline-cored poly(aryl ether) dendritic organogelators were designed, synthesized and fully characterized. The gelation behaviour of the dendritic organogelator was tested in organic solvents, mixed solvents and ionic liquids. The dendron Q-G1 was found to be an efficient and versatile organogelator toward various apolar and polar organic solvents with the critical gelation concentrations (CGCs) approaching 1.2×10-2  mol/L, indicating one dendritic organogelator could immobilize 1.2×103 solvent molecules in the organogel network. Interestingly, these dendrons exhibited excellent gel formation in ionic liquids. Notably, these dendritic organogels were found to display multiple stimuli-responsive properties toward external stimuli including heat, ultrasound and shear stress, with a reversible sol-gel phase transition. In addition, the dendritic organogel could effectively adsorb heavy metals and organic dyes. The removal rate of Pb2+ was up to 20% and the adsorption rate for Rhodamine B was as high as 89%.