Bifunctional Dendrimers Research Articles

Well-Defined Bifunctional Dendrimer Bearing 54 Nitric Oxide-Releasing Moieties and 54 Ursodeoxycholic Acid Groups Presenting High Anti-Inflammatory Activity.

Nitric oxide (NO) and ursodeoxycholic acid (UDCA) are endogenous molecules involved in physiological processes associated with inflammation. Since inflammatory processes are present in the mechanisms of many diseases, these molecules are important for the development of new drugs. Herein, we describe the synthesis of a well-defined bifunctional dendrimer with 108 termini bearing 54 NO-releasing groups and 54 UDCA units (Dendri-(NO/UDCA)54). For comparison, a lower-generation dendrimer bearing 18 NO-releasing groups and 18 UDCA units (Dendri-(NO/UDCA)18) was also synthesized. The anti-inflammatory activity of these dendrimers was evaluated, showing that the bifunctional dendrimers have an inverse correlation between concentration and anti-inflammatory activity, with an effect dramatically pronounced for Dendri-(NO/UDCA)54 20, which at just 0.25 nM inhibited 76.1% of IL-8 secretion. Data suggest that nanomolar concentrations of these dendrimers aid in releasing NO in a safe and controlled way. This bifunctional dendrimer has great potential as a drug against multifactorial diseases associated with inflammatory processes.

Water‐Soluble Well‐Defined Bifunctional Ferrocenyl Dendrimer with Anti‐Cancer Activity

AbstractCombination of advantages of ferrocenyl compounds and multifunctional dendrimer scaffold afforded a water‐soluble well‐defined bifunctional dendrimer with polyamide backbone and thirty two termini: eighteen carboxylic acid groups and eighteen triazolylferrocenyl moieties. The structure of the new dendrimer was thoroughly characterized by nuclear magnetic resonance (NMR) spectroscopy, absorbance spectroscopy in the UV‐vis, and MALDI‐TOF mass spectrometry. The MALDI‐TOF spectrum of the final dendrimer showed the [M]2+ ion peak at 4820.1 m/z unambiguously confirming the successful synthesis of the water‐soluble well‐defined bifunctional dendrimer. The cytotoxicity of the well‐defined bifunctional triazolylferrocenyl dendrimer 4 was evaluated against MCF‐7 (breast adenocarcinoma), HeLa (cervical cancer), PC3 (prostate adenocarcinoma), Caco‐2 (colorectal cancer), and PNT2 (normal prostate cells) cell lines. The cytotoxicity assays showed that the dendrimer exhibits moderate anticancer activity and targets cancer cells selectively over normal cells.

Clicked Bifunctional Dendrimeric and Cyclopeptidic Addressable Redox Scaffolds for the Functionalization of Carbon Nanotubes with Redox Molecules and Enzymes.

Carbon nanotube electrodes were modified with ferrocene and laccase using two different click reactions strategies and taking advantage of bifunctional dendrimers and cyclopeptides. Using diazonium functionalization and the efficiency of oxime ligation, the combination of both multiwalled carbon nanotube surfaces and modified dendrimers or cyclopeptides allows the access to a high surface coverage of ferrocene in the order of 50 nmol cm-2, a 50-fold increase compared to a classic click reaction without oxime ligation of these highly branched macromolecules. Furthermore, this original immobilization strategy allows the immobilization of mono- and bi-functionalized active multicopper enzymes, laccases, via copper(I)-catalyzed azide-alkyne cycloaddition. Electrochemical studies underline the high efficiency of the oxime-ligated dendrimers or cyclopeptides for the immobilization of redox entities on surfaces while being detrimental to electron tunneling with enzyme active sites despite controlled orientation.

OP#39 - Bifunctional dendrimer scaffold leads to increased tumor uptake

OP#39 - Bifunctional dendrimer scaffold leads to increased tumor uptake

Synthesis of Well-Defined Bifunctional Newkome-Type Dendrimers

Four bifunctional Newkome-type 1 → 3 branched polyamide-based dendrimers with different spatial arrangements of azido and alkenyl termini were synthesized. The dendrimer synthesis started with three building blocks containing two different ester protecting groups that can be deprotected in an orthogonal fashion. This orthogonal deprotection strategy allowed for the synthesis of three bifunctional dendrimers in a convergent fashion and one dendrimer via a divergent synthetic route. These four dendrimers have different spatial arrangements of termini capable of undergoing further functionalization using 1,3-dipolar cycloaddition and thiol–ene type click chemistries. The precise placement of the functional moieties along the dendrimer surface allows for dendrimer functionalization with a known ratio of cargo and exact placement on the periphery.

Silica Functionalized by Bifunctional Dendrimers: Hybrid Nanomaterials for Trapping CO2

Three types of poly(phosphorhydrazone) dendrimeric structures bearing function(s) suitable for grafting to silica and trapping CO2 have been grafted to different types of silica with various textural properties (e.g., different surface areas, porous or nonporous, pore sizes). These hybrid hard/soft and inorganic/organic nanomaterials have been characterized. Some representative examples of these hybrid materials were chosen for trapping CO2 and their performances have been analyzed.

Synthesis and Electrophoretic Properties of Novel Nanoparticles for Colored Electronic Ink and e-Paper Applications.

A new approach based on non-pigmented, stable colored nanoparticles able to migrate upon application of an electrical field (10-60 V) has been developed for the improvement of the color brightness of e-displays. The scientific challenges comprised the development of efficient syntheses of tri- and bifunctional dendrimers including branching points for further extension and individual decoration with dye (yellow, magenta, cyan). The covalent attachment of these scaffolds to silica nanoparticles was performed via hydrosilylation and final in situ charging generated attractive silica shells for the substractive CMY color space model.

Synthesis of a bi-functional dendrimer-based nanovehicle co-modified with RGDyC and TAT peptides for neovascular targeting and penetration

The dual-ligand dendritic polyamidoamine-(polyethylene glycol)n-cyclic RGDyC peptide-(TAT peptide) (PPnR(T)) with various supplied molar ratios of polyethylene glycol (PEG) to polyamidoamine (PAMAM) (n=5, 15, 30) were designed as drug-carriers for the treatment of neovascular diseases; their targeting and penetrating effects were subsequently evaluated. 1H NMR demonstrated PPnR(T) was successfully synthesized. Compared with the unmodified PAMAM, in vitro cytotoxicity of PPnR(T) to αvβ3 negative cells (αvβ3-) was significantly reduced, whereas the lethality to pathologic neovascular endothelial cells (αvβ3+) was efficiently increased compared to PPn. Compared to PP5R(T) and PP15R(T), PP30R(T) exhibited the most selective and efficient cellular uptake by human umbilical vein endothelial cells (HUVECs, αvβ3+). Membrane interaction study indicated the cellular uptake process of PP30R(T) of HUVECs mainly involved specific RGD-αvβ3 recognition as well as electrostatic interactions. Intracellular localization results confirmed PP30R(T) was distributed in the cytoplasm in HUVECs. 3D tumor spheroids penetration studies demonstrated that PP30R(T) penetrated the A549 cells to reach the depths of the avascular tumor spheroids. In vivo imaging further demonstrated that PP30R(T) achieved profoundly improved distribution in tumor tissues where angiogenesis existed. Therefore, the bi-functional dendrimer PP30R(T) displayed great potential as a nano-carrier for targeted drug delivery both in vitro and in vivo, and had broad prospects as nanocarriers for the targeted treatment of neovascular diseases.

Water-Soluble Polyglycerol Dendrimers with Two Orthogonally Reactive Core Functional Groups for One-Pot Functionalization.

The synthesis of a water-soluble polyglycerol dendrimer with two orthogonal functional groups at the core is reported. The two groups, an azide and amine group, are highly reactive towards alkyne and activated ester moieties, respectively. The orthogonality of the two chemical reactions is demonstrated by the ability to conjugate quantitatively either group, independent of the other and in either order. The orthogonal functionalization of the azide- and amine-cored dendrimer can be accomplished in a stepwise or a one-pot synthetic protocol. All resulting bifunctional dendrimers are fully soluble in water as the water-soluble dendritic scaffold decorated with 48 hydroxyl groups on the surface successfully solubilizes both the hydrophobic fluorophore and targeting group.

Preparation and characterization of bifunctional dendrimer modified Fe3O4/CdTe nanoparticles with both luminescent and superparamagnetic properties

Magnetic nanoparticles Fe3O4 were prepared by hydrothermal coprecipitation of ferric and ferrous ions using NaOH. The surface modification of Fe3O4 nanoparticle by dendrimers has rendered the nanoparticle surface with enriched amine groups which facilitated the adsorption and conjugation of thioglycolic acid (TGA) modified CdTe quantum dots to form a stable hybrid nanostructure. Three generations (first generation: G0F, second generation: G1F, third generation: G3F) of bifunctional dendrimeric Fe3O4/CdTe nanoparticles were successfully prepared using this technique and characterized by microscopy. The optical and magnetic properties of the dendrimeric Fe3O4/CdTe nanoparticle were also investigated. The microscopic study reveals 3 different sizes for 3 generations, 16nm (G0F), 31nm (G1F) and 47nm (G3F). Among three generations of nanoparticles, the G1F has the best optical property with a luminescent quantum yield of 25.6% and the G0F has the best magnetic property with a saturation magnetization of 19.3emμ/g.

Synthesis and characterization of bifunctional dendrimers: preliminary use for the coating of gold surfaces and the proliferation of human osteoblasts (HOB)

Dendrimers having one dithiolane and ammonium or carboxylate functions have been synthesized for coating gold surfaces interacting with human osteoblasts.

Bifunctional metallodendrimers based on AB5 derivatives of cyclotriphosphazene as core and P,N ligands as terminal functions

The specific functionalization of hexachlorocyclotriphosphazene with one function different from the five others was used for the synthesis of bifunctional dendrimers having one protected amine linked to the core and either 5 phosphines or 10 phosphine imines (P,N ligands) as terminal groups. In the latter case, reaction with PdCl2(COD) affords the corresponding complexes of the P,N ligands. All compounds were characterized by multinuclear NMR, and particularly by 31P NMR, which proved to be a very precious tool for the characterization of sophisticated structures such as dendrimers.

Biocompatible Polyurea Dendrimers with pH‐Dependent Fluorescence

dendrimers emerge as powerful nanotools.Herein, we describe the synthesis and properties (up tothe fourth generation in this report) of polyurea (PURE)dendrimers. PURE dendrimers are a new family of water-soluble blue photoluminescent biocompatible and biodegrad-able “green” bifunctional dendrimers. The synthesis wasperformed in supercritical carbon dioxide (scCO

Bifunctional PAMAM Dendrimer Conjugates of Folic Acid and Methotrexate with Defined Ratio

Our group previously developed a multifunctional, targeted cancer therapeutic based on Generation 5 (G5) polyamidoamine (PAMAM) dendrimers. In those studies we conjugated the targeting molecule folic acid (FA) and the chemotherapeutic drug methotrexate (MTX) sequentially. This complex macromolecule was shown to selectively bind and kill KB tumor cells that overexpress folate receptor (FR) in vitro and in vivo. However, the multistep conjugation strategy employed in the synthesis of the molecule resulted in heterogeneous populations having differing numbers and ratios of the functionally antagonistic FA and MTX. This led to inconsistent and sometimes biologically inactive batches of molecules, especially during large-scale synthesis. We here resolved this issue by using a novel triazine scaffold approach that reduces the number of dendrimer conjugation steps required and allows for the synthesis of G5 conjugates with defined ratios of FA and MTX. Although an unoccupied γ-glutamyl carboxylate of FA has been previously suggested to be nonessential for FR binding, the functional requirement of an open α-carboxylate still remains unclear. In an attempt to also address this question, we have synthesized isomeric FA dendrimer conjugates (α-carboxyl or γ-carboxyl linked). Competitive binding studies revealed that both linkages have virtually identical affinity toward FR on KB cells. Our studies show that a novel bifunctional triazine-based conjugate G5-Triazine-γMTX-αFA with identical numbers of FA and MTX binds to FR through a polyvalent interaction and induces cytotoxicity in KB cells through FR-mediated cellular internalization, inducing higher toxicity as compared to conjugates synthesized by the multistep strategy. This work serves as a proof of concept for the development of bifunctional dendrimer conjugates that require a defined ratio of two functional molecules.

Bifunctional Dendrimers: From Robust Synthesis and Accelerated One‐Pot Postfunctionalization Strategy to Potential Applications

A fourth wheel: Two sets of bifunctional AB(2)C dendrimers having internal acetylene/azides and external hydroxy groups were constructed utilizing benign synthetic protocols. An in situ postfunctionalization strategy was successfully carried out to illustrate the chemoselective nature of these dendrimers. The dendrimers were also transformed into dendritic nanoparticles or utilized as dendritic crosslinkers for the fabrication hydrogels.

Bifunctional Dendrimers: From Robust Synthesis and Accelerated One‐Pot Postfunctionalization Strategy to Potential Applications

AbstractZwei Sätze von difunktionellen AB2C‐Dendrimeren mit internen Acetylen/Azid‐ und externen Hydroxygruppen wurden synthetisiert. Eine erfolgreiche Funktionalisierung in situ belegte das chemoselektive Verhalten der Dendrimere, die außerdem in dendritische Nanopartikel umgewandelt oder als dendritische Vernetzer beim Aufbau von Hydrogelen eingesetzt werden konnten.magnified image

Facile Synthesis of Bifunctional Dendritic Block Copolymers

Dendrimers are attractive materials due to the dense functionality present at the branch termini. Synthesizing multifunctional dendrimers with directional control of the functional groups, however, remains a challenge. Hawker et al. have achieved this goal in a remarkably simple synthesis for a bifunctional dendrimer by utilizing the highly efficient and functional group-tolerant copper(I)-catalyzed azide-alkyne cycloaddition reaction to link two dendrons. In one example, the amphiphilic dendritic block copolymer was further functionalized with α-d-mannopyranoside and 7-diethylaminocoumarin dyes using the cycloaddition reaction.

Multivalent, Bifunctional Dendrimers Prepared by Click Chemistry

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Multivalent, bifunctional dendrimers prepared by click chemistry

Unsymmetrical dendrimers, containing both mannose binding units and coumarin fluorescent units, have been prepared using click chemistry and shown to be highly efficient, dual-purpose recognition/detection agents for the inhibition of hemagglutination.