Monofunctionalization of dendrimers with use of microwave-assisted 1,3-dipolar cycloadditions

Monofunctionalized polyamide-based dendrimers containing either a terminal azide or alkyne moiety have been designed and synthesized via a convergent synthetic approach. The monofunctionalization allows for the single attachment of a functional moiety in quantitative yields by using 1,3-dipolar cycloadditions, thereby opening the possibility for targeted dendrimer functionalization.     

A Review of Surface Functionalized Amine Terminated Dendrimers for Application in Biological and Molecular Sensing

Dendrimers are three dimensional nanosized synthetic molecules that have internal cavities and numerous surface groups. In recent times they have received increased attention in sensing applications. For dendrimers to be used as sensors, they most commonly require functionalization at their surface. This is because the surface is generally the first point of contact between the dendrimer and the outside world, hence surface functionalization serves to selectively home in on the target analyte. Further, sensor signals may be transmitted through surface functionalities e.g. fluorochromic molecules. It is therefore important to document surface functionalization approaches. Dendrimers with amine surface groups have the advantage of being able to be conjugated to other molecules via an amide linkage, which is one of the most fundamental and widespread chemical bonds in nature. In this paper we demonstrate the properties of dendrimers that make them so applicable to sensing. We review several methods for functionalizing dendrimers via an amide linkage, as well as present a review of surface functionalized polyamidoamine, polyamine, and polypeptide dendrimers that have been employed for biological, chemical and molecular sensing.     

Design of biocompatible dendrimers for cancer diagnosis and therapy: current status and future perspectives

In the past decade, nanomedicine with its promise of improved therapy and diagnostics has revolutionized conventional health care and medical technology. Dendrimers and dendrimer-based therapeutics are outstanding candidates in this exciting field as more and more biological systems have benefited from these starburst molecules. Anticancer agents can be either encapsulated in or conjugated to dendrimer and be delivered to the tumour via enhanced permeability and retention (EPR) effect of the nanoparticle and/or with the help of a targeting moiety such as antibody, peptides, vitamins, and hormones. Imaging agents including MRI contrast agents, radionuclide probes, computed tomography contrast agents, and fluorescent dyes are combined with the multifunctional nanomedicine for targeted therapy with simultaneous cancer diagnosis. However, an important question reported with dendrimer-based therapeutics as well as other nanomedicines to date is the long-term viability and biocompatibility of the nanotherapeutics. This critical review focuses on the design of biocompatible dendrimers for cancer diagnosis and therapy. The biocompatibility aspects of dendrimers such as nanotoxicity, long-term circulation, and degradation are discussed. The construction of novel dendrimers with biocompatible components, and the surface modification of commercially available dendrimers by PEGylation, acetylation, glycosylation, and amino acid functionalization have been proposed as available strategies to solve the safety problem of dendrimer-based nanotherapeutics. Also, exciting opportunities and challenges on the development of dendrimer-based nanoplatforms for targeted cancer diagnosis and therapy are reviewed (404 references).     

Fabrication of carbon nanotube-molecule-silicon junctions

A hybridization strategy for the covalent connection of single wall carbon nanotubes to silicon surfaces via oligo(phenylene ethynylene)s has been demonstrated using an orthogonal bisdiazonium functionalization protocol.     

Synthesis and photophysical properties of triphenylamine-based dendrimers with 1,3,5-triphenylbenzene cores

Two new conjugated dendrimers bearing a triphenylamine moiety as dendrons and 1,3,5-triphenylbenzene as a core have been synthesized through a convergent synthetic strategy. These conjugated dendrimers have high fluorescence quantum yields and exhibit similar absorption and emission behaviors in solutions and in solid films, which demonstrate that these dendrimers form good amorphous states.     

Extended pi-conjugated dendrimers based on truxene

The largest pi-conjugated dendrimers containing up to nine 10,15-dihydro-5H-diindeno[1,2-alpha;1',2';-c]fluorene (truxene) moieties have been prepared with good yields by repetitive Friedel-Crafts acetylation and acid-promoted cyclotrimerization reactions. An alternative approach to the convergent synthesis of desired dendrimers has been developed, in which the core is generated "in-situ" by acid-promoted cyclotrimerizations of aryl methyl ketones. This proves valuable to afford large-size and precisely well-defined dendrimers in an accelerated dendrimer-growth strategy utilizing enlarged repeat units. The increasing amount of SiCl4 dramatically improves the yield of cyclotrimerization reactions. The introduction of hexahexyl groups onto C-5, C-10, C-15 positions of the truxene moiety greatly enhances the solubility of our compounds. Further investigation indicates that the torsion angle between the truxene segment and the benzene ring might play a key role in determining the photo properties of pi-conjugated dendrimers.     

Guest–host chemistry with dendrimers: Stable polymer assemblies by rational design

A new type of guest has been designed and synthesized for the exo‐type supramolecular functionalization of adamantyl‐urea‐terminated poly(propylene imine) dendrimers. This new type of guest motif features a uriedo methane sulfonic acid moiety that binds very selectively to the surfaces of dendrimers via a combination of noncovalent interactions forming well‐defined complexes. The guest–host properties have been examined for a fifth‐generation adamantyl‐urea‐functionalized poly(propylene imine) dendrimer capable of binding 32 guest molecules and for a model host molecule that can bind only one guest molecule. The guest–host chemistry has been studied with ¹H NMR spectroscopy, nuclear Overhauser enhancement spectroscopy NMR spectroscopy, T₁‐relaxation NMR experiments, and IR spectroscopy. The 1:32 ratio with the dendrimer has been confirmed unambiguously from ¹H NMR spectra of the complex after size exclusion chromatography. Competition experiments with guests bearing a carboxylic acid instead of a sulfonic acid in the binding motif have demonstrated that the sulfonic acid has superior binding strength. Also, the importance of a combination of noncovalent interactions has been shown via competition experiments with a guest lacking the uriedo moiety. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 3792–3799, 2004     

One-step multifunctionalization of random copolymers via self-assembly

A novel methodology for random copolymer functionalization based on a noncovalent, one-step, multifunctionalization strategy has been developed. Random copolymers possessing both palladated-pincer complexes and diaminopyridine moieties (hydrogen-bonding entities) have been synthesized using ring-opening metathesis polymerization. Noncovalent functionalization of the resultant copolymers is accomplished via (1) directed self-assembly, (2) multistep self-assembly, and (3) one-step orthogonal self-assembly. This system shows complete specificity of each recognition motif for its complementary unit, with no observable changes in the association constants regardless of the degree of functionalization.     

Synthesis and photophysical properties of tetraphenylethylene-based conjugated dendrimers with triphenylamine core

Two new conjugated dendrimers bearing a tetraphenylethylene moiety as dendrons and triphenylamine as a core have been synthesized through a convergent synthetic strategy using threefold Heck/threefold Sonogashira coupling reaction. These dendrimers showed excellent solubility in common organic solvents and emit light in the blue and violet regions.     

Photoswitchable flexible and shape-persistent dendrimers: comparison of the interplay between a photochromic azobenzene core and dendrimer structure

Two analogous classes of dendrimers with a single azobenzene moiety at the core have been prepared. Flexible benzyl aryl ether dendrimers 1a-e were obtained in good yields by direct alkylation of diphenolic azobenzene 3 with benzyl aryl ether dendrons [G-n]-Br (n = 0-4). In rigid dendrimers 2a-e, the azobenzene configurational switch was linked to phenylacetylene dendrons through acetylenic linkages to maintain the shape-persistent nature of these dendrimers. A comparison of these two different classes of dendrimers with azobenzene cores reveals a difference in the properties of the photochromic moiety upon dendritic incorporation as well as a significant difference in the photomodulation of dendrimer properties. The E --> Z photoisomerization quantum yield decreased markedly with increasing generation for dendrimers 1a-e but only slightly for dendrimers 2a-e. However, increasing generation did not significantly alter thermal isomerization kinetics or activation barriers. The hydrodynamic volumes of azobenzene-containing dendrimers 2b-e were significantly modulated when the azobenzene unit is subjected to irradiation, while those of dendrimers 1b-e were only slightly affected.     

Paramagnetic cobalt(II) as an NMR probe of dendrimer structure: mobility and cooperativity of dendritic arms

Cobalt(II) has been utilized as an external paramagnetic (1)H NMR probe for the study of the structure of dendrimers that possess specifically located metal recognition sites. The hyperfine-shifted (1)H NMR signals of the Co(II) complexes of several 2,6-diamidopyridine-containing dendrimers have been fully assigned by means of 1D and 2D NMR techniques, including NOE difference, EXSY, COSY, and TOCSY. Temperature-dependent T(1) values of the hyperfine-shifted signals were used to conclude that the Co(II)-dendrimer complexes are in the "liquidlike" regime, indicative of a shell-like structure instead of a "dense-core" structure. The presence of sizable cavities within the dendrimers was observed including a loosely packed conformation for the 2,6-diamidopyridino moiety to bind to potential guest molecules. Cooperativity among the dendritic arms in metal binding is also observed, whereby two dendritic arms bind to the metal center at the same time. In the case of dendrimers with the metal binding site located near the surface of the molecule, such binding cooperativity is still observed despite the large degree of freedom of the metal-binding moiety. Cooperativity among the dendritic arms can thus be considered an intrinsic property, which has to be taken into consideration in future design of functional dendrimers for the purpose of specific recognition and catalysis. The hydrodynamic radii of these dendrimers have been determined by means of nuclear Overhouser effect at low temperature. The study offers a method for the study of the dynamics of dendrimers in solution under different conditions and upon ligand binding and recognition. The study also provides a tool for monitoring systematic variation of the metal binding site in different dendrimer frameworks for specific applications, such as catalysis and molecular recognition.     

Synthesis, optical, electrochemical, and thermal studies on triazole-based dendrimers with diphenylamine as surface group

Fréchet-type dendrimers with hole-transporting diphenylamine as surface group and electron-transporting triazole moiety as building block have been synthesized by convergent synthetic strategy through ‘click chemistry’ methodology. First generation dendrimer exhibits longer relaxation time, higher quantum yield in the fluorescence spectrum, and better thermal stability than the zero and second generation dendrimers. CV studies showed irreversible reduction potential and the formation of radical cation due to diphenylamine moiety.     

Cross-linked and functionalized ‘universal polymer backbones’ via simple, rapid, and orthogonal multi-site self-assembly

A novel route to cross-linked and functionalized random copolymers using a rapid, one-step, and orthogonal copolymer cross-linking/functionalization strategy has been developed. Random terpolymers possessing high concentrations of pendant alkyl chains and either (1) palladated-pincer complexes and diaminopyridine moieties (DAD hydrogen-bonding entities) or (2) palladated-pincer complexes and cyanuric wedges (ADAADA hydrogen-bonding entities) have been synthesized using ring-opening metathesis polymerization. Non-covalent cross-linking of the resultant copolymers using a directed functionalization strategy leads to dramatic increases in solution viscosities for cross-linked polymers via metal-coordination while only minor changes in viscosity were observed when hydrogen-bonding motifs were employed for cross-linking. The cross-linked materials could be further functionalized via self-assembly by employing the second recognition motif along the polymeric backbones giving rise to highly functionalized materials with tailored cross-links. This novel non-covalent polymer cross-linking/functionalization strategy allows for rapid and tunable materials synthesis by overcoming many difficulties inherent to the preparation of covalently cross-linked polymers.     

Synthesis of Pyrrolophenanthridine Alkaloids Based on C(sp3)H and C(sp2)H Functionalization Reactions

Assoanine, pratosine, hippadine, and dehydroanhydrolycorine belong to the pyrrolophenanthridine family of alkaloids, which are isolated from plants of the Amaryllidaceae species. Structurally, these alkaloids are characterized by a tetracyclic skeleton that contains a biaryl moiety and an indole core, and compounds belonging to this class have received considerable interest from researchers in a number of fields because of their biological properties and the challenges associated with their synthesis. Herein, a strategy for the total synthesis of these alkaloids by using C? H activation chemistry is described. The tetracyclic skeleton was constructed in a stepwise manner by C(sp³)? H functionalization followed by a Catellani reaction, including C(sp²)? H functionalization. A one‐pot reaction involving both C(sp³)? H and C(sp²)? H functionalization was also attempted. This newly developed strategy is suitable for the facile preparation of various analogues because it uses simple starting materials and does not require protecting groups.     

Trifluoroacetyl as an orthogonal protecting group for guanidines

The trifluoroacetyl moiety has been used as a new protecting group for guanidine functionality. The protecting group is easily cleaved under mild basic conditions and is complementary to the Boc, Cbz, and Ddpe protecting groups. The protecting group can be applied to peptide synthesis in solution as well as on a solid phase as it is orthogonal to a Boc and Cbz strategy and semiorthogonal to an Fmoc strategy.     

Site-specific assembly of DNA and appended cargo on arrayed carbon nanotubes

We describe a strategy that permits discrete regions of arrayed carbon nanotubes (CNTs) to be functionalized simultaneously and specifically with DNA oligonucleotides. The different chemical properties of two regions on single CNTs and orthogonal chemical coupling strategies have been exploited to derivatize CNTs within highly ordered arrays with multiple DNA sequences. Through duplex hybridization, we then targeted different DNA sequences with appended metal nanoparticles to distinct sites on the CNT architecture with precise spatial control. The materials generated from these studies represent the first CNTs with bipartite functionalization. The approach described provides a high level of precision in parallel and directed assembly of DNA sequences and appended cargo and is useful for the preparation of novel hybrid bionanomaterials.     

Dendrimer interior functional group conversion and dendrimer metamorphosis--new approaches to the synthesis of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers

A series of [G1] to [G3]-oligo(dibenzylsulfide) dendrimers containing up to 21 interior dibenzylsulfide moieties was prepared as starting materials toward the syntheses of two new series of oligo(dibenzyl sulfone) and oligo(phenylenevinylene) dendrimers using two different dendrimer-to-dendrimer conversion strategies. The first strategy entailed the interior functionalization of the [G1] to [G3]-oligo(dibenzylsulfide)s to the corresponding [G1] to [G3]-oligo(dibenzyl sulfone)s via hydrogen peroxide oxidation. Successful conversions of up to 21 interior dibenzylsulfide moieties to the corresponding dibenzyl sulfone groups were demonstrated. The second involved the skeletal rearrangements, also named as dendrimer metamorphosis, of the [G1] and [G2]-oligo(dibenzyl sulfone) dendritic backbones to the corresponding [G1] and [G2]-oligo(phenylenevinylene)s dendrimers via the Ramberg-Backlund (RB) reaction. Up to nine RB rearrangements on a dendrimer skeleton were realized and the conversion efficiency of each single RB rearrangement reaction was found to be 96%.     

Free Carboxylic Acids: The Trend of Radical Decarboxylative Functionalization

The exceptional versatility of carboxylic acids has been extensively exploited in organic synthesis across several decades. There has been a recent upsurge of radical decarboxylative transformations. The process can be initiated under mild conditions, and the resultant radicals have orthogonal reactivities to closed-shell species, thus providing immense opportunities for streamlining novel reactions. The use of free carboxylic acids is the most desirable owing to its high atom and step economy. Aiming to demonstrate the attractiveness of the strategy and to inspire chemists to tackle existing challenges, this review outlines the recent advances on radical decarboxylative functionalization of free carboxylic acids.     

Enantioselective Palladium-Catalyzed Directed Migratory Allylation of Remote Dienes

Chain walking has been an efficient route to realize the functionalization of inert C(sp³)−H bonds, but this strategy is limited to mono-olefin migration and functionalization. Herein, we demonstrate the feasibility of tandem directed simultaneous migrations of remote olefins and stereoselective allylation for the first time. The adoption of palladium hydride catalysis and secondary amine morpholine as solvent is critical for achieving high substrate compatibility and stereochemical control with this method. The protocol is also applicable to the functionalization of three vicinal C(sp³)−H bonds and thus construct three continuous stereocenters along a propylidene moiety via a short synthetic process. Preliminary mechanistic experiments corroborated the design of simultaneous walking of remote dienes.     

A facile convergent procedure for the preparation of triphenylamine-based dendrimers with truxene cores

A simple convergent procedure has been developed for the preparation of triphenylamine dendrons containing an alkene at the center, which can be coupled in a single step to give dendrimers that contain truxene for the core without any protection-deprotection chemistry. These conjugated dendrimers exhibit similar absorption and emission behaviors in solutions and in thin films, which are indicative of the high isolation effect of well-organized three-dimensional dendrimers. They also have high fluorescence quantum yields and high glass transition temperatures, which indicate that these dendrimers are candidates for the application in OLED as light emitting materials.