Synthesis and biological evaluation of 3-amino-propan-1-ol based poly(ether imine) dendrimers

A general synthetic strategy for the rapid construction of poly(ether imine) dendrons and dendrimers with a nitrogen core, originating from 3-amino-propan-1-ol, is described. A new trifunctional monomer, namely, 3-[bis-(3-hydroxypropyl)amino]propan-1-ol, was used in a divergent synthesis of dendrimers up to the third generation. This method permitted installation of, either alcohol, amine, nitrile, ester or carboxylic acid groups at the peripheries the dendrimers. Cytotoxicity studies on water-soluble carboxylic acid terminated dendrimers were conducted and these studies revealed that poly(ether imine) dendrimers were non-toxic. These results illustrate that poly(ether imine) dendrimers are useful for biological studies.     

Expanding the structural diversity of self-assembling dendrons and supramolecular dendrimers via complex building blocks

The design and synthesis of the first examples of AB4 and AB5 dendritic building blocks with complex architecture are reported. Structural and retrostructural analysis of supramolecular dendrimers self-assembled from hybrid dendrons based on different combinations of AB4 and AB5 building blocks with AB2 and AB3 benzyl ether dendrons demonstrated that none of these new hybrid dendrons exhibit the previously encountered conformations of libraries of benzyl ether dendrons. These hybrid dendrons enabled the discovery of some highly unusual tapered and conical dendrons generated by the intramolecular back-folding of their repeat units and of their apex. The new back-folded tapered dendrons have double thickness and self-assemble into pine-tree-like columns exhibiting a long-range 7/2 helical order. The back-folded conical dendrons self-assemble into spherical dendrimers. Non-back-folded truncated conical dendrons were also discovered. They self-assemble into spherical dendrimers with a less densely packed center. The discovery of dendrons displaying a novel crown-like conformation is also reported. Crown-like dendrons self-assemble into long-range 5/1 helical pyramidal columns. The long-range 7/2 and 5/1 helical structures were established by applying, for the first time, the helical diffraction theory to the analysis of X-ray patterns obtained from oriented fibers of supramolecular dendrimers.     

The synthesis and properties of iridium(III)-cored dendrimers with carbazole peripherally functionalized beta-diketonato dendrons

A simple convergent synthetic approach has been developed for the synthesis of iridium(III)-cored dendrimers with carbazole peripherally functionalized beta-diketonato dendrons. The zeroth- to third-generation green-emitting dendrimers were synthesized by reacting the corresponding beta-diketonato dendrons with iridium(III) dimer under mild conditions with good yields, respectively. This approach proved to be modular, and could be used to prepare blue-green-emitting and red-emitting dendrimers with the same beta-diketonato dendrons only by using different cyclometallating ligands. The resulting dendritic ligands and iridium(III)-cored dendrimers were well characterized. Their photoluminescent properties both in solution and in the solid state were tested. It was found that all the dendrimers retained the photophysical properties of the corresponding small analogues with high emission quantum yields (0.06-0.30). Preliminary results indicated that these dendrimers functionalized carbazole units exhibited distinct light-harvesting potential, resulting in a strong intense emission from the iridium core of the dendrimers.     

Design, synthesis, and photochemical behavior of poly(benzyl ester) dendrimers with azobenzene groups throughout their architecture

A new class of dendrons and dendrimers containing azobenzene units (bearing up to 29 azobenzene groups for four generations) were designed and synthesized with the convergent method, which uses azobenzene derivatives as monomers and benzyl ester groups as linkages leading to photoresponsive dendrons and dendrimers with azobenzene units throughout their architecture. Photochemical isomerization experiments revealed that all of the dendrons and dendrimers undergo trans-cis isomerization by irradiation and cis-trans isomerization by either irradiation or heating.     

Second-harmonic properties of dendritic polymers skeleton-constructed with azobenzene moiety used for nonlinear optical materials

A series of dendrons and dendrimers skeleton-constructed with azobenzene moiety were synthesized and doped in a high T_g polycarbonate (PC) as a host for nonlinear optical (NLO) materials. The optimal loading density and poling conditions were investigated using UV-vis spectral and second-harmonic generation (SHG) measurements. The results showed that the dendrons and dendrimers have good solubility in PC host, which increased with the generation increased. Moreover, the SHG measurements indicated that the dendrons possess higher nonlinearity than the dendrimers. The chromophores of lower generation dendrons were easier to orient along the poling electric field and gave a cone shape with the azobenzene branching units, which coherently contributed to the molecular hyperpolarizability and resulted in the higher SHG intensity. The temporal stability of the dendrons with 15% loading density was also investigated, and showed that the decaying in nonlinearity was slower for higher generation dendrons.     

Synthesis of poly(propyl ether imine) dendrimers and evaluation of their cytotoxic properties

In this paper, we report the synthesis of several poly(propyl ether imine) dendrons and dendrimers. These dendrons and dendrimers were constructed by involving an ether as the linker component and an imine as the branching component. The divergent syntheses of dendrons and dendrimers were established with the aid of two alternate Michael addition reactions and two alternate reduction reactions in a four-step iterative synthetic sequence. Dendrons up to three generations were synthesized and some of the dendrons were attached to a benzenoid core so as to obtain dendrimers up to two generations containing 12 carboxylic acids at the periphery. Divergent synthesis involving ether as the core was found to be more facile, and dendrimers up to three generations having 16 carboxylic acids at the periphery were achieved in good to excellent yields in each individual step. The adopted synthetic sequence allows us to install either alcohol, an amine, or a carboxylic acid at their peripheries. The carboxylic acid-terminated dendrons and dendrimers were evaluated as to their cytotoxic properties, and while most dendrons and dendrimers did not exhibit any measurable cytotoxicity, even up to 100 microg/mL, the second-generation dendrimer with the benzenoid core exhibited a mild toxicity at concentrations above 30 microg/mL.     

Comparison of facially amphiphilic biaryl dendrimers with classical amphiphilic ones using protein surface recognition as the tool

Facially amphiphilic biaryl dendrimers are compared with the more classical benzyl ether amphiphilic dendrimers for molecular recognition, using protein binding as the probe. The protein used for the proposed study is chymotrypsin (ChT). A generation-dependent binding affinity was observed with the benzyl ether dendrimers, while the affinities were independent of generation in the case of the biaryl dendrimers. Similarly, although the ligands incorporated in both dendrons are the same, the biaryl dendrimers are able to bind more proteins compared to the benzyl ether dendrimers. For example, G3-dendron of biaryl dendrimer can bind six molecules of chymotrypsin, whereas G3-analogue of benzyl ether dendrimers can bind only three molecules of chymotrypsin. This result is consistent with our hypothesis that the internal layers of the facially amphiphilic biaryl dendrons are solvent-exposed and accessible for recognition. In addition, the systematic size differences in dendrons were also used to gain insights into the substrate selectivity that the enzyme gains upon binding to a ligand scaffold.     

Multifunctional Supramolecular Dendrimers with an s‐Triazine Ring as the Central Core: Liquid Crystalline,Fluorescence and Photoconductive Properties

Novel liquid crystal (LC) dendrimers have been synthesised by hydrogen bonding between an s‐triazine as the central core and three peripheral dendrons derived from bis(hydroxymethyl)propionic acid. Symmetric acid dendrons bearing achiral promesogenic units have been synthesised to obtain 3:1 complexes with triazine that exhibit LC properties. Asymmetric dendrons that combine the achiral promesogenic unit and an active moiety derived from coumarin or pyrene structures have been synthesised in order to obtain dendrimers with photophysical and electrochemical properties. The formation of the complexes was confirmed by IR and NMR spectroscopy data. The liquid crystalline properties were investigated by differential scanning calorimetry, polarising optical microscopy and X‐ray diffractometry. All complexes displayed mesogenic properties, which were smectic in the case of symmetric dendrons and their complexes and nematic in the case of asymmetric dendrons and their dendrimers. A supramolecular model for the lamellar mesophase, based mainly on X‐ray diffraction studies, is proposed. The electrochemical behaviour of dendritic complexes was investigated by cyclic voltammetry. The UV/Vis absorption and emission properties of the compounds and the photoconductive properties of the dendrons and dendrimers were also investigated     

Segment block dendrimers via Diels-Alder cycloaddition

Segment block dendrimers consisting of polyester and polyaryl ether dendrons were synthesized using reagent free Diels-Alder cycloaddition reactions. Three generations of furan functionalized polyaryl ether dendrons were reacted with maleimide functionalized polyester dendrons of the same generation to obtain segment block dendrimers in good yields. The thermoreversible nature of these macromolecules was investigated by subjecting them to elevated temperatures in the presence of anthracene as a scavenger diene.     

Hydrodynamic, conformational, and electrooptical properties of cylindrical dendrimers with dendron ionic addition in solutions

Cylindrical dendrimers of first, second, and third generations with side dendrons based on L-aspartic acid which are attached to poly(styrenesulfonic acid) chains via ionic bonds are studied by molecular hydrodynamic, optical, and electrooptical measurements. Macromolecules of the said dendrimers demonstrate significant kinetic rigidity in external electric and hydrodynamic fields simultaneously with moderate equilibrium chain rigidity. The comparative analysis of the experimental data on various cylindrical dendrimers with the polyvinyl backbone and L-aspartic acid-based dendrons is performed. It has been shown that, in solvents not disturbing intramolecular hydrogen bonds between side dendrons, the conformational and dynamic properties of various cylindrical dendrimers are similar. The molecular characteristics of cylindrical dendrimers in non-dissociating solvents are insignificantly affected by the mode of dendron attachment to the backbone (covalent or ionic binding).     

Thermally responsive dendrons and dendrimers based on reversible furan-maleimide Diels-Alder adducts

[reaction: see text]. Benzyl aryl ether dendrons and dendrimers containing thermally reversible furan-maleimide Diels-Alder adducts were prepared up to the third generation. The covalent cleavage and reassembly of the dendrons and dendrimers were evaluated by 1H NMR.     

Synthesis of Novel Biodegradable Cationic Dendrimers

Summary: Dendrons and dendrimers with cationic amino groups at their periphery were successfully synthesized up to the third and second generation, respectively. The results obtained by ¹H NMR spectroscopy and gel permeation chromatography analysis supported the formation of the targeted dendrons and dendrimers. The dendrons were grown via ester linkages, which endowed them with biodegradability in D₂O at 37 °C. The degradation rate depends upon the steric hindrance and reactivity caused by the bulkiness and compact structure of the dendrons. All of the synthesized dendrons were degraded within a month, while 60% of the ester groups in the sterically crowded dendrimers were degraded over the same time period. The cytotoxicity of the dendrons was evaluated by the MTT assay on a 293T cell line which indicated that the obtained dendrons were completely non‐toxic. These non‐toxic, biodegradable cationic dendrons and dendrimers are believed to have potential applications in the biomedical field.

Synthetic procedure of dendrons and dendrimers.     

Convergent synthesis of platinum-acetylide dendrimers

An efficient convergent route to the main chain type of organometallic dendrimers, in which platinum moieties are linked by 1,3,5-triethynylbenzene, has been developed. The synthesis of platinum-acetylide dendrons involved the use of two types of trialkylsilyl groups for protection of the terminal acetylene. The platinum-acetylide dendrimers were prepared up to the third generation by reacting dendrons with a triplatinum core and a tetraplatinum core. Spectroscopic characterization and trace experiments by gel permeation chromatography indicated that the dendrimer molecules have no structural defects. Although a pi-conjugated system was used as the bridging ligand, electronic and fluorescence spectra suggested that the interaction among the platinum-acetylide moieties in the dendrimers was small.     

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.     

Relationship between incoherent excitation energy migration processes and molecular structures in zinc(II) porphyrin dendrimers

Multiporphyrin dendrimers are among the most promising architectures to mimic the oxygenic light-harvesting complex because of their structural similarities and synthetic convenience. The overall geometries of dendrimers are determined by the core structure, the type of dendron, and the number of generations of interior repeating units. The rigid core and bulky volume of exterior porphyrin units in multiporphyrin dendrimers give rise to well-ordered three-dimensional structures. As the number of generations of interior repeating units increases, however, the overall structures of dendrimers become disordered and randomized due to the flexibility of the repeating units. To reveal the relationship between molecular structure and processes of excitation-energy migration in multiporphyrin dendrimers, we calculated the molecular structure and measured the time-resolved transient absorption and fluorescence anisotropy decays for various hexaarylbenzene-anchored polyester zinc(II) porphyrin dendrimers along with three types of porphyrin dendrons as references. We found that the congested two-branched type dendrimers exhibit more efficient energy migration processes than one- or three-branched type dendrimers because of multiple energy migration pathways, and the three-dimensional packing efficiency of dendrimers strongly depends on the type of dendrons.     

Exploring and expanding the structural diversity of self-assembling dendrons through combinations of AB, constitutional isomeric AB2, and AB3 biphenyl-4-methyl ether building blocks

General, efficient and inexpensive methods for the synthesis of dendritic building blocks methyl 3',4'-dihydroxybiphenyl-4-carboxylate, 3',5'-dihydroxybiphenyl-4-carboxylate, and methyl 3',4',5'-trihydroxybiphenyl-4-carboxylate were elaborated. In all syntheses the major step involved an inexpensive Ni(II)-catalyzed Suzuki cross-coupling reaction. These three building blocks were employed together with methyl 4'-hydroxybiphenyl-4-carboxylate in a convergent iterative strategy to synthesize seven libraries containing up to three generations of 3',4'-, 3',5'-, and 3',4',5'-substituted biphenyl-4-methyl ether based amphiphilic dendrons. These dendrons self-assemble into supramolecular dendrimers that self-organize into periodic assemblies. Structural and retrostructural analysis of their assemblies demonstrated that these dendrons self-assemble into hollow and non-hollow supramolecular dendrimers exhibiting dimensions of up to twice those reported for architecturally related dendrons based on benzyl ether repeat units. These new dendrons expand the structural diversity and demonstrate the generality of the concept of self-assembling dendrons based on amphiphilic arylmethyl ethers.     

New dendrimers containing a single cobaltocenium unit covalently attached to the apical position of Newkome dendrons: electrochemistry and guest binding interactions with cucurbit[7]uril

Two new dendrimer series were prepared and characterized. These dendrimers contain a single bis(cyclopentadienyl)cobalt(III) (cobaltocenium, Cob+) unit covalently attached to the apical (focal) position of Newkome-type dendrons, ranging in size from first to third generation. The dendrimers in the first series (1ECob+-3ECob+) are hydrophobic and have 3, 9, and 27 tert-butyl esters on their peripheries, whereas the dendrimers in the second series (1Cob+-3Cob+) are hydrophilic with 3, 9, and 27 carboxylic acid groups on their surfaces, respectively. In voltammetric experiments, all dendrimers showed the expected one-electron reversible reduction of the cobaltocenium center, and the heterogeneous rate of electron transfer decreased with generation in both dendrimer series. The host-guest binding interactions between water-soluble dendrimers 1Cob+-3Cob+ and the cucurbit[7]uril (CB7) host were investigated using 1H NMR spectroscopy, MALDI-TOF mass spectrometry, and electrochemical techniques. The association equilibrium constants (K) for all dendrimer guests were significantly lower than that measured for the inclusion complex between underivatized Cob+ and CB7 (K = 5.7 x 10(9) M(-1)). Nonetheless, among the three dendrimers surveyed, the second-generation dendrimer, 2Cob+, afforded optimum stabilization for the CB7 inclusion complex.     

Core Functionality and Scaling Behavior of Lysine Dendrimers

Summary: A scaling exponent to describe the dependence of the hydrodynamic radius as a characteristic length of the molecule on the molecular weight, has been determined for low generation dendrimers with a thiacalixarene core and lysine dendrons. The hydrodynamic radius has been calculated from the diffusion coefficient measured by pulsed‐field‐gradient NMR spectroscopy. Scaling exponents of 2.0 for the lysine monodendron, 2.3 for a dendrimer with a bifunctional core, and 3.9 for a dendrimer with a tetrafunctional core have been determined. For a given structure of the dendrons, the scaling exponent reflects the functionality of the core of the dendrimers.

Hydrodynamic radius of lysine dendrons as a function of molar mass.     

Synthesis and photoluminescent properties of 1,1'-binaphthyl-based chiral phenylenevinylene dendrimers

New chiral, soluble binaphthyl derivatives that incorporate stilbenoid dendrons at the 6,6'-positions have been prepared. The synthesis of the new enantiopure dendrimers was performed in a convergent manner by Horner-Wadsworth-Emmons (HWE) reaction of the appropriately functionalized 1,1'-binaphthyl derivative (R)-1 and the appropriate dendrons (R)(2n)G(n)-CHO. Different electroactive units were incorporated in the peripheral positions of the dendrons in order to tune both the optical and electrochemical behavior of these systems. Fluorescence measurements on the chiral dendrimers reveal a strong emission with maxima between 409 and 508 nm depending upon the substitution pattern. Finally, the redox properties of the dendrimers were determined by cyclic voltammetry, showing the influence of the functional groups at the peripheral positions of the dendrimer on the redox behavior of these systems.     

Convergent synthesis of dendrimers via the Passerini three-component reaction

Tuning properties by programming the surface functional group composition of surface-block dendrimers has been limited to dendrimers with only two types of surface functionality (i.e., surface-diblock dendrimers). The Passerini reaction provides dendrimer products from precursor dendrons in reasonable yields. This proof-of-principle experiment opens the door to making surface-triblock dendrimers.