Reduced number of steps for the synthesis of dense and highly functionalized dendrimers

A series of densely functionalized dendrimers is synthesized using two branched monomers of type AB₂ and CD₂, in which the A function (NH₂) reacts with D (CHO) and the B function (Cl) reacts with C (OH). The reaction has been carried out up to the fourth generation possessing 96 end groups and has been obtained in only four steps.     

Solid-phase construction: high efficiency dendrimer synthesis using AB3 isocyanate-type monomers

Solid-phase synthesis is an ideal tool for reactions that require high concentrations and excess reagents and forcing chemical conditions. One such chemistry is that required for dendrimer construction. In this paper the synthesis of a series of symmetrical AB₃ isocyanate-type monomers is reported and used for the preparation of tri-branched dendrimers on the solid-phase. This method not only allows isolable dendrimer but can generate high-loading supports and devices for multivalent presentation.     

"Lego" chemistry for the straightforward synthesis of dendrimers

A new straightforward method of synthesis of dendrimers, using two branched monomers (CA(2) and DB(2)), is described. Each generation is obtained in a single quantitative step, with only N(2) or H(2)O as byproducts; generation 4 is obtained in only four steps. The end groups are alternatively phosphines and hydrazines; their versatile reactivity is illustrated by the reaction of generation 4 with a branched CD(5) monomer, which increases the number of end groups in a single step from 48 to 250.     

Dendritic aromatic polyamides and polyimides

The syntheses and properties of dendritic and hyperbranched aromatic polyamides and polyimides are reviewed. In addition to conventional stepwise reactions for dendrimer synthesis, an orthogonal/double‐stage convergent approach and dendrimer syntheses with unprotected building blocks are described as new synthetic strategies for dendritic polyamides. Hyperbranched polyamides and polyimides composed of various repeating units are presented. Besides the self‐polycondensation of AB₂‐type monomers, new polymerization systems with AB₄, AB₈, A₂ + B₃, and A₂ + BB′₂ monomers have been developed for hyperbranched polyamides and polyimides. The copolymerization of AB₂ and AB monomers is discussed separately with respect to the effects of branching units on the properties. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 1293–1309, 2004     

Dendrimer polyaluminosilicates as a matrix for filled coatings

Sol-gel synthesis of filled polyaluminosilicates with macromolecules having a dendrimer morphology (M _calc ≈ 480 000) was developed. The software package Gaussian B3LYP/6-31G(d) was used to assess the possible mechanism by which nuclei of dendrimer molecules are created, with the subsequent generation of crowns of branched ensembles capable of accommodating up to 70 wt % nano-Al₂O₃ as a filler. The data furnished by transmission electron microscopy of the samples are in agreement with the suggested mechanism of generation and growth of dendrimers. The main results were obtained on filled aluminosilicate samples that contain 70 wt % nano-Al₂O₃ and exhibit a high wear resistance in tribological tests.     

Perfectly branched and hyperbranched poly(ether amide)s

Poly(ether amide) dendrimer segments based on 5-(2-aminoethoxy)-isophthalic acid have been synthesized using the convergent approach and mild reaction conditions. The monodendrons were combined to dendrimers via different core molecules and the resulting properties of the molecules were compared to those of the monodendrons. The melt polycondensation of the AB₂ monomers with analog structure resulted first in undefined polymer structures. However, by thermal polyaddition reaction of suitable functionalized oxazoline monomers, well defined hyperbranched poly(ether amide)s with phenol terminal groups could be synthesized.     

Synthesis and catalytic activities of Pd-phosphine complexes modified poly(ether imine) dendrimers

In this paper, we report synthesis of new alkyldiphenyl phosphine ligand modified poly(ether imine) dendrimers up to the third generation. The phosphinated dendrimers were obtained by functional group transformations of the alcohols present at the periphery of the dendrimers to chloride, followed by phosphination using LiPPh₂. The modification at the peripheries of the dendrimers was performed successfully to obtain up to 16 alkyl diphenylphosphines in the case of a third generation dendrimer, in good yields for each individual step. After phosphination, dendritic ligands were complexed with Pd(COD)Cl₂ to give dendritic phosphine-Pd^II complexes. Both the ligands and the metal complexes were characterized by spectroscopic and spectrometric techniques including high-resolution mass spectral analysis for the lower generations. Evaluation of the catalytic efficacies of the dendrimer-Pd^II metal complexes in mediating a prototypical C-C bond forming reaction, namely the Heck reaction, was performed using various olefin substrates. While the substrate conversion lowered with catalyst in the order from monomer to third generation dendrimer, the second and third generation dendrimers themselves were found to exhibit significantly better catalytic activities than the monomer and the first generation dendrimer.     

Reaction of Amino-Terminated PAMAM Dendrimers with Carbon Dioxide in Aqueous and Methanol Solutions

Polyamines have been used as active materials to capture carbon dioxide gas based on its well-known reaction with amines to form carbamates. This work investigates the reactions between three amino-terminated poly(amidoamine) (PAMAM) dendrimers (G1, G3 and G5) and CO₂(g) in aqueous (D₂O) and methanolic (CD₃OD) solutions. The reactions were monitored using ¹H NMR spectroscopy, and yielded dendrimers with a combination of terminal carbamate and terminal ammonium groups. In aqueous media the reaction was complicated by the generation of soluble carbonate and bicarbonate ions. The reaction was cleaner in CD₃OD, where the larger G5 dendrimer solution formed a gel upon exposure to CO₂(g). All reactions were reversible, and the trapped CO₂ could be released by treatment with N₂(g) and mild heating. These results highlight the importance of the polyamine dendrimer size in terms of driving changes to the solution’s physical properties (viscosity, gel formation) generated by exposure to CO₂(g).     

Practical computational toolkits for dendrimers and dendrons structure design

Dendrimers and dendrons offer an excellent platform for developing novel drug delivery systems and medicines. The rational design and further development of these repetitively branched systems are restricted by difficulties in scalable synthesis and structural determination, which can be overcome by judicious use of molecular modelling and molecular simulations. A major difficulty to utilise in silico studies to design dendrimers lies in the laborious generation of their structures. Current modelling tools utilise automated assembly of simpler dendrimers or the inefficient manual assembly of monomer precursors to generate more complicated dendrimer structures. Herein we describe two novel graphical user interface toolkits written in Python that provide an improved degree of automation for rapid assembly of dendrimers and generation of their 2D and 3D structures. Our first toolkit uses the RDkit library, SMILES nomenclature of monomers and SMARTS reaction nomenclature to generate SMILES and mol files of dendrimers without 3D coordinates. These files are used for simple graphical representations and storing their structures in databases. The second toolkit assembles complex topology dendrimers from monomers to construct 3D dendrimer structures to be used as starting points for simulation using existing and widely available software and force fields. Both tools were validated for ease-of-use to prototype dendrimer structure and the second toolkit was especially relevant for dendrimers of high complexity and size.     

Divergent synthesis of triazine dendrimers using a trimethylene-dipiperidine linker that increases efficiency, simplifies analysis, and improves product solubility

To combine benefits stemming from the high nucleophilicity of piperidine and the flexibility afforded by aliphatic triamine linkers, a trimethylene-dipiperidine linker has been used to synthesize triazine dendrimers using a divergent route. The cyclic, secondary amine of the linker reacts with monochlorotriazine monomer units, 1, leading to a dendrimer growth strategy that requires two-steps-per-generation. This strategy reduces the number of steps required for synthesis by 50%. The new linker also reduces complexity in the NMR spectra because rotational isomerism observed in linkers with primary amines is not present. In addition, the final products contain no interior hydrogen-bond donating groups. The high solubility observed in organic solvents for protected dendrimers is attributed to this factor and the inherent flexibility provided by the linker. Gas phase simulation suggests that globular structure emerges after generation three, whereafter the core of the dendrimer is effectively shielded from solvent.     

AB3 building blocks for the synthesis of polyester dendrimers

Syntheses of several examples of a new type of trivalent building blocks for the preparation of aliphatic polyester dendrimers are presented. Starting from the well-known mono-O-benzylidenepentaerythritol, AB₃ type acid dendrons can be obtained in high yield in only two steps. Other triprotected bis-2,2-(hydroxymethyl)-3-hydroxypropanoic acid derivatives with varying protecting groups were also synthesized readily. This type of dendron was used in combination with 2,2′-bis(hydroxymethyl) propanoic acid (bis-HMPA) divalent dendrons to produce low generation mixed polyester dendrimers with increased number of branching points.     

Synthesis of poly(ester‐amide) dendrimers based on 2,2‐Bis(hydroxymethyl) propanoic acid and glycine

Water‐soluble, biodegradable, and biocompatible poly(ester‐amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB₂ adduct of 2,2‐bis(hydroxymethyl) propanoic acid (bis‐MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester‐amide) dendrimers as well as commercially available bis‐MPA dendrimers, poly(ester‐amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water‐solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 3292–3301     

Ester‐ and amide‐terminated dendrimers with alternating amide and ether generations

Ester‐terminated polyamide dendrimers up to the third generation and amide‐terminated polyamide dendrimers of the first generation were synthesized by convergent growth. The Williamson ether synthesis and diphenylphosphoryl azide (DPPA) coupling of amines to carboxylic acids were used for the construction of the dendrimers, having alternate ether and amide generations. The methyl ester‐ and N,N‐diethylamide‐terminated dendrimers were readily soluble in common organic solvents while the N‐methylamide‐ and N‐benzylamide‐terminated dendrimers were soluble only in DMF and DMSO. Both the end and internal amide groups of the N,N‐diethylamide‐terminated dendrimer were reduced by LiAlH₄ to form a polyamine dendrimer. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 1533–1543, 2000     

Designing Branched Deoxybenzoin Polyesters as Polymeric Flame Retardants

AB₂ monomers present opportunities to conduct one‐pot syntheses of highly branched or “hyperbranched” polymers, which are known for their distinct physical and chemical properties relative to linear polymers. This paper describes the synthesis of a deoxybenzoin‐containing AB₂ monomer and its use in step‐growth polymerization to prepare branched aromatic polyesters. Highly soluble deoxybenzoin polymers were obtained with degrees of branching reaching 0.36 and estimated molecular weights approaching 20 kDa. The phenolic chain ends of the polymer allowed for post‐polymerization modification by silylation and esterification chemistry. TGA and microscale combustion calorimetry revealed these novel aromatic polyesters to possess the critically important characteristics of flame‐retardant polymers, such as high char yield and low heat release. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1765–1770     

Comparison of AB2 and AB4 monomers in ferrocene-cored benzyl ether dendrimers

Ferrocene-cored unsymmetric and symmetric arylalkyl ether dendrimers based on an AB₂ monomer (3,5-dihydroxybenzyl alcohol) were prepared. Their electrochemical properties were compared with the unsymmetric and symmetric ferrocene-cored dendrimers based on a relatively rigid and three-dimensionally disposed AB₄ monomer. The thermodynamics and kinetics of heterogeneous electron transfer in these dendrimers show that G_2n of AB₂ dendrimers behave similar to G_n of AB₄ dendrimers. For example, the redox reaction shows significant irreversibility especially at higher scan rates in the case of G₄ didendron based on AB₂ monomer and G₂ didendron based on AB₄ monomer. Despite the fact that AB₄ building blocks are more rigid, the effective encapsulation in both these dendrimers are similar. This result is attributed to the three dimensional disposition of the branching points in the AB₄ monomer.     

Viologen-based benzylic dendrimers: selective synthesis of 3,5-bis(hydroxymethyl)benzylbromide and conformational analysis of the corresponding viologen dendrimer subunit

Convergent and divergent strategies for the synthesis of viologen dendrimers with 1,3,5-tri-methylene-branching units are discussed. The title compound is easily transformed into 1-[3,5-bis(hydroxymethyl)benzyl]-4-(pyridin-4-yl)pyridinium hexafluorophosphate, which is used in sequential growth and activation steps as a CB₂ compound in the cascade-type dendrimer synthesis (B = -OH, activation = -OH → Br). Analysis of the dendrimer structure reveals that three torsional angles, that is, τ₁ between the two pyridinium units, τ₂ between the methylene and pyridinium and τ₃ between the methylene and phenyl, determine the conformational space of the dendrimers. We report here the crystal structure of 1-[3,5-bis(hydroxymethyl)benzyl]-4-(pyridin-4-yl)pyridinium as PF₆⁻ salt which represents the smallest subunit of the dendrimer that shows the same three torsional angles. The crystal structure together with the results from PM3 calculations opens an avenue to judge the structure of benzylic viologen-based dendrimers.     

Syntheses and nickel coordination properties of cyclen substituted with mixed stilbene/poly(ethylene glycol) dendritic arms

We synthesized a series of cyclens substituted with mixed stilbene and poly(ethylene glycol) dendritic arms. All dendrimers terminated with different peripheral groups had good solubility in common organic solvents, and dendrimers terminated with ? CO₂H groups (CO₂H‐dendrimers) were also soluble in alkaline solutions. The nickel coordination properties of these dendrimers were investigated in organic solvents. Dendrimers terminated with ? CN groups (CN‐dendrimers) and the second‐generation CO₂H‐dendrimer [(CO₂H)₈L2] could produce pentacoordinated nickel complexes; the third‐generation CO₂H‐dendrimer [(CO₂H)₁₆L3] could form tetra‐ and pentacoordinated nickel complexes, and the nickel complex of the fourth‐generation CO₂H‐dendrimer [(CO₂H)₃₂L4] could not be obtained. This result was due to the fact that the globular surface of (CO₂H)₁₆L3 formed a hydrogen‐bond network that selectively penetrated cations and inhibited the access of anions to the core. The formation of the hydrogen‐bond network was confirmed by Fourier transform infrared, ¹H NMR, and fluorescence data. The CN‐dendrimers could not form hydrogen bonds on the surface, and the first‐ and second‐generation CO₂H‐dendrimers could not form intramolecular hydrogen‐bond networks. Therefore, they had no selectivity for positive nickel ions and negative chloride ions. (CO₂H)₃₂L4 could not produce a nickel complex because it had a crammed backbone structure that could not penetrate nickel and chloride ions. Therefore, it was possible to control the ion access of cations and anions with the hydrogen‐bond network of (CO₂H)₁₆L3. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5414–5428, 2005     

HyperMacs. Long Chain Branched Analogues of Hyperbranched Polymers Prepared by the Polycondensation of AB2 Macromonomers

We describe here a new strategy for the synthesis of polymers with highly branched architectures. The strategy involves the synthesis by anionic polymerization of well-defined AB₂ polystyrene macromonomers with molecular weights from 3,600 to 94,000 gmol⁻¹, which are then converted via a one-pot polycondensation reaction into high molecular weight, long-chain (hyper)branched architectures. Since the Hyperbranched structures are built up from condensation Macromonomers we have coined the term ‘HyperMac’ to describe these branched polymers. In this paper we report the synthesis of the HyperMacs, the optimal conditions for the polycondensation reaction and some preliminary characterization studies.     

Novel carbazole dendrimers having a metal coordination site as a unique hole-transport material

We have synthesized novel carbazole dendrimers via the cyclotrimerization of aminophenylketones in the presence of titanium tetrachloride. These dendrimers have the ability to assemble metal ions such as Sn²⁺ and Eu³⁺ with no significant difference in their generation, suggesting the dendrimer with an interior with a small density up to the third generation. We show the dendrimers with higher generations have the higher HOMO values. The most electron rich molecule, the G3 dendrimer, has the highest HOMO value of −5.2 eV. However, for the HOMO energy levels of the carbazole dendrimer complex with Eu(OTf)₃, the energy levels of the carbazoles did not change based on almost the same redox potentials as those of the dendrimers, themselves. Using the carbazole dendrimers and their europium complex, a homogeneous film was produced, which enhanced the performance of the electroluminescence device in comparison with only the dendrimer as the hole-transporting layer. This approach was managed by a solution process, i.e., the spin-coating method, without using the coevaporation technique based on the large equilibrium constants of the coordination of metal ions on the imine sites (K = 10⁵ M⁻¹).     

Spongipyran synthetic studies. Total synthesis of (+)-spongistatin 2

Evolution of a convergent synthetic strategy to access (+)-spongistatin 2 (2), a potent cytotoxic marine macrolide, is described. Highlights of the synthesis include: development of a multicomponent dithiane-mediated linchpin union tactic, devised and implemented specifically for construction of the spongistatin AB and CD spiro ring systems; application of a Ca^II ion controlled acid promoted equilibration to set the thermodynamically less stable axial-equatorial stereogenicity in the CD spiroketal; use of sulfone addition/Julia methylenation sequences to unite the AB and CD fragments and introduce the C(44)-C(51) side chain; and fragment union and final elaboration to (+)-spongistatin 2 (2) exploiting Wittig olefination to unite the advanced ABCD and EF fragments, followed by regioselective Yamaguchi macrolactonization and global deprotection. Correction of the CD spiro ring stereogenicity was subsequently achieved via acid equilibration in the presence of Ca^II ion to furnish (+)-spongistatin 2 (2). The synthesis proceeded with a longest linear sequence of 41 steps.