Polymers 2012, 4(1), 794-879; doi:10.3390/polym4010794

Review
Polyester Dendrimers
Jean-d’Amour K. Twibanire and T. Bruce Grindley *
Department of Chemistry, Dalhousie University, 6274 Coburg Road, P.O. Box 15000, Halifax, NS B3H 4R2, Canada; Email: twibanire@dal.ca
*
Author to whom correspondence should be addressed; Email: bruce.grindley@dal.ca; Tel.: +1-902-494-2041; Fax: +1-902-494-1310.
Received: 29 January 2012; in revised form: 1 March 2012 / Accepted: 2 March 2012 /
Published: 7 March 2012

Abstract

: Polyester dendrimers have been comprehensively reviewed starting from their first synthesis in the early 1990s by Hawker and Fréchet. Polyester dendrimers have attracted and continue to attract extensive interest because they are comparatively easy to make and because, whenever they have been tested, they have been found to be non-toxic. A number of different strategies for their synthesis have been examined and the methods employed for formation of the ester bond during dendrimer assembly have been summarized. The newest approaches, including the use of bifunctional orthogonally reacting dendrons and accelerated synthesis have been surveyed.
Keywords:
dendrimers; dendrons; hyperbranched polymers; polyester dendrimers; alternating dendrimers

Abbreviations

ADHalcohol dehydrogenase
ADH-LBalcohol dehydrogenase from Lactobacillus brevis
ADH-Talcohol dehydrogenase from Thermoanaerobacter sp.
ATRPatom transfer radical polymerization
bis-HMPA 2,2-bis(hydroxymethyl)propanoic acid
BOPbenzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate
CCScore cross-linked star
COMU1-[(1-(cyano-2-ethoxy-2-oxoethylideneaminooxy)dimethylaminomorpho-linomethylene)] methanaminium hexafluorophosphate
DBU1,8-diazabicyclo[5.4.0]undec-7-ene
DCCdicyclohexylcarbodiimide
DEADdiethyl azodicarboxylate
DIADdiisopropyl azodicarboxylate
DIEAdiisopropylethylamine
DMAP4-dimethylaminopyridine
DMPA2,2-dimethoxy-1,2-diphenylacetophenone
DPPAdiphenylphosphoryl azide
DPTS4-(dimethylamino)pyridinium p-toluenesulfonate
EDCIN-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride
FDLCPferroelectric dendritic liquid crystalline polymer
FLCPsferroelectric liquid crystalline polymers
HBTU2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate
HOBT1-hydroxybenzotriazole
LCPslinear crystalline polymers
MTBD7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene
MOMClmethoxymethyl chloride
NADPHnicotinamide adenine dinucleotide phosphate
PAMAMpolyamidoamine
PEO-NH2amine functionalized polyethylene oxide
PTPproton-transfer polymerization
ROPring opening polymerization
SCROPself-condensing ring-opening polymerization
SCVPself-condensing vinyl polymerization
SECsize exclusion chromatography
SET-LRPsingle electron transfer living radical polymerization
SPECTsingle photon emission computed tomography
TATU2-(1H-7-azabenzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate
TBAFtetrabutylammonium fluoride
TBDMSCltert-butyldimethylsilyl chloride
TBTU2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate
TEAtriethylamine
TPPtriphenylphosphine
TPPH2tetraphenylporphyrin
TPPZnzinc-cored tetraphenylporphyrin
TsEt2-p-toluenesulfonylethyl

1. Introduction

The first description of molecules that have come to be known as dendrimers appeared in 1978. Vögtle and coworkers made highly branched molecules by exhaustively performing Michael-type reactions of acrylonitrile with an amine followed by the reduction of nitrile groups to primary amines [1]. When this first generation polyamine was treated with acrylonitrile followed by reduction in the same way, a second generation dendrimer was produced. Further repetition produced higher generation highly branched amines with defined structures [1]. The field developed slowly through the 1980s. In 1981, Denkewalter et al. at Allied Corporation described dendritic polylysine [2]. A few years later, Tomalia et al. reported the synthesis and characterization of the first dendritic family [3,4], now commercialized as PAMAM dendrimers. In 1985, Newkome et al. reported initial results about the synthesis of tribranched dendritic amides [5]. Further developments occurred in the late 1980s but the review by Tomalia et al. [6] sparked an explosion of research that has continued to the present, including the first syntheses of polyester dendrimers [7,8], the subject of this review. This interest has prompted the publication of at least 3 books [9,10,11] and many review articles, including one in 2000 on polyester dendrimers [12]. Some of the other recent reviews of dendrimer synthesis, properties, and applications are listed in the bibliography [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37].

A major incentive for the use of polyester dendrimers as frameworks for biological applications is that whenever they have been tested, they have been found to have low toxicity [38,39,40], unlike many other dendrimers [33].

Hyperbranched polymers are branched molecules synthesized under conditions where the resulting structures cannot be precisely defined. Polymers of this type have been known since Berzelius condensed tartaric acid (A2B2 monomer) and glycerol (B3 monomer) in the 1800s [41] followed by Watson Smith [42] and Kienle et al. [41,43,44,45] using phthalic anhydride or phthalic acid (both A2 monomers) with glycerol. Baekeland developed the first commercial plastics through polymerization of formaldehyde (latent A2 monomer) and phenol (latent B3 monomer) [46,47]. Hyperbranched polymers from single branched monomers came later. Flory [48,49,50] and Stockmayer [51] developed theory relating molecular size distributions to the degree of branching in the monomer and in 1952 Flory predicted molecular size distributions if they were made from ABx-type monomers [52] and provided initial examples [53]. The first synthesis of a hyperbranched polyester from a single monomer was only reported in 1991, when Hawker and Fréchet reported the one-step thermal self-condensation of 3,5-bis(trimethylsilyloxy)benzoyl chloride [54]. A few years later, Malmström and coworkers presented a hyperbranched aliphatic system based on 2,2-bis(hydroxymethyl)propanoic acid (1) as the building block, and 2-ethyl-2-(hydroxymethyl)-l,3-propanediol (2) as the core moiety [55], commercialized as Boltorn℘ dendritic polymers by Perstop. The topic of hyperbranched polymers is very extensive and includes many types of structures including dendronized polymers [56,57,58,59,60], dendrigrafts [61,62] and other types of structures [63]. At least one book [63] and numerous reviews have appeared on this topic [24,55,64,65,66,67,68,69,70,71,72,73,74], including two recent reviews on hyperbranched polyesters based on 2,2-bis(hydroxymethyl)propanoic acid [72,74] and one on hyperbranched aromatic polyesters [70]. This review will examine polyester dendrimers. Hyperbranched polyesters are closely related and will be discussed briefly but they are adequately described by the recent reviews [70,72,74].

2. Structure and Synthetic Strategies

2.1. Dendrimers

A dendrimer is a polymeric molecule composed of multiple perfectly branched monomers that elongate radially from a central core, similar to branches of some trees. The dendritic architecture can be divided into three different regions: the core, the interior, and the periphery or end groups (Figure 1). The number of branch points encountered upon moving outward from the core to its periphery defines its generation (G1, G2, G3, etc.). These macromolecules are prepared in a stepwise fashion [4,75,76,77] and therefore, the products are theoretically monodisperse in size. A monodisperse product is extremely desirable not only for synthetic reproducibility, but also for reducing experimental and therapeutic variability [78,79]. Vögtle and coworkers have termed perfectly monodisperse dendrimers, cascadanes [11].

Polymers 04 00794 g001 200
Figure 1. The architecture of a dendrimer.

Click here to enlarge figure

Figure 1. The architecture of a dendrimer.
Polymers 04 00794 g001 1024

A dendrimer may be based on practically any type of chemistry, the nature of which can determine its solubility, degradability and biological activity if any.

Two strategies have been formulated for dendrimer synthesis. The divergent approach is more obvious and was used by most of the early workers in the area [1,3,4,5]. In this method, dendrimers grow outwards from a multifunctional core molecule. The core molecule reacts with monomeric molecules containing one reactive and various dormant groups giving the first generation dendrimer. Then the new periphery of the molecule is activated for reactions with more monomers. The process is repeated several times and a dendrimer is built layer after layer. See Scheme 1 for the first example of polyester dendrimer synthesis using this approach [80]. The number of functional groups in the outermost layer increases exponentially with the generation number. The synthesis is elaborate and the conversion of the functional groups has to be perfect at each stage in order to guarantee a defect-free product. To prevent side reactions and to force the reaction to completion, excess reagents may be required, which causes problems in the purification of the final product. In addition, steric hindrance increases as the generation level increases so that defects and hence polydispersity increases with generation level.

Polymers 04 00794 g002 200
Scheme 1. The first example of the divergent growth approach to polyester dendrimers [80].

Click here to enlarge figure

Scheme 1. The first example of the divergent growth approach to polyester dendrimers [80].
Polymers 04 00794 g002 1024

The second method, the convergent route was developed by Hawker and Fréchet [77]. In this approach, the units that will be attached to the core, the dendrons, are constructed first. When the growing dendrons have reached the desired size, they are attached to the multifunctional core molecule. This method has several advantages. It is relatively easy to purify the final product and the occurrence of defects in the final structure is minimised. The convergent route provides better structural control since intermediates are purified better at successive stages of the synthesis. However, this method may not allow the formation of high generations, because steric problems may occur in the reactions of the dendrons with the core molecule. Scheme 2Scheme illustrates this approach [8]. Reduction in the number of both synthetic and purification steps in convergent dendrimer synthesis can be achieved if a convergent approach is taken to dendron synthesis rather than the strictly divergent synthesis of the dendron illustrated in Scheme 2. This approach, termed double exponential growth [81,82,83], is illustrated for polyester dendrimers in Scheme 3 [84]. In this methodology, both components for formation of the higher generation structure, the polyol and the carboxylic acid for polyester dendrimers, are prepared using a single starting material.

Polymers 04 00794 g003 200
Scheme 2. The first convergent synthesis of a deprotected polyester dendrimer [8].

Click here to enlarge figure

Scheme 2. The first convergent synthesis of a deprotected polyester dendrimer [8].
Polymers 04 00794 g003 1024
Polymers 04 00794 g004 200
Scheme 3. Double exponential dendron growth [84].

Click here to enlarge figure

Scheme 3. Double exponential dendron growth [84].
Polymers 04 00794 g004 1024

Different types of dendrimers, called alternating dendrimers here, can be produced if orthogonal coupling methods are used in alternation to produce dendrimers with different functional groups joining alternate dendrons [40,73,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101]. The first example of this strategy incorporating ester units, shown in Scheme 4 and Scheme 5, used the Mitsunobu reaction to form esters [102] and Sonagashira coupling as its orthogonal partner [102]. More recent examples of orthogonal coupling in which ester formation is one of the two coupling reactions include the following: ester formation and click reactions [103], ester formation and thiol-ene reactions [104,105], thiol displacement of α-ketohalides and ester formation [95], ester and amide formation [106], and thiol-yne reaction and ester formation [107] (see Section 4.4).

A variant of this approach can yield dendrimers with a greater number of functional groups on the periphery with fewer synthetic steps if the two orthogonal reactions both employ branched dendrons [93,98,103,104,108,109,110]. Majoral and coworkers have termed this approach LEGO chemistry [98]; Antoni et al. called this strategy accelerated synthesis [103]. An example involving ester formation is shown in Scheme 6 [103].

Polymers 04 00794 g005 200
Scheme 4. Formation of the dendron for an alternating polyester dendrimer [102].

Click here to enlarge figure

Scheme 4. Formation of the dendron for an alternating polyester dendrimer [102].
Polymers 04 00794 g005 1024
Polymers 04 00794 g006 200
Scheme 5. Formation of an alternating polyester dendrimer [102].

Click here to enlarge figure

Scheme 5. Formation of an alternating polyester dendrimer [102].
Polymers 04 00794 g006 1024

The highly congested branching that occurs in the bulk of the dendrimer interior can have interesting effects on the dendrimer’s conformation. Because dendrimer diameters increase linearly while the number of surface groups increase exponentially with generation number, the space between groups decreases with generation [111]. For example, at low generations, a dendrimer typically has a floppy, flat structure, but at higher generations (usually > G-4), the polymer adopts a more globular or even spherical conformation [112] and rigidity increases with generation [113]. The behaviour of these compounds is complex with backfolding being significant [114,115,116].

Polymers 04 00794 g007 200
Scheme 6. Accelerated synthesis of a G4 polyester dendrimer in four steps by using two different AB2 dendrons [103].

Click here to enlarge figure

Scheme 6. Accelerated synthesis of a G4 polyester dendrimer in four steps by using two different AB2 dendrons [103].
Polymers 04 00794 g007 1024

2.2. Hyperbranched Polymers

Hyperbranched polymers are usually the product of random or non-controlled synthetic procedures. They exhibit an irregular architecture with many defects throughout the structure as a result of incompletely reacted functional groups. Even though they lack the advantages of having well defined structures and molecular weight, hyperbranched polymers are often easily synthesized on a large scale which brings down their cost and makes them important for large-scale and industrial applications.

If dendronized polymers and dendrigrafts are excluded, two broad types of hyperbranched polymers can be defined. One type is obtained using polymerization of a single monomer unit. Many methods have been used for polymerization, including proton-transfer polymerization (PTP) [117], self-condensing vinyl polymerization (SCVP) [118], self-condensing ring-opening polymerization (SCROP) [119], and condensation [120]. Many of the hyperbranched polyesters reported in the literature have been prepared using a one-pot polycondensation of AxB monomers.

Polymers 04 00794 g008 200
Scheme 7. An A2B monomer polycondensation.

Click here to enlarge figure

Scheme 7. An A2B monomer polycondensation.
Polymers 04 00794 g008 1024

In this approach toward hyperbranched polymers [54,121], monomers containing A functional groups with similar reactivity react with functional group B as shown in Scheme 7. The final mixture usually contains highly branched polymers having a similar focal point B but with varying molecular weights and varying degree of branching. The use of AxB monomers where x is > 2 has also been exploited. As the number of A functionalities in a monomer increases, the degree of branching tends to reduce for steric reasons. Examples include those of Mathias [122], Hunter [123], and Yoon [124] for the use of A3B monomers and the work of Miravet and Fréchet for the use of both A4B and A6B monomers [125]. This approach can be used without adding core molecules or with added core molecules.

Polymers 04 00794 g009 200
Scheme 8. Polycondensation of A2B and A3 monomers with excess A2B monomer.

Click here to enlarge figure

Scheme 8. Polycondensation of A2B and A3 monomers with excess A2B monomer.
Polymers 04 00794 g009 1024

A second type of hyperbranched polymers is formed by polymerization of two different types of monomers of which, at least one must be branched. Many different combinations are possible including A2B2 + B3 of Berzelius’ first hyperbranched polymers [41] and A2B + A3 of the commercial Boltorn hyperbranched polyesters [55]. In the case of the Boltorn polyesters [55], the monomers with two functional groups, A2B in this case, are used in a large excess so that the next layer of reactive centers can only come from such a monomer. Scheme 8 below illustrates a schematic representation for the polycondensation of A2B and A3 monomers.

Hyperbranched polymers have continued to be the backbone of many industrial processes and over the years, new methodologies for their synthesis have continued to be developed.

3. Methods Used for Ester Bond Formation

The method chosen for ester bond formation during the synthesis of polyester dendrons and dendrimers must not result in cleavage of other functional groups or in transesterification reactions.

The first method used for ester bond formation in dendrimer synthesis involved the reaction of the carboxylic acid and the alcohol activated by dicyclohexylcarbodiimide (DCC) under mild acid catalysis (Scheme 2) [8] and this procedure has been used often. Formation of acid chlorides followed by reaction with the alcohol under mild base activation was also used early (Scheme 1) [80] but has only been used occasionally [103,126] because the dendron must survive the vigorous conditions used to make the acid chloride.

One of the methods used most often is to convert the alcohol-protected carboxylic acid into the anhydride (Scheme 9), then react the anhydride with the alcohol in the presence of DMAP or other mildly basic promoters [127]. The anhydrides of acetal-protected 2,2-bis-(hydroxymethyl)propanoic acid have been used often [127,128]. Restricting the mobility of the alcohol-terminated chains through formation of a cyclic acetal decreases steric hindrance during ester formation, allowing facile access to high generation dendrimers [129]. Using NMR parameters, we have recently established that the configuration of the O-benzylidene derivative of 2,2’-bis(hydroxymethyl)propanoic acid is cis [130].

Polymers 04 00794 g010 200
Scheme 9. Formation of the anhydride of benzylidene-protected 2,2-bis-(hydroxymethyl)propanoic acid (14) [127].

Click here to enlarge figure

Scheme 9. Formation of the anhydride of benzylidene-protected 2,2-bis-(hydroxymethyl)propanoic acid (14) [127].
Polymers 04 00794 g010 1024

Two alternatives have been proposed recently. We used the urononium-based coupling agents, TBTU [131], TATU [132], and COMU [133] (See Figure 2 for structures), to promote ester formation [134]. An example is shown in Scheme 10. This method has the advantage that primary hydroxyls can be selected over secondary by choosing to use TATU or TBTU with a trialkylamine as base. Secondary alcohols react with carboxylic acids using all three uronium-based agents if the stronger base, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), is used. Tertiary alcohols form esters only when the promoter is COMU and a still stronger base, 7-methyl-1,5,7-triazabicyclo[4.4.0]dec-5-ene (MTBD), is used [134].

Polymers 04 00794 g011 200
Figure 2. Structures of uronium-based compounds used to promote ester formation [134].

Click here to enlarge figure

Figure 2. Structures of uronium-based compounds used to promote ester formation [134].
Polymers 04 00794 g011 1024
Polymers 04 00794 g012 200
Scheme 10. Use of an uronium-based promoter for ester bond formation in assembly of a second generation dendrimer [134].

Click here to enlarge figure

Scheme 10. Use of an uronium-based promoter for ester bond formation in assembly of a second generation dendrimer [134].
Polymers 04 00794 g012 1024

Bouillon et al. have synthesized amine-containing polyester dendrimers by activating the carboxylic acids as cyanomethyl ester intermediates (Scheme 11) [135,136]. This method has been used previously for acylation of ribonucleotide derivatives with N-protected amino acids [137].

Polymers 04 00794 g013 200
Scheme 11. Ester formation from carboxylic acids containing tertiary amines [135].

Click here to enlarge figure

Scheme 11. Ester formation from carboxylic acids containing tertiary amines [135].
Polymers 04 00794 g013 1024

As shown in Scheme 4 and Scheme 5, Zeng and Zimmerman used a Mitsunobu reaction with an aromatic biscarboxylic acid as the nucleophile to form alternating polyester dendrimers [102].

4. Advances in the Synthesis of Polyester Dendrons and Dendrimers

4.1. The Use of 2,2-Bis(Hydroxymethyl)Propanoic Acid-Derived Dendrons

Ever since its first use for dendrimer formation [126], one aliphatic building block has been and continues to be the dendron of choice. 2,2-Bis(hydroxymethyl)propanoic acid (1) (bis-HMPA) is commercially available at a low cost, and most importantly, the resulting polyester dendrimers are non-toxic and biodegradable [38], which makes them attractive for biological and drug delivery applications.

The first report on the synthesis of aliphatic polyester dendrimers based on 1 was by Ihre, Hult, and Söderlind [126]. First to fourth generation dendrons were synthesized from 1 by protecting the carboxylic acid as a benzyl ester group and the hydroxyls as acetate esters (Scheme 12). Esterifications were performed by conversion of the acid into the corresponding acid chloride with oxalyl chloride followed by reaction of the acid chloride with the hydroxyl groups in the presence of triethylamine (TEA) and 4-(dimethylamino)pyridine (DMAP). Deprotection by hydrogenolysis allowed repetition. Acetate-terminated polyester dendrimers with 1,1,1-tris(p-hydroxyphenyl)ethane (9) as a core were synthesized from generation one to four (Mw: 906, 1,856, 3,754, and 7,549 g/mol) by adding the above dendrons in a convergent growth approach (Scheme 13). The simplicity of the 1H NMR and 13C NMR spectra and elemental analyses suggest that pure and monodisperse dendrimers were obtained. However, attempts to selectively remove the acetate groups in order to obtain the corresponding hydroxyl-terminated dendrimers for further chemical surface modification were not successful due to the lack of selectivity in the hydrolysis of the acetate and ester groups. In addition, lower yields were obtained in the final coupling step of the fourth generation dendrons to the core molecule when compared to the coupling steps used to prepare lower generation dendrimers.

Polymers 04 00794 g014 200
Scheme 12. Synthetic route to first to fourth generation dendrons [126].

Click here to enlarge figure

Scheme 12. Synthetic route to first to fourth generation dendrons [126].
Polymers 04 00794 g014 1024
Polymers 04 00794 g015 200
Scheme 13. Synthesis of first to fourth generation acetate-terminated dendrimers [126].

Click here to enlarge figure

Scheme 13. Synthesis of first to fourth generation acetate-terminated dendrimers [126].
Polymers 04 00794 g015 1024

The problems accompanying acetate protection was remedied two years later by using isopropylidene acetals for protection of the 1,3-propanediol in 1 (see Scheme 3) [84]. The six-membered ring acetal is very easily hydrolylized in acid allowing deprotection in the presence of benzyl esters. A further improvement was the use of DCC and 4-(dimethylamino)pyridinium p-toluenesulfonate (DPTS) to promote ester formation directly from the hydroxyl and carboxylic acid groups rather than activate the carboxylic acid as the acid chloride. As shown in Scheme 14, reacting the fourth generation dendron (12) with 9 gave a fourth generation polyester dendrimer in good yield. The periphery of the hydroxyl-terminated polyester dendrimer was then functionalized using reactions of its hydroxyl groups with various acid chlorides (benzoyl, octanoyl, and palmitoyl chloride) in the presence of TEA and DMAP in CH2Cl2 to give high yields of monodisperse dendrimers, according to 1H and 13C NMR spectra, size exclusion chromatography, and elemental analyses of the products.

Polymers 04 00794 g016 200
Scheme 14. Synthesis of fourth generation dendrimer [84].

Click here to enlarge figure

Scheme 14. Synthesis of fourth generation dendrimer [84].
Polymers 04 00794 g016 1024

In order to evaluate this type of non-toxic dendrimer for drug delivery applications, a modified core moiety was prepared by reacting an excess amount of 1,1,1-tris(p-hydroxyphenyl)ethane (9) with benzyl chloroformate, affording a monoprotected trisphenolic in 50% yield after purification [138] (Scheme 15). Reacting this divalent core with two equivalents of the [G-4]-COOH dendron (12Scheme 3) in the presence of DCC followed by the cleavage of the acetonide groups under mild acidic conditions produced a water soluble system containing 32 free hydroxyl groups on the surface. Finally, the benzyl carbonate group was cleaved by hydrogenolysis to provide the free phenol.

To evaluate the effect of increasing the mass of the dendritic system, a second dendritic model compound was prepared. The preparation involved the surface functionalization of dendrimers 24/ 25.

Polymers 04 00794 g017 200
Scheme 15. Preparation of a divalent fourth generation polyester dendrimer (first section) and its surface functionalization (second section) [138].

Click here to enlarge figure

Scheme 15. Preparation of a divalent fourth generation polyester dendrimer (first section) and its surface functionalization (second section) [138].
Polymers 04 00794 g017 1024

For the preparation of these higher molecular mass dendrimers (27 and 28), a capping agent 26 consisting of monomethyl ether tri(ethylene glycol) was used, because poly(ethylene glycol) and its derivatives have advantages for biological applications due to their high water solubility and biocompatibility properties [139]. To couple this moiety to the periphery of the hydroxyl-terminated dendrimer 24, an acid derivative of the monomethyl ether of tri(ethylene glycol) was prepared by reaction with diglycolic anhydride in the presence of DMAP as the catalyst. An excess of the acid capping agent 26 was then reacted with the polyhydroxylated surface of 24 using DCC as the coupling agent to afford 27. As earlier, the phenolic protecting group located at the core was removed using hydrogenolysis to give 28 with an exposed free phenol for radio labelling purposes.

When conventional mesogenic groups in linear crystalline polymers (LCPs) are replaced by chiral mesogens, ferroelectric liquid crystalline polymers (FLCPs) are obtained [140,141,142]. FLCPs are regarded as important species for optical switching and electrooptical applications [143,144]. Because of chain entanglements however, their viscosity is often high which leads to slow switching thereby narrowing the field of their potential practical applications. Knowing that using dendritic structures may result in monodisperse FLCPs and therefore low viscosity and less chain entanglements, Busson et al. synthesized and characterized the first ferroelectric dendritic liquid crystalline polymer (FDLCP). In this work [145], a third generation aliphatic polyester dendrimer, bearing 24 hydroxyl groups on its surface, was functionalized using a ferroelectric mesogen. The mesogenic group, 4"-((R)-1-methylheptyloxy)phenyl 4-(4’-(10-(hydroxycarbonyl)decyloxy)-phenyl)benzoate, responsible for realization of the liquid crystalline state, was coupled to the dendritic matrix via an acid chloride reaction as shown in Scheme 16. The purity and hence the monodispersity of the final compound was established using 1H NMR spectroscopy and size exclusion chromatography (SEC) measurements.

In 1998, another new type of polyester dendrimer was prepared using a novel approach [146]. The goal here was to extend the possibilities of dual living polymerizations (either consecutive or concurrent) to encompass new and complex molecular architectures, ultimately leading to structures that may mimic unimolecular polymeric micelles. The type of dendrimers reported in this paper, denoted as dendrimer-like star block copolymers, are described by a radial geometry where the different generations or layers are comprised of high molecular weight polymer emanating from a central core. For their synthesis, 1,1,1-tris(p-hydroxyphenyl)ethane (9) and 1 were reacted to produce a hexahydroxyl-terminated first generation dendrimer (30) which became the functional initiator for the “living” ring opening polymerization (ROP) of ε-caprolactone producing a hydroxyl terminated six-arm star polymer with controlled molecular weight (31) as shown in Scheme 17. The arms ends were then capped with dendrons containing activated bromide moieties to furnish “macro-initiators” for atom transfer radical polymerization (ATRP) [147,148]. Scheme 18 and Scheme 19 illustrate the synthesis of one of the “micro-initiators”. Methyl methacrylate was polymerized from these macro-initiators in the presence of an organometallic promoter to produce dendrimer-like star polymers with high molecular weights and low polydispersity (<1.2). In addition, amphiphilic character could be introduced by designing different generations as either hydrophobic or hydrophilic.

Polymers 04 00794 g018 200
Scheme 16. Synthesis of the first ferroelectric dendritic liquid crystalline polymer [145].

Click here to enlarge figure

Scheme 16. Synthesis of the first ferroelectric dendritic liquid crystalline polymer [145].
Polymers 04 00794 g018 1024
Polymers 04 00794 g019 200
Scheme 17. Ring opening polymerization of ε-caprolactone [146].

Click here to enlarge figure

Scheme 17. Ring opening polymerization of ε-caprolactone [146].
Polymers 04 00794 g019 1024
Polymers 04 00794 g020 200
Scheme 18. Convergent synthesis of the AB4 dendron [146].

Click here to enlarge figure

Scheme 18. Convergent synthesis of the AB4 dendron [146].
Polymers 04 00794 g020 1024

While exploring various routes to dendrimers, Annby et al. demonstrated that benzylidene-protected bis-HMPA (14) was a versatile reagent for the formation of polyester dendrimers [149]. Polyester dendrimers were prepared up to the fourth generation using even sterically congested cores like pentaerythritol in good yields using DMAP and DCC to promote ester formation. Since then, a number of research groups have utilized the benzylidene-protected bis-HMPA as a convenient building block [127,129,130,146,150,151,152,153].

Polymers 04 00794 g021 200
Scheme 19. Synthesis of a dendritic macro-initiator for atom transfer radical polymerization [146].

Click here to enlarge figure

Scheme 19. Synthesis of a dendritic macro-initiator for atom transfer radical polymerization [146].
Polymers 04 00794 g021 1024

A significant advance in dendrimer synthesis using 1 occurred when it was discovered that the anhydride of 14 (15) could be formed readily by dehydration of the carboxylic acid using DCC [127]. Its preparation and utilization in the formation of a first generation dendrimer using 1,1,1-tris(p-hydroxyphenyl)ethane (9) as the core is shown in Scheme 20 [127]. Repetition of the ester formation and deprotection steps gave up to the sixth generation dendrimer in good yield using this divergent approach (Figure 3) [127]. In the divergent approach, structural uniformity is usually difficult to maintain, because the number of reactions that must be completed at each step of growth increases exponentially, thus requiring large excesses of reagents. The anhydride method however, unlike others, required only a small excess of reagent to achieve quantitative growth, and only simple solvent extraction or precipitation was sufficient purification to obtain monodisperse dendritic structures up to the sixth generation. The amount of anhydride used was only 1.25 equiv per hydroxyl group. Further evidence of the effectiveness of this route was obtained by Parrott et al. who prepared up to eighth generation dendrons using this method achieving yields of >90% at every stage without altering reaction conditions [129].

Polymers 04 00794 g022 200
Scheme 20. Preparation of first generation dendrimers using benzylidene-protected 1 (14) [127].

Click here to enlarge figure

Scheme 20. Preparation of first generation dendrimers using benzylidene-protected 1 (14) [127].
Polymers 04 00794 g022 1024
Polymers 04 00794 g023 200
Figure 3. Hydroxyl-terminated fourth generation polyester dendrimer [127].

Click here to enlarge figure

Figure 3. Hydroxyl-terminated fourth generation polyester dendrimer [127].
Polymers 04 00794 g023 1024

In efforts to establish a large library comprised of dendritic compounds based on bis-HMPA, Malkoch et al. made use of the efficiency of the above anhydride chemistry [128]. To complement the benzylidene-protected anhydride esterification strategy reported by Fréchet and coworkers [127], acetonide-protected bis-HMPA anhydride was introduced to combine anhydride chemistry with the use of a benzyl and 2,2,2-trichloroethyl ester-protected focal points (see Scheme 21 and Scheme 22) [128]. In the same year, Gillies and Fréchet described the use of the acetonide-protected bis-HMPA anhydride in their synthesis of “bow-tie dendrimers” (see below) [154].

Polymers 04 00794 g024 200
Scheme 21. Preparation of the acetonide-protected bis-HMPA anhydride [128].

Click here to enlarge figure

Scheme 21. Preparation of the acetonide-protected bis-HMPA anhydride [128].
Polymers 04 00794 g024 1024
Polymers 04 00794 g025 200
Scheme 22. Preparation of 2,2,2-tris(chloroethyl) ester and benzyl ester protected dendrons [128].

Click here to enlarge figure

Scheme 22. Preparation of 2,2,2-tris(chloroethyl) ester and benzyl ester protected dendrons [128].
Polymers 04 00794 g025 1024
Polymers 04 00794 g026 200
Scheme 23. Preparation of protected fourth generation dendrons [128].

Click here to enlarge figure

Scheme 23. Preparation of protected fourth generation dendrons [128].
Polymers 04 00794 g026 1024

Three different monodisperse fourth generation acetonide-protected dendrons based on 2,2,2-tris(chloroethyl) ester 47 and benzyl ester 48 as focal points were divergently synthesized in high yields (Scheme 23) [128]. In order to demonstrate the versatility of the anhydride chemistry, a fourth generation acetonide-protected polyester dendrimer 52 was also divergently constructed as illustrated in Scheme 24 [128].

Gillies and Fréchet described dendrimers with two dendrons orthogonally protected and covalently attached as “bow-tie” dendrons and synthesized the first examples using acetonide-protected bis-HMPA anhydride for synthesis of one-half of the growing dendrimer and benzylidene-protected bis-HMPA for synthesis of the other half (Scheme 25) [154]. These authors then attached amine functionalized polyethylene oxide (PEO-NH2) to the deprotected half of the dendrimer via reaction with p-nitrophenylcarbonates to form carbamate linkages and cleaved the protecting acetonides to create potential water soluble drug carriers (Scheme 26) [154]. Reaction of four PEO-NH2 samples with molecular weights of 5 to 20 kDa with p-nitrophenylcarbonates derived from 45 and 46 yielded a library of eight compounds with molecular weights of 22 to ~150 kDa [154].

Polymers 04 00794 g027 200
Scheme 24. Divergently-grown acetonide-protected fourth generation dendrimer [128].

Click here to enlarge figure

Scheme 24. Divergently-grown acetonide-protected fourth generation dendrimer [128].
Polymers 04 00794 g027 1024
Polymers 04 00794 g028 200
Scheme 25. Synthesis of “bow-tie” dendrimers [154].

Click here to enlarge figure

Scheme 25. Synthesis of “bow-tie” dendrimers [154].
Polymers 04 00794 g028 1024
Polymers 04 00794 g029 200
Scheme 26. Addition of PEG chains to “bow-tie” dendrimers [154].

Click here to enlarge figure

Scheme 26. Addition of PEG chains to “bow-tie” dendrimers [154].
Polymers 04 00794 g029 1024

Two years later, Malmström, Hult and coworkers reported the synthesis and characterization of dendron-coated porphyrins up to the fifth generation [155]. Here, both free base and zinc-cored tetraphenylporphyrin (TPPH2 and TPPZn) were used, from which the dendrons were divergently grown using 38. Porphyrins were selected as core molecules because of their potential applications in many areas [156,157,158,159]. Reports dealing with porphyrins decorated with dendrimers had previously appeared [112,160,161,162,163,164,165,166,167,168]. After investigating three different synthetic strategies for this study, it was concluded that a spacer was required to be attached to the porphyrin to increase the hydrolytic stability and allow synthesis of higher generations. Normally, acidic DOWEX-50-X2 resin is used for the deprotection of the acetonide groups, but here the porphyrin core attached irreversibly to the DOWEX-50-X2 resin. A number of various dilute acids were explored for this deprotection but the results from these acidic deprotections showed that the porphyrin phenolic ester linkage also hydrolyzes, hence the need for a spacer. The spacer was added through the reaction of the porphyrin with 1,3-bromopropanol to afford 48 (Scheme 27). The dendrimers were then grown by subsequent addition of acetonide-protected bis-HMPA followed by deprotection with 2M H2SO4 in tetrahydrofuran. The preparation of a fourth generation free base porphyrin-cored polyester dendrimer of this type is shown in Scheme 28.

Polymers 04 00794 g030 200
Scheme 27. Spacer addition to the porphyrin core [155].

Click here to enlarge figure

Scheme 27. Spacer addition to the porphyrin core [155].
Polymers 04 00794 g030 1024

Dendritic species based on bis-HMPA containing carboranes were reported by both Adronov [153] and Zharov [169]. These compounds are of interest because of their potential use for boron neutron capture therapy in the treatment of diseases such as cancer.

The noncovalent synthesis of polyester dendritic bow-ties based on anhydrides 15 and 38 using the complementary bis-(adamantylurea)-glycinylurea system [170,171] at the focal point of the bow-tie was reported by Gillies and Fréchet (Scheme 29 and Scheme 30) [172]. The system allows the possibility of bringing together two orthogonally functionalized dendrons since it is not self-complementary. Self-assembled polyester dendritic bow-ties with various peripheral groups were prepared, and their association constants were measured by 1H NMR spectroscopy in CDCl3.

Polymers 04 00794 g031 200
Scheme 28. Divergent construction of a fourth generation (acetonide-protected) free base porphyrin-cored polyester dendrimer [155].

Click here to enlarge figure

Scheme 28. Divergent construction of a fourth generation (acetonide-protected) free base porphyrin-cored polyester dendrimer [155].
Polymers 04 00794 g031 1024
Polymers 04 00794 g032 200
Scheme 29. Divergent growth of a third generation dendron [172].

Click here to enlarge figure

Scheme 29. Divergent growth of a third generation dendron [172].
Polymers 04 00794 g032 1024
Polymers 04 00794 g033 200
Scheme 30. Preparation of a bow-tie polyester dendron 55 [172].

Click here to enlarge figure

Scheme 30. Preparation of a bow-tie polyester dendron 55 [172].
Polymers 04 00794 g033 1024

Initially, a trimethylsilylethyl ester was used as the protecting group for the acid focal point by coupling trimethylsilylethanol with 15. The removal of the benzylidene acetal protecting group using hydrogenolysis provided 50. Coupling and deprotection procedures were repeated until dendron 51 was obtained. The trimethylsilylethyl ester protecting group was removed using tetrabutylammonium fluoride (TBAF), yielding acid 52 with four peripheral benzylidene acetals. To synthesize the adamantylurea moiety, the dinitrile 53 [173] was protected as the MOM ether as shown in Scheme 30, and then the nitrile groups were reduced to amines using Raney nickel under basic conditions. The amine groups were reacted with adamantyl isocyanate to form bis(adamantylurea) 54. The MOM protecting group was then removed under acidic conditions and the product was coupled to 52 to provide dendron 55 after deprotection.

Scheme 30 and Scheme 31 illustrate the chemistry used for further protection of the acid focal point. In addition, oligo(ethylene oxide) units were introduced to the periphery of dendrons such as 61 (Scheme 32 to yield acid 64 after removal of the benzyl ester at the focal point. When equimolar amounts of 60 and the benzylidene-protected version of 55 (65 not previously drawn) were dissolved in CDCl3, the orthogonally-protected parent dendrimer complex [65 60] shown in Figure 4 was formed and its structure was confirmed using NMR spectroscopy.

Polymers 04 00794 g034 200
Scheme 31. Synthesis of dendron 60 [172].

Click here to enlarge figure

Scheme 31. Synthesis of dendron 60 [172].
Polymers 04 00794 g034 1024
Polymers 04 00794 g035 200
Scheme 32. Dendron functionalization using oligo(ethylene oxide) units [172].

Click here to enlarge figure

Scheme 32. Dendron functionalization using oligo(ethylene oxide) units [172].
Polymers 04 00794 g035 1024
Polymers 04 00794 g036 200
Figure 4. Orthogonally-protected parent dendrimer complex [172].

Click here to enlarge figure

Figure 4. Orthogonally-protected parent dendrimer complex [172].
Polymers 04 00794 g036 1024

Another novel development was the use of cyclic carbonates on the periphery of polyester dendrimers [174]. This functional group reacts with amines [175], even in water with quantitative yields [176], to yield bifunctional products. In the reaction, the amine opens the carbonate ring to form a carbamate with liberation of an alcohol that may then be used for a subsequent functionalization step.

Polymers 04 00794 g037 200
Scheme 33. Synthesis of [G-2] bis-HMPA dendrimer with a cyclic carbonate periphery [174].

Click here to enlarge figure

Scheme 33. Synthesis of [G-2] bis-HMPA dendrimer with a cyclic carbonate periphery [174].
Polymers 04 00794 g037 1024
Polymers 04 00794 g038 200
Figure 5. Second generation dendrimer having a bifunctionalized periphery [174].

Click here to enlarge figure

Figure 5. Second generation dendrimer having a bifunctionalized periphery [174].
Polymers 04 00794 g038 1024

Two different moieties may be added in immediate succession without any deprotection steps or functional group conversions. To provide a model platform for testing the reaction, dendrimer 68 with eight hydroxyl groups was prepared from pentaerythritol (Scheme 33). DCC-promoted coupling of 67 and 68 furnished carbonate-bearing dendrimer 69. Finally, reacting 69 with (MeOH)2CHCH2NH2 and then propargyl bromide afforded dendrimer 70 (Figure 5). This is an example of how dendrimers can be precisely designed and functionalized to impart desired properties.

The coupling of preformed dendrons with bifunctional monomers to form core cross-linked star (CCS) polymers is a versatile strategy which has been widely used [177,178,179,180,181,182,183,184]. In order to explore this approach, the so-called “arm first” synthetic strategy, Hawker and coworkers prepared dendrons as functional initiators capable of initiating polymerization by atom transfer radical polymerization (Scheme 34, Scheme 35, Scheme 36, Scheme 37) [185]. The synthesis of polyester dendrons up to the fifth generation by the divergent route using 38 is described. Dendrons were then functionalized at the focal point using a single 2-hydroxyethyl 2-bromo-2-methylpropanoate moiety to form dendron functional macroinitiators. A library of highly branched, 3-dimensional, dendron functional CCS polymers were prepared from these macroinitiators by varying generation number and polystyrene chain length, followed by reaction with divinyl benzene, utilizing the “arm first” approach.

Polymers 04 00794 g039 200
Scheme 34. Divergent growth of acetonide-protected fifth generation polyester dendron [185].

Click here to enlarge figure

Scheme 34. Divergent growth of acetonide-protected fifth generation polyester dendron [185].
Polymers 04 00794 g039 1024
Polymers 04 00794 g040 200
Scheme 35. Synthesis of fifth generation dendron with initiating moiety for atom transfer radical polymerization at the focal point [185].

Click here to enlarge figure

Scheme 35. Synthesis of fifth generation dendron with initiating moiety for atom transfer radical polymerization at the focal point [185].
Polymers 04 00794 g040 1024
Polymers 04 00794 g041 200
Scheme 36. Focal point functionalization using atom transfer radical polymerization [185].

Click here to enlarge figure

Scheme 36. Focal point functionalization using atom transfer radical polymerization [185].
Polymers 04 00794 g041 1024
Polymers 04 00794 g042 200
Scheme 37. Preparation of a fifth generation functionalized core cross-linked star (CCS) polymers via the “Arm First” approach [185].

Click here to enlarge figure

Scheme 37. Preparation of a fifth generation functionalized core cross-linked star (CCS) polymers via the “Arm First” approach [185].
Polymers 04 00794 g042 1024

Until the work of Sanyal and coworkers was published in 2008 [186], few reports describing dendrimer synthesis using the Diels-Alder reaction had appeared. However, these reports described the combination of identical dendrons to furnish symmetrical dendrimers [187,188]. Sanyal’s work was the first example of the synthesis of segment block dendrimers using the Diels-Alder-based synthetic strategy toward the synthesis of unsymmetrical dendrimers. Here, 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. Acetonide-protected polyester dendrons were prepared divergently starting from a furan-protected N-hydroxypropylmaleimide 74. Reacting 74 with anhydride 43 in the presence of DMAP produced 75, which was refluxed in toluene at 110 °C to yield second generation dendron 76 containing the reactive dienophile maleimide group at the focal point. The removal of acetonide-protecting group of compound 75 followed by another coupling step with anhydride 43 furnished 77, which was also refluxed in toluene to yield 78, a second generation dienophile. Another round of the three steps from 77 gave a third generation dienophile 80 as shown in Scheme 38. To prepare the Diels-Alder coupling partners, the acid-functionalized Fréchet dendrons [189,190] were coupled with furfuryl alcohol in the presence of DMAP and DCC to yield three generations of furan-functionalized polyaryl ether dendrons in 88%, 90%, and 58% yields, respectively (Scheme 39).

Polymers 04 00794 g043 200
Scheme 38. Divergent syntheses of maleimide-functionalized dendrons [186].

Click here to enlarge figure

Scheme 38. Divergent syntheses of maleimide-functionalized dendrons [186].
Polymers 04 00794 g043 1024
Polymers 04 00794 g044 200
Scheme 39. Preparation of diene partners [186].

Click here to enlarge figure

Scheme 39. Preparation of diene partners [186].
Polymers 04 00794 g044 1024

The reaction of furan-functionalized dienes 82–84 with dienophiles 77, 79, and 81 in benzene at 85 °C for 24 h afforded the three generations of unsymmetrical dendrimers 85–87 in 98%, 76%, and 79% yields, respectively (see Figure 6). This reagent free Diels-Alder cycloaddition is attractive as the resulting dendrimers are free of impurities such as metals which are usually toxic and therefore problematic in biological applications.

Polymers 04 00794 g045 200
Figure 6. Unsymmetrical dendrimers [186].

Click here to enlarge figure

Figure 6. Unsymmetrical dendrimers [186].
Polymers 04 00794 g045 1024

Antoni et al. prepared azide-terminated bis-HMPA-based polyester dendrons (see Figure 7) up to the fourth generation in order to perform photophysical studies on their products with alkynes [191]. New dendrimer architectures were produced by the “click reaction” [192,193] of these dendrons with a tetravalent alkyne functionalized cyclen core [191]. The preparation of tetravalent alkyne functional cyclen core is shown in Scheme 40.

Polymers 04 00794 g046 200
Figure 7. Azide-functionalized polyester dendrons [191].

Click here to enlarge figure

Figure 7. Azide-functionalized polyester dendrons [191].
Polymers 04 00794 g046 1024
Polymers 04 00794 g047 200
Scheme 40. Synthesis of a tetravalent alkyne-functionalized cyclen core [191].

Click here to enlarge figure

Scheme 40. Synthesis of a tetravalent alkyne-functionalized cyclen core [191].
Polymers 04 00794 g047 1024

The preparation of the fourth generation polyester dendrimer is shown in Scheme 41. These dendrimers are interesting because triazole groups were shown to be stable, intra-locked between the cyclen and dendron wedges. The incorporation of a lanthanide metal ion, europium, into the interior of all cyclen dendrimers was monitored by FT-IR and the photophysical results showed that the proximate triazole acts as both a stable linker and sensitizer, transferring its singlet-singlet excitation in the ultraviolet region (270–290 nm) to the partially filled luminescent lanthanide 4f shell [191].

Polymers 04 00794 g048 200
Scheme 41. Assembly of a fourth generation polyester dendrimer using a click reaction [191].

Click here to enlarge figure

Scheme 41. Assembly of a fourth generation polyester dendrimer using a click reaction [191].
Polymers 04 00794 g048 1024

Azobenzene-containing dendrimers [194] have continued to draw interest because of their optical properties [195,196,197,198,199,200,201,202]. Rissanen’s group has shown interest in the synthesis of Janus-type dendrimers having possible non-linear optical properties arising from the non-centrosymmetric structure of chiral azobenzene conjugates. One report describes the synthesis of bisfunctionalized Janus-type polyester dendrimers, which consist of a polar hydroxyl functionalized end, and a photoactive end constructed from donor–acceptor azobenzenes and chiral naproxen units [203]. An aliphatic polyester skeleton was constructed by reacting monobenzylidene pentaerythritol with the anhydride of acetonide-protected bis-HMPA. Azobenzene moieties, previously reported by the same research group [204], were chosen to be incorporated as electron donor–acceptor chromophores, since they possess non-linear optical properties [205]. Shown in Scheme 42 and Scheme 43 are the syntheses of the first and second generations for this type of unsymmetrical dendrimers.

Polymers 04 00794 g049 200
Scheme 42. Synthesis of acetonide-protected first generation dendrimer (95) [203].

Click here to enlarge figure

Scheme 42. Synthesis of acetonide-protected first generation dendrimer (95) [203].
Polymers 04 00794 g049 1024
Polymers 04 00794 g050 200
Scheme 43. Synthesis of second generation unsymmetrical polyester dendrimer [203].

Click here to enlarge figure

Scheme 43. Synthesis of second generation unsymmetrical polyester dendrimer [203].
Polymers 04 00794 g050 1024

Parrott et al. recently introduced a new carboxylic acid protecting group for the synthesis of polyester dendrons based on bis-HMPA [129], the 2-p-toluenesulfonylethyl group [129]. Dendrons up to the eighth generation were prepared in excellent yields using benzylidene-protected bis-HMPA as the unit being added as shown in Scheme 44 [129]. The protecting group was removed under mild conditions with the non-nucleophilic base DBU in dichloromethane (Scheme 45).

Polymers 04 00794 g051 200
Scheme 44. Divergently-grown fifth generation dendron 105 [129].

Click here to enlarge figure

Scheme 44. Divergently-grown fifth generation dendron 105 [129].
Polymers 04 00794 g051 1024

This group was interested in the preparation of high generations of well-defined and robust 99mTc-labeled dendrimers suitable for single photon emission computed tomography (SPECT) imaging. The γ-emitting 99mTc is the most commonly used medical isotope in diagnostic medicine due to its ideal half-life (6 h) and γ-energy (140 keV), low dose burden to patients, and the universal availability of low cost 99Mo/ 99mTc-generators [206]. A single high-affinity Tc ligand at the core of the dendrimer was desired to ensure that radiolabeling occurs in a well-defined, site-specific manner and at only a single point within the dendrimer skeleton. In addition, the incorporation of the radionuclide was not to significantly affect the overall size, shape, polarity, and mode of interaction of the dendrimer periphery with its external environment so as not to alter the biodistribution of the non- radiolabeled dendrimer.

Polymers 04 00794 g052 200
Scheme 45. Deprotection of the periphery and focal point of the 2-p-toluenesulfonylethyl protected dendron [129].

Click here to enlarge figure

Scheme 45. Deprotection of the periphery and focal point of the 2-p-toluenesulfonylethyl protected dendron [129].
Polymers 04 00794 g052 1024
Polymers 04 00794 g053 200
Scheme 46. Amidation of the focal point using aminohexyl-functionalized bis(pyridyl)amine ligand [129].

Click here to enlarge figure

Scheme 46. Amidation of the focal point using aminohexyl-functionalized bis(pyridyl)amine ligand [129].
Polymers 04 00794 g053 1024

Amidation of the deprotected core with an aminoalkyl-functionalized bis(pyridyl)amine ligand allowed the introduction of an extremely efficient single-site chelator 108 for 99mTc. Dendron labelling was then accomplished by first converting sodium pertechnetate (Na99mTcO4) from the 99Mo/ 99mTc-generator to [99mTc(CO)3(H2O)3]+. Microwave irradiation of amidated dendrons in the presence of the aqua species at 130 °C gave the desired radiolabelled dendons within 5 min (Scheme 47).

Polymers 04 00794 g054 200
Scheme 47. Direct radiolabelling of dendrons using the tris-aqua species [99mTc(CO)3(H2O)3]+[129].

Click here to enlarge figure

Scheme 47. Direct radiolabelling of dendrons using the tris-aqua species [99mTc(CO)3(H2O)3]+[129].
Polymers 04 00794 g054 1024

The process by which information from a source is converted into symbols to be communicated or information encoding is an important field owing to its potential applications [207,208,209]. While exploring chirality for the development of encodeable macromolecules, which can be read out by simple optical rotation measurements or by enantioselective bioresponse, Heise and coworkers reported the synthesis of encoded dendrimers with defined chiral composition via ‘click’ reactions of enantiopure building blocks [210]. Heise and coworkers had previously reported the synthesis of copolymers from the enantiomerically pure monomers of (R) and (S)-p-vinylphenylethanol [211] but copolymers have a disadvantage in that there is uncertainty about the distribution of chiral units along the polymer skeleton. A viable approach was to use dendrimers of well-defined architectures in which orthogonal functionalization encodes a defined optical rotation into the dendrimer by the use of enantiomerically pure (R) and (S) building blocks. Here, an azide-terminated dendrimer (Figure 8) based on bis-HMPA was divergently constructed as previously described [212] and functionalized using 1,3-dipolar cycloadditions (click reactions) with different ratios of the matching alkyne functional enantiopure building blocks (Scheme 49). Scheme 48 shows the selective alcohol dehydrogenase (ADH) reduction of 1-(4-ethynylphenyl)ethanone to give the desired chiral building blocks. When measurements of the optical rotation were taken, it was found that the specific optical rotation of the dendrimers increased linearly with increasing percentage of (R) end-groups in the dendrimer, indicating that both (R) and (S) building blocks had been incorporated into the dendrimer in agreement with the enantiomeric feed ratio.

Polymers 04 00794 g055 200
Figure 8. Azide-terminated third generation dendrimer [212].

Click here to enlarge figure

Figure 8. Azide-terminated third generation dendrimer [212].
Polymers 04 00794 g055 1024
Polymers 04 00794 g056 200
Scheme 48. Enzymatic preparation of enantiopure building blocks [211].

Click here to enlarge figure

Scheme 48. Enzymatic preparation of enantiopure building blocks [211].
Polymers 04 00794 g056 1024
Polymers 04 00794 g057 200
Scheme 49. Modification of azide functional dendrimers using different ratios of enantiomers [210].

Click here to enlarge figure

Scheme 49. Modification of azide functional dendrimers using different ratios of enantiomers [210].
Polymers 04 00794 g057 1024

4.2. The Use of Other Aliphatic Dendrons

Other aliphatic dendrons have been used less often than bis-HMPA. Carnahan and Grinstaff developed tetraol dendrons 113 by esterification of the hydroxyl group of cis-5-hydroxy-2-phenyl-1,3-dioxane with succinic or adipic anhydride as shown in Scheme 50 [213,214]. Up to fourth generation dendrimers were prepared by DCC-promoted esterification of tetraols 113 with the benzylidene-protected monocarboxylic acid 114, then deprotection of the latent hydroxyls (Scheme 51) [213]. It should be noted that these materials will be diastereomeric mixtures because the plane of symmetry present in the starting material, cis-5-hydroxy-2-phenyl-1,3-dioxane, is not present in the dendritic products. Dendrimers were prepared containing only succinic acid, only adipic acid, and mixtures of the two [214]. The properties of the latter dendrimers rely heavily on the composition of the outer generation layer [214]. By esterifying the dendrimers with succinic acid monomethylallyl ether, and photochemically polymerizing the alkenes, soft gels were produced [213]. These materials are used as corneal adhesives [215,216] and for cartilage repair [217,218].

Polymers 04 00794 g058 200
Scheme 50. Preparation of tetraol dendrons [213,214].

Click here to enlarge figure

Scheme 50. Preparation of tetraol dendrons [213,214].
Polymers 04 00794 g058 1024
Polymers 04 00794 g059 200
Scheme 51. Synthesis of a third generation dendrimer [213,214].

Click here to enlarge figure

Scheme 51. Synthesis of a third generation dendrimer [213,214].
Polymers 04 00794 g059 1024

We have synthesized tribranched dendrons in order to prepare dendrimers that have denser layers than those derived from bis-HMPA (Scheme 52) [130,219]. Polyester dendrimers with denser layers are likely to be longer lived under physiological conditions. As shown in Scheme 53, we have recently used the TsEt protecting group in the synthesis of a second generation acid dendron [134]. A tri-branched acid anhydride dendron 115 [130] was reacted with TsEtOH in the presence of DMAP to give benzyl-protected first generation 117. Hydrogenolysis then gave 118 in good yield.

Polymers 04 00794 g060 200
Scheme 52. Synthesis of tribranched dendrons [130].

Click here to enlarge figure

Scheme 52. Synthesis of tribranched dendrons [130].
Polymers 04 00794 g060 1024
Polymers 04 00794 g061 200
Scheme 53. Divergent syntheses of a second generation tribranched dendron and a second generation dendrimer incorporating a tribranched dendron [130].

Click here to enlarge figure

Scheme 53. Divergent syntheses of a second generation tribranched dendron and a second generation dendrimer incorporating a tribranched dendron [130].
Polymers 04 00794 g061 1024

Reacting 117 with benzylidene-protected anhydride 15 followed by deprotection of the focal point using DBU gave the desired acid dendron 120 (Scheme 53). Using coupling agent 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) [130] in the presence of an organic base, ester formation between 120 and various alcohols was achieved in good yield [134]. Scheme 53 also illustrates the preparation of a second generation dendrimer using this approach. Core moiety 121 have also been used to prepare other polyester dendrimers [130] and compound 122 has also been prepared using a divergent approach.

Hirayama et al. devised a synthesis of polyester dendrimers using benzyl acetoacetate and tert-butyl acrylate or 3-hydroxyacetophenone as starting materials [220,221]. Shown in Scheme 54 is the preparation of the AB2 dendron from the Michael addition of benzyl acetoacetate to two equivalents of tert-butyl acrylate followed by hydrogenolysis of the benzyl group, spontaneous decarboxylation, and reduction of the ketone. Scheme 55 shows the assembly of the dendrimer, which used 123 as bivalent core. Up to the fourth generation dendrimer was prepared with all steps being performed in good yield [221]. Similar dendrimers were prepared where 3-hydroxyacetophenone and its tert-butyldimethylsilyl ether served as the Michael nucleophile [220]. These compounds were designed as drug delivery systems.

Polymers 04 00794 g062 200
Scheme 54. Synthesis of an AB2 dendron [221].

Click here to enlarge figure

Scheme 54. Synthesis of an AB2 dendron [221].
Polymers 04 00794 g062 1024

Bouillon prepared a series of tertiary amine-containing polyester dendrimers [136] from the starting materials shown in Figure 9, where 125 is the core and 126 and 127 are the dendrons. The ester bonds were formed by making cyanomethyl esters that react with excess alcohol (the dendron) in the presence of DBU as shown in Scheme 56. Excess alcohol was removed by reaction with benzoic anhydride after each ester bond forming step (not shown in Scheme 56) [136]. Poly(amino)ester dendrimers are particularly attractive as drug delivery systems because the amine functionalities present in the dendrimers can serve as buffers to neutralize the acids generated from ester hydrolysis during dendrimer degradation.

Polymers 04 00794 g063 200
Scheme 55. Synthesis of an acetoacetate tert-butyl acrylate derived dendrimer [221].

Click here to enlarge figure

Scheme 55. Synthesis of an acetoacetate tert-butyl acrylate derived dendrimer [221].
Polymers 04 00794 g063 1024
Polymers 04 00794 g064 200
Figure 9. Starting materials for amine-containing polyester dendrimers [136].

Click here to enlarge figure

Figure 9. Starting materials for amine-containing polyester dendrimers [136].
Polymers 04 00794 g064 1024
Polymers 04 00794 g065 200
Scheme 56. Synthesis of a second generation amine-containing dendrimer [136].

Click here to enlarge figure

Scheme 56. Synthesis of a second generation amine-containing dendrimer [136].
Polymers 04 00794 g065 1024

Another interesting development was the synthesis of polyester dendrimers bearing functional groups capable of orthogonal reactions, that is, bifunctional dendrimers [40]. A complex carboxylic acid bearing a latent diol and an alkyne, an AB2C dendron (132), was prepared and then esterified with a triol to give a first generation dendrimer bearing three alkyne units and six latent hydroxyls (133) (Scheme 57). The latent hydroxyls were exposed by hydrolysis of the acid-labile six-membered isopropylidene ring with an acidic ion exchange resin, and then the process was repeated twice more with added 132 to give the bifunctional product 135 bearing 21 alkyne groups and 24 hydroxyl groups as shown in Scheme 58 [40]. The second generation dendrimer 134 was tested for cytotoxicity on a MG-63 osteoblast cell line and found to have no or low toxicity at the concentrations tested. Second and third generation intermediates on the route to 135 were reacted with alkyl azides in click reactions as shown in Scheme 59. Compound 137, a candidate for atom transfer radical polymerization (ATRP) was obtained in 77% yield and the second generation analog of 135 was also reacted with an azide derivative of PEG8000 to yield a hydrogel in good yield. A bifunctional dendrimer having azide and alcohol functionality was also synthesized as outlined in Scheme 60 [40].

Polymers 04 00794 g066 200
Scheme 57. Synthesis of an AB2C dendron (132) and a first generation dendrimer bearing three alkyne groups and six latent hydroxyls [40].

Click here to enlarge figure

Scheme 57. Synthesis of an AB2C dendron (132) and a first generation dendrimer bearing three alkyne groups and six latent hydroxyls [40].
Polymers 04 00794 g066 1024
Polymers 04 00794 g067 200
Scheme 58. Synthesis of the third generation bifunctional dendrimer [40].

Click here to enlarge figure

Scheme 58. Synthesis of the third generation bifunctional dendrimer [40].
Polymers 04 00794 g067 1024
Polymers 04 00794 g068 200
Scheme 59. Click reactions of azide-terminated molecules with the bifunctional dendrimers [40].

Click here to enlarge figure

Scheme 59. Click reactions of azide-terminated molecules with the bifunctional dendrimers [40].
Polymers 04 00794 g068 1024
Polymers 04 00794 g069 200
Scheme 60. Preparation of bifunctional dendrimers bearing azide and alcohol groups [40].

Click here to enlarge figure

Scheme 60. Preparation of bifunctional dendrimers bearing azide and alcohol groups [40].
Polymers 04 00794 g069 1024

4.3. The Use of Aromatic Dendrons

Aromatic polyester dendrimers were the first polyester dendrimers to be made [8] and the synthetic route of Hawker and Frechét introduced the convergent approach (Scheme 2). A similar approach was published by the same authors at about the same time (Scheme 61 and Scheme 62) [7].

The first divergent approach to polyester dendrimers also used aromatic carboxylic acids (see Scheme 1) [80].

Bo et al. used methyl 3,5-dihydroxybenzoate to produce an AB4 dendron (142) for the synthesis of aromatic polyester dendrimers as illustrated in Scheme 63 [222]. They were unable to use benzyl groups for hydroxyl protection when the focal carboxylic acid was protected as a methyl ester because the deprotection conditions for the latter (NaI and AlCl3 in acetonitrile) also removed the benzyl ethers. They were able to use 142 to make up to fourth generation protected dendrons (Scheme 64) and, using 1,4-dihydroxybenzene and 1,3,5-trihydroxybenzene as cores, up to third generation dendrimers (Scheme 65) [222]. The same group prepared a dendron with a carboxylic acid focal point linked through alkyl ether linkers to carbazole units. Attachment of this dendron to polyester dendrimers terminated in phenolic groups produced dendrimers of interest for their electro-optical properties (Scheme 66) [223].

Polymers 04 00794 g070 200
Scheme 61. Synthesis of a third generation aromatic polyester dendron [7].

Click here to enlarge figure

Scheme 61. Synthesis of a third generation aromatic polyester dendron [7].
Polymers 04 00794 g070 1024
Polymers 04 00794 g071 200
Scheme 62. Synthesis of a third generation aromatic polyester dendrimer [7].

Click here to enlarge figure

Scheme 62. Synthesis of a third generation aromatic polyester dendrimer [7].
Polymers 04 00794 g071 1024
Polymers 04 00794 g072 200
Scheme 63. Synthesis of an AB4 dendron, its protection as the perbenzoate, and deprotection of the focal point [222].

Click here to enlarge figure

Scheme 63. Synthesis of an AB4 dendron, its protection as the perbenzoate, and deprotection of the focal point [222].
Polymers 04 00794 g072 1024
Polymers 04 00794 g073 200
Scheme 64. Synthesis of a fourth generation protected dendron [222].

Click here to enlarge figure

Scheme 64. Synthesis of a fourth generation protected dendron [222].
Polymers 04 00794 g073 1024
Polymers 04 00794 g074 200
Scheme 65. Synthesis of a third generation dendrimer with 4,4'-dihydroxybiphenyl as the core [222].

Click here to enlarge figure

Scheme 65. Synthesis of a third generation dendrimer with 4,4'-dihydroxybiphenyl as the core [222].
Polymers 04 00794 g074 1024
Polymers 04 00794 g075 200
Scheme 66. Synthesis of a second generation aromatic polyester dendrimer bearing carbazole groups on the periphery [223].

Click here to enlarge figure

Scheme 66. Synthesis of a second generation aromatic polyester dendrimer bearing carbazole groups on the periphery [223].
Polymers 04 00794 g075 1024

Do et al. also prepared polyester dendrimers of interest for their optical properties [224,225]. They made polyester dendrimers of the type prepared by Hawker and Frechét [8] (see Figure 10), then added chromophores through Mitsunobu reactions on benzylic alcohols bearing chromophores using the phenolic groups of the dendrimers as nucleophiles. Generation zero to generation three materials were prepared and tested for their optical properties [224,225]. The generation one compound showed the best optical non-linearity of the four optical dendrimers.

Polymers 04 00794 g076 200
Figure 10. Optical dendrimers were prepared by using the G0 to G3 (shown on left) polyester dendrimers as nucleophiles in multiple substitutions of the benzylic hydroxyl of the chromophore on the right [224,225].

Click here to enlarge figure

Figure 10. Optical dendrimers were prepared by using the G0 to G3 (shown on left) polyester dendrimers as nucleophiles in multiple substitutions of the benzylic hydroxyl of the chromophore on the right [224,225].
Polymers 04 00794 g076 1024

4.4. Alternating Polyester Dendrimers

A number of polyester dendrimers have been synthesized where the ester linkages alternate with other types of linkages, the orthogonal coupling strategy, since the first example prepared by Zeng and Zimmerman (Scheme 4) [102].

Romagnoli et al. prepared ester-amide dendrimers as outlined in Scheme 67, Scheme 68, Scheme 69, Scheme 70 using 1,3-diamino-2-propanol (147) and 4-carboxybenzaldehyde (148) as starting materials [106]. They evaluated a number of coupling agents for the amide bond forming steps and found that DPPA was best for the initial coupling of the dendron 149 with 147 (Scheme 67) but BOP was best for the subsequent coupling reactions (Scheme 68 and Scheme 69). Most yields in the synthetic sequences were good but the yields in the oxidation of aldehyde to carboxylic acid were moderate with the larger dendrons (Scheme 68 and Scheme 69).

Polymers 04 00794 g077 200
Scheme 67. Preparation of the AB2 dendron [106].

Click here to enlarge figure

Scheme 67. Preparation of the AB2 dendron [106].
Polymers 04 00794 g077 1024
Polymers 04 00794 g078 200
Scheme 68. Synthesis of the G2 to G3 dendrons [106].

Click here to enlarge figure

Scheme 68. Synthesis of the G2 to G3 dendrons [106].
Polymers 04 00794 g078 1024
Polymers 04 00794 g079 200
Scheme 69. Preparation of the G2 dendrimer [106].

Click here to enlarge figure

Scheme 69. Preparation of the G2 dendrimer [106].
Polymers 04 00794 g079 1024
Polymers 04 00794 g080 200
Scheme 70. Synthesis of a chiral core [226].

Click here to enlarge figure

Scheme 70. Synthesis of a chiral core [226].
Polymers 04 00794 g080 1024

The same group utilized some of the above dendrons to synthesize chiral dendrimers by replacing the achiral tetraamine core of 151 with a chiral triol (152) [226], synthesized as in Scheme 70 from L-Garner aldehyde (153), itself synthesized from serine using the method of Taylor and coworkers [227]. Scheme 71 shows the reaction with the G2 dendron; dendrimers bearing G1 and G2 dendrons were synthesized by reaction with core 152 and its enantiomer [226].

Polymers 04 00794 g081 200
Scheme 71. Synthesis of a chiral amide-ester dendrimer [226].

Click here to enlarge figure

Scheme 71. Synthesis of a chiral amide-ester dendrimer [226].
Polymers 04 00794 g081 1024

Antoni et al. alternated ester formation with click reactions using two different AB2 dendrons, 153 and 154, for the accelerated synthesis of dendrimers as shown in Scheme 72 [103]. Because these orthogonal reactions did not require any activation or deprotection steps, the preparation of a quite large dendrimer was accomplished very rapidly. Only five steps yielded the fourth generation dendrimer (see Scheme 73) [103]. It is surprising that the acid chloride functional group of 153 survived the aqueous THF solution used for the click reaction but other conditions (e.g., DCC) could have been used for the esterification step.

Polymers 04 00794 g082 200
Scheme 72. The starting materials and second generation dendron for accelerated synthesis [103].

Click here to enlarge figure

Scheme 72. The starting materials and second generation dendron for accelerated synthesis [103].
Polymers 04 00794 g082 1024
Polymers 04 00794 g083 200
Scheme 73. A fourth generation dendrimer resulting from accelerated synthesis [103].

Click here to enlarge figure

Scheme 73. A fourth generation dendrimer resulting from accelerated synthesis [103].
Polymers 04 00794 g083 1024

Montañez utilized AB2 dendrons that combined ester formation with thiol-ene reactions to provide another approach for the accelerated synthesis of dendrimers [104]. These authors combined the dendrons shown in Figure 11 as shown in Scheme 74. The thiol-ene reactions were conducted by irradiation with 356 nm light in the presence of the photoinitiator, 2,2-dimethoxy-1,2-diphenylacetophenone (DMPA).

Polymers 04 00794 g084 200
Figure 11. Monomers and cores employed for the synthesis of dendrimers using thiol-ene and esterification reactions [104].

Click here to enlarge figure

Figure 11. Monomers and cores employed for the synthesis of dendrimers using thiol-ene and esterification reactions [104].
Polymers 04 00794 g084 1024
Polymers 04 00794 g085 200
Scheme 74. Synthesis of a second generation dendrimer using thiol-ene and esterification reactions [104].

Click here to enlarge figure

Scheme 74. Synthesis of a second generation dendrimer using thiol-ene and esterification reactions [104].
Polymers 04 00794 g085 1024
Polymers 04 00794 g086 200
Scheme 75. Synthesis of a fourth generation dendrimers using thiol-ene and esterification reactions [104].

Click here to enlarge figure

Scheme 75. Synthesis of a fourth generation dendrimers using thiol-ene and esterification reactions [104].
Polymers 04 00794 g086 1024

Walter et al. developed this theme further by creating a series of macrothiols bearing latent hydroxyls through reduction of dendronized disulfides (see Scheme 76 for one example) [105]. Dendrimers were obtained through the light-promoted addition of these thiols to core molecules terminating in alkenes. Deprotection of the latent hydroxyls gave a hydroxyl-terminated dendrimer, as shown in Scheme 77 [105]. These dendrimers can then be reacted further to give products with desired properties.

Polymers 04 00794 g087 200
Scheme 76. Synthesis of a macrothiol [105].

Click here to enlarge figure

Scheme 76. Synthesis of a macrothiol [105].
Polymers 04 00794 g087 1024
Polymers 04 00794 g088 200
Scheme 77. Thiol-ene reaction of the macrothiol [105].

Click here to enlarge figure

Scheme 77. Thiol-ene reaction of the macrothiol [105].
Polymers 04 00794 g088 1024

Chen et al. described a very efficient alternating convergent dendrimer synthesis where the reaction complementing esterification was photochemically induced addition of a thiol to an alkyne (see Scheme 78 and Scheme 79) [107]. Tris-3-propynyl 1,3,5-benzenetricarboxylate served as the starting material and provided a trivalent core. Photochemically-aided addition of 1-thioglycerol (164) gave the first generation dendrimer that was esterified with anhydride 165, terminated by an alkyne. Repetition of these two steps twice gave a dendrimer termed by Chen et al., the third generation dendrimer, although most workers in the area of alternating dendrimers call the product of each addition the next generation. Following this latter convention, we have named the product the sixth generation dendrimer in the title of Scheme 79 and G6 in the Scheme. The thiol-yne addition is very efficient because each step is a double addition, in this case raising the number of peripheral groups by four. Because the 1-thioglycerol used as the thiol was racemic, the resulting dendrimer was a mixture of diastereomers, a disadvantage for characterization. Chen et al. went on to add 1-thioglycolic acid to 166, yielding a dendrimer bearing 24 peripheral carboxylic acid groups [107]. This compound was shown to bind the anti-cancer drug, cis-dichlorodiammineplatinum(II), effectively.

Polymers 04 00794 g089 200
Scheme 78. Convergent synthesis of a second generation dendrimer by alternating thiol-yne reactions with esterification [107].

Click here to enlarge figure

Scheme 78. Convergent synthesis of a second generation dendrimer by alternating thiol-yne reactions with esterification [107].
Polymers 04 00794 g089 1024
Polymers 04 00794 g090 200
Scheme 79. Convergent synthesis of a sixth generation dendrimer by alternating thiol-yne reactions with esterification [107].

Click here to enlarge figure

Scheme 79. Convergent synthesis of a sixth generation dendrimer by alternating thiol-yne reactions with esterification [107].
Polymers 04 00794 g090 1024

Another approach that yields alternating polyester dendrimers was described by Rosen et al. [95,228]. The two reactions involved are the displacement of bromide from α-bromo esters by thiols that are also alcohols and esterification of the alcohols by α-bromoacyl bromides (see Scheme 80).

Polymers 04 00794 g091 200
Scheme 80. Synthesis of alternating polyester dendrimers by thiol-α-bromo ester reactions and esterification [95].

Click here to enlarge figure

Scheme 80. Synthesis of alternating polyester dendrimers by thiol-α-bromo ester reactions and esterification [95].
Polymers 04 00794 g091 1024
Polymers 04 00794 g092 200
Scheme 81. Synthesis of a G3 alternating polyester dendrimer by thiol-α-bromo ester reactions and esterification [95].

Click here to enlarge figure

Scheme 81. Synthesis of a G3 alternating polyester dendrimer by thiol-α-bromo ester reactions and esterification [95].
Polymers 04 00794 g092 1024

Yields for the two-step sequence are good, on the order of 85% and up to the G4-Br dendrimer has been produced (see Scheme 81). These products are also mixtures of diastereomers. Compounds containing α-bromo esters are candidates for single electron transfer living radical polymerization (SET-LRP) and Rosen et al. have demonstrated that compounds similar to 167 are effective substrates [228]. They polymerized low generation dendrimers with methyl acrylate to produce star polymers. Because the termination step of the polymerization is reaction of an acrylate-derived radical with an α-bromoester, the dendritic polymers have dendrimer units at the centre and on the periphery. This three step sequence has been termed a “branch and grow” strategy [228].

5. Conclusions

Although many types of structures have been synthesized, the enormous structural diversity of both organic and inorganic chemistry guarantees that there are a huge number of potential novel types of polyester dendrimers yet to be synthesized. The efficient synthesis of dendrimers through orthogonal reactions is just beginning to be studied. Consequently, properties and new potential applications are still essentially unexplored.

Acknowledgments

We thank NSERC for support.

References

  1. Buhleier, E.; Wehner, W.; Vögtle, F. “Cascade”- and “nonskid-chain-like” syntheses of molecular cavity topologies. Synthesis 1978, 1978, 155–158, doi:10.1055/s-1978-24702.
  2. Denkewalter, R.G.; Kolc, J.; Kukasavage, W.J. Macromolecular highly branched homogeneous compound based on lysine units. U.S. Patent 4289872, 15 September 1981.
  3. Tomalia, D.A.; Dewald, J.R.; Hall, M.R.; Martin, S.J.; Smith, P.B. 1st International Polymer Conference, Kyoto, Japan, August 1984; Society of Polymer Science of Japan; p. 65.
  4. Tomalia, D.A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. A new class of polymers: Starburst-dendritic macromolecules. Polym. J. 1985, 17, 117–132, doi:10.1295/polymj.17.117.
  5. Newkome, G.R.; Yao, Z.Q.; Baker, G.R.; Gupta, V.K. Micelles. 1. Cascade molecules—A new approach to micelles—A [27]-arborol. J. Org. Chem. 1985, 50, 2003–2004, doi:10.1021/jo00211a052.
  6. Tomalia, D.A.; Naylor, A.M.; Goddard, W.A. Starburst dendrimers—Molecular-level control of size, shape, surface chemistry, topology, and flexibility from atoms to macroscopic matter. Angew. Chem. Int. Ed. 1990, 29, 138–175, doi:10.1002/anie.199001381.
  7. Hawker, C.J.; Fréchet, J.M.J. Unusual macromolecular architectures—The convergent growth approach to dendritic polyesters and novel block copolymers. J. Am. Chem. Soc. 1992, 114, 8405–8413, doi:10.1021/ja00048a009.
  8. Hawker, C.J.; Fréchet, J.M.J. Monodispersed dendritic polyesters with removable chain ends—A versatile approach to globular macromolecules with chemically reversible polarities. J. Chem. Soc. Perkin Trans. 1 1992, 2459–2469.
  9. Fréchet, J.M.J.; Tomalia, D.A. Dendrimers and Other Dendritic Polymers; Wiley: Hoboken, NJ, USA, 2001; p. 647.
  10. Newkome, G.R.; Morefield, C.N.; Vögtle, F. Dendritic Molecules: Concepts, Synthesis, Perspectives; Wiley-VCH: New York, NY, USA and Weinheim, Germany, 2001; p. 261.
  11. Vögtle, F.; Richardt, G.; Werner, N. Dendrimer Chemistry: Concepts, Syntheses, Properties, Applications; Wiley-VCH: Weinheim, Germany, 2009; p. 342.
  12. Nummelin, S.; Skrifvars, M.; Rissanen, K. Polyester and ester functionalized dendrimers. Topics Curr. Chem. 2000, 210, 1–67, doi:10.1007/3-540-46577-4_1.
  13. Newkome, G.R.; Shreiner, C. Dendrimers derived from 1 to 3 branching motifs. Chem. Rev. 2010, 110, 6338–6442, doi:10.1021/cr900341m.
  14. Astruc, D.; Boisselier, E.; Ornelas, C. Dendrimers designed for functions: From physical, photophysical, and supramolecular properties to applications in sensing, catalysis, molecular electronics, photonics, and nanomedicine. Chem. Rev. 2010, 110, 1857–1959, doi:10.1021/cr900327d.
  15. Boas, U.; Heegaard, P.M.H. Dendrimers in drug research. Chem. Soc. Rev. 2004, 33, 43–63, doi:10.1039/b309043b.
  16. Heegaard, P.M.H.; Boas, U.; Sorensen, N.S. Dendrimers for vaccine and immunostimulatory uses. A review. Bioconjugate Chem. 2010, 21, 405–418, doi:10.1021/bc900290d.
  17. Fréchet, J.M.J. Dendrimers and other dendritic macromolecules: From building blocks to functional assemblies in nanoscience and nanotechnology. J. Polym. Sci. Part A 2003, 41, 3713–3725, doi:10.1002/pola.10952.
  18. Grayson, S.M.; Fréchet, J.M.J. Convergent dendrons and dendrimers: From synthesis to applications. Chem. Rev. 2001, 101, 3819–3867, doi:10.1021/cr990116h.
  19. Menjoge, A.R.; Kannan, R.M.; Tomalia, D.A. Dendrimer-based drug and imaging conjugates: Design considerations for nanomedical applications. Drug Discov. Today 2010, 15, 171–185, doi:10.1016/j.drudis.2010.01.009.
  20. Tomalia, D.A. Birth of a new macromolecular architecture: Dendrimers as quantized building blocks for nanoscale synthetic polymer chemistry. Prog. Polym. Sci. 2005, 30, 294–324, doi:10.1016/j.progpolymsci.2005.01.007.
  21. Medina, S.H.; El-Sayed, M.E.H. Dendrimers as carriers for delivery of chemotherapeutic agents. Chem. Rev. 2009, 109, 3141–3157, doi:10.1021/cr900174j.
  22. Jang, W.D.; Selim, K.M.K.; Lee, C.H.; Kang, I.K. Bioinspired application of dendrimers: From bio-mimicry to biomedical applications. Prog. Polym. Sci. 2009, 34, 1–23, doi:10.1016/j.progpolymsci.2008.08.003.
  23. Cameron, D.J.A.; Shaver, M.P. Aliphatic polyester polymer stars: Synthesis, properties and applications in biomedicine and nanotechnology. Chem. Soc. Rev. 2011, 40, 1761–1776, doi:10.1039/c0cs00091d.
  24. Scholl, M.; Kadlecova, Z.; Klok, H.A. Dendritic and hyperbranched polyamides. Prog. Polym. Sci. 2009, 34, 24–61, doi:10.1016/j.progpolymsci.2008.09.001.
  25. Satija, J.; Sai, V.V.R.; Mukherji, S. Dendrimers in biosensors: Concept and applications. J. Mater. Chem. 2011, 21, 14367–14386, doi:10.1039/c1jm10527b.
  26. Lin, Q.M.; Jiang, G.H.; Tong, K.K. Dendrimers in drug-delivery applications. Des. Monomers Polym. 2010, 13, 301–324, doi:10.1163/138577210X509552.
  27. Hourani, R.; Kakkar, A. Advances in the elegance of chemistry in designing dendrimers. Macromol. Rapid Commun. 2010, 31, 947–974, doi:10.1002/marc.200900712.
  28. Villalonga-Barber, C.; Micha-Screttas, M.; Steele, B.R.; Georgopoulos, A.; Demetzos, C. Dendrimers as biopharmaceuticals: Synthesis and properties. Curr. Top. Med. Chem. 2008, 8, 1294–1309, doi:10.2174/156802608785849012.
  29. Cheng, Y.Y.; Zhao, L.B.; Li, Y.W.; Xu, T.W. Design of biocompatible dendrimers for cancer diagnosis and therapy: Current status and future perspectives. Chem. Soc. Rev. 2011, 40, 2673–2703, doi:10.1039/c0cs00097c.
  30. Soliman, G.M.; Sharma, A.; Maysinger, D.; Kakkar, A. Dendrimers and miktoarm polymers based multivalent nanocarriers for efficient and targeted drug delivery. Chem. Commun. 2011, 47, 9572–9587, doi:10.1039/c1cc11981h.
  31. Wolinsky, J.B.; Grinstaff, M.W. Therapeutic and diagnostic applications of dendrimers for cancer treatment. Adv. Drug Deliv. Rev. 2008, 60, 1037–1055, doi:10.1016/j.addr.2008.02.012.
  32. Newkome, G.R.; Shreiner, C.D. Poly(amidoamine), polypropylenimine, and related dendrimers and dendrons possessing different 1 -> 2 branching motifs: An overview of the divergent procedures. Polymer 2008, 49, 1–173, doi:10.1016/j.polymer.2007.10.021.
  33. Jain, K.; Kesharwani, P.; Gupta, U.; Jain, N.K. Dendrimer toxicity: Let’s meet the challenge. Int. J. Pharm. 2010, 394, 122–142, doi:10.1016/j.ijpharm.2010.04.027.
  34. Nanjwade, B.K.; Bechra, H.M.; Derkar, G.K.; Manvi, F.V.; Nanjwade, V.K. Dendrimers: Emerging polymers for drug-delivery systems. Eur. J. Pharm. Sci. 2009, 38, 185–196, doi:10.1016/j.ejps.2009.07.008.
  35. Simanek, E.E.; Abdou, H.; Lalwani, S.; Lim, J.; Mintzer, M.; Venditto, V.J.; Vittur, B. The 8year thicket of triazine dendrimers: Strategies, targets and applications. Proc. R. Soc. A 2010, 466, 1445–1468, doi:10.1098/rspa.2009.0108.
  36. Konkolewicz, D.; Monteiro, M.J.; Perrier, S. Dendritic and hyperbranched polymers from macromolecular units: Elegant approaches to the synthesis of functional polymers. Macromolecules 2011, 44, 7067–7087, doi:10.1021/ma200656h.
  37. Harvison, M.A.; Lowe, A.B. Combining RAFT radical polymerization and click/highly efficient coupling chemistries: A powerful strategy for the preparation of novel materials. Macromol. Rapid Commun. 2011, 32, 779–800, doi:10.1002/marc.201100156.
  38. Gillies, E.R.; Dy, E.; Fréchet, J.M.J.; Szoka, F.C. Biological evaluation of polyester dendrimer: Poly(ethylene oxide) “Bow-Tie” hybrids with tunable molecular weight and architecture. Mol. Pharm. 2005, 2, 129–138, doi:10.1021/mp049886u.
  39. Morgan, M.T.; Carnahan, M.A.; Immoos, C.E.; Ribeiro, A.A.; Finkelstein, S.; Lee, S.J.; Grinstaff, M.W. Dendritic molecular capsules for hydrophobic compounds. J. Am. Chem. Soc. 2003, 125, 15485–15489, doi:10.1021/ja0347383.
  40. Antoni, P.; Hed, Y.; Nordberg, A.; Nyström, D.; von Holst, H.; Hult, A.; Malkoch, M. Bifunctional dendrimers: From robust synthesis and accelerated one-pot postfunctionalization strategy to potential applications. Angew. Chem. Int. Ed. 2009, 48, 2126–2130, doi:10.1002/anie.200804987.
  41. Kienle, R.H.; Hovey, A.G. The polyhydric alcohol-polybasic acid reaction I Glycerol-phthalic anhydride. J. Am. Chem. Soc. 1929, 51, 509–519, doi:10.1021/ja01377a021.
  42. Smith, W. A new glyceride: Glycerine phthalate. J. Soc. Chem. Ind. 1901, 20, 1075–1076.
  43. Kienle, R.H.; van der Meulen, P.A.; Petke, F.E. Polyhydric alcohol-polybasic acid reaction. III. Further studies of the glycerol-phthalic anhydride reaction. J. Am. Chem. Soc. 1939, 61, 2258–2268, doi:10.1021/ja01878a001.
  44. Kienle, R.H.; van der Meulen, P.A.; Petke, F.E. Polyhydric alcohol-polybasic acid reaction. IV. Glyceryl phthalate from phthalic acid. J. Am. Chem. Soc. 1939, 61, 2268–2271, doi:10.1021/ja01878a002.
  45. Kienle, R.H.; Petke, F.E. The polyhydric alcohol-polybasic acid reaction. V. The glyceryl succinate and glyceryl maleate polyesters. J. Am. Chem. Soc. 1940, 62, 1053–1056, doi:10.1021/ja01862a019.
  46. Baekeland, L.H. The synthesis, constitution, and uses of bakelite. Ind. Eng. Chem. 1909, 1, 149–161, doi:10.1021/ie50003a004.
  47. Baekeland, L.H.; Bender, H.L. Phenol resins and resinoids. Ind. Eng. Chem. 1925, 17, 225–237, doi:10.1021/ie50183a002.
  48. Flory, P.J. Molecular size distribution in three dimensional polymers. I. Gelation. J. Am. Chem. Soc. 1941, 63, 3083–3090, doi:10.1021/ja01856a061.
  49. Flory, P.J. Molecular size distribution in three dimensional polymers. II. Trifunctional branching units. J. Am. Chem. Soc. 1941, 63, 3091–3096, doi:10.1021/ja01856a062.
  50. Flory, P.J. Molecular size distribution in three dimensional polymers. III. Tetrafunctional branching units. J. Am. Chem. Soc. 1941, 63, 3096–3100, doi:10.1021/ja01856a063.
  51. Stockmayer, W.H. Theory of molecular size distribution and gel formation in branched-chain polymers. J. Chem. Phys. 1943, 11, 45–55, doi:10.1063/1.1723803.
  52. Flory, P.J. Molecular size distribution in three dimensional polymers. VI. Branched polymers containing A-R-Bf−1 type units. J. Am. Chem. Soc. 1952, 74, 2718–2723, doi:10.1021/ja01131a008.
  53. Schaefgen, J.R.; Flory, P.J. Synthesis of multichain polymers and investigation of their viscosities. J. Am. Chem. Soc. 1948, 70, 2709–2718, doi:10.1021/ja01188a026.
  54. Hawker, C.J.; Lee, R.; Fréchet, J.M.J. One-step synthesis of hyperbranched dendritic polyesters. J. Am. Chem. Soc. 1991, 113, 4583–4588, doi:10.1021/ja00012a030.
  55. Malmström, E.; Johansson, M.; Hult, A. Hyperbranched aliphatic polyesters. Macromolecules 1995, 28, 1698–1703, doi:10.1021/ma00109a049.
  56. Schlüter, A.D.; Rabe, J.P. Dendronized polymers: Synthesis, characterization, assembly at interfaces, and manipulation. Angew. Chem. Int. Ed. 2000, 39, 864–883, doi:10.1002/(SICI)1521-3773(20000303)39:5<864::AID-ANIE864>3.0.CO;2-E.
  57. Zhang, A.; Shu, L.; Bo, Z.; Schlüter, A.D. Dendronized polymers: Recent progress in synthesis. Macromol. Chem. Phys. 2003, 204, 328–339, doi:10.1002/macp.200290086.
  58. Frauenrath, H. Dendronized polymers—Building a new bridge from molecules to nanoscopic objects. Prog. Polym. Sci. 2005, 30, 325–384, doi:10.1016/j.progpolymsci.2005.01.011.
  59. Zhang, A. Synthesis, characterization and applications of dendronized polymers. Prog. Chem. 2005, 17, 157–171.
  60. Carlmark, A.; Hawker, C.J.; Hult, A.; Malkoch, M. New methodologies in the construction of dendritic materials. Chem. Soc. Rev. 2009, 38, 352–362, doi:10.1039/b711745k.
  61. Gauthier, M. Arborescent polymers and other dendrigraft polymers: A journey into structural diversity. J. Polym. Sci. Part A 2007, 45, 3803–3810, doi:10.1002/pola.22242.
  62. Wurm, F.; Frey, H. Linear-dendritic block copolymers: The state of the art and exciting perspectives. Prog. Polym. Sci. 2011, 36, 1–52, doi:10.1016/j.progpolymsci.2010.07.009.
  63. Yan, D.; Gao, C.; Frey, H. Hyperbranched Polymers: Synthesis, Properties and Applications; John Wiley & Sons: New York, NY, USA, 2011; p. 480.
  64. Hult, A.; Johansson, M.; Malmström, E. Hyperbranched polymers. Adv. Polym. Sci. 1999, 143, 1–34, doi:10.1007/3-540-49780-3_1.
  65. Gao, C.; Yan, D. Hyperbranched polymers: From synthesis to applications. Prog. Polym. Sci. 2004, 29, 183–275, doi:10.1016/j.progpolymsci.2003.12.002.
  66. Voit, B. Hyperbranched polymers—All problems solved after 15 years of research? J. Polym. Sci. Part A 2005, 43, 2679–2699, doi:10.1002/pola.20821.
  67. Yates, C.R.; Hayes, W. Synthesis and applications of hyperbranched polymers. Eur. Polym. J. 2004, 40, 1257–1281, doi:10.1016/j.eurpolymj.2004.02.007.
  68. McKee, M.G.; Unal, S.; Wilkes, G.L.; Long, T.E. Branched polyesters: Recent advances in synthesis and performance. Prog. Polym. Sci. 2005, 30, 507–539, doi:10.1016/j.progpolymsci.2005.01.009.
  69. Voit, B.I.; Lederer, A. Hyperbranched and highly branched polymer architectures-synthetic strategies and major characterization aspects. Chem. Rev. 2009, 109, 5924–5973, doi:10.1021/cr900068q.
  70. Zhang, X. Hyperbranched aromatic polyesters: From synthesis to applications. Prog. Org. Coat. 2010, 69, 295–309, doi:10.1016/j.porgcoat.2010.08.007.
  71. Calderón, M.; Quadir, M.A.; Strumia, M.; Haag, R. Functional dendritic polymer architectures as stimuli-responsive nanocarriers. Biochimie 2010, 92, 1242–1251, doi:10.1016/j.biochi.2010.02.017.
  72. Žagar, E.; Žigon, M. Aliphatic hyperbranched polyesters based on 2,2-bis(methylol)propionic acid-Determination of structure, solution and bulk properties. Prog. Polym. Sci. 2011, 36, 53–88, doi:10.1016/j.progpolymsci.2010.08.004.
  73. Binauld, S.; Damiron, D.; Connal, L.A.; Hawker, C.J.; Drockenmuller, E. Precise synthesis of molecularly defined oligomers and polymers by orthogonal iterative divergent/convergent approaches. Macromol. Rapid Commun. 2011, 32, 147–168, doi:10.1002/marc.201000548.
  74. Zhang, X. Modifications and applications of hyperbranched aliphatic polyesters based on dimethylolpropionic acid. Polym. Int. 2011, 60, 153–166, doi:10.1002/pi.2930.
  75. Newkome, G.R.; Nayak, A.; Behera, R.K.; Moorefield, C.N.; Baker, G.R. Chemistry of micelles series. 22. Cascade polymers—synthesis and characterization of 4-directional spherical dendritic macromolecules based on adamantane. J. Org. Chem. 1992, 57, 358–362, doi:10.1021/jo00027a061.
  76. De Brabander-van den Berg, E.M.M.; Meijer, E.W. Poly(propylene imine) dendrimers: Large-scale synthesis by hetereogeneously catalyzed hydrogenations. Angew. Chem. Int. Ed. 1993, 32, 1308–1311, doi:10.1002/anie.199313081.
  77. Hawker, C.J.; Fréchet, J.M.J. Preparation of polymers with controlled molecular architecture—A new convergent approach to dendritic macromolecules. J. Am. Chem. Soc. 1990, 112, 7638–7647, doi:10.1021/ja00177a027.
  78. Gillies, E.R.; Fréchet, J.M.J. Dendrimers and dendritic polymers in drug delivery. Drug Discov. Today 2005, 10, 35–43, doi:10.1016/S1359-6446(04)03276-3.
  79. Lee, C.C.; Gillies, E.R.; Fox, M.E.; Guillaudeu, S.J.; Fréchet, J.M.J.; Dy, E.E.; Szoka, F.C. A single dose of doxorubicin-functionalized bow-tie dendrimer cures mice bearing C-26 colon carcinomas. Proc. Nat. Acad. Sci. USA 2006, 103, 16649–16654, doi:10.1073/pnas.0607705103.
  80. Haddleton, D.M.; Sahota, H.S.; Taylor, P.C.; Yeates, S.G. Synthesis of polyester dendrimers. J. Chem. Soc. Perkin Trans. 1 1996, 649–656.
  81. Kawaguchi, T.; Walker, K.L.; Wilkins, C.L.; Moore, J.S. Double exponential dendrimer growth. J. Am. Chem. Soc. 1995, 117, 2159–2165, doi:10.1021/ja00113a005.
  82. Klopsch, R.; Franke, P.; Schlüter, A.-D. Repetitive strategy for exponential growth of hydroxy-functionalized dendrons. Chem. Eur. J. 1996, 2, 1330–1334, doi:10.1002/chem.19960021021.
  83. Ashton, P.R.; Hounsell, E.F.; Jayaraman, N.; Nilsen, T.M.; Spencer, N.; Stoddart, J.F.; Young, M. Synthesis and biological evaluation of α-D-mannopyranoside-containing dendrimers. J. Org. Chem. 1998, 63, 3429–3437, doi:10.1021/jo9804184.
  84. Ihre, H.; Hult, A.; Fréchet, J.M.J.; Gitsov, I. Double-stage convergent approach for the synthesis of functionalized dendritic aliphatic polyesters based on 2,2-bis(hydroxymethyl)propionic acid. Macromolecules 1998, 31, 4061–4068, doi:10.1021/ma9718762.
  85. Spindler, R.; Fréchet, J.M.J. 2-Step approach towards the accelerated synthesis of dendritic macromolecules. J. Chem. Soc. Perkin Trans. 1 1993, 913–918.
  86. Xu, Z.F.; Moore, J.S. Stiff dendritic macromolecules. 3. Rapid construction of large-size phenylacetylene dendrimers up to 12.5 nonometers in molecular diameter. Angew. Chem. Int. Ed. Engl. 1993, 32, 1354–1357, doi:10.1002/anie.199313541.
  87. Zeng, F.W.; Zimmerman, S.C. Rapid synthesis of dendrimers by an orthogonal coupling strategy. J. Am. Chem. Soc. 1996, 118, 5326–5327, doi:10.1021/ja960317s.
  88. Deb, S.K.; Maddux, T.M.; Yu, L.P. A simple orthogonal approach to poly(phenylenevinylene) dendrimers. J. Am. Chem. Soc. 1997, 119, 9079–9080, doi:10.1021/ja971790o.
  89. Klopsch, R.; Koch, S.; Schlüter, A.-D. Amino-functionalized, second-generation dendritic building blocks. Eur. J. Org. Chem. 1998, 1275–1283.
  90. Ingerl, A.; Neubert, I.; Klopsch, R.; Schlüter, A.D. Hydroxy-functionalized dendritic building blocks. Eur. J. Org. Chem. 1998, 2551–2556.
  91. Ishida, Y.; Jikei, M.; Kakimoto, M.A. Rapid synthesis of aromatic polyamide dendrimers by an orthogonal and a double-stage convergent approach. Macromolecules 2000, 33, 3202–3211, doi:10.1021/ma991700v.
  92. Burai, R.; Chatwichien, J.; McNaughton, B.R. A programmable “build-couple” approach to the synthesis of heterofunctionalized polyvalent molecules. Org. Biomol. Chem. 2011, 9, 5056–5058, doi:10.1039/c1ob05606a.
  93. Antoni, P.; Robb, M.J.; Campos, L.; Montanez, M.; Hult, A.; Malmström, E.; Malkoch, M.; Hawker, C.J. Pushing the limits for thiol-ene and CuAAC reactions: Synthesis of a 6th generation dendrimer in a single day. Macromolecules 2010, 43, 6625–6631, doi:10.1021/ma101242u.
  94. Ma, X.; Tang, J.; Shen, Y.; Fan, M.; Tang, H.; Radosz, M. Facile synthesis of polyester dendrimers from sequential click coupling of asymmetrical monomers. J. Am. Chem. Soc. 2009, 131, 14795–14803, doi:10.1021/ja9037406.
  95. Rosen, B.M.; Lligadas, G.; Hahn, C.; Percec, V. Synthesis of dendrimers through divergent iterative thio-bromo “click” chemistry. J. Polym. Sci. Part A 2009, 47, 3931–3939, doi:10.1002/pola.23519.
  96. In, I.; Kim, S.Y. Orthogonal synthesis of poly(aryl ether amide) dendrons. Macromolecules 2005, 38, 9399–9401, doi:10.1021/ma051538y.
  97. Kozaki, M.; Okada, K. Snowflake-like dendrimers via site-selective synthesis of dendrons. Org. Lett. 2004, 6, 485–488, doi:10.1021/ol036011p.
  98. Maraval, V.; Pyzowski, J.; Caminade, A.M.; Majoral, J.P. “Lego” chemistry for the straightforward synthesis of dendrimers. J. Org. Chem. 2003, 68, 6043–6046, doi:10.1021/jo0344438.
  99. Zhang, W.; Nowlan, D.T.; Thomson, L.M.; Lackowski, W.M.; Simanek, E.E. Orthogonal, convergent syntheses of dendrimers based on melamine with one or two unique surface sites for manipulation. J. Am. Chem. Soc. 2001, 123, 8914–8922, doi:10.1021/ja0041369.
  100. Leu, C.M.; Shu, C.F.; Teng, C.F.; Shiea, J. Dendritic poly(ether-imide)s: Synthesis, characterization, and modification. Polymer 2001, 42, 2339–2348, doi:10.1016/S0032-3861(00)00611-X.
  101. Wong, E.H.H.; Altintas, O.; Stenzel, M.H.; Barner-Kowollik, C.; Junkers, T. Nitrone-mediated radical coupling reactions: A new synthetic tool exemplified on dendrimer synthesis. Chem. Commun. 2011, 47, 5491–5493, doi:10.1039/c1cc10322a.
  102. Zeng, F.; Zimmerman, S.C. Rapid synthesis of dendrimers by an orthogonal coupling strategy. J. Am. Chem. Soc. 1996, 118, 5326–5327, doi:10.1021/ja960317s.
  103. Antoni, P.; Nyström, D.; Hawker, C.J.; Hult, A.; Malkoch, M. A chemoselective approach for the accelerated synthesis of well-defined dendritic architectures. Chem. Commun. 2007, 2249–2251.
  104. Montañez, M.I.; Campos, L.M.; Antoni, P.; Hed, Y.; Walter, M.V.; Krull, B.T.; Khan, A.; Hult, A.; Hawker, C.J.; Malkoch, M. Accelerated growth of dendrimers via thiol-ene and esterification reactions. Macromolecules 2010, 43, 6004–6013, doi:10.1021/ma1009935.
  105. Walter, M.V.; Lundberg, P.; Hult, A.; Malkoch, M. Novel macrothiols for the synthesis of a structurally comprehensive dendritic library using thiol-ene click chemistry. J. Polym. Sci. Part A 2011, 49, 2990–2995, doi:10.1002/pola.24742.
  106. Romagnoli, B.; Ashton, P.R.; Harwood, L.M.; Philp, D.; Price, D.W.; Smith, M.H.; Hayes, W. Synthesis and properties of polyaromatic dendrimers possessing a repetitive amide-ester coupling sequence. Tetrahedron 2003, 59, 3975–3988, doi:10.1016/S0040-4020(03)00466-6.
  107. Chen, G.J.; Kumar, J.; Gregory, A.; Stenzel, M.H. Efficient synthesis of dendrimers via a thiol-yne and esterification process and their potential application in the delivery of platinum anti-cancer drugs. Chem. Commun. 2009, 6291–6293.
  108. Maraval, V.; Caminade, A.M.; Majoral, J.P.; Blais, J.C. Dendrimer design: How to circumvent the dilemma of a reduction of steps or an increase of function multiplicity? Angew. Chem. Int. Ed. 2003, 42, 1822–1826, doi:10.1002/anie.200250827.
  109. Servin, P.; Rebout, C.; Laurent, R.; Peruzzini, M.; Caminade, A.M.; Majoral, J.P. Reduced number of steps for the synthesis of dense and highly functionalized dendrimers. Tetrahedron Lett. 2007, 48, 579–583, doi:10.1016/j.tetlet.2006.11.112.
  110. Maraval, V.; Laurent, R.; Marchand, P.; Caminade, A.M.; Majoral, J.P. Accelerated methods of synthesis of phosphorus-containing dendrimers. J. Organomet. Chem. 2005, 690, 2458–2471, doi:10.1016/j.jorganchem.2004.10.021.
  111. De Gennes, P.G.; Hervet, H. Statistics of starburst polymers. J. Phys. Lett. 1983, 44, L351–L360, doi:10.1051/jphyslet:01983004409035100.
  112. Hecht, S.; Fréchet, J.M.J. Dendritic encapsulation of function: Applying nature’s site isolation principle from biomimetics to materials science. Angew. Chem. Int. Ed. 2001, 40, 74–91, doi:10.1002/1521-3773(20010105)40:1<74::AID-ANIE74>3.0.CO;2-C.
  113. Bosman, A.W.; Janssen, H.M.; Meijer, E.W. About dendrimers: Structure, physical properties, and applications. Chem. Rev. 1999, 99, 1665–1688, doi:10.1021/cr970069y.
  114. Moreno, K.X.; Simanek, E.E. Conformational analysis of triazine dendrimers: Using NMR spectroscopy to probe the choreography of a dendrimer’s dance. Macromolecules 2008, 41, 4108–4114, doi:10.1021/ma702143f.
  115. Tanis, I.; Karatasos, K. Local dynamics and hydrogen bonding in hyperbranched aliphatic polyesters. Macromolecules 2009, 42, 9581–9591, doi:10.1021/ma901890f.
  116. Tanis, I.; Karatasos, K.; Assimopoulou, A.N.; Papageorgiou, V.P. Modeling of hyperbranched polyesters as hosts for the multifunctional bioactive agent shikonin. Phys. Chem. Chem. Phys. 2011, 13, 10808–10817, doi:10.1039/c1cp20271e.
  117. Chang, H.T.; Fréchet, J.M.J. Proton-transfer polymerization: A new approach to hyperbranched polymers. J. Am. Chem. Soc. 1999, 121, 2313–2314, doi:10.1021/ja983797r.
  118. Fréchet, J.M.J.; Henmi, M.; Gitsov, I.; Aoshima, S.; Leduc, M.R.; Grubbs, R.B. Self-condensing vinyl polymerization: An approach to dendritic materials. Science 1995, 269, 1080–1083, doi:10.1126/science.269.5227.1080.
  119. Suzuki, M.; Ii, A.; Saegusa, T. Multibranching polymerization: Palladium-catalyzed ring-opening polymerization of cyclic carbamate to produce hyperbranched dendritic polyamine. Macromolecules 1992, 25, 7071–7072, doi:10.1021/ma00051a055.
  120. Flory, P.J. Kinetics of condensation polymerization: The reaction of ethylene glycol with succinic acid. J. Am. Chem. Soc. 1937, 59, 466–470, doi:10.1021/ja01282a011.
  121. Flory, P.J. Molecular size distribution in three dimensional polymers. 6 branched polymers containing A-R-BF-1 type units. J. Am. Chem. Soc. 1952, 74, 2718–2723, doi:10.1021/ja01131a008.
  122. Mathias, L.J.; Carothers, T.W. Hyperbranched poly(siloxysilanes). J. Am. Chem. Soc. 1991, 113, 4043–4044, doi:10.1021/ja00010a084.
  123. Hunter, W.H.; Woollett, G.H. A catalytic decomposition of certain phenol silver salts. IV. The constitution of the amorphous oxides. J. Am. Chem. Soc. 1921, 43, 135–151, doi:10.1021/ja01434a018.
  124. Yoon, K.; Son, D.Y. Syntheses of hyperbranched poly(carbosilarylenes). Macromolecules 1999, 32, 5210–5216, doi:10.1021/ma9901902.
  125. Miravet, J.F.; Fréchet, J.M.J. New hyperbranched poly(siloxysilanes): Variation of the branching pattern and end-functionalization. Macromolecules 1998, 31, 3461–3468, doi:10.1021/ma971778g.
  126. Ihre, H.; Hult, A.; Söderlind, E. Synthesis, characterization, and H-1 NMR self-diffusion studies of dendritic aliphatic polyesters based on 2,2-bis(hydroxymethyl)propionic acid and 1,1,1-tris(hydroxyphenyl)ethane. J. Am. Chem. Soc. 1996, 118, 6388–6395, doi:10.1021/ja954171t.
  127. Ihre, H.; Padilla De Jesús, O.L.; Fréchet, J.M.J. Fast and convenient divergent synthesis of aliphatic ester dendrimers by anhydride coupling. J. Am. Chem. Soc. 2001, 123, 5908–5917, doi:10.1021/ja010524e.
  128. Malkoch, M.; Malmström, E.; Hult, A. Rapid and efficient synthesis of aliphatic ester dendrons and dendrimers. Macromolecules 2002, 35, 8307–8314, doi:10.1021/ma0205360.
  129. Parrott, M.C.; Benhabbour, S.R.; Saab, C.; Lemon, J.A.; Parker, S.; Valliant, J.F.; Adronov, A. Synthesis, radiolabeling, and bio-imaging of high-generation polyester dendrimers. J. Am. Chem. Soc. 2009, 131, 2906–2916, doi:10.1021/ja8078175.
  130. Twibanire, J.K.; Al-Mughaid, H.; Grindley, T.B. Synthesis of new cores and their use in the preparation of polyester dendrimers. Tetrahedron 2010, 66, 9602–9609, doi:10.1016/j.tet.2010.10.018.
  131. Knorr, R.; Trzeciak, A.; Bannwarth, W.; Gillessen, D. New coupling reagents in peptide chemistry. Tetrahedron Lett. 1989, 30, 1927–1930, doi:10.1016/S0040-4039(00)99616-3.
  132. Carpino, L.A. 1-Hydroxy-7-azabenzotriazole—An efficient peptide coupling additive. J. Am. Chem. Soc. 1993, 115, 4397–4398, doi:10.1021/ja00063a082.
  133. El-Faham, A.; Subirós-Funosas, R.; Prohens, R.; Albericio, F. Comu: A safer and more effective replacement for benzotriazole-based uronium coupling reagents. Chem. Eur. J. 2009, 15, 9404–9416, doi:10.1002/chem.200900615.
  134. Twibanire, J.K.; Grindley, T.B. Efficient and controllably selective preparation of esters using uronium-based coupling agents. Org. Lett. 2011, 13, 2988–2991, doi:10.1021/ol201005s.
  135. Bouillon, C.; Quelever, G.; Peng, L. Efficient synthesis of esters containing tertiary amine functionalities via active cyanomethyl ester intermediates. Tetrahedron Lett. 2009, 50, 4346–4349, doi:10.1016/j.tetlet.2009.05.034.
  136. Bouillon, C.; Tintaru, A.; Monnier, V.; Charles, L.; Quelever, G.; Peng, L. Synthesis of poly(amino)ester dendrimers via active cyanomethyl ester intermediates. J. Org. Chem. 2010, 75, 8685–8688, doi:10.1021/jo101739x.
  137. Robertson, S.A.; Ellman, J.A.; Schultz, P.G. A general and efficient route for chemical aminoacylation of transfer-RNAs. J. Am. Chem. Soc. 1991, 113, 2722–2729, doi:10.1021/ja00007a055.
  138. Ihre, H.R.; Padilla De Jesús, O.L.; Szoka, F.C.; Fréchet, J.M.J. Polyester dendritic systems for drug delivery applications: Design, synthesis, and characterization. Bioconjugate Chem. 2002, 13, 443–452, doi:10.1021/bc010102u.
  139. Greenwald, R.B.; Conover, C.D.; Choe, Y.H. Poly(ethylene glycol) conjugated drugs and prodrugs: A comprehensive review. Crit. Rev. Ther. Drug Carr. Syst. 2000, 17, 101–161.
  140. Kapitza, H.; Zentel, R.; Twieg, R.J.; Nguyen, C.; Vallerien, S.U.; Kremer, F.; Willson, C.G. Ferroelectric liquid-crystalline polysiloxanes with high spontaneous polarization and possible applications in nonlinear optics. Adv. Mater. 1990, 2, 539–543, doi:10.1002/adma.19900021106.
  141. Keller, P.; Shao, R.F.; Walba, D.M.; Brunet, M. The first high polarization ferroelectric main-chain liquid-crystalline polymers. Liq. Cryst. 1995, 18, 915–918, doi:10.1080/02678299508036710.
  142. Walba, D.M.; Keller, P.; Shao, R.F.; Clark, N.A.; Hillmyer, M.; Grubbs, R.H. Main-chain ferroelectric liquid crystal oligomers by acyclic diene metathesis polymerization. J. Am. Chem. Soc. 1996, 118, 2740–2741, doi:10.1021/ja953779z.
  143. Hermann, D.S.; Hult, A.; Komitov, L.; Lagerwall, S.T.; Lindgren, M. Pyroelectric polymers for nonlinear optics. Ferroelectrics 1998, 213, 405–415.
  144. Hermann, D.S.; Hult, A.; Komitov, L.; Lagerwall, S.T.; Sahlen, F.; Trollsås, M. The influence of chiral strength on the spontaneous polarization and the second-order nonlinear optical susceptibility in ferroelectric liquid crystals. Ferroelectrics 1998, 213, 417–427.
  145. Busson, P.; Ihre, H.; Hult, A. Synthesis of a novel dendritic liquid crystalline polymer showing a ferroelectric SmC* phase. J. Am. Chem. Soc. 1998, 120, 9070–9071, doi:10.1021/ja9813562.
  146. Hedrick, J.L.; Trollsås, M.; Hawker, C.J.; Atthoff, B.; Claesson, H.; Heise, A.; Miller, R.D.; Mecerreyes, D.; Jérôme, R.; Dubois, P. Dendrimer-like star block and amphiphilic copolymers by combination of ring opening and atom transfer radical polymerization. Macromolecules 1998, 31, 8691–8705, doi:10.1021/ma980932b.
  147. Kato, M.; Kamigaito, M.; Sawamoto, M.; Higashimura, T. Polymerization of methyl-methacrylate with the carbon-tetrachloride dichlorotris(triphenylphosphine) ruthenium(II) methylaluminum bis(2,6-di-tert-butylphenoxide) initiating system—Possibility of living radical polymerization. Macromolecules 1995, 28, 1721–1723, doi:10.1021/ma00109a056.
  148. Wang, J.S.; Matyjaszewski, K. Controlled living radical polymerization—Atom-transfer radical polymerization in the presence of transition-metal complexes. J. Am. Chem. Soc. 1995, 117, 5614–5615, doi:10.1021/ja00125a035.
  149. Annby, U.; Malmberg, M.; Pettersson, B.; Rehnberg, N. Benzylidene protected bis-MPA—A convenient dendrimer building block. Tetrahedron Lett. 1998, 39, 3217–3220, doi:10.1016/S0040-4039(98)00395-5.
  150. Trollsås, M.; Atthoff, B.; Claesson, H.; Hedrick, J.L. Hyperbranched poly(epsilon-caprolactone)s. Macromolecules 1998, 31, 3439–3445, doi:10.1021/ma980241f.
  151. Hao, X.J.; Nilsson, C.; Jesberger, M.; Stenzel, M.H.; Malmström, E.; Davis, T.P.; Östmark, E.; Barner-Kowollik, C. Dendrimers as scaffolds for multifunctional reversible addition-fragmentation chain transfer agents: Syntheses and polymerization. J. Polym. Sci. Part A 2004, 42, 5877–5890, doi:10.1002/pola.20434.
  152. Wang, L.L.; Meng, Z.L.; Yu, Y.L.; Meng, Q.W.; Chen, D.Z. Synthesis of hybrid linear-dendritic block copolymers with carboxylic functional groups for the biomimetic mineralization of calcium carbonate. Polymer 2008, 49, 1199–1210, doi:10.1016/j.polymer.2008.01.023.
  153. Parrott, M.C.; Marchington, E.B.; Valliant, J.F.; Adronov, A. Synthesis and properties of carborane-functionalized aliphatic polyester dendrimers. J. Am. Chem. Soc. 2005, 127, 12081–12089, doi:10.1021/ja053730l.
  154. Gillies, E.R.; Fréchet, J.M.J. Designing macromolecules for therapeutic applications: Polyester dendrimer-poly(ethylene oxide) “bow-tie” hybrids with tunable molecular weight and architecture. J. Am. Chem. Soc. 2002, 124, 14137–14146, doi:10.1021/ja028100n.
  155. Vestberg, R.; Nystrom, A.; Lindgren, M.; Malmström, E.; Hult, A. Porphyrin-cored 2,2-bis(methylol)propionic acid dendrimers. Chem. Mater. 2004, 16, 2794–2804, doi:10.1021/cm035354e.
  156. Nishiyama, N.; Stapert, H.R.; Zhang, G.D.; Takasu, D.; Jiang, D.L.; Nagano, T.; Aida, T.; Kataoka, K. Light-harvesting ionic dendrimer porphyrins as new photosensitizers for photodynamic therapy. Bioconjugate Chem. 2003, 14, 58–66, doi:10.1021/bc025597h.
  157. Armstrong, N.R. Phthalocyanines and porphyrins as materials. J. Porphyrins Phthalocyanines 2000, 4, 414–417, doi:10.1002/(SICI)1099-1409(200006/07)4:4<414::AID-JPP247>3.0.CO;2-B.
  158. Krivokapic, A.; Anderson, H.L.; Bourhill, G.; Ives, R.; Clark, S.; McEwan, K.J. Meso-tetra-alkynyl porphyrins for optical limiting—A survey of group III and IV metal complexes. Adv. Mater. 2001, 13, 652–656, doi:10.1002/1521-4095(200105)13:9<652::AID-ADMA652>3.0.CO;2-3.
  159. Finikova, O.; Galkin, A.; Rozhkov, V.; Cordero, M.; Hagerhall, C.; Vinogradov, S. Porphyrin and tetrabenzoporphyrin dendrimers: Tunable membrane-impermeable fluorescent pH nanosensors. J. Am. Chem. Soc. 2003, 125, 4882–4893, doi:10.1021/ja0341687.
  160. Pollak, K.W.; Sanford, E.M.; Fréchet, J.M.J. Comparison of two convergent routes for the preparation of metalloporphyrin-core dendrimers: Direct condensation vs. chemical modification. J. Mater. Chem. 1998, 8, 519–527, doi:10.1039/a705410f.
  161. Pollak, K.W.; Leon, J.W.; Fréchet, J.M.J.; Maskus, M.; Abruna, H.D. Effects of dendrimer generation on site isolation of core moieties: Electrochemical and fluorescence quenching studies with metalloporphyrin core dendrimers. Chem. Mater. 1998, 10, 30–38, doi:10.1021/cm970312+.
  162. Maes, W.; Amabilino, D.B.; Dehaen, W. Synthesis of novel dendrimers containing pyrimidine units. Tetrahedron 2003, 59, 3937–3943, doi:10.1016/S0040-4020(03)00462-9.
  163. Capitosti, G.J.; Guerrero, C.D.; Binkley, D.E.; Rajesh, C.S.; Modarelli, D.A. Efficient synthesis of porphyrin-containing, benzoquinone-terminated, rigid polyphenylene dendrimers. J. Org. Chem. 2003, 68, 247–261, doi:10.1021/jo026520p.
  164. Yeow, E.K.L.; Ghiggino, K.P.; Reek, J.N.H.; Crossley, M.J.; Bosman, A.W.; Schenning, A.; Meijer, E.W. The dynamics of electronic energy transfer in novel multiporphyrin functionalized dendrimers: A time-resolved fluorescence anisotropy. J. Phys. Chem. B 2000, 104, 2596–2606, doi:10.1021/jp993116u.
  165. Rajesh, C.S.; Capitosti, G.J.; Cramer, S.J.; Modarelli, D.A. Photoinduced electron-transfer within free base and zinc porphyrin containing poly(amide) dendrimers. J. Phys. Chem. B 2001, 105, 10175–10188, doi:10.1021/jp010575y.
  166. Jiang, D.L.; Aida, T. Morphology-dependent photochemical events in aryl ether dendrimer porphyrins: Cooperation of dendron subunits for singlet energy transduction. J. Am. Chem. Soc. 1998, 120, 10895–10901, doi:10.1021/ja9823520.
  167. Matos, M.S.; Hofkens, J.; Verheijen, W.; De Schryver, F.C.; Hecht, S.; Pollak, K.W.; Fréchet, J.M.J.; Forier, B.; Dehaen, W. Effect of core structure on photophysical and hydrodynamic properties of porphyrin dendrimers. Macromolecules 2000, 33, 2967–2973, doi:10.1021/ma991786s.
  168. Kimura, M.; Shiba, T.; Yamazaki, M.; Hanabusa, K.; Shirai, H.; Kobayashi, N. Construction of regulated nanospace around a porphyrin core. J. Am. Chem. Soc. 2001, 123, 5636–5642, doi:10.1021/ja004312d.
  169. Galie, K.M.; Mollard, A.; Zharov, I. Polyester-based carborane-containing dendrons. Inorg. Chem. 2006, 45, 7815–7820, doi:10.1021/ic060866r.
  170. Baars, M.; Meijer, E.W. Host-guest chemistry of dendritic molecules. Dendrimers Ii 2000, 210, 131–182, doi:10.1007/3-540-46577-4_3.
  171. Baars, M.; Karlsson, A.J.; Sorokin, V.; de Waal, B.F.W.; Meijer, E.W. Supramolecular modification of the periphery of dendrimers resulting in rigidity and functionality. Angew. Chem. Int. Ed. 2000, 39, 4262–4265, doi:10.1002/1521-3773(20001201)39:23<4262::AID-ANIE4262>3.0.CO;2-Y.
  172. Gillies, E.R.; Fréchet, J.M.J. Synthesis and self-assembly of supramolecular dendritic “Bow-Ties”: Effect of peripheral functionality on association constants. J. Org. Chem. 2004, 69, 46–53, doi:10.1021/jo035329s.
  173. Bell, J.A.; Kenworthy, C. Cyanoethylation of some alkanolamines. Synthesis 1971, 650–652.
  174. Goodwin, A.P.; Lam, S.S.; Fréchet, J.M.J. Rapid, efficient synthesis of heterobifunctional biodegradable dendrimers. J. Am. Chem. Soc. 2007, 129, 6994–6995, doi:10.1021/ja071530z.
  175. Burgel, T.; Fedtke, M.; Franzke, M. Reaction of cyclic carbonates with amines—Linear telechelic oligomers. Polym. Bull. 1993, 30, 155–162, doi:10.1007/BF00296844.
  176. Ochiai, B.; Satoh, Y.; Endo, T. Nucleophilic polyaddition in water based on chemo-selective reaction of cyclic carbonate with amine. Green Chem. 2005, 7, 765–767, doi:10.1039/b511019j.
  177. Gurr, P.A.; Qiao, G.G.; Solomon, D.H.; Harton, S.E.; Spontak, R.J. Synthesis, characterization, and direct observation of star microgels. Macromolecules 2003, 36, 5650–5654, doi:10.1021/ma030122m.
  178. Bosman, A.W.; Vestberg, R.; Heumann, A.; Fréchet, J.M.J.; Hawker, C.J. A modular approach toward functionalized three-dimensional macromolecules: From synthetic concepts to practical applications. J. Am. Chem. Soc. 2003, 125, 715–728, doi:10.1021/ja028392s.
  179. Lord, H.T.; Quinn, J.F.; Angus, S.D.; Whittaker, M.R.; Stenzel, M.H.; Davis, T.P. Microgel stars via reversible addition fragmentation chain transfer (RAFT) polymerisation—A facile route to macroporous membranes, honeycomb patterned thin films and inverse opal substrates. J. Mater. Chem. 2003, 13, 2819–2824, doi:10.1039/b304208c.
  180. Wiltshire, J.T.; Qiao, G.G. Synthesis of core cross-linked star polymers with adjustable coronal properties. Macromolecules 2008, 41, 623–631, doi:10.1021/ma071651j.
  181. Wiltshire, J.T.; Qiao, G.G. Selectively degradable core cross-linked star polymers. Macromolecules 2006, 39, 9018–9027, doi:10.1021/ma0622027.
  182. Hawker, C.J.; Wooley, K.L. The convergence of synthetic organic and polymer chemistries. Science 2005, 309, 1200–1205, doi:10.1126/science.1109778.
  183. Abrol, S.; Kambouris, P.A.; Looney, M.G.; Solomon, D.H. Studies on microgels. 3. Synthesis using living free radical polymerization. Macromol. Rapid Commun. 1997, 18, 755–760, doi:10.1002/marc.1997.030180901.
  184. Baek, K.Y.; Kamigaito, M.; Sawamoto, M. Star-shaped polymers by metal-catalyzed living radical polymerization. 1. Design of Ru(II)-based systems and divinyl linking agents. Macromolecules 2001, 34, 215–221, doi:10.1021/ma000751l.
  185. Connal, L.A.; Vestberg, R.; Hawker, C.J.; Qiao, G.G. Synthesis of dendron functionalized core cross-linked star polymers. Macromolecules 2007, 40, 7855–7863, doi:10.1021/ma070661h.
  186. Kose, M.M.; Yesilbag, G.; Sanyal, A. Segment block dendrimers via Diels-Alder cycloaddition. Org. Lett. 2008, 10, 2353–2356, doi:10.1021/ol800553t.
  187. McElhanon, J.R.; Wheeler, D.R. Thermally responsive dendrons and dendrimers based on reversible furan-maleimide Diels-Alder adducts. Org. Lett. 2001, 3, 2681–2683, doi:10.1021/ol0101281.
  188. Szalai, M.L.; McGrath, D.V.; Wheeler, D.R.; Zifer, T.; McElhanon, J.R. Dendrimers based on thermally reversible furan-maleimide Diels-Alder adducts. Macromolecules 2007, 40, 818–823, doi:10.1021/ma062093w.
  189. Kawa, M.; Fréchet, J.M.J. Enhanced luminescence of lanthanide within lanthanide-cored dendrimer complexes. Thin Solid Films 1998, 331, 259–263, doi:10.1016/S0040-6090(98)00928-6.
  190. Kawa, M.; Fréchet, J.M.J. Self-assembled lanthanide-cored dendrimer complexes: Enhancement of the luminescence properties of lanthanide ions through site-isolation and antenna effects. Chem. Mater. 1998, 10, 286–296, doi:10.1021/cm970441q.
  191. Antoni, P.; Malkoch, M.; Vamvounis, G.; Nyström, D.; Nyström, A.; Lindgren, M.; Hult, A. Europium confined cyclen dendrimers with photophysically active triazoles. J. Mater. Chem. 2008, 18, 2545–2554, doi:10.1039/b802197j.
  192. Tornoe, C.W.; Christensen, C.; Meldal, M. Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. J. Org. Chem. 2002, 67, 3057–3064, doi:10.1021/jo011148j.
  193. Kolb, H.C.; Finn, M.G.; Sharpless, K.B. Click chemistry: Diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 2001, 40, 2004–2021, doi:10.1002/1521-3773(20010601)40:11<2004::AID-ANIE2004>3.0.CO;2-5.
  194. Mekelburger, H.B.; Rissanen, K.; Vögtle, F. Repetitive synthesis of bulky dendrimers—A reversibly photoactive dendrimer with six azobenzene side-chains. Chem. Berichte 1993, 126, 1161–1169, doi:10.1002/cber.19931260516.
  195. Momotake, A.; Arai, T. Photochemistry and photophysics of stilbene dendrimers and related compounds. J. Photochem. Photobiol. C 2004, 5, 1–25, doi:10.1016/j.jphotochemrev.2004.01.001.
  196. Liao, L.X.; Stellacci, F.; McGrath, D.V. Photoswitchable flexible and shape-persistent dendrimers: Comparison of the interplay between a photochromic azobenzene core and dendrimer structure. J. Am. Chem. Soc. 2004, 126, 2181–2185, doi:10.1021/ja036418p.
  197. Puntoriero, F.; Ceroni, P.; Balzani, V.; Bergamini, G.; Vögtle, F. Photoswitchable dendritic hosts: A dendrimer with peripheral azobenzene groups. J. Am. Chem. Soc. 2007, 129, 10714–10719, doi:10.1021/ja070636r.
  198. Gabriel, C.J.; Parquette, J.R. Expanding dendrons. The photoisomerism of folded azobenzene dendrons. J. Am. Chem. Soc. 2006, 128, 13708–13709, doi:10.1021/ja066126z.
  199. Kumar, G.S.; Neckers, D.C. Photochemistry of azobenzene-containing polymers. Chem. Rev. 1989, 89, 1915–1925, doi:10.1021/cr00098a012.
  200. Yagai, S.; Karatsu, T.; Kitamura, A. Photocontrollable self-assembly. Chem. Eur. J. 2005, 11, 4054–4063, doi:10.1002/chem.200401323.
  201. Barrett, C.J.; Mamiya, J.I.; Yager, K.G.; Ikeda, T. Photo-mechanical effects in azobenzene-containing soft materials. Soft Matter 2007, 3, 1249–1261, doi:10.1039/b705619b.
  202. Yager, K.G.; Barrett, C.J. Photomechanical surface patterning in azo-polymer materials. Macromolecules 2006, 39, 9320–9326, doi:10.1021/ma061733s.
  203. Tuuttila, T.; Lipsonen, J.; Lahtinen, M.; Huuskonen, J.; Rissanen, K. Synthesis and characterization of chiral azobenzene dye functionalized Janus dendrimers. Tetrahedron 2008, 64, 10590–10597, doi:10.1016/j.tet.2008.08.078.
  204. Tuuttila, T.; Lipsonen, J.; Huuskonen, J.; Rissanen, K. Synthesis and characterization of polyene chromophores with hydroxyl functionalization. Dyes Pigment. 2008, 77, 357–362, doi:10.1016/j.dyepig.2007.06.003.
  205. Yokoyama, S.; Nakahama, T.; Otomo, A.; Mashiko, S. Intermolecular coupling enhancement of the molecular hyperpolarizability in multichromophoric dipolar dendrons. J. Am. Chem. Soc. 2000, 122, 3174–3181, doi:10.1021/ja993569c.
  206. Abram, U.; Alberto, R. Technetium and rhenium—Coordination chemistry and nuclear medical applications. J. Braz. Chem. Soc. 2006, 17, 1486–1500, doi:10.1590/S0103-50532006000800004.
  207. Kim, S.K.; Lee, S.B. Highly encoded one-dimensional nanostructures for rapid sensing. J. Mater. Chem. 2009, 19, 1381–1389, doi:10.1039/b814408g.
  208. Finkel, N.H.; Lou, X.H.; Wang, C.Y.; He, L. Barcoding the microworld. Anal. Chem. 2004, 76, 353A–359A.
  209. White, K.A.; Chengelis, D.A.; Gogick, K.A.; Stehman, J.; Rosi, N.L.; Petoud, S. Near-infrared luminescent lanthanide MOF barcodes. J. Am. Chem. Soc. 2009, 131, 18069–18071, doi:10.1021/ja907885m.
  210. Yeniad, B.; Naik, H.; Amir, R.J.; Koning, C.E.; Hawker, C.J.; Heise, A. Encoded dendrimers with defined chiral composition via ‘click’ reaction of enantiopure building blocks. Chem. Commun. 2011, 47, 9870–9872, doi:10.1039/c1cc12434j.
  211. Duxbury, C.J.; Hilker, I.; de Wildeman, S.M.A.; Heise, A. Enzyme-responsive materials: Chirality to program polymer reactivity. Angew. Chem. Int. Ed. 2007, 46, 8452–8454, doi:10.1002/anie.200702438.
  212. Vestberg, R.; Malkoch, M.; Kade, M.; Wu, P.; Fokin, V.V.; Sharpless, K.B.; Drockenmuller, E.; Hawker, C.J. Role of architecture and molecular weight in the formation of tailor-made ultrathin multilayers using dendritic macromolecules and click chemistry. J. Polym. Sci. Part A 2007, 45, 2835–2846.
  213. Carnahan, M.A.; Grinstaff, M.W. Synthesis and characterization of poly(glycerol-succinic acid) dendrimers. Macromolecules 2001, 34, 7648–7655, doi:10.1021/ma010848n.
  214. Carnahan, M.A.; Grinstaff, M.W. Synthesis of generational polyester dendrimers derived from glycerol and succinic or adipic acid. Macromolecules 2006, 39, 609–616, doi:10.1021/ma0518407.
  215. Oelker, A.M.; Grinstaff, M.W. Ophthalmic adhesives: A materials chemistry perspective. J. Mater. Chem. 2008, 18, 2521–2536, doi:10.1039/b719791h.
  216. Oelker, A.M.; Berlin, J.A.; Wathier, M.; Grinstaff, M.W. Synthesis and characterization of dendron cross-linked PEG hydrogels as corneal adhesives. Biomacromolecules 2011, 12, 1658–1665, doi:10.1021/bm200039s.
  217. Söntjens, S.H.M.; Nettles, D.L.; Carnahan, M.A.; Setton, L.A.; Grinstaff, M.W. Biodendrimer-based hydrogel scaffolds for cartilage tissue repair. Biomacromolecules 2006, 7, 310–316, doi:10.1021/bm050663e.
  218. Berdahl, J.P.; Johnson, C.S.; Proia, A.D.; Grinstaff, M.W.; Kim, T. Comparison of sutures and dendritic polymer adhesives for corneal laceration repair in an in vivo chicken model. Arch. Ophthalmol. 2009, 127, 442–447, doi:10.1001/archophthalmol.2008.582.
  219. Twibanire, J.K.; Al-Mughaid, H.; MacIsaac, E.; Huesis, M.; Grindley, T.B.. Unpublished results.
  220. Hirayama, Y.; Sakamoto, Y.; Yamaguchi, K.; Sakamoto, S.; Iwamura, M. Synthesis of polyester dendrimers and dendrons starting from Michael reaction of acrylates with 3-hydroxyacetophenone. Tetrahedron Lett. 2005, 46, 1027–1030, doi:10.1016/j.tetlet.2004.12.004.
  221. Hirayama, Y.; Nakamura, T.; Uehara, S.; Sakamoto, Y.; Yamaguchi, K.; Sei, Y.; Iwamura, M. Synthesis and characterization of polyester dendrimers from acetoacetate and acrylate. Org. Lett. 2005, 7, 525–528, doi:10.1021/ol0482184.
  222. Bo, Z.S.; Zhang, X.; Zhang, C.M.; Wang, Z.Q.; Yang, M.L.; Shen, J.C.; Ji, Y.P. Rapid synthesis of polyester dendrimers. J. Chem. Soc. Perkin Trans. 1 1997, 2931–2935.
  223. Bo, Z.S.; Zhang, W.K.; Zhang, X.; Zhang, C.M.; Shen, J.C. Synthesis and properties of polyester dendrimers bearing carbazole groups in their periphery. Macromol. Chem. Phys. 1998, 199, 1323–1327, doi:10.1002/(SICI)1521-3935(19980701)199:7<1323::AID-MACP1323>3.0.CO;2-J.
  224. Do, J.Y.; Park, S.K.; Ju, J.J.; Park, S.; Lee, M.H. Electro-optic materials: Hyperbranched chromophores attached linear polyimide and dendritic polyesters. Polym. Adv. Technol. 2005, 16, 221–226, doi:10.1002/pat.554.
  225. Do, J.Y.; Jung, J.J. Polyester dendrimers carrying NLO chromophores: Synthesis and optical characterization. Macromol. Chem. Phys. 2005, 206, 1326–1331, doi:10.1002/macp.200400547.
  226. Romagnoli, B.; van Baal, I.; Price, D.W.; Harwood, L.M.; Hayes, W. Chiral poly(aromatic amide ester) dendrimers bearing an amino acid derived C-3-symmetric core—Synthesis and properties. Eur. J. Org. Chem. 2004, 4148–4157.
  227. Campbell, A.D.; Raynham, T.M.; Taylor, R.J.K. A simplified route to the (R)-Garner aldehyde and (S)-vinyl glycinol. Synthesis 1998, 1707–1709.
  228. Rosen, B.M.; Lligadas, G.; Hahn, C.; Percec, V. Synthesis of dendritic macromolecules through divergent iterative thio-bromo “click” chemistry and SET-LRP. J. Polym. Sci. Part A 2009, 47, 3940–3948, doi:10.1002/pola.23518.
Polymers EISSN 2073-4360 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert