Dendrophanes: Water-Soluble Dendritic Receptors. Preliminary communication

The dendritic cyclophanes (dendrophanes ) 1–3 containing a [6.1.6.1]paracyclophane as the initiator core embedded in dendritic poly(ether-amide) shells of first ( 1 ), second ( 2 ), and third ( 3 ) generation were prepared and characterized. The X-ray crystal-structure analyses of esters 7 and 4 , derivatives of cyclophane core 9 and first-generation dendrophane 1 , respectively, displayed open cavity binding sites suitable for the inclusion complexation of aromatic substrates. With their carboxylate surface groups, dendrophanes 1–3 were readily soluble in aqueous phosphate buffer (pH 8.0), and the complexation of naphthalene derivatives was investigated by ¹H-NMR and fluorescence titrations. The binding studies demonstrated that the cyclophane cavity remains open and accessible to appropriate substrates even at higher dendritic generations. The 1:1 complexes formed in aqueous buffer were of similar stability to those formed by the unbranched core 9 (K_a between 1000 and 10000 1 mol^?1, 300 K). Investigations with the fluorescent probe 6-(p-toluidino)naphthalene-2-sulfonate ( 12 ) showed that the micropolarity at the dendrophane core decreases with increasing generation number.     

Catalytic Dendrophanes as Enzyme Mimics: Synthesis,Binding Properties,Micropolarity Effect,and Catalytic Activity of Dendritic Thiazolio-cyclophanes

Catalytic dendrophanes 9 and 10 were prepared as functional mimics of the thiamine-diphosphate-dependent enzyme pyruvate oxidase, and studied as catalysts in the oxidation of naphthalene-2-carbaldehyde ( 4 ) to methyl naphthalene-2-carboxylate ( 8 ) (Scheme 1). They are composed of a thiazolio-cyclophane initiator core with four generation 2 (G-2) poly(etheramide) dendrons attached. The two dendrophanes were synthesized by a convergent growth strategy by coupling dendrons 11 and 12 , respectively (Scheme 2) with (chloromethyl)-cyclophane 42 (Scheme 5) and subsequent conversion with 4-methylthiazole (Scheme 7). The X-ray crystal structures of cyclophane precursors 30 (Scheme 3), 37 , and 38 (Scheme 5) on the way to dendrophanes were determined (Fig. 1). The crystal-structure analysis of the benzene clathrate of 37 revealed the formation of channel-like stacks by the cyclophane which incorporate its morpholinomethyl side chain and the enclathrated benzene molecule (Fig. 2). The interactions of the enclathrated benzene molecule with the phenyl rings of the two adjacent cyclophane molecules in the stack closely resemble those between neighboring benzene molecules in crystalline benzene (Fig. 3). The characterization by MALDI-TOF-MS (Fig. 4), and ¹H- and ¹³C-NMR spectroscopy (Fig. 5) proved the monodispersity of the G-2 dendrophanes 9 and 10 with molecular weights up to 11500 Da (for 10 ). ¹H-NMR and fluorescence binding titrations in H₂O and aqueous MeOH showed that 9 and 10 form stable 1 : 1 complexes with naphthalene-2-carbaldehyde ( 4 ) and 6-(p-toluidino)naphthalene-2-sulfonate ( 48 , TNS) (Tables 1 and 2). The evaluation of the fluorescence emission maxima of bound TNS revealed that the dendritic branching creates a microenvironment of distinctly reduced polarity at the cyclophane core by limiting its exposure to bulk solvent. Initial rate studies for the oxidation of naphthalene-2-carbaldehyde to methyl naphthalene-2-carboxylate in basic aqueous MeOH in the presence of flavin derivative 6 revealed only a weak catalytic activity of dendrophanes 9 and 10 (Table 3), despite the favorable micropolarity at the cyclophane active site. The low catalytic activity in the interior of the macromolecules was explained by steric hindrance of reaction transition states by the dendritic branches.     

New Cyclophanes as Initiator Cores for the Construction of Dendritic Receptors: Host-guest complexation in aqueous solutions and structures of solid-state inclusion compounds

Cyclophanes 3 and 4 were prepared as initiator cores for the construction of dendrophanes (dendritic cydophanes) 1 and 2 , respectively, which mimic recognition sites buried in globular proteins. The tetra-oxy[6.1.6.1]paracyclophane 3 was prepared by a short three-step route (Scheme 1) and possesses a cavity binding site shaped by two diphenylmethane units suitable for the inclusion of flat aromatic substrates such as benzene and naphthalene derivatives as was shown by ¹H-NMR binding titrations in basic D₂O phosphate buffer (Table 1). The larger cyclophane 4 , shaped by two wider naphthyl(phenyl)methane spacers, was prepared in a longer, ten-step synthesis (Scheme 2) which included as a key intermediate the tetrabromocyclophane 5 . ¹H-NMR Binding studies in basic borate buffer in D₂O/CD₃OD demonstrated that 4 is an efficient steroid receptor. In a series of steroids (Table 1), complexation strength decreased with increasing substrate polarity and increasing number of polar substituents; in addition, electrostatic repulsion between carboxylate residues of host and guest also affected the binding affinity strongly. The conformationally flexible tetrabromocyclophane 5 displayed a pronounced tendency to form solid-state inclusion compounds of defined stoichiometry, which were analyzed by X-ray crystallography (Fig. 2). 1,2-Dichloroethane formed a cavity inclusion complex 5a with 1:1 stoichiometry, while in the 1:3 inclusion compound 5b with benzene, one guest is fully buried in the macrocyclic cavity and two others are positioned in channels between the Cyclophanes in the crystal lattice. In the 1:2 inclusion compound 5c , two toluene molecules penetrate with their aromatic rings the macrocyclic cavity from opposite sides in an antiparallel fashion. On the other hand, p-xylene (= 1,4-dimethylbenzene) in the 1:1 compound 5d is sandwiched between the cyclophane molecules with its two Me groups penetrating the cavities of the two macrocycles. In the 1:2 inclusion compound 5e with tetralin (= 1,2,3,4-tetrahydronaphthalene), both host and guest are statically disordered. The shape of the macrocycle in 5a – e depends strongly on the nature of the guest (Fig. 4). Characteristic for these compounds is the pronounced tendency of 5 to undergo regular stacking and to form channels for guest inclusion; these channels can infinitely extend across the macrocyclic cavities (Fig. 6) or in the crystal lattice between neighboring cyclophane stacks (Fig. 5). Also, the crystal lattice of 5c displays a remarkable zig-zag pattern of short Br…?O contacts between neighboring macrocycles (Fig. 7).     

Dendrophanes: Novel Steroid-Recognizing Dendritic Receptors. Preliminary Communication

The H₂O-soluble dendritic cyclophanes (dendrophanes) 3–5 of first to third generation with molecular weights up to nearly 20 kD were synthesized, purified, and characterized. Cyclophane 2 , which served as the initiator core (generation zero), was prepared from tetrabromocyclophane 10 in a four-step sequence which involved as the first transformation a high-yielding, four-fold Pd(0)-catalyzed Suzuki cross-coupling reaction with 4-(benzyloxy)-phenyl-boronic acid to give 18 . The X-ray crystal-structure analysis of tetrabromocyclophane 10 displayed an open, nearly rectangular box with opposite aromatic walls being 8.3 and 11.4 Å apart and of suitable size for the incorporation of steroidal substrates. ¹H-NMR Binding titrations in borate-buffered D₂O/CD₃OD 1:1 showed that cyclophane-tetracarboxylate 2 forms 1:1 inclusion complexes with steroids (Table 2). Complexation was found to be enthalpically driven with higher binding affinities measured for the more apolar substrates. ¹H-NMR Titrations in the same solvent also provided clear evidence for core-selective complexation of testosterone ( 21 ) by the dendrophanes 3 (1st), 4 (2nd), and 5 (3rd generation) carrying up to 108 carboxylate surface groups. The stability of the corresponding 1:1 complexes was hardly affected by the size of the dendritic shell, although some generation-dependent conformational changes in the receptor cavity seemed to take place. Remarkably, host-guest exchange kinetics in all recognition processes were fast on the ¹H-NMR time scale.     

Cyclophane-lectin Conjugates as a New Class of Water-soluble Host

A conjugate composed of tetraaza[6.1.6.1]paracyclophane bearing carboxylic acids and lectin, a carbohydrate binding protein, was prepared. The specific saccharide-binding abilities as well as the secondary structural features of the lectin were not disturbed, when the cyclophane were covalently bound to the lectin. The conjugate was found to act as a water-soluble host for inclusion of anionic guest molecules such as 6-p-toluidino-naphthalene-2-sulfonate (TNS) and 8-anilinonaphthalene-1-sulfonate (ANS) in aqueous acetate buffer (pH 4.0) with binding constants of 4.2 × 10⁴ and 1.5 × 10⁴ dm³ mol⁻¹, respectively. The obtained binding constants were much larger than those by untethered water-soluble cyclophane. A highly desolvated microenvironment was provided by the cyclophane cavity on the protein surfaces so that the tight host–guest interaction, which brought about the marked motional repression of the entrapped guests, became effective. The conjugate also showed molecular discrimination capabilities toward the anionic guests through electrostatic repulsion mechanism originating from acid-dissociation equilibrium of carboxylic acids of the cyclophane branches.     

Macrotricyclic Steroid Receptors by Pd°-Catalyzed Cross-Coupling Reactions: Dissolution of cholesterol in aqueous solution and investigations of the principles governing selective molecular recognition of steroidal substrates

Three double-decker cyclophane receptors, (±)- 2 , (±)- 3 , and (±)- 4 with 11–13-Å deep hydrophobic cavities were prepared and their steroid-binding properties investigated in aqueous and methanolic solutions. Pd°-Catalyzed cross-coupling reactions were key steps in the construction of these novel macrotricyclic structures. In the synthesis of D₂-symmetrical (±)- 2 , the double-decker precursor (±)- 7 was obtained in 14% yield by fourfold Stille coupling of equimolar amounts of bis(tributylstannyl)acetylene with dibromocyclophane 5 (Scheme 1). For the preparation of the macrotricyclic precursor (±)- 15 of D₂-symmetrical (±)- 3 , diiodocylophane 12 was dialkynylated with Me₃SiC?CH to give 13 using the Sonogashira cross-coupling reaction; subsequent alkyne deprotection yielded the diethynylated cyclophane 14 , which was transformed in 42% yield into (±)- 15 by Glaser-Hay macrocyclization (Scheme 2). The synthesis of the C₂-symmetrical conical receptor (±)- 4 was achieved via the macrotricyclic precursor (±)- 25 , which was prepared in 20% yield by the Hiyama cross-coupling reaction between the diiodo[6.1.6.1]paracyclophane 19 and the larger, dialkynylated cyclophane 17 (Scheme 4). Solid cholesterol was efficiently dissolved in water through complexation by (±)- 2 and (±)- 3 , and the association constants of the formed 1:1 inclusion complexes were determined by solid-liquid extraction as K_a = 1.1 × 10⁶ and 1.5 × 10⁵ l mol^?1, respectively (295 K) (Table 1). The steroid-binding properties of the three receptors were analyzed in detail by ¹H-NMR binding titrations in CD₃OD. Observed steroid-binding selectivities between the two structurally closely related cylindrical receptors (±)- 2 and (±)- 3 (Table 2) were explained by differences in cavity width and depth, which were revealed by computer modeling (Fig. 4). Receptor (±)- 2 , with two ethynediyl tethers linking the two cyclophanes, possesses a shallower cavity and, therefore, is specific for flatter steroids with a C(5)?C(6) bond, such as cholesterol. In contrast, receptor (±)- 3 , constructed with longer buta-1,3-diynediyl linkers, has a deeper and wider hydrophobic cavity and prefers fully saturated steroids with an aliphatic side chain, such as 5α-cholestane (Fig. 7). In the 1:1 inclusion complexes formed by the conical receptor (±)- 4 (Table 3), testosterone or progesterone penetrate the binding site from the wider cavity side, and their flat A ring becomes incorporated into the narrower [6.1.6.1]paracyclophane moiety. In contrast, cholesterol penetrates (±)- 4 with its hydrophobic side chain from the wider rim of the binding side. This way, the side chain is included into the narrower cavity section shaped by the smaller [6.1.6.1]paracyclophane, While the A ring protrudes with the OH group at C(3) into the solvent on the wider cavity side (Fig. 8). The molecular-recognition studies with the synthetic receptors (±)- 2 , (±)- 3 , and (±)- 4 complement the X-ray investigations on biological steroid complexes in enhancing the understanding of the principles governing selective molecular recognition of steroids.     

Dendroclefts: Optically Active Dendritic Receptors for the Selective Recognition and Chiroptical Sensing of Monosaccharide Guests

The enantiomerically pure dendritic receptors with cleft-type recognition sites (dendroclefts) of generation zero ((−)- G0 ), one ((−)- G1 ), and two ((−)- G2 ) (Fig. 1) were prepared for the complexation of monosaccharides via H-bonding. They incorporate a rigid, optically active 9,9′-spirobi[9H-fluorene] core bearing 2,6-bis(carbonylamino)pyridine moieties as H-bonding sites in the 2,2′-positions. The dendritic shells in (−)- G1 and (−)- G2 are made out of a novel type of dendritic wedges of the first ( 8 ; Scheme 2) and second ( 13 ; Scheme 3) generations, which contain only donor O-atoms and are attached to the H-bonding edges of the core via glycine spacers (Scheme 4). The formation of stable 1 : 1 complexes (association constants K_a between 100 and 600 M ⁻¹, T=298 K; Table 2) between the three receptors and pyranosides in CHCl₃ was confirmed by ¹H-NMR and CD binding titrations as well as by Job plot analyses. The degree of dendritic branching was found to exert a profound effect on the stereoselectivity of the recognition processes. The binding enantioselectivity decreases with increasing degree of branching, whereas the diastereoselectivity increases. The ¹H-NMR analysis showed that the N−H⋅⋅⋅O H-bonds between the amide NH groups around the core and the sugar O-atoms become weakened with increasing dendritic generation, presumably due to steric factors and competition from intramolecular H-bonding between these amide groups and the O-atoms of the dendritic shell. The chiroptical properties of the dendroclefts respond to guest binding in a stereoselective manner. Whereas large differential changes are seen in the circular dichroism (CD) spectra of (−)- G0 and (−)- G1 upon complexation of the enantiomeric monosaccharides (Figs. 3 and 4), the CD spectra of the higher-generation derivative (−)- G2 respond to a lesser extent to guest complexation (Fig. 5). This is indicative of a different binding geometry, more remote from the core chromophore. With their higher masses, the dendroclefts (−)- G1 and (−)- G2 are readily recycled from host-guest solutions by gel-permeation chromatography. The strong CD sensory response and the easy recyclability suggest applications of chiral dendroclefts as sensors for biologically important molecules.     

A variety of poly(m-benzamide)s with low polydispersities from inductive effect-assisted chain-growth polycondensation

Chain-growth polycondensation of 3-(alkylamino)benzoic acid alkyl esters 1 was investigated for obtaining poly(m-benzamide)s with defined molecular weights and low polydispersities. Polymerization conditions were first studied to find that ethyl 3-(octylamino)benzoate ( 1b ) polymerized in a chain polymerization manner in the presence of lithium 1,1,1,3,3,3-hexamethyldisilazide (LiHMDS) as a base and phenyl 4-methylbenzoate ( 2b ) as an initiator in THF at 0 °C. The molecular weight of the polymer was controlled by the feed ratio of monomer to initiator. The polymerization of 1c – i with a variety of N-alkyl groups was then carried out under the established conditions to yield well-defined poly(m-benzamide)s, which showed higher solubility than those of the corresponding poly(p-benzamide)s. Furthermore, the 4-octyloxybenzyl group on the amide nitrogen in poly 1i was removed by treatment with trifluoroacetic acid (TFA) to give N-unsubstituted poly(m-benzamide) (poly 1j ) with a low polydispersity, which is soluble in DMAc and DMSO, contrary to the para-substituted counterpart. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 4990–5003, 2006     

Synthesis and properties of poly(phenylacetylenes) having two polar groups or one cyclic polar group on the phenyl ring

Phenylacetylene (PA) derivatives having two polar groups (ester, 2a – d ; amide, 4) or one cyclic polar group (imide, 5a – c ) were polymerized using (nbd)Rh⁺[(η⁶‐C₆H₅)B^?(C₆H₅)₃] catalyst to afford high molecular weight polymers (～1 × 10⁶ – 4 × 10⁶). The hydrolysis of ester‐containing poly(PA), poly( 2a) , provided poly(3,4‐dicarboxyPA) [poly ( 3 )], which could not be obtained directly by the polymerization of the corresponding monomer. The solubility properties of the present polymers were different from those of poly(PA) having no polar group; that is, poly( 2a )–poly( 2d ) dissolved in ethyl acetate and poly( 4 ) dissolved in N,N‐dimethylformamide, while poly(PA) was insoluble in such solvents. Ester‐group‐containing polymers [poly( 2a )–poly( 2d )] afforded free‐standing membranes by casting from THF solutions. The membrane of poly( 2a ) showed high carbon dioxide permselectivity against nitrogen (PCO₂/PN₂ = 62). © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5943–5953, 2006     

SYNTHESIS AND CHARACTERIZATION OF FOUR-ARMED BLOCK POLY(STYRENE-b-p-NITROPHENYL METHACRYLATE)PREPARED BY THE ATRP METHOD*

A novel tetrafunctional initiator, C [CH_2O (CH_2)_3 OOCCH(Br)CH_3]_4 (1), was synthesized through the reaction oftetraol with α-bromopropionyl chloride, and then was used as initiator of atom transfer radical polymerization (ATRP) in thepreparation of 4-armed polystyrene (PSt) with narrow polydispersity. The structure, molecular weight and molecular weightdistribution (MWD) of each arm were studied by ~1H-NMR and GPC data of hydrolyzed products of the 4-armed PSt. TheATRP of St using 1/CuBr/bpy as initiator system is of "living" character based on the following evidence: narrow MWD,constant concentration of chain radical during the polymerization, control of molecular weight by the molar ratio of monomerconsumed to 1. The 4-armed poly(St-b-p-nitrophenyl methacrylate) [poly(St-b-NPMA)] was prepared by the ATRP ofNPMA using 4-armed PSt with terminal bromine as the initiator, and characterized by FT-IR, ~1H-NMR spectra and GPCcurves. The micelles with PSt as core, and PNPMA as shell were formed by dropping DMSO into a solution of 4-armedpoly(St-b-NPMA) in DMF, as proved by laser light scatter (LLS) method.     

Dendritic Iron Porphyrins with Tethered Axial Ligands: New Model Compounds for Cytochromes

The novel dendritic iron porphyrins of generation zero ([ 1 ⋅Fe^III]Cl), one ([ 2 ⋅Fe^III]Cl), and two ([ 3 ⋅Fe^III]Cl) (Fig. 1) were prepared as models of cytochromes (Schemes 1 and 2). They feature controlled axial ligation at the iron center by two imidazoles tethered to the porphyrin core. Similar to the core compound [ 4 ⋅Fe^III]Cl, they are six‐coordinate low‐spin complexes as demonstrated by UV/VIS (Figs. 3 and 4) and EPR spectroscopy, as well as measurements of the magnetic moments by the Evans‐Scheffold method. The coordination environment does not change upon reduction to the corresponding iron(II) complexes. The dendritic iron porphyrins were purified by size‐exclusion chromatography and shown by matrix‐assisted laser‐desorption‐ionization mass spectrometry (MALDI‐TOF‐MS; Figs. 5 and 6) to be free of structural defects. With their triethyleneglycol monomethyl ether surface groups, the three dendritic mimics are soluble in solvents of widely differing polarity. Electrochemical studies (Figs. 7 and 8) and optical redox titrations (Fig. 9) revealed that the potential of the Fe^III/Fe^II couple in CH₂Cl₂, MeCN, and H₂O shifts strongly to more positive values (by as much as 380 mV) with increasing dendritic generation (Fig. 10). The redox potential of the second‐generation complex [ 3 ⋅Fe^III]Cl is, within experimental error, identical in all three solvents, which clearly demonstrates that the dendritic branching creates a unique local microenvironment around the isolated electroactive core. Whereas, in the organic solvents, the largest anodic potential shift is measured upon changing from generation zero to one, the largest shift in H₂O occurs only at the level of the second generation, when the dendritic superstructure is sufficiently dense to prevent access of bulk solvent to the electroactive core.     

Complexation of neurotransmitters ‒ dopamine,serotonin and melatonin ‒ with a DTPA-based cyclophane of high rigidity: 1H NMR shift and line-broadening

The ¹H NMR signals of the titled neurotransmitters undergo up-field shift accompanied by line-broadening in NMR titration with the DTPA-based cyclophane at pD 7.3; the cyclophane consists of a 4,4′-bis(1,1′-biphenyl-4,4′-dihydroxy)dianiline unit cyclised by a DTPA (diethylenetriaminepentaacetate) group through two amide linkages. Changes in chemical shifts of dopamine indicate the formation of a 1:1 complex with the formation constant K₁ 400 M^?1; the complex of serotonin is likely to form a 2:1 host?guest complex with β₂ ≈ 10⁵ M^?2; melatonin does not form a complex with definite stoichiometry. The primary binding forces in the dopamine and serotonin complexes are electrostatic interaction between cationic neurotransmitter and anionic cyclophane molecules, and the resulting ionic pairs are stabilised by encapsulation. The electrostatic interaction is weakened by electrolytes; in 0.1 M Trizma buffer, dopamine does not yield a definite complex, and serotonin forms a 1:1 complex with K₁ 80 M^?1. Extreme line-broadening of neurotransmitter signals suggests that the molecular motion of the guest molecule is slowed in the complex by interactions with the receptor molecule whose internal molecular motion is quenched partially. The high rigidity of the cyclophane enhances intermolecular interaction in the hydrophobic regions to prolong the lifetime of the complex.     

Synthesis of imidazole‐terminated hyperbranched polymers with POSS‐branching points and their pH responsive and coordination properties

An imidazole‐terminated hyperbranched polymer with octafunctional POSS branching units denoted as POSS‐HYPAM‐Im was prepared by the polymerization of excess amounts of tris(2‐aminoethyl)amine with the first‐generation methyl ester‐terminated POSS‐core poly(amidoamine)‐typed dendrimer, reacting with methyl acrylate, and ester‐amide exchange reaction with 3‐aminopropylimidazole. The imidazole‐terminated hyperbranched poly(amidoamine) denoted as HYPAM‐Im was also synthesized with 1‐(3‐aminopropyl)imidazole from a methyl ester‐terminated hyperbranched poly(amidoamine) by the ester‐amide exchange reaction. The transmittance of the POSS‐HYPAM‐Im solution drastically decreased when the solution pH was greater than 8.2. On the other hand, the transmittance of the HYPAM‐Im solution gradually decreased when the solution pH at 8.5 and was greater than 9. Spectrophotometric titrations of the hyperbranched polymer aqueous solutions with Cu²⁺ ions indicated the variation of the coordination modes of POSS‐HYPAM‐Im from the Cu²⁺–N₄ complex to the Cu²⁺–N₂O₂ complex and the existence of the only one complexation mode of Cu²⁺–N₄ between Cu²⁺ ion and HYPAM‐Im with increasing the concentrations. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2695–2701     

Insulated Molecular Wires: Dendritic Encapsulation of Poly(triacetylene) Oligomers,Attempted Dendritic Stabilization of Novel Poly(pentaacetylene) Oligomers,and an Organometallic Approach to Dendritic Rods

Multinanometer‐long end‐capped poly(triacetylene) (PTA) and poly(pentaacetylene) (PPA) oligomers with dendritic side chains were synthesized as insulated molecular wires. PTA Oligomers with laterally appended Fréchet‐type dendrons of first to third generation were prepared by attaching the dendrons ( 8 , 13 , and 17 , respectively, Scheme 1) to (E)‐enediyne 18 by a Mitsunobu reaction and subsequent Glaser‐Hay oligomerization under end‐capping conditions (Scheme 2). Whereas first‐generation oligomers up to the pentamer were isolated ( 1a – e ), for reasons of steric overcrowding, only oligomers up to the trimer ( 2a – c ) were formed at the second‐generation level, and only the end‐capped monomer and dimer ( 3a , b ) were isolated at the third‐generation level. By repetitive sequences of hydrosilylation (with the Karstedt catalyst), followed by allylation or vinylation, a series of carbosilane dendrons were also prepared (Schemes 3 and 4). Attachment of the second‐generation wedge 40 to (E)‐enediyne 18 , followed by deprotection and subsequent end‐capping Hay oligomerization, provided PTA oligomers 4a – d with lateral carbosilane dendrons (Scheme 5). UV/VIS Studies (Figs. 5 – 10) demonstrated that the insulating dendritic layers did not alter the electronic characteristics of the PTA backbone, even at the higher‐generation levels. Despite distortion from planarity due to the bulky dendritic wedges, no loss of π‐electron conjugation along the PTA backbone was detected. A surprising (E)→(Z) isomerization of the diethynylethene (DEE) core in the third generation derivative 3a was observed, possibly photosensitized by the bulky Fréchet‐type dendritic wedge. Electrochemical investigations by steady‐state voltammetry and cyclic voltammetry showed that the first reduction potential of the PTA oligomer with Fréchet‐type dendrons is shifted to more negative values as the dendritic coverage increases. With compounds 5a – c , the first oligomers with a poly(pentaacetylene) backbone were obtained by oxidative Hay oligomerization under end‐capping conditions (Scheme 6). The synthesis of dendritic PPA oligomers by oxidative coupling of (E)‐enetetrayne 60 under end‐capping conditions provided oligomers 61a – d , which were formed as mixtures of stereoisomers due to unexpected thermal (E)→(Z) isomerization (Scheme 8). In another novel approach towards dendritic encapsulation of molecular wires with a Pt‐bridged tetraethynylethene (TEE) oligomeric backbone, the trans‐dichloroplatinum(II) complex trans‐ 67 with dendritic phosphane ligands (Fig. 14) was coupled under Hagihara conditions to mono‐deprotected 69 under formation of the extended monomer 65 (Scheme 12). Again, an unexpected thermal (E)→(Z) isomerization, possibly induced by steric strain between TEE moieties and dendritic phosphane ligands in the unstable complex, led to the isolation of 65 as an isomeric mixture only.     

Synthesis and characterization of new poly(ether amide)s based on a new cardo monomer

A new cardo diamine monomer 3, 3‐bis‐[4‐{2′trifluoromethyl 4′‐(4″‐aminophenyl) phenoxy} phenyl]‐2‐phenyl‐2, 3‐dihydro‐isoindole‐1‐one ( 4 ) has been synthesized from potentially cheap phenolphthalein as the starting material. This diamine was used for the synthesis of a new poly(ether amide) and two co‐poly(ether amide)s using 4, 4′‐diaminodiphenyl ether (ODA) as co‐monomer by direct solution polycondensation with 5‐t‐butyl iso‐phthalic acid. These new polymers showed inherent viscosities of 0.48–0.62 dL g^?1. The resulting poly(ether amide) and co‐poly(ether amide)s were readily soluble in polar aprotic solvents like NMP, DMF, DMAc, DMSO, and pyridine. The polymers have been fully characterized by ¹H and ¹³C NMR, FTIR spectroscopy, and elemental analysis. These polymers showed glass transition temperatures in the range of 267–310°C. Thermogravimetric analysis indicated high thermal stability of these polymers at 5 and 10% weight loss temperature in air above 357°C and 419°C, respectively. The poly(ether amide) films cast from DMAc were flexible with tensile strength up to 91 MPa, elongations at break up to 11%, and modulus of elasticity up to 1.82 GPa. X‐ray diffraction measurements indicate the amorphous nature of the poly(ether amide)s. Copyright © 2009 John Wiley & Sons, Ltd.     

Dendrimers with Porphyrin Cores: Synthetic models for globular heme proteins

Dendritic iron porphyrins were synthesized as functional mimics of globular electron-transfer heme proteins. The cascade molecules 1 · Zn ? 3 Zn of first to third generation were obtained starting from the (meso-diarylporphyrin) zinc 6 · Zn which contains four carboxylate arms for attachment of the poly(ether-amide) dendritic branches by peptide-coupling methodology (Scheme 1). Generation 3 compound 3 · Zn with 108 methyl-carboxylate end groups has a molecular weight of 19054. D, and computer modeling suggests that its structure is globular and densely-packed, measuring ca. 4 nm in diameter and, therefore, similar in dimensions to the electron-transfer protein cytochrome-c. Starting from the generation 1 poly(carboxylic acid) 11 · Zn and the generation 2 analog 12 · Zn the dendritic Zn^II porphyrins 4 · Zn and 5 · Zn , respectively, were obtained by esterification with triethyleneglycol monomethyl ether (Schemes 3 and 4). Demetallation followed by insertion of Fe^II and in situ oxidation afforded the water-soluble dendritic iron porphyrins 4 FeCl and 5 FeCl . The electrochemical behavior of esters 1 · Zn ? 3 · Zn in organic solvents changed smoothly with increasing dendritic generation (Table 1). Progressing from 1 · Zn to 3 · Zn in THF, the first porphyrin-centered oxidation and reduction potentials become more negative by 320 and 210mV, respectively. These changes were attributed to strong microenvironmental effects imposed on the electroactive core by the densely packed dendritic surroundings. The electrochemical properties of 4 · FeCl and 5 · FeCl were investigated by cyclic voltammetry in both CH₂Cl₂ and H₂O (Tables 2 and 3). Progressing from 4 · FeCl to 5 · FeCl in CH₂Cl₂, the redox potential of the biologically relevant Fe^III/Fe^II couple remained virtually unchanged, whereas in aqueous solution, 5 FeCl exhibited a potential 420 mV more positive than did 4 FeCl. The large difference between these potentials in H₂O was attributed to differences in solvation of the core electrophore. Whereas the relatively open dendritic branches in 4 · Fecl do not impede access of bulk solvent to the central core, the densely packed dendritic superstructure of 5 · FeCl significantly reduces contact between the heme and external solvent. As a result, the more charged Fe^III state is destabilized relative to Fe^II, and the redox potential is strongly shifted to a more positive value.     

Structure-Function Relationships in the Complexation of Steroids by a Synthetic Receptor

The complexation between the double-decker cyclophane (±)- 1 and a series of 30 steroids was investigated in CD₃OD by ¹H-NMR titrations. The geometries of the complexes, in which the substrates are axially included in the 13-Å deep and 9 Å×12 Å wide receptor cavity, were estimated based on the complexation-induced changes in chemical shift (CIS) of the steroidal Me group resonances. Computer modeling provided additional support for the geometries deduced from the experimental data. The log P (octanol/H₂O) values of the steroids were determined experimentally by HPLC or calculated using the program CLOGP. Although steroids with a high log P form some of the most stable complexes with (±)- 1 , a general correlation between the thermodynamic driving force for association −ΔG⁰ and the partition coefficient was not observed. It can, therefore, be concluded that inclusion complexation is not only driven by the preference of the steroid to transfer from the polar solvent into the lipophilic binding cavity but also by specific host-guest interactions. A series of structure-function relationships was revealed. i) Steroids with an isoprenoidal side chain at C(17) form some of the most stable complexes (−ΔG⁰ up to 4.8 kcal mol⁻¹), with side-chain encapsulation contributing as much as 1.2 kcal mol⁻¹ to the association strength. In these complexes, the receptor is slipping in a dynamic process over both the tetracyclic core and the lipophilic side chain. ii) Pregnane derivatives, which lack the isoprenoidal side chain, are tightly encapsulated with their tetracyclic core. Upon introduction of double bonds, the core flattens, and binding affinity drops substantially. iii) The presentation of steroidal OH groups to the receptor cavity is accompanied by energetically unfavorable functional-group desolvation, which strongly reduces the host-guest binding affinity. In contrast, inclusion of steroidal carboxylate or keto groups into the cavity does not substantially change complexation strength as compared to the unsubstituted derivatives. iv) Addition of extra Me groups to the steroidal A ring does not have a large effect on the association strength; however, complex geometries may change significantly. v) Receptor (±)- 1 shows a remarkably high affinity towards progesterone (−ΔG⁰=4.7 kcal mol⁻¹) despite the low log P value (3.87) of this steroid. Small changes in the progesterone structure lead to large reductions in complex stability, which clearly demonstrates that the double-decker cyclophane is a selective molecular receptor.     

Synthesis, characterization and ion transportation studies of some novel cyclophane amides

Various novel cyclophane amides with a large cavity have been synthesized. The structures of cyclophane amides 14 and 15 were resolved using XRD studies. Cyclophane amide 28 shows a shift in λ_max in the UV/Vis. spectra when treated with Cu (II) ion as well as with Pb (II) ion. Ion transportation studies were carried out with cyclophane amide 14 which proved that the Na⁺ ion passes through the cavity while K⁺ ions are retained.     

Synthesis of well‐defined,soluble poly(3‐alkyl‐4‐benzamide) by chain‐growth condensation polymerization

Well‐defined poly(3‐alkyl‐4‐benzamide) was synthesized by means of chain‐growth condensation polymerization of phenyl 3‐octyl‐4‐(4‐octyloxybenzyl(OOB)amino)benzoate ( 1c ) from initiator 2 , followed by removal of the OOB groups on amide nitrogen of poly 1c . Polymerization of 1c with phenyl 4‐(trifluoromethyl)benzoate ( 2b ) in the presence of 1,1,1,3,3,3‐hexamethyldisilazide (LiHMDS) and LiCl in THF at ?10 °C gave poly 1c with a narrow molecular weight distribution (M_w/M_n ≤ 1.08) and a well‐defined molecular weight (M_n = 4480–12,700) determined by the feed ratio of monomer to initiator (from 10 to 30). The OOB groups of poly 1c were removed with H₂SO₄ to give the corresponding N‐unsubstituted poly(p‐benzamide) (poly 1c′ ) with low polydispersity. The solublity of poly 1c′ in polar organic solvents was dramatically higher than that of poly(p‐benzamide), demonstrating that introduction of an alkyl group on the aromatic ring is very effective for improving the solubility of poly(p‐benzamide). © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014 , 52, 360–365     

Facile synthesis of dumbbell‐shaped dendritic‐linear‐dendritic triblock copolymer via reversible addition‐fragmentation chain transfer polymerization

We report the first instance of facile synthesis of dumbbell‐shaped dendritic‐linear‐dendritic triblock copolymer, [G‐3]‐PNIPAM‐[G‐3], consisting of third generation poly(benzyl ether) monodendrons ([G‐3]) and linear poly(N‐isopropylacrylamide) (PNIPAM), via reversible addition‐fragmentation chain transfer (RAFT) polymerization. The key step was the preparation of novel [G‐3]‐based RAFT agent, [G‐3]‐CH₂SCSSCH₂‐[G‐3] (1), from third‐generation dendritic poly(benzyl ether) bromide, [G‐3]‐CH₂Br. Due to the bulky nature of [G‐3]‐CH₂Br, its transformation into trithiocarbonate 1 cannot go to completion, a mixture containing ～80 mol % of 1 and 20 mol % [G‐3]‐CH₂Br was obtained. Dumbbell‐shaped [G‐3]‐PNIPAM₃₁₀‐[G‐3] triblock copolymer was then successfully obtained by the RAFT polymerization of N‐isopropylacylamide (NIPAM) using 1 as the mediating agent, and trace amount of unreacted [G‐3]‐CH₂Br was conveniently removed during purification by precipitating the polymer into diethyl ether. The dendritic‐linear‐dendritic triblock structure was further confirmed by aminolysis, and fully characterized by gel permeation chromatography (GPC) and ¹H‐NMR. The amphiphilic dumbbell‐shaped triblock copolymer contains a thermoresponsive PNIPAM middle block, in aqueous solution it self‐assembles into spherical nanoparticles with the core consisting of hydrophobic [G‐3] dendritic block and stabilized by the PNIPAM central block, forming loops surrounding the insoluble core. The micellar properties of [G‐3]‐PNIPAM₃₁₀‐[G‐3] were then fully characterized. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 1432–1445, 2007