Jones, Jason William 11_Chapter_3.pdf

CHAPTER III: POLYMERIC SUPRAMOLECULAR ASSEMBLIES III.1.0 INTRODUCTION The previous two chapters have dealt with two separate issues in contemporary material science: the controlled functionalization of surfaces and the preparation of nanoscopic self-assembled supermolecules. This final chapter will marry the two seemingly unrelated studies in the form of receptor functionalized dendrimers. 90 III.1.1 CROWN ETHER FUNCTIONALIZED DENDRITIC POLY(PROPYLENEIMINE) POLYPSEUDOROTAXANES III.1.1.1 GENERAL Due in large part to the architectural features of ideal dendrimers, which are nearperfect, monodisperse macromolecules with highly branched three-dimensional skeletons, they are prime candidates for surface functionalization. prepared. First conceptualized by Flory in 1941, it was reasoned that trifunctional monomers with only two unique functional groups (ABB or AAB functionality) could polymerize without crosslinking provided the functional groups were prepared in such a way that A reacted solely with B and vice versa. [1] In 1952, Flory prepared a hyperbranched polymer based on the idea of a multifunctional and selective monomer. [2] Hyperbranched polymers differ conceptually from dendrimers in that dendrimers are prepared in an iterative sequencing of events, yielding successive generations of macromolecule whereas hyperbranched polymers are formed in a batch type process and thus do not build themselves into uniform generations. The first example of an effective iterative synthesis was reported in 1978 when Vögtle et al. published their results of a “cascade” molecule synthesis. [3] MerriamWebster defines a cascade as “something arranged or occurring in a series or in a succession of stages so that each stage derives from or acts upon the product of the preceding.” [4] It is thus fitting that Vögtle’s synthetic technique has come to be referred to as the divergent approach to dendrimer preparation, where the dendrimer is grown stepwise about a central core (Scheme 1a). Contrast this to the convergent approach of dendrimer synthesis first reported by Hawker and Fréchet in 1990 in which the This unique architecture results from the iterative, stepwise synthesis in which the dendrimer is 91 macromolecule is synthesized from the outside in before attaching the separate arms onto a core unit (Scheme 1b). [5] In the divergent approach (Scheme 1a), the purity of the dendrimer is a function of the selectivity of successive reactions. For example, if the divergent coupling reaction proceeds with a selectivity of 99.5%, a fifth generation dendrimer with 64 terminal end groups will result in 0.995248 = 29% of defect-free macromolecule, where the exponent refers to the total number of reactions needed to reach the fifth generation. [6] As the complete purification of successive generations is a daunting, if not impossible task, statistical defects cannot be avoided. Additional polydispersities arise in higher generation dendrimers as steric hindrance at a crowded periphery most certainly limits the ability of end groups to be converted to successive generations. In the convergent approach (Scheme 1b), the number of overall reactions performed on one starting molecule is greatly reduced by building the arms of the dendrimer individually before attaching each branch to a central core. In so doing, the number of coupling reactions performed for each generation remains constant and manageable. Very few side products are possible at each step, while the purification of successive generations can be accomplished with marginal effort. possible to produce nearly defect-free macromolecules in this manner. [7] Initial interest in dendritic chemistry arose from the unique physical properties displayed by these molecules, particularly when comparing the dendrimer’s properties to that of its linear analogue. In solution, rather than increasing with molecular mass as linear polymers tend to behave, the intrinsic viscosity of dendrimers reaches a maximum at a certain generation. Other physical studies have been performed on dendrimers in both solution and the solid state. [8] Due to their commercial availability, a great number of studies have looked at poly(propyleneimine) dendrimers (1) which were first prepared in a divergent manner by Mülhaupt [9] and Meijer (Scheme 2). [10] These dendrimers will be the focus of the research discussed below. Convergent dendrimers are therefore less polydisperse than are divergent dendrimers. In fact, it is 92 Scheme 1. Divergent (a) and Convergent (b) Approaches to Dendritic Synthesis. a A A b A A 4 X X X B X X X X X CC CC X X X X X X X transform X to A transform R to A 3 X B X X A R A A X X X X X X CC C X R X X 12 X B X X XX X XXX XX X 1/4 B B B B X X C C C X X X X C C X X C C C C C X X C C C X X X X X X C C C X X X X XX XX XXX 93 Current interest in dendritic chemistry stems from the utilization of the large number of end groups available to the chemist on a non-crosslinked system. The modification of such end groups allows for a wide variety of functionalities to be present on the periphery. One only need look as far as Mother Nature’s creations to understand the ramifications of such features: the high local density of functional units affords important roles in many biological interactions. Whitesides and co-workers recently published a review of relevant polyvalent interactions in human biology. [11] Among the interactions listed, virus and bacterium adhesion to cell surfaces, binding of antibodies and macrophages to cells, and the binding of transcription factors to DNA are all included. It is therefore of interest to combine the aforementioned area of supramolecular chemistry, which in and of itself bears important bio- and nano-technological ramifications, with dendritic chemistry by adding polyvalent functionality in the form of crown ethers to the periphery of poly(propyleneimine) dendrimers. Several host-guest systems based on dendrimers containing specific receptors inside the dendrimer are known. [12] Diederich et al. have prepared the first representatives of dendrophanes (dendrimer-cylophanes) in an effort to investigate the influence of shielding superstructure on the thermodynamics and kinetics of molecular binding by benzene and naphthalene derivatives (Figure 1). [12a, b] Here, a cyclophane receptor is used as the initiator core onto which water soluble surface groups are grown in a divergent manner. Zimmerman et al. have reported on the binding of benzamidinium guests 2 and 3 with naphthyridine cored dendritic hosts 4 and 5 (Figure 2). [12c] Moving towards potential polyvalent interactions of functionalized dendrimers, Newkome and coworkers have incorporated 2,6-diamidopyridine moieties into dendritic mesomolecules. [12d] More specifically, they studied the titration of a quad-diamidopyridine host dendrimer 6 with glutarimide 7 (Scheme 3) and found apparent association constants on the order of 70 M-1 in CDCl3 using 1H NMR experiments. This value is comparable with reported association constants for the simple diamidopyridine host system. [13] Curiously, the titration curves are not reported using typical Scatchard or Hill plots. Thus the reader knows nothing about possible polyvalent interactions, which will be discussed blah 94 Scheme 2. Divergent Poly(propyleneimine) Growth.† CN H2N CN NH2 A NC N N CN CN Raney Co B H2 H2N N N H2N H2N H2N H2N H2N N N N N NH2 N N N N NH2 NH2 N NH2 NH2 N N NH2 B NH2 NH2 N H2N H2N H2N N H2N N NH2 NH2 D3 DAB-dend-(NH2)16 1 Many common dendrimers are frequently abbreviated according to generation (first generation = D1, third = D3, fifth = D5, etc) followed by an acronym for the central core (here, DAB = Di-Amino Butane), then the abbreviation dend, terminating in the number and type of end groups found on the periphery (here, 16 NH2 functionalities). † 95 Figure 1. Representative Dendrophane. [12a, b] O O O X X O O O HN O X O O O R R O R O O HN H2C O O O O R R O R X= Figure 2. Benzamidinium Guests 2 and 3, Which Bind to the Naphthyridine Cores of 4 and 5. [12c] H N H N H H N H N H H tBu H tBu tBu tBu 2 tBu A B tBu tBu B A tBu tBu B tBu tBu A B A B A tBu n A n B N tBu 3 tBu tBu A B A B A B n tBu tBu A B A B tBu tBu A n tBu tBu tBu N B 4: A-B = H2C O 5: A-B = C C 96 below, within Newkome’s tetra-functional system. Zimmerman. [14] Other examples on the use of dendrimers in supramolecular chemistry can be found in a review by Zeng and Standing in stark contrast to the multiple reports of receptor functionalization within the dendritic interior, binding of specific guests at their periphery has had only limited Scheme 3. Quad-diaminopyridine 6 Interior Binding of Glutarimide 7. [12d] O OR O C O N N N H H O O N H O H N O O OR 6 3 4 OR H O N O 7 O OR O C O O N N N H H H O N O O N H O H N O O OR 3 4 OR 97 limited attention. Researchers from the University Autónoma of Madrid have reported a novel class of organometallic dendrimers whose surfaces are functionalized with ferrocene units. [15] Kaifer recently teamed up with the Madrid group to study the ferrocene-functionalized substrate for the inclusion complexation of β-cyclodextrin (βCD). [16] The collaboration found that the water solubility of ferrocene functionalized dendrimers increased substantially in the presence of β−CD, indicating complexation. Interestingly, the solubility measured for 8-10 in the presence of cyclodextrin decreases as a function of generation (Figure 3). This observation was ascribed to the greater steric hindrance associated with complexation of β−CD at the surfaces of the larger macromolecules. The collaboration has since reported on the synthesis of cobaltocenium-functionalized dendrimers and their complexation with β−CD. [17] Using cyclic voltammetry to probe electrochemical behavior, they have shown that these dendrimers readily deposit onto an electrode upon one electron reduction of the cobaltocenium end groups to cobaltocene. Subsequent addition of β−CD to this deposit solubilizes the reduced dendrimer; association is only possible upon electrochemical activation of the end groups. The use of crown systems in dendritic molecules is rare; the use of polycrown networks is even more unique. Yamaguchi et al. have taken advantage of pseudorotaxane formation between dibenzo-24-crown-8 (DB24C8) and dibenzyl ammonium hexafluorophosphate to selectively assemble supramolecular dendrimers (Scheme 4). [18] Dendrimers modified with crown ether moieties at the core have been used to assemble dendritic wedges. [19] Shinkai et al. have prepared ‘crowned’ arborols in which the repeat 98 Figure 3. Ferrocene Functionalized Dendrimers (First Generation: 8, Second Generation: 9, Third Generation: 10) 99 repeat branch had been functionalized with a diaza-18-crown-4 ether (Figure 4). [20] Every subsequent generation thus has twice as many crown ether host units as the previous. The terminus of the dendrimer is based on ester linkages that provide the impetus for further nucleation. Shinkai and co-workers later went on to study various physical properties of the ‘crowned’ arborols upon the introduction of alkali metal ions. [21] Percec and colleagues have demonstrated self-assembled supramolecular rod-like bbbb Scheme 4. Formation of Dendritic Pseudorotaxanes. [18] 100 dendrimers via ion-mediated complexation processes between first generation 15-crown5 ether functionalized dendrons (15C5) with Na+, Li+, and K+ trifluoromethanesulfonates. [22] Fitzmaurice and co-workers have prepared a dispersion of gold 13 [23a] and silver [23b] nanocrystals that are stabilized by a chemisorbed monolayer of DB24C8 branches 12 (Scheme 5).† Their initial interest was in establishing a systematic strategy focus Figure 4. First Generation ‘Crowned’ Arborol. [20] OEt O O O OEt O O O N O O O N O O O O EtO O EtO O N O O N O O N O O O N O O O OEt O OEt O † The investigation of derivatized gold clusters has become an active area of interdisciplinary research: the first derivation was reported by Brust et al. [24a] Kaifer and co-workers have modified the surface of gold colloidal particles with ferrocene functionalized alkane branches capable of forming inclusion complexes with α-CD. [24b] Kaifer has gone on to modify similar surfaces with cyclodextrin moieties, which are capable of binding multiple guest molecules. [24c] 101 to develop the parallel and identical assembly of nanocrystal dispersion architectures not previously realized by Langmuir-Blodgett techniques [25] or by controlled solvent evaporation. [26] It has been reasoned that such programmed nanocrystal assembly might receive a huge boost from the selective interaction of host-guest chemistry. In much the same way Yamaguchi et al. were able to program dendritic growth, so too might unique nanocrystals be grown. Fitzmaurice et al. report on the binding of free dibenzylammonium [23a] and bis-dibenzylammonium [23b] cations by the chemisorbed DB24C8 chains in chloroform. Despite the slow exchange regime present in the hostguest system, the group found that the complexed Au nanocrystal precipitated out of solution over time, indicating a single point determination of Ka (as is commonly found in such slow exchange scenarios) is not appropriate. This observation led the group to notice non-linearity of the resultant Scatchard plot. Preparation of a Hill plot, discussed below, confirms a positive co-operation of the binding process. This co-operation has been attributed to an increased affinity of dibenzylammonium cations for the chemisorbed hosts as the surface becomes more polar/hydrophilic with each bound guest. Such a finding ties in nicely with the polyvalent interactions found in natural systems and brings us to the topic of this chapter: polyvalent interactions in dendritic pseudorotaxanes. Before continuing forward with experimental details, it will be helpful to review the theories and ideas associated with polyvalent interactions found in Appendix I. Below, and in collaboration with the Meijer Group at the Laboratorium of Macromolecular and Organic Chemistry, the University of Technology Eindhoven, we have combined the chemistry of dendrimers with the supramolecular interactions of pseudorotaxanes, resulting in three generations of poly(propyleneimine) dendrimers functionalized with DB24C8 at the periphery which are capable of binding secondary ammonium salts. [27] We have also prepared two generations of poly(propyleneimine) dendrimers functionalized with bis(m-phenylene)-32-crown-10 (BMP32C10), which is known to bind paraquat salts. [28] 102 Scheme 5. Pseudorotaxane Assembly at the Surface of a Nanocrystal. [23] O O O O O O O O O O SH PF6 N H2 + + + 13 + + + + ≡ ≡ ≡ ≡ 12 + ≡ ≡ ≡ ≡ + + + + + + + + 103 III.1.1.2 COMPLEXATION FUNCTIONALIZED OF DIBENZO-24-CROWN-8 POLY(PROPYLENEIMINE) DENDRIMERS WITH DIBENZYL AMMONIUM HEXAFLUOROPHOSPHATE III.1.1.2.1 EXPERIMENTAL III.1.1.2.1.1 Preparation of Dibenzo-24-crown-8 Functionalized Poly(propyleneimine) Dendrimers Hydroxymethyl DB24C8 14 was prepared according to the literature. [29] The DB24C8 functionalized poly(propyleneimine) dendrimers were obtained by injection of the polyamine (114 mg) dissolved in chloroform (5 mL) to a stirred chloroform solution (15 mL) containing 2 equivalents of di-t-butyltricarbonate (959 mg). The solution was stirred at room temperature for 15 minutes under an argon atmosphere. Formation of isocyanate was checked via IR spectroscopy (ν = 2265 cm-1). Endgroup functionalization took place after the addition of 14 (862 mg) and zirconium(IV) acetylacetonate (0.1 mol%). After 16 hours the reaction mixture was precipitated in ice-chilled heptane (250 mL) and purified by subsequent size exclusion chromatography over a Bio-Beads SX-1 column with dichloromethane as the eluent. After solvent removal in vacuo, a highly viscous yellow oil was obtained for every generation (15, 16, and 17) prepared. HO O O O O 14 O O O O 104 15: Chemical yield: 53% (466 mg). 1H-NMR (CDCl3, 400 MHz) δ 1.35 (4H, br), 1.57 (8H, br), 2.29 (4H, br), 2.36 (8H, br.t., J = 6 Hz), 3.16 (8H, q, J = 6 Hz), 3.80 (32H, s), 3.89 (32H, s), 4.12 (32 H s), 4.95 (8H, s), 5.47-5.63 (4H, br), 6.74-6.81 (4H, m), 6.826.92 (24H, m). 13 C-NMR (CDCl3, 100 MHz) δ 25.0, 27.2, 40.1, 52.2, 54.0, 66.6, 69.7, 70.1, 71.5, 113.9, 114.4, 114.6, 121.7, 130.1, 149.0, 149.2, 156.7. IR: νmax 3329(w.br), 2926 (m), 2868(m), 1710 (s), 1505 (s), 1252 (s), 1123 (s), 1051 (s) cm-1. m/z (MALDITOF) 2357 [M + Na]+. 16: Chemical yield: 43% (480 mg). 1H-NMR (CDCl3, 400 MHz) δ 1.38 (4H, br), 1.451.72 (56H, br), 2.23-2.66 (84H, br), 3.04-3.29 (32H, br), 3.79 (128H), 3.88 (128H, br), 4.03-4.19 (128 H br), 4.88-4.98 (32H, s), 5.58-5.89 (16H, br), 6.70-6.94 (112H, br). 13 C- NMR (CDCl3, 100 MHz) δ 25.2, 28.9, 40.0, 52.4 (br), 66.6, 69.7, 70.2, 71.5,113.9, 114.3, 114.5, 121.6, 130.0, 148.9, 149.0, 156.7. IR: νmax 3329(w.br), 2926 (m), 2868(m), 1710 (s), 1505 (s), 1252 (s), 1123 (s), 1051 (s) cm-1. m/z (MALDI-TOF) 9779 [M + Na]+. 17: Chemical yield: 73% (458 mg). 1 H-NMR (CDCl3, 400 MHz) δ 1.30-1.84 (252H, br), 2.20-2.58 (372H, br), 2.99-3.29 (128H, br), 3.75 (512H, s), 3.77-3.93 (512H, br), 4.01-4.22 (512 H br), 4.84-4.99 (128H, br), 5.84-6.21 (64H, br), 6.56-7.06 (448H, br). 13 C-NMR (CDCl3, 100 MHz) δ 25.2, 28.9, 40.0, 52.4 (br), 66.6, 69.7, 70.2, 71.5,113.9, IR: νmax 3329(w.br), 2926 (m), 114.3, 114.5, 121.6, 130.0, 148.9, 149.0, 156.7. 2868(m), 1710 (s), 1505 (s), 1252 (s), 1123 (s), 1051 (s) cm-1. MALDI-TOF did not give any results, presumably a result of the high molecular weight. 105 Scheme 6. Peak Numbering and Cartoons of Dibenzo-24-crown-8 Functionalized Poly(propyleneimine) Dendrimers 15-17 with Dibenzyl Ammonium Hexafluorophosphate (18-H•PF6). Hα Hβ Hγ Ha O O O O O O O O O O N O O O O O O O O O NH O NH N O O O O O O O O O O NH O NH O O O O O Hb O O O O H1 H2 NH 2 PF6 15 18-H PF6 = O O O O O O O O R 16 17 106 III.1.1.2.1.2 Complexation of 15, 16, and 17 with Dibenzyl Ammonium Hexafluorophosphate (18). NMR-titrations at ambient temperatures (23.0 oC) were performed on the functionalized dendrimers 15, 16, and 17 (3-4 mM macrocycle concentration in CDCl3/CD3CN, 9/1 by volume) and the chemical shifts observed upon addition of aliquots of dibenzyl ammonium hexafluorophosphate (18-H•PF6) in CD3CN. of a solution of trifluoroacetic acid in CDCl3. As discussed below, protonation of the host macromolecules was achieved via the addition III.1.1.2.2 Results and Discussion To study the binding behavior of the crown ether functionalized dendrimers 15-17 towards secondary ammonium salts, the hexafluorophosphate salt of dibenzylammonium (18-H•PF6) was portion-wise added to 15-17 in a CDCl3/CD3CN (9/1 v/v) mixture and monitored via 1H NMR spectroscopy. The upfield shifts of the crown ether signals and the downfield shift of the benzylic methylene protons of 18-H+ (Figure 5) support formation of pseudorotaxane-like motifs. [27] In addition, and in accordance with a slow exchange regime, both signals belonging to the complexed and uncomplexed species were detected. The obtained titration curves (Figure 6) clearly show aberrant behavior for every generation at low guest concentration. This can be explained by the coexistence of two different mechanisms. First, the polyamine interior of the dendrimer is known to behave as a base. [30] Therefore, initial addition of 18-H•PF6 serves only to protonate the interior (see Figure 7). Similar results have been seen by Crooks et al. [31] Moreover, the concentration of uncomplexed protonated guest (18-H+) (Figure 5) increases relative to that of uncomplexed deprotonated guest (18): the signal belonging to the methylene protons of the uncomplexed guest shifts from 3.81 (18) to 4.03 ppm (18-H+) when more ammonium salt is added. 107 Figure 5. Changes in 1H NMR Spectra (500 MHz, 23.0 oC, CDCl3/CD3CN (9/1)) Upon Addition of 18-H•PF6 to 0.93 mM 15; Respectively 0, 1.3, 2.6, and 5.2 Equivalents of Guest Per Crown. Species Involved in Complexation Have Suffix c, Otherwise uc. Aromatic Protons of the Host are Labeled Ar(h). See Scheme 6 for Other Peak Assignments. Aruc,(h) Arc,(h) 1:5.2 1uc a 1c αc b 1:2.6 Aruc,(h) 1:1.3 αuc a b 1:0 equivalent Host:Guest 108 Figure 6. Titraton Curves Reflecting the Aberrant Behavior for Dendrimers 15, 16, and 17 Upon Complexation with 18-H•PF6. Concentrations of Dendritic End Groups are 2.8, 3.2, and 3.6 mM, Respectively. 15 0.6 fraction ammonium 0.4 bound 16 17 0.2 0.0 0.0 0.5 1.0 1.5 equiv. 18-H•PF6 109 Figure 7. Acid as a Cofactor of Amine Binding. O O O O O O O O O O N N H N H H N+ O O O O O O O O O O N H H N+ H N H N H O O H N N H + H +N 110 MALDI TOF mass spectrometry revealed additional information on the nature of binding between 18-H•PF6 and 15 (Figure 8). The mass spectrum of a mixture of 15 and 18-H•PF6 (1:6 mole) revealed the almost complete disappearance of the [15+Na]+ peak fff respectively. Figure 8. MALDI TOF MS of a Mixture of 15 and 18-H•PF6 (1:6 Mole Ratio). 2531:[15•(Guest-H)]+ 2676:[15•(Guest-H)•PF6+H]+ 2874:[15•(Guest-H)2•PF6+H]+ 3022:[15•(Guest-H)2•2PF6+H]+ 3217:[15•(Guest-H)3•2PF6]+ 0 m/z 4000 111 (2357 amu) and a base peak at 2531 amu, ascribed to the complex [15•18-H]+. In addition, peaks of lower intensity were observed at 2874 and 3217 amu (resp. 30 and 4% compared to the base peak), attributed to [15•(18-H)2•PF6]+ and [15•(18-H)3•2PF6]+, respectively. Interestingly, peaks which can be attributed to protonated dendritic-guest systems were also found at 2677 and 3022 amu (attributed to [15•18-H•PF6+H]+ and [15•(18-H)2•2PF6+H]+. More structural information was obtained with 2D NOESY from a solution of unprotonated dendrimer 17 and 18-H•PF6 in deuterated chloroform (Figure 9). [32] The bbbb Figure 9. 2D NOESY of a Solution of Unprotonated Dendrimer 17 and 18-H•PF6 (1:1 Mole Ratio) in Deuterated Chloroform. 1u Arg,c 2c αu+c γu & βc+u γc 1c 112 resulting spectrum shows the presence of through-space interactions between guest and host. The methylene protons of bound 18-H+ show cross peaks with the crown ether protons Hαc, Hβc, and Hγc, as do the signals belonging to the ammonium and the aromatic protons of the bound guest. NOE interactions are also observed between the aromatic protons of bound guest and complexed host. These results subscribe pseudorotaxane formation and are in agreement with NOE data found for the corresponding monofunctional system. [19a] In order to eliminate the competing deprotonation of 18-H+, the amine moieties of the dendritic frameworks 15-17 were protonated by the addition of an equivalent amount of trifluoroacetic acid. Subsequent binding studies revealed binding of 18-H+ by protonated 15-17 with no change in the 1H NMR absorptions belonging to the dendrimer interior observed. Moreover, uncomplexed guest had a constant chemical shift of 4.03 ppm, confirming that deprotonation of 18-H+ is eliminated.† Although all binding sites are identical, the resulting Scatchard plots (Figure 10) are non-linear, indicating that the binding sites are not independent; the convex slopes indicate cooperative binding. [33-35] Consequently, the data was interpreted using the Hill-equation (see Appendix 1, Equation 17 for a more detailed description):  θ   = nH 1−θ   1    Ka  log  log[G ] eq − log (1) For all generations investigated the Hill-coefficient is around 2.1 (Figure 11, Table 1), revealing that binding is cooperative. An explanation for cooperativity may be favorable π−π interactions between the aromatic rings of neighboring bound guest molecules. These interactions are present in several solid-state structures of DB24C8•18-H•PF6 based systems. [36] Moreover, cooperativity has also been found in a comparable polypseudorotaxane system confined to a nanocrystal. [22] Gibson et al. have recently demonstrated that linear polymethacrylate copolymers containing hydroxymethyl † While addition of a second counterion into the dendritic system may yet complicate subsequent complexation studies, the role of triflouroacetate on the binding of secondary ammonium salts by DB24C8 has been neglected in the following analysis. Thus, a cautionary note should be extended; the role of TFA in complexation studies is currently being investigated. 113 DB24C8 undergo complexation with 18-H•PF6 in an anticooperative manner. [37] Noting that the apparent Ka values decreased with the concentration of ammonium salt in such polymethacryalte copolymers, Gibson and co-workers reasoned that increasing the concentration of salt inevitably changed the polymeric medium, resulting in conformational changes, and thus altering the crown ether accessibility. [37] It should be obvious from such studies that the poly(propyleneimine) dendritic structure is enabling in the DB24C8 functionalized case, a theory which is further advanced below. A second explanation for cooperativity may also be a direct result of conformational changes due to addition of guest salts. Small crown ethers such as 2carboxy-1,3-phenylene-18-crown-6 are known to bind 1o ammonium salts in a perching formation (see section II.1.2.1, page 52). Given the inherent flexibility of the dendrimer, [38] the 24C8 moieties on the periphery may be capable of folding back upon the dendrimer to form dynamic perching complexes through favorable H-bonding interactions. Introduction of a 2o ammonium salt would result in a more stable pseudorotaxane: thus forcing the peripheral 24C8 moieties into a more static conformation. The increase in entropy might be thought to ultimately have the effect of decreasing overall free energy, thereby enhancing subsequent binding. Significantly, the host systems were only allowed to reach 60% saturation upon complexation with guest. As noted in Appendix I, it is important to extend binding into at least the 80% complexation range for the most accurate results. Others have stated that a degree of saturation of at least 90% is optimal for Hill studies. [39] As a result, the Hill plots are not entirely conclusive. Nonetheless, also described in Appendix I, the Hill plot only changes slope at very low levels of saturation or very high levels of saturation; thus a description of nH between 20 and 60% binding is somewhat appropriate.† Furthermore, the Hill coefficients do not appear to be influenced by generation size. Described in Appendix I, according to the Hill equation nH would be expected to approach n, or the number of crown ether endgroups, as the dendrimer grows up to a point where steric crowding influences binding, thereby reversing the cooperative trend; For 15, the first and fourth binding account for 50% of the overall complexation; thus the most reliable description of nH falls between 25 and 75% loading. For 16, the first and sixteenth binding account for 12.5% of the overall complexation; the first and sixty-fourth binding account for 3% in 17. Thus a description of nH between the theoretical limits of 20 and 80% is most appropriate for 16 and 17. † 114 Figure 10. Scatchard Plots for the Binding of Protonated 15 (A), 16 (B), and 17 (C) with 18-H+. 700 600 500 400 300 200 100 0 0 300 250 200 150 100 50 0 0 A 0.1 0.2 0.3 0.4 0.5 0.6 B 0.1 0.2 0.3 0.4 0.5 0.6 400 / [G] eq 300 200 100 0 0 C 0.1 0.2 0.3 0.4 0.5 0.6 θ = fraction of host sites bound 115 Figure 11a. Hill Plot for the Binding of Protonated 15 with 18-H+. 1.0 0.8 0.6 0.4 0.2 0.0 log ( θ / 1 - θ ) -0.2 -0.4 -0.6 -0.8 -1.0 -1.2 -1.4 -1.6 -1.8 -2.0 -3.7 -3.6 -3.5 -3.4 -3.3 -3.2 -3.1 -3.0 -2.9 -2.8 -2.7 -2.6 log [G]eq Figure 11b. 1.0 0.8 0.6 0.4 0.2 Hill Plot for the Binding of Protonated 16 with 18-H+. log ( θ / 1 - θ ) 0.0 -0.2 -0.4 -0.6 -0.8 -1.0 -1.2 -1.4 -1.6 -1.8 -2.0 -3.7 -3.6 -3.5 -3.4 -3.3 -3.2 -3.1 -3.0 -2.9 -2.8 -2.7 -2.6 log [G]eq 116 Figure 11c. 1.0 0.8 0.6 0.4 0.2 0.0 -0.2 -0.4 -0.6 -0.8 -1.0 -1.2 -1.4 -1.6 -1.8 Hill Plot for the Binding of Protonated 17 with 18-H+. log ( θ / 1 - θ ) -2.0 -3.7 -3.6 -3.5 -3.4 -3.3 -3.2 -3.1 -3.0 -2.9 -2.8 -2.7 -2.6 log [G]eq Table 1. Hill Coefficients and Association Constants for the Complexation of Protonated Dendrimers 15-17 with 18-H+. 2 Dendrimer 15 16 17 n 4 16 64 nH pK a R 2.1 ± 0.1 6.4 ± 0.4 2.1 ± 0.1 5.8 ± 0.3 2.1 ± 0.1 5.9 ± 0.4 0.971 0.991 0.972 117 for dendrimers 15-17, all Hill coefficients approach 2.1. The consistency of nH may be ascribed to the flexibility of the dendrimer, [38] whereby two adjacent crown functionalities effectively stack on top of each other through π-π communications. In this formation, threading of DB24C8 by a singular 18-H+ may promote successive binding through similar π-π stacking of individual 18-H+ pendant aromatic substituents.† Indeed, Stoddart has seen a continuous cation-threaded channel present in the crystal packing structure of DB24C8+18-H+, attributable to adjacent guest phenyl groups aligning parallel to each other. [19a] Having established the formation of pseudorotaxane motifs between 15-17 with 18H•PF6, and noting that acid behaves as a cofactor of amine binding, the releasing mechanism described by Stoddart and others [40] was investigated. Reversibility of pseudorotaxane formation was established by addition of base (DABCO) to a 9:1 mixture of CDCl3 and CD3CN containing protonated 17 loaded with 18-H•PF6, as this immediately led to deprotonation and subsequent decomplexation of the guest (Figure 12). Because the dendritic crown ether systems contain both binding moieties and basic functions, a mechanism exists to switch the functionalized dendrimers on or off for the binding of 18 a priori. This was confirmed by the addition of amine 18 to each of the hosts 15-17: complexation of the guest did not occur. However, when the dendrimers had been protonated by TFA prior to the addition of equivalent amounts of amine 18 to host macrocycle, binding of 18-H+ was observed in amounts equal to 8, 15, and 12 percent of added amine 18 to 15, 16, and 17, respectively. Binding in these cases is enabled by utilizing the proton-reservoir in the dendritic core to acidify amine 18, although the low basicity of amine 18 compared to the dendritic amines hampers more profound complexation. This point is emphasized by noting that a) the nature, and basicity, of the 3o amine groups varies substantially from the core of the dendrimer to its periphery, [37] while b) the ratio of 3o amine to DB24C8 moieties ranges from 2:4 for 15 to 14:16 for 16 and 62:64 for 17. † In this manner, the fifth generation dendrimer 17 may halve its effective binding surface area, negating the pronounced steric influences one might expect to see in such a crowded network, by stacking two adjacent host molecules on top of each other. 118 Figure 12. Switching Mechanism Induced by Addition of DABCO to Protonated 16 Loaded with 18-H•PF6 in a 9:1 Mixture of CDCl3 and CD3CN; 16:18:DABCO = 1:24:2. N + [16•Guest] Arg,c + N 1uc [16•Guest]+ 1c [16•Guest]+ + DABCO ppm 8.0 7.0 6.0 5.0 4.0 119 III.1.1.2.3 Conclusion In conclusion, we have shown that it is possible to construct poly(pseudorotaxane)s based on poly(propyleneimine) dendrimers functionalized with terminal DB24C8 moieties. These systems show cooperative binding towards secondary ammonium salts, and, because the dendrimers can be charged with acidic protons, they can be programmed to bind secondary amines. Further work will investigate the influence of saturation, counterions, and solvent on binding and will attempt to justifiably explain the cooperative nature of complexation. 120 III.1.1.3 COMPLEXATION CROWN-10 OF BIS(M-PHENYLENE)-32POLY- FUNCTIONALIZED POLY(PROPYLENEIMINE) DENDRIMERS WITH PARAQUAT DIOL DIHEXAFLUOROPHOSPHATE III.1.1.3.1 EXPERIMENTAL III.1.1.3.1.1 Preparation of Bis(m-phenylene)-32-Crown-10 Functionalized Polypoly(propyleneimine) Dendrimers Hydroxymethyl BMP32C10 (19) was prepared according to the literature. [41] The BMP32C10 functionalized poly(propyleneimine) dendrimers were obtained by injection of the polyamine dissolved in chloroform to a stirred chloroform solution containing 2 equivalents of di-t-butyltricarbonate. The solution was stirred at room temperature for 15 minutes under an argon atmosphere. Formation of isocyanate was checked via IR spectroscopy (ν = 2265 cm-1). Endgroup functionalization took place after the addition of 19 and zirconium(IV) acetylacetonate. After 16 hours the reaction mixture was precipitated in ice-chilled heptane and purified by subsequent size exclusion chromatography over a Bio-Beads SX-1 column with dichloromethane as the eluent. After solvent removal in vacuo, a highly viscous yellow oil was obtained for both generations (20 and 21) prepared. O HO O O O O O O 19 O O O 121 Scheme 7. Peak Numbering and Cartoons of BMP32C10 Functionalized Poly(propyleneimine) Dendrimers 20 and 21 with Paraquat Diol 22•2PF6. O O O O O Hb O O O O O CH2CO2CHN NHCO2 CH2 O N N O O O O Hb, ar O Ha O O Hc O O O O O O O O CH2CO2CHN O O O O NHCO2 CH2 O O O O O 20 O O O O O O O O O O O O O O O 19 2 P F6 HO + - 21 N+ OH N 22 122 20: Chemical yield: 93% (860 mg). 1H-NMR (CDCl3, 400 MHz) δ 1.38 (4H, br), 1.60 (8H, br), 2.34 (4H, br), 2.40 (8H, br), 3.18 (8H, q, J = 6 Hz), 3.68 (64H, s), 3.81 (32H, quint. 5 Hz), 4.04 (32 H, quint, J = 5 Hz), 4.96 (8H, s), 5.68 (4H, br), 6.40 (4H, s), 6.47 (20H, m), 7.11 (4H, t, J = 8 Hz). 13 C-NMR (CDCl3, 100 MHz) δ 25.1, 27.4, 40.3, 52.3, 53.8, 54.1, 66.5, 67.8, 69.9, 71.1, 101.1, 101.9, 106.8, 107.3, 129.9, 139.1, 156.5, 160.0. IR: νmax 3339 (w, br), 2926 (m), 2871(m), 1713 (s), 1594 (s), 1494 (s), 1125 (s), 1067 (s) cm-1. m/z (MALDI-TOF) 2709 [M + Na]+. 21: Chemical yield: 83% (362 mg). 1H-NMR (CDCl3, 400 MHz) δ 1.36 (4H, br), 1.441.64 (56H, br), 2.28-2.44 (84H, br), 3.10-3.18 (32H, br), 3.60-3.64 (128H), 3.72-3.80 (128H, br), 3.96-4.06 (128H br), 4.92 (32H, s), 5.76-5.90 (16H, br), 6.37 (H, br.), 6.406.48 (112H, m, br), 7.09 (16H, t, J = 8 Hz). 13 C-NMR (CDCl3, 100 MHz) δ 24.2, 27.3, 39.8, 51.7, 52.2, 66.2, 67.6, 69.7, 70.8, 100.9, 101.8, 106.7, 107.2, 129.9, 139.1, 156.6, 160.0. IR: νmax 3339 (w.br), 2926 (m), 2870(m), 1711 (s), 1594 (s), 1449 (s), 1125 (s), 1067 (s) cm-1. m/z (MALDI-TOF) 11167 [M + H]+. 123 III.1.1.3.1.2 Complexation of 20 and 21 with 22•2PF6 Continuous titration in acetone-d6 at ambient temperature (21.8 oC) was employed to study the binding behavior of the BMP32C10 functionalized dendrimers, 20 and 21, with paraquat diol 22•2PF6 using 1H NMR spectroscopy. Upon mixing the first and third generation dendritic hosts with the bipyridine salt 22•2PF6, a bright orange colored solution resulted, indicating rapid pseudorotaxane or cradled barbell formation via through space π-stacking interactions of host and guest. [28, 42] Additionally, the time averaged signals of Ha as well as Hb,aromatics (see Scheme 7 for proton assignments, as well as Tables 2 and 3) were shifted upfield relative to those of pure 20 and 21 upon complexation with 22•2PF6.† III.1.1.3.2 RESULTS AND DISCUSSION As the BMP32C10 host + 22•2PF6 supramolecular complexes exhibit fast exchange on the NMR time scale, analysis of the multi-functional dendritic system proves difficult. First, and as described in section II.2.0, not known are δHG, or the chemical shift of the fully complexed components, and the mole fractions of complexed versus uncomplexed species, NHG and NG. Second, the existing methods to solve for such unknowns are useful only for systems void of allosteric, or cooperative, effects. To describe cooperativity, the Hill equation must be used (see Appendix I). However, the unknowns from above cannot be derived graphically using Hill plots. In an effort to decipher the multi-site binding present in the complexation of 20 and 21 with 22•2PF6, results from the simple crown + guest systems studied by Gibson et al. [42] have been utilized. Gibson and co-workers studied the complexation of diacetoxymethyl BMP32C10 (23) with 22•2PF6 at 21.8 oC. Importantly, the constant ∆0, The binding of 22•2PF6 by 20 has also been investigated by low temperature 1H NMR. In the low temperature studies, the time averaged 1H NMR signals were determined to coalesce at –45 oC. However, analysis of the separated signals yielded inconclusive results. † 124 Table 2. 1 H NMR (400 MHz, 21.8 oC, acetone-d6) Shifts of Ha and Hb,aromatics of 20 Upon Continuous Titration with 22•2PF6. [20]0 (mM) 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 [host]0 (mM) 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 [guest]0 / [host]0 0 1 2 3 4 5 7 10 13 16 20 25 δ Ha (ppm) 7.134 7.041 7.016 6.996 6.982 6.968 6.945 6.917 6.902 6.892 6.878 6.870 δ Hb, Aromatics (ppm) 6.458 6.337 6.291 6.256 6.233 6.208 6.169 6.122 6.097 6.079 6.059 6.039 [22•2PF6 ]0 (mM) 0.000 3.227 6.252 9.094 11.77 15.50 21.06 30.24 39.41 48.29 60.02 75.02 Table 3. 1 H NMR (400 MHz, 21.8 oC, acetone-d6) Shifts of Ha and Hb,aromatics of 21 Upon Continuous Titration with 22•2PF6. [21]0 (mM) 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 [host]0 (mM) 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 [guest]0 / [host]0 δ Ha (ppm) 7.121 7.103 7.091 7.084 7.074 7.071 7.061 7.049 7.037 7.029 7.017 7.000 6.992 6.981 6.965 6.958 6.964 6.934 6.935 6.925 6.916 6.907 δ Hb, Aromatics (ppm) 6.500 6.458 6.439 6.422 6.408 6.396 6.381 6.349 6.328 6.313 6.291 6.268 6.248 6.234 6.224 6.207 6.201 6.186 6.174 6.158 6.148 6.125 [22•2PF6 ]0 (mM) 0.000 0.489 1.421 2.295 3.117 3.891 5.313 7.458 9.720 11.93 14.92 18.64 22.37 25.87 31.06 34.45 37.79 41.07 45.90 52.17 59.73 67.01 0 0.167 0.500 0.714 1.0 1.2 1.8 2.5 3.2 4 5 6 7.4 8.6 10.4 11.5 12.6 13.7 15.3 17.4 19.9 22.3 125 or the absolute chemical shift difference between the fully complexed and the fully uncomplexed species, has been described for the model system. [42] Having in hand ∆0 from the simple 1:1 case for proton Ha of 23 (∆0 = 0.5427), which corresponds to Hb+aromatics in 20 and 21, it is possible to estimate the fraction of total binding sites occupied, θ, by determining the ratio ∆ / ∆0 (recall from chapter II.2.0.1 that ∆ / ∆0 is referred to as the saturation factor and is equivalent to θ).† [42] Furthermore, the equilibrium concentration of guest, [22•2PF6]uc, may be estimated by equation 18. [22 • 2PF6 ]uc = [22 • 2PF6 ]0 - (θ x [20 or 21]0 ) (18) Thus, all unknowns may be estimated from the model case (see Tables 4 and 5). The resulting Scatchard plots‡ (Figures 13 and 14) are non-linear, indicating that the binding sites are not independent; the concave slopes indicate anti-cooperative binding. [33-35] Consequently, the data was interpreted using the Hill-equation (see equation 1 above or Appendix I, equation 17). O CH3COCH2 O O O O O O CH2OCCH3 O O O O O 23 † ‡ In both cases, the fractional binding (∆ / ∆0) falls within the 20-70% range (see Appendix I, Figure 2). While it is possible to interpret the data based on Ha of 20 and 21, the following analyses utilize by convention the observed shifts of Hb,aromatics, as these protons exhibit the greatest environmental change (∆). 126 Table 4. Values for the Binding of 22•2PF6 by 20.a [20]0 (mM) 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 0.7443 [Crown]0 [22•2PF6]uc (mM) 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 2.977 (mM) 0.000 2.563 5.336 7.985 10.53 14.13 19.47 28.40 37.43 46.21 57.83 72.72 ∆a (ppm) 0.000 0.093 0.118 0.138 0.152 0.166 0.189 0.217 0.232 0.242 0.256 0.264 ∆/∆0a (θ) (Ha) 0.000 0.171 0.217 0.254 0.280 0.306 0.348 0.400 0.427 0.446 0.472 0.486 Calc Ka b [22•2PF6]0 (mM) 0.000 3.227 6.252 9.094 11.77 15.50 21.06 30.24 39.41 48.29 60.02 75.02 a ∆b,aromatics (ppm) 0.000 0.121 0.167 0.202 0.225 0.250 0.289 0.336 0.361 0.379 0.399 0.419 ∆/∆0a (θ) (Hb,ar) 0.000 0.223 0.308 0.372 0.415 0.461 0.533 0.619 0.665 0.698 0.735 0.772 Calc Ka b (Ha, M ) 0 81 52 43 37 31 27 23 20 17 15 13 -1 (Hb,ar, M ) 0 112 83 74 67 60 59 57 53 50 48 47 -1 ∆0 defined as the average value determined by the Benesi-Hildebrand, Scatchard, and Creswell-Allred plotting techniques found by Gong et al. for proton Ha in the association of paraquat diol bis(hexafluorophosphate) (22) with bis(5-acetoxymethyl-1,3-phenylene)32-crown-10 (23) at 21.8 oC; ave. ∆0 = 0.5427. [42] b The calculated Ka is a macroscopic association constant, given as the average among all four crown moieties. 127 Table 5. Values for the Binding of 22•2PF6 by 21.a [22•2PF6 ]0 [21]0 (mM) 0.000 0.489 1.421 2.295 3.117 3.891 5.313 7.458 9.720 11.93 14.92 18.64 22.37 25.87 31.06 34.45 37.79 41.07 45.90 52.17 59.73 67.01 [Crown]0 [22•2PF6 ]uc (mM) 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 3.008 ∆a (ppm) 0.000 0.018 0.030 0.037 0.047 0.050 0.060 0.072 0.084 0.092 0.104 0.121 0.129 0.140 0.156 0.163 0.157 0.187 0.186 0.196 0.205 0.214 ∆/∆0a (θ) Calc Kab ∆b,aromatics ∆/∆0a (θ) Calc Kab (Ha) 0.000 0.033 0.055 0.068 0.087 0.092 0.111 0.133 0.155 0.170 0.192 0.223 0.238 0.258 0.287 0.300 0.289 0.345 0.343 0.361 0.378 0.394 (mM) 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 0.1880 (mM) 0.000 0.256 1.082 1.862 2.607 3.315 4.653 6.621 8.767 10.90 13.76 17.36 20.98 24.39 29.53 32.83 36.13 39.33 44.10 50.27 57.78 64.93 (Ha, M ) 0 134 54 39 36 31 27 23 21 19 17 17 15 14 14 13 11 13 12 11 11 10 -1 (ppm) 0.000 0.042 0.061 0.078 0.092 0.104 0.119 0.151 0.172 0.187 0.209 0.232 0.252 0.266 0.276 0.293 0.299 0.314 0.326 0.342 0.352 0.375 (Hb,ar) 0.000 0.077 0.112 0.144 0.170 0.192 0.219 0.278 0.317 0.345 0.385 0.428 0.464 0.490 0.509 0.540 0.551 0.579 0.601 0.630 0.649 0.691 (Hb,ar, M ) 0 327 117 90 78 72 60 58 53 48 46 43 41 39 35 36 34 35 34 34 32 34 -1 a ∆0 defined as the average value determined by the Benesi-Hildebrand, Scatchard, and Creswell-Allred plotting techniques found by Gong et al. for proton Ha in the association of paraquat diol bis(hexafluorophosphate) (22) with bis(5-acetoxymethyl-1,3-phenylene)-32-crown10 (23) at 21.8 oC; ave. ∆0 = 0.5427. [42] The calculated Ka is a macroscopic association constant, given as the average among all four crown moieties. 128 b Figure 13. 100 80 / [G] uc 60 40 20 0 Scatchard Plots for the Binding of 20 and 21 with 22•2PF6, Based on Hb,aromatics . 20 + 22•2PF6 21 + 22•2PF6 0.10 0.30 0.50 0.70 0.90 θ Figure 14. 0.80 0.60 0.40 log[ θ / (1- θ )] 0.20 0.00 -0.20 -0.40 -0.60 -0.80 -2.75 Hill Plots for the Binding of 20 and 21 with 22•2PF6, Based on Hb,aromatics. -1.77 -1.60 -2.50 -2.25 -2.00 -1.75 log[G]uc -1.50 -1.25 20 + 22•2PF6 21 + 22•2PF6 -1.00 -0.75 129 For both generations the Hill coefficient is somewhat less than unity (Figure 14, Table 6), confirming that binding is anti-cooperative. Two possibilities exist which may account for such allosteric behavior. First, the crown ether may adopt a “cradled barbell” formation around the inflexible paraquat guest, leading to steric crowding about the periphery of the crown ether functionalized dendrimer, which would result in anticooperative binding behavior. [44] Secondly, the complex may adopt a pseudorotaxane conformation. The electrostatic repulsions amongst neighboring guest moieties may thereby inhibit subsequent guest binding. Unlike the 24C8 functionalized dendrimers of Section III.1.1.2, binding appears to be influenced by generation size. As can be seen from Figure 13, 20 + 22•2PF6 displays a more pronounced binding curve than does 21 + 22•2PF6, indicating that binding of 22•2PF6 is facilitated by 20 relative to 21. Additionally, and as demonstrated in Figure 14, at the 50% loading point [log (θ / 1-θ ) = 0.00], the first generation dendrimer 20 shows a [G]uc of 0.017 versus 0.025 for the third generation dendrimer 21. Thus, the binding efficiency of 20 is greater than that of 21. This finding is not unexpected: if the crown ether adopts a “cradled barbell” formation around the inflexible paraquat guest, a higher degree of steric crowding about the periphery of the larger crown ether Table 6. Hill Coefficients and Association Constants for the Complexation of Dendrimers 20 and 21 with 22•2PF6. Dendrimer 20 21 n 4 16 nH pK a R 2 0.8 ± 0.1 1.0 ± 0.1 0.7 ± 0.1 1.0 ± 0.1 0.997 0.996 130 ether functionalized dendrimer would result relative to 20. If, instead, the complex adopts a pseudorotaxane formation, the greater steric affects (in the form of electrostatic repulsions amongst neighboring guest ions) at the periphery of the larger dendrimer would again result in less efficient binding than in dendrimer 20. Additional information on the nature of host:guest interaction was derived from protonation studies conducted on the BMP32C10 functionalized poly(propyleneimine) dendrimers (Table 7, Figure 15) . Much like the protonation studies performed in section III.1.1.2.2, the amines of the dendritic framework 21 were protonated by the addition of an equivalent amount of trifluoroacetic acid. Because paraquat diol does not have acidic hydrogen atoms with which to donate to the poly(propyleneimine) dendrimers, protonation of 21 a priori furthers discussion on the influence of host conformations.† Interestingly, the Scatchard plot (Figure 16) shows a linear trend (R=0.9837) indicating independence of binding sites. This observation may be explained by rigidification of the dendrimer in which the macromolecule is electrostatically forced to adopt a conformation that maximizes host binding site separation. Standing in contrast to the DB24C8 functionalized dendrimers, larger crown ethers are not known to perch 1o ammonium ions and therefore do not experience the envisioned gain in entropy (and subsequent loss in free energy) associated with host rearrangement from perched to pseudorotaxane complexation. Instead, the acidified conformation may assist in overcoming the anticooperative influence of neighboring guest pseudorotaxanes, resulting in an independent binding regime. All of the above results should be compared to the linear main chain polypseudorotaxane prepared by Gibson et al. in which a poly(ester BMP32C10 ether) undergoes complexation with 22•2PF6 in a non-allosteric fashion. [42] While direct comparison between systems is difficult, one might predict that the crown ether in the main chain polypseudorotaxane has a much higher barrier to folding than does the corresponding crown in the polypoly(propyleneimine) dendrimer. Ergo, formation of a cradled barbell-like polypseudorotaxane would be less likely in the linear polymer. Furthermore, the host moieties of the linear polymer are confined within the chain. They † While the BMP32C10 moiety is fundamentally different than that discussed in Appendix II, the influence of a second counter ion has again been neglected in the analysis of protonated 21. 131 Figure 15. H NMR (400 MHz, 21.8 oC, acetone-d6) Shifts of Ha and Hb,aromatics of Protonated 21 Upon Continuous Titration with 22•2PF6. 1 [Guest]0 / [Host]0 434 190 78 34 Ha Hb,ar 0 132 Table 7. H NMR (400 MHz, 21.8 oC, acetone-d6) Shifts of Ha and Hb,aromatics of Protonated 21 Upon Continuous Titration with 22•2PF6. [20]0 (mM) 0.0000 3.2258 6.2500 9.0909 14.2857 21.0526 34.7826 45.4545 67.0330 79.5918 [host]0 (mM) 2.936 2.936 2.936 2.936 2.936 2.936 2.936 2.936 2.936 2.936 [guest]0 / [host]0 δ Ha (ppm) 7.131 7.086 7.063 7.043 7.016 6.987 6.951 6.943 6.927 6.919 δ Hb, Aromatics (ppm) 6.500 6.414 6.368 6.331 6.283 6.240 6.184 6.168 6.136 6.123 1 [22•2PF6 ]0 (mM) 0.1835 0.1835 0.1835 0.1835 0.1835 0.1835 0.1835 0.1835 0.1835 0.1835 0.0 17.6 34.1 49.5 77.9 114.7 189.6 247.7 365.3 433.7 Figure 16. 0.07 0.06 0.05 θ / [S]eq 0.04 0.03 0.02 0.01 The Scatchard Plot for the binding of 22•2PF6 by Protonated 21. y = -0.085x + 0.0665 R2 = 0.9837 0.00 0.10 0.20 0.30 0.40 θ 0.50 0.60 0.70 0.80 133 are therefore less likely to interact with neighboring crown ethers due to mobility restraints than are the corresponding surface bound hosts of the dendrimer. All of these predictions would result in a system less likely to experience anticooperative interactions. These results may also be compared to the linear polymethacrylate copolymers containing hydroxymethyl DB24C8, which bind dibenzyl ammonium guest ions in an anti-cooperative manner (see section III.1.1.2.2, p. 132), [37] and may be contrasted with the DB24C8 functionalized dendrimers as discussed above. II.1.1.3.3 Conclusion dendrimers functionalized with The construction of polypseudorotaxanes or poly(pseudo-like rotaxanes) have been prepared utilizing polypoly(propyleneimine) BMP32C10 moieties, which bind anti-cooperatively with paraquat diol guest molecules. Further work must be done to investigate the anti-cooperative nature of complexation, focusing on the structure of the supramolecular complex formed. 134 III.1.2 REFERENCES [1] [2] [3] [4] [5] [6] Flory, P. J. J. Am. Chem. Soc. 1941, 63, a) 3083. b) 3091. c) 3096. d) Flory, P. J. J. Am. Chem. Soc. 1942, 46, 132. Flory, P. J. J. Am .Chem. Soc. 1952, 74, 2718. Buhleier, E. W.; Wehner, V.; Vögtle, F. Synthesis 1978, 155. 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Utilization of ∆o as determined for the model complex [ref 42] is an approximation that allows the system to be analyzed without assumptions about cooperativity. It is noteworthy that the ∆o value for a polyester analog of 23 in complexation with 22 was very similar (0.5321). An error in ∆o of 0.01 would result in a relative error of ≤ 2% in ∆ / ∆o in the 0.2 – 0.8 complexation range. [44] To date, no pseudorotaxane crystal structures of the complex formed between BMP32C10 crowns + paraquat derivatives exist in the literature. There are, however, multiple reports of cradled barbell formation between the same components. Nevertheless, pseudorotaxane formation of BMP32C10 + PQ has been shown to exist in the formation of catenane structures. 138