New Insights into Interactions between Dendrimers and Surfactants. 4

Apr 16, 2010 - (1) Surfactant monomers can form globular aggregates through ... (AFM),(50) fluorescence spectroscopy,(50-54) Krafft temperature,(55) ...
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New Insights into Interactions between Dendrimers and Surfactants. 4. Fast-Exchange/ Slow-Exchange Transitions in the Structure of Dendrimer-Surfactant Aggregates Min Fang,†,‡ Yiyun Cheng,*,†,§ Jiahai Zhang,| Qinglin Wu,| Jingjing Hu,† Libo Zhao,† and Tongwen Xu*,† CAS Key Laboratory of Soft Matter Chemistry, School of Chemistry and Material Science, UniVersity of Science and Technology of China, Hefei, Anhui, 230026, People’s Republic of China, School of Life Sciences, East China Normal UniVersity, Shanghai, 200062, People’s Republic of China, Department of Chemistry, Anhui UniVersity, Hefei, Anhui, 230027, People’s Republic of China, and Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, UniVersity of Science and Technology of China, Hefei, Anhui, 230027, People’s Republic of China ReceiVed: January 27, 2010; ReVised Manuscript ReceiVed: March 12, 2010

The interactions between poly(amidoamine) (PAMAM) dendrimer and surfactant (sodium dodecyl sulfate, SDS) in aqueous solutions were investigated by a combination of 1H NMR, diffusion measurements (PFG NMR), and NOE techniques. The diffusion studies suggested that different types of dendrimer-surfactant aggregates are formed by varying surfactant concentrations in the dendrimer solution. The 1H NMR analysis proved that the presence of fast-exchange/slow-exchange transitions in the dendrimer-surfactant aggregates. The supramolecular structure of the aggregate was based on the hydrophobic interactions between the dendrimer scaffold and the surfactant aliphatic chain, as well as electrostatic/hydrogen-bond interactions between dendrimers and SDS monomers, bilayers, or globular micelles. In comparison with previous investigations, the present study provides a new insight into interactions between dendrimers and surfactants, which may be helpful for the design of dendrimer-based microreactors or nanovehicles. 1. Introduction Surfactant, the shortened form of “surface-active agent”, is an amphiphilic molecule containing hydrophobic chains and hydrophilic heads. It stabilizes mixtures of oil and water by reducing the surface tension at the interface between them.1 Surfactant monomers can form globular aggregates through hydrophobic or dipole-dipole in solutions. The concentration at which the surfactant begins to form micelles is known as the critical micelle concentration (cmc). Due to their unique physicochemical properties, surfactants have been widely used as detergents, foamers, wetting agents, solubilizers, emulsifiers, and cosmetic additives.2,3 Polymer-surfactant systems are the subject of significant research interest.4-9 The addition of polymers into the surfactants significantly influences the properties of the surfactant solutions such as rheology, viscosity, electroconductivity, transparence, and interfacial properties due to several types of intermolecular interactions.4 These interactions include hydrophobic interactions between the hydrophobic chains of polymer and surfactant and electrostatic or hydrogenbond interactions between the polymer and the hydrophilic head of surfactant.10,11 The hydrophobic chains and charged groups in the polymer facilitate the formation of surfactant micelles. As a general trend, the presence of polymers decreases the cmc of the surfactant to a lower concentration known as the critical aggregation concentration (cac), especially if the polymer has * To whom correspondence should be addressed. E-mail: yycheng@ mail.ustc.edu.cn (Y.C.), [email protected] (T.X.). † CAS Key Laboratory of Soft Matter Chemistry, School of Chemistry and Material Science, University of Science and Technology of China. ‡ Anhui University. § East China Normal University. | Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China.

opposite charges compared to the surfactant.4 Water-soluble polymers such as poly(ethylene oxide)(PEO),4,12-14 poly(vinylpyrrolidone)(PVP),8 poly(styrene sulfonate) (PSS),15 and poly(acrylic acid) (PAA)5,15-18 have been used to optimize the physicochemical properties of surfactants like sodium dodecyl sulfate (SDS) and dodecyltrimethylammonium (DTAB). As a new class of artificial polymers, dendrimer with unique properties like monodispersity, globular shape, well-defined size and number of peripheral groups, and relative nonpolar cavities, is considered as an exciting and promising “star” in miscellaneous fields.19-25 The dendrimer chemistry has brought out lots of versatile macromolecules since the first report on the successful synthesis of dendrimers by Tomalia et al. in 1985.26 This new field is of great interest to both academic researches and industrial applications.27-46 The well-defined number of functional groups (amine, carboxyl, or hydroxyl groups) on the dendrimer surface and the nonpolar pockets in the dendrimer interior provide the abilities of dendrimers to bind or encapsulate different kinds of guests.23,47 Surfactants are ideal guests for dendrimers because of their amphiphilic properties and nanoscaled sizes.4,17,18 In addition, the interactions between dendrimers and surfactants are helpful to the design, understanding, and optimization of new polymer-surfactant systems. Therefore, the studies on the structure, nature, and interaction mechanisms of dendrimer-surfactant aggregates are of fundamental significance to both dendrimer-based host-guest systems and polymer-surfactant systems. In the past decade, techniques including electrical conductivity,48 surfactant selective electrode,9,17 surface tension, viscosity,49 isothermal titration calorimetry (ITC),9,14 atom force microscopy (AFM),50 fluorescence spectroscopy,50-54 Krafft temperature,55 electromotive force (EMF),9 dynamic light scattering (DLS),56 small angle neutron scattering (SANS),9 and

10.1021/jp100805u  2010 American Chemical Society Published on Web 04/16/2010

Exchange Transitions in PAMAM-SDS Aggregates electron paramagnetic resonance (EPR)57 were used to investigate the structure of dendrimer-surfactant complexes. Tomalia and Turro reported the presence of noncooperative and cooperative interactions between dendrimers and ionic surfactants. EPR studies using paramagnetic probe labeled surfactants revealed that there are several types of dendrimer-surfactant aggregates depending on dendrimer generation, system temperature, and dendrimer-surfactant concentration.57,58 Esumi and Bakshi emphasized the importance of ionic interactions between dendrimers and ionic surfactants (SDS and DTAB) in the formation of aggregates.53,55 The binding of surfactant molecules on the surface of functional dendrimers was proposed. WynJones et al. obtained the cac of different types of surfactants (cationic, anionic, and nonionic) in the presence of dendrimers by surfactant-selective electrode, SANS, and ITC.9 Dendrimer generation slightly influences the cac of surfactants but significantly affects the saturated binding concentration (Csat), while the dendrimer surface functionality plays an important role in the dendrimer-surfactant interaction. Cheng and Xu provided new insights into the system by different NMR techniques that molecular inclusion participates in the intermolecular interactions between dendrimers and surfactants.59-61 The localization of surfactant monomers in the dendritic pockets depends on dendrimer generation, surfactant concentration, and dendrimersurface charge. Although lots of studies focused on the interactions between dendrimer and surfactant have been conducted, the detailed interaction mechanisms are not clear. Insights into intermolecular interactions, physicochemical properties, and dynamics of the dendrimer-surfactant complexes are still lacking. Here we investigated the aggregate structure of dendrimer-SDS complexes by a combination of 1H NMR titration, diffusion measurement, and nuclear Overhauser enhancement (NOE) analysis. 1H NMR titrations were used to analyze the types of interaction force between dendrimer and surfactant, and the exchange rate between bound-surfactant and free-surfactant in the complexes. The diffusion measurement (pulsed field gradient, PFG NMR) was used to characterize the size of the aggregates, and the molar fractions of the bound and free surfactants. NOE analysis was used to confirm the presence of surfactant encapsulation in the dendrimer-surfactant complexes. To the best of our knowledge, this is the first report on the fastexchange/slow-exchange transitions in the dendrimersurfactant systems. 2. Experimental Section 2.1. Materials. Generation 4 (G4) ethylenediamine (EDA)cored and primary amine-terminated poly(amidoamine) (PAMAM) dendrimer was purchased from Dendritech, Inc. (Midland, MI). The average number of primary amine groups on the surface of G4 dendrimer in this study is measured to be 62.7 (the theoretical number is 64) by a ninhydrin assay. The molecular weight of the G4 dendrimer is 14 195 by MALDITOF mass spectrum, and the polydispersity index of the polymer is 1.01 characterized by gel permeation chromatography. The hydrodynamic diameter of G4 dendrimer is calculated to be 4.5 nm by the pulsed field gradient spin-echo method and Einstein-Stocks equation. SDS and 1,4-dioxane were obtained from Shanghai BBI Co. Ltd. (Shanghai, China). Deuterium oxide (D2O) was obtained from Beijing Chongxi High-Tech Incubator Co., Ltd. (Beijing, China). PAMAM dendrimer stored in methanol solution was distilled to remove the solvent before the NMR studies. G4 dendrimer aqueous solutions (10 mg/mL) were prepared and used as stock solutions.

J. Phys. Chem. B, Vol. 114, No. 18, 2010 6049 2.2. NMR Experiments. 1,4-Dioxane was used as an internal standard in the 1H NMR and diffusion measurements. All 1H NMR spectra of dendrimer-SDS complexes in D2O solutions were obtained with a 500.132 MHz NMR spectrometer (Bruker, German) at 298.2 ( 0.1 K. The self-diffusion coefficient was measured for dendrimerSDS complexes in D2O by the pulsed field gradient spin-echo pulse sequence.62 The intensity of the spin-echo signal is given by the following equation:

A(δ) ) A(0) exp[-γ2Dδ2(∆ - δ/3)g2]

(1)

where A(δ) and A(0) are the intensities of spin-echo signal when the sine-shaped field gradient is present and absent. D is the self-diffusion coefficient for dendrimer or surfactant, γ is the proton magnetogyric ratio (2.68 × 108 s-1 T-1), ∆ is the time interval between gradient pulses (600 ms), δ is the duration of gradient pulses (3 ms), and g is the strength of gradient pulse; the strength g of the pulses was increased in a linear sequence from 10% to 90% of 10 G/cm in eight steps to attenuate the spin-echo signal. The self-diffusion coefficient D was obtained by fitting the spin-echo data by eq 1. Two-dimensional NOESY experiments were obtained for dendrimer-SDS complex solutions at 500.132 MHz with a mixing time of 300 ms and 8.2 µs 1H 90° pulse width.59,63-65 The relaxation delay and acquisition time were set at 2 s and 205 ms, respectively. Eight transients were averaged for each 400 × 1024 complex t1 increments. The data were processed with Lorentz-Gauss window function and zero-filling in both dimensions to display data on a 2048 × 2048 2D matrix. All data were processed with NMRPipe software on a Linux workstation. 3. Results and Discussion NMR is a real-time, in situ, noninvasive, sensitive, and powerful method for the determination of intermolecular interactions, especially for the noncovalent interactions between a ligand and a receptor.66 It gives information on the formation of aggregates, ion pairing, encapsulation, molecular orientation, and size variation. In a ligand and receptor binding system, the molecular recognition of the ligand to the receptor will induce the following changes: (1) decreased self-diffusion coefficient of the ligand and the receptor, (2) decreased spatial distance between the ligand and receptor nuclei which causes the presence of NOE interactions between the nuclei, (3) chemical shift of ligand-receptor nuclei, and (4) relaxation behavior of the ligand and receptor molecules. Here we use diffusion analysis, NOE measurement, and 1H NMR titration to investigate the structure of dendrimer-surfactant aggregates. PAMAM dendrimers belong to the first dendrimer family to be commercialized and represent the most extensively characterized and frequently applied series, while SDS was the most investigated anionic surfactant in the literature. Therefore, PAMAM dendrimer and SDS were selected as models of the receptor and ligand in the present study. 3.1. Structures of Dendrimer-Surfactant Aggregates Determined from Diffusion and NOE Measurements. Selfdiffusion is the random translational motion of a molecule driven by its internal kinetic energy. The diffusion coefficient of a molecule in solution depends on the molecular size, the systematic temperature, and the solvent viscosity.66 The diffusion coefficient can be converted into the hydrodynamic radius (rs) of the molecule through the Stocks-Einstein equation:

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D)

kT 6πηrs

Fang et al.

(2)

where k is the Boltzmann constant, T is the systematic temperature, η is the viscosity of the solution, and rs is the effective hydrodynamic radius of a spherical particle. The size is informative on the determination of the complex structure. If there is a specific interaction such as ionic pairing, molecular encapsulation, self-assembly, and aggregation between dendrimer and surfactant, the molecular size of surfactant significantly increases, while the relaxation time and the self-diffusion coefficient of the aggregate decrease in comparison with the free state. It is not surprising that the diffusion measurements such as PFG spin-echo NMR and DOSY experiments have become important tools in such ligand-receptor recognition studies. PFG studies are able to determine association constant, number of binding sites, and aggregation sizes in the dendrimersurfactant systems.67 The DOSY spectrum, in which the components of a mixture are separated by self-diffusion of the compound, has boosted the popularity of diffusion NMR. The data can be displayed as a high-resolution pseudo-2D NMR spectrum with chemical shift and diffusion coefficient in two dimensions.66 It is able to identify compounds bound to a specific receptor in NMR screening.67 Here, we use the PFG NMR technique to characterize the hydrodynamic size of both dendrimer and SDS in the complex solution. The self-diffusion coefficient of SDS obtained from PFG NMR studies in the presence of PAMAM dendrimer is shown in Figure 1. The diffusion coefficient of 1,4-dioxane in dendrimer/D2O solution does not change during the addition of surfactant, indicating that there is no change in solution viscosity in this period. The increase or decrease in SDS (dendrimer) diffusion coefficient is solely attributed to the variation of molecular size. When the SDS/dendrimer ratio ranges from 4 to 16, the diffusion coefficient of SDS linearly decreased. If the diffusion coefficient of SDS is influenced by the presence of dendrimer, the following interactions can be considered: hydrogen-bonding, ion-pair/ion-dipole, and molecular inclusion. The decreased SDS mobility is probably due to the ionic (hydrogen-bond) attachment of SDS monomers on the surface of dendrimer or molecular encapsulation of SDS in the interior of dendrimer pockets.59,63 The pure SDS diffusion coefficient in D2O is around 4.3 × 10-10 m2/s at a concentration below the cmc of SDS (8 mM), while the pure dendrimer value is about 8 × 10-11 m2/s. In this range, the diffusion coefficient of SDS in the complex solution approaches that of the dendrimer, indicating that the SDS monomer strongly binds to the dendritic host and moves at a rate close to that of the dendrimer. Therefore, SDS should be encapsulated in the interior pocket rather than on the surface at this stage. This conclusion is further confirmed by the NOE analysis. NOESY analysis is capable of revealing spatial relationships among protons in a complex of molecules.68-72 If the protons of dendrimer and SDS are within a distance of 5 Å, cross-peaks should be seen in the corresponding spectral region at a sufficiently short mixing time. Indirect magnetization transfer occurring at long mixing times gives rise to pseudo-cross-peaks in the NOESY spectrum. However, the NOE measurements at a mixing time of 100-500 ms can exclude the contribution of indirect magnetization transfer between the protons.59 Here, the NOESY spectra of dendrimer-SDS (molar ratio of SDS and dendrimer is 8 and 128) in D2O at a mixing time of 300 ms are shown in Figure 2 and Figure S1 (Supporting Information), respectively. Strong NOE interactions between protons (3) and protons (a-d) of G4

Figure 1. Diffusion coefficient of SDS in the presence of G4 PAMAM dendrimer as a function of the SDS/G4 dendrimer molar ratio (G4 dendrimer concentration being a constant of 2 mg/mL).

Figure 2. The 1H-1H NOESY spectrum of G4 dendrimer/SDS/D2O at a mixing time of 300 ms (SDS/dendrimer molar ratio is 8, dendrimer concentration is 2 mg/mL).

dendrimer are observed. The presence of NOE cross-peaks between protons of dendrimer and SDS cannot be explained by the attachment of SDS on dendrimer surface because the distance between protons in the two species are out of the distance limit of 5 Å.59,73 In combination with the results from dendrimer-DTAB and dendrimer-bile salt systems,61 the NOE cross-peaks can be used to conclude the formation of molecular inclusions in the dendrimer-SDS complex (Figure 3). Additional evidence from 1H NMR titrations on this issue will be given in section 3.2. It is worth noticing that the cac of SDS in the presence of G4 amine-terminated PAMAM dendrimers was reported to be 0.7 mM in EMF or SDS selective electrode studies.9 However, the PFG NMR results indicate that the interaction of dendrimer and SDS begins at a concentration lower than the value (0.7 mM corresponds to the SDS/dendrimer ratio of 5 in the study). This is due to the high sensitivity of NMR techniques in the determination of intermolecular interactions. Later on, the diffusion coefficient of SDS significantly increases when the ratio of SDS and dendrimer increases from 16 to 128. It is well-known that if there is a fast exchange (lifetime of the complex is short on time scale of NMR) between the free and bound ligand, the observed diffusion coefficient

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Figure 3. Cross sections taken at the position of protons (a-d) in dendrimer along ω1 from 1H-1H NOESY spectrum of G4 dendrimer/SDS/D2O (SDS/G4 ratio is 128) at a mixing time of 300 ms.

will be a time-weighted average of the free state and bound state of the ligand,74 and can be described by the following equation:

Dobs ) DfPf + DbPb

(3)

where Dobs, Df, Db are the observed, free-state, and bound-state diffusion coefficient, respectively, while Pf and Pb are the fractions of free state and bound state, respectively. Here, Pf +Pb ) 1. During this period, the free SDS concentration in the solution increases, causing the increase of observed selfdiffusion coefficient of SDS. Though the lowest diffusion coefficient at SDS/dendrimer ratio of 16 is not the real saturated SDS concentration encapsulated in the dendritic cavities, we define it as Csat to help with the analysis of generation effect on the encapsulation in the future. Again, we observed the decrease of SDS diffusion coefficient with SDS concentration in the molar ratio range of 128-1024. This is due to the formation of SDS bilayers and SDS globular micelles at this stage. The cmc of SDS in the absence of dendrimer is 8 mM, which corresponds to the SDS/dendrimer ratio range of 32-64 in this study. The increase in SDS concentration causes two effects: (1) the enhancement of freestate fraction increases the SDS diffusion coefficient in the mixing system, and (2) the formation of SDS bilayers or micelles in the concentration above the cmc of SDS causes the decrease in the mobility of SDS. Therefore, the observed diffusion coefficient of SDS can be described as

Dobs ) DfPf + DbPb + DmPm

(4)

where Dm is the diffusion coefficient of the SDS micelle, and Pm is the fraction of micelle in the mixture.74 Here, Pf +Pb + Pm ) 1. The amount of SDS monomers encapsulated in the dendritic pockets keeps constant in this period, while the amount of SDS attached on the surface of dendrimer by ionic/ion-dipole interactions or hydrogen-bond interactions increases with increasing SDS concentration. Therefore, a competition among bound-SDS, free-SDS, and micelle-SDS occurs in the solution, which generates a maximum value of diffusion coefficient at the SDS/dendrimer ratio of 128 in Figure 1. Above the ratio of 128, a significant decrease of SDS diffusion coefficient was observed, indicating the formation of stable dendrimer-SDS aggregates. SDS bilayer micelles may form on the surface of dendrimers and further decrease SDS diffusion coefficient. Also, the ionic/ion-dipole interactions between SDS globular micelle and dendrimer increase the “size” of SDS in the solution. As a result, the mobility and relaxation of SDS monomers in these structures decrease. This is in accordance with the decrease in G4 diffusion coefficient as shown in Figure 4. Figure 4 shows that the diffusion coefficient of G4 dendrimer in the increasing amount of SDS molecules. The methylene protons (a) in the interior of dendrimer were selected to probe the mobility of dendrimer in PFG NMR studies. PAMAM dendrimer has a relative hydrophobic interior and a polar/ charged surface. The encapsulation of SDS in the interior of dendrimer caused by hydrophobic interactions reduces the size of cavities and causes the shrink of dendritic structure and the decrease of dendrimer size. The increase of dendrimer diffusion coefficient at ratio range of 4-8 confirmed the inclusion of SDS monomers in the dendritic cavities. However, though the SDS

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Figure 4. Diffusion coefficient of G4 dendrimer in the presence of SDS as a function of the SDS/G4 dendrimer molar ratio (G4 dendrimer concentration being a constant of 2 mg/mL).

mobility is further slower in the ratio range of 8-16, the dendrimer size increases during this period. This is due to the adsorption of SDS monomers on the surface of dendrimers, which decreases the diffusion of both dendrimer and SDS. Therefore, the saturated amount of SDS encapsulated in G4 dendrimer is 8-16, which is in accordance with the value deduced from Figure 1. At later stages, no matter what kinds of SDS molecules (monomers, bilayers, or globular micelles) attached on the surface of dendrimers, the decrease of dendrimer mobility is observed. 3.2. Fast-Exchange/Slow-Exchange Transitions from 1H NMR Studies. According to our previous results, PAMAM dendrimers have two groups of proton signals in D2O, the methylene protons (a-d) in the hydrophobic interior and the methylene protons (b′ and d′) adjacent to the surface functional groups (Scheme S1 in the Supporting Information).59 When the surface functionality such as amine group is protonated in acidic solutions or interacted with an oppositely charged ion, a downfield or upfield shift of the methylene protons (b′ and d′) is observed.64,65 If the interior tertiary amine of PAMAM dendrimer is quaternized, the dendritic cavities are converted from nonpolar into polar.64 As a result, the downfield shift of all the interior protons (a-d) can be observed. If no interaction occurs between dendrimer and a guest molecule, the chemical shift of protons b′ is equal to that of protons c, while the chemical shift of d′ is equal to that of protons d. Similarly, we assign the four groups of protons for SDS molecules in Figure S2 (Supporting Information) with the labels 1-4. Figure 5 shows the 1H NMR spectra of the dendrimer/SDS/ D2O solution. When the SDS/dendrimer molar ratio is below 16, no change in chemical shift of protons b′ and protons d′ is observed, indicating the absence of ionic interactions between dendrimer surface functionality and SDS. The results from PFG studies and 1H NMR titrations further conclude that the interaction between dendrimer and SDS at this stage is due to the formation of molecular inclusion in the complex. In previous studies, Esumi pointed out that the interaction between sugarmodified PAMAM dendrimer and SDS monomer is a hydrophobic interaction on the hydrophobic region of dendrimer surface.52 Here, the hydrophobic interaction between the aliphatic chain of SDS and the dendrimer scaffold and/or the hydrogen-bond interaction between the sulfate of SDS and the amide/tertiary groups in dendrimer pockets contribute to the formation of dendrimer-SDS inclusions. Upon the addition of more SDS (g16) into G4 dendrimer solution, a fraction of dendrimer protons (b′ and d′) exhibits a downfield shift. During this period, the SDS concentration is above the cac value of SDS in the presence of PAMAM

Fang et al. dendrimer. Since the dendrimer-SDS complex solutions in this study have pH values around 11 and the primary amine and tertiary amine groups of dendrimer have pKa values of 10 and 6.5, respectively,23 these functional groups should be rarely charged or noncharged in the solutions. Therefore, the formation of dendrimer-SDS aggregates is predominantly due to the ion-dipole interaction or hydrogen-bond interaction between the sulfate group of SDS and amine group of dendrimer. In previous results, SDS monomers were reported to be adsorbed on the surface of dendrimer by ionic interaction, hydrogen-bond interaction, or regional hydrophobic interaction.9,57,75,80-82 The primary driving force during the formation of dendrimersurfactant aggregates was reported to be ionic interaction, which occurs between the positive charge on the surface of dendrimer and the negative charge group of the surfactant. Also, the moderate net positive charge on the nitrogen atom in PAMAM dendrimer also interacts with the surfactant, which is similar to that found in the studies of surfactants with poly(vinylpyrrolidone), polyvinylimidazole, and some vinyl copolymers.80 The results from 1H NMR and charge density calculation reveal that ion-dipole/hydrogen-bond interaction contributes more in the formation of dendrimer-SDS complexes than ionic interactions during this period. With the increase of SDS concentration, the fraction of bound state for G4 dendrimer increases, causing further downfield shifts of peaks for protons (b′ and d′). Surprisingly, we observed two independent peaks for protons b′ and two peaks for protons d′ when the molar ratio of SDS and dendrimer is 128. In a 1H NMR spectrum, if the exchange rate of the free state and bound state is fast, the spectrum contains only one signal for both free and bound state, and the observed chemical shift is a weighted average of the chemical shifts for free state and bound state. On the other hand, if the binding is tight between the ligand and the receptor, there are two individual signals for the free and bound state. The ion-dipole interaction between dendrimer and SDS belongs to the fast exchange, which is evident from the 1H NMR studies at the molar ratio of 16-64. The two peaks for protons b′ at the SDS/dendrimer ratio of 128 cannot be explained by the formation of slow exchange structures in the complexes because the chemical shift of protons b′ in free-state dendrimer is equal to that of protons c in Figure 5. Therefore, the peak with a higher chemical shift corresponds to the stable complex in which the interaction is slow exchange, while the peak with a lower chemical shift is for the ion-dipole interaction-driven structure of dendrimer-SDS complex (fast exchange). For the slowexchange structure, SDS may interact with the dendrimer surface in the form of bilayer micelles, which is a cooperative interaction model proposed by Turro and Tomalia in earlier studies.76 In a cooperative interaction model, one SDS monomer escaped from the dendrimer surface does not influence the observed chemical shift in the 1H NMR spectrum. At the SDS/dendrimer ratio of 256, the peak corresponding to fast exchange interaction disappears, while the peak for cooperative binding moves to a higher chemical shift. The result reveals that all the SDS molecules interact with dendrimer in the form of bilayer micelles. More dendrimer surface functionalities participate in this process, which induces the increase in the faction of bound-state dendrimer and the downfield shift of peaks for protons (b′ and d′). The fully cooperative binding of SDS with dendrimer is stable in solution. At the molar ratio of 512-1024, the increase of SDS concentration generates more and more SDS globular micelles in dendrimer solution. These micelles can interact with dendrimer by ion-dipole/hydrogen-bond/ionic interactions. How-

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Figure 5. Expanded region of the 1H NMR spectra for G4 dendrimer/SDS/D2O solution (SDS/G4 dendrimer ratio ranges from 4 to 1024).

ever, the interaction between dendrimer and the globular micelle is a fast-exchange process, since only a few SDS monomers in the micelles contact with dendrimer surface. The entry and departure of the globular micelle from dendrimer surface are rapid. Therefore, we observed a slightly upfield shift of the peaks for protons b′ and protons d′ in Figure 5. Before the PFG and 1H NMR analysis, we attempted to calculate the binding constant of dendrimer and SDS and the number of binding sites for each dendrimer. The following equation was used to describe the relationship of observed chemical shift and dendrimer/SDS molar ratio77-79

{(

)

[SDS]0 1 1+ + nKa[Den]0 n[Den]0 [SDS]0 2 4[SDS]0 1/2 1 1+ + nKa[Den]0 n[Den]0 n[Den]0

∆δmax ∆δ ) 2

[(

)]

}

Figure 6. The relationship between the chemical shift variations of dendrimer protons (d′) and SDS/dendrimer ratio. The points were fitted by eq 5 as described in the text.

(5)

where [SDS]0 and [Den]0 are the initial concentration of SDS and dendrimer, respectively, ∆δ is variation of chemical shift for each SDS/dendrimer ratio, ∆δmax is the maximum variation of chemical shift during the experiment, Ka is the binding constant between dendrimer and SDS, and n is the number of binding sites for each G4 dendrimer. When fitting the chemical shift data obtained in Figure 5 by eq 5 described above, the Ka and n are calculated to be 380 M-1 and 49 ((43), respectively (Figure 6). It is obvious that these binding parameters are obtained with non-neglected errors. Equation 5 is established on the basis of the fast-exchange interactions between two species. However, as discussed above, the dendrimer-SDS interaction is neither a simple fast-exchange nor a slow-exchange process. Transitions between the two types of interactions occur during the addition of SDS molecules into dendrimer solution. Therefore, the fitting results are not accurate, which further confirms the presence of multiple structures in the binding process. By a combination of analysis from PFG NMR and 1H NMR titration results, the detailed interaction models between SDS and dendrimer are proposed in Scheme 1. First, SDS molecules

penetrate into the interior cavities of dendrimers by hydrophobic/ hydrogen-bond interactions (Scheme 1a, SDS/dendrimer ) 4-8). After the saturated point for encapsulation (SDS/ dendrimer ) 8-16), SDS molecules interact with the surface amine groups via ion-dipole interactions (Scheme 1b, SDS/ dendrimer ) 8-64). During this period, the free SDS concentration increases due to the fast exchange interactions between dendrimer and SDS. As SDS concentration increases, SDS globular micelles form in the solution, but these micelles do not interact with the dendrimer surface due to their low concentrations (Scheme 1c, SDS/dendrimer ) 56-128). At SDS/dendrimer ratio of 128, both SDS monomer and SDS bilayer micelles adsorb on the dendrimer surface via noncooperative and cooperative interactions, respectively (Scheme 1d), while only SDS bilayer micelle structures are observed on dendrimer at a ratio of 256 (Scheme 1e). Of course, the SDS globular micelles exist in the solution. It is worth noticing that the formation of dendrimer-bound SDS aggregates here is different from that of polymer-surfactant aggregates with linear polymers (such as poly(vinylpyrrolidone), polyvinylimidazole, and some vinyl copolymers) and SDS, in which polymers wrap themselves around the surface of SDS micelles followed by the formation of a beadlike necklace structure. This is because of the conformational flexibility of linear polymers and the

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SCHEME 1: Proposed Aggregate Structures for Dendrimer-SDS Complexes at Different SDS/Dendrimer Molar Ratios

Fang et al. findings are of great importance in the fundamental studies of polymer-surfactant interactions and helpful for the in-depth understanding of dendrimer-based host-guest systems. Since dendrimers are ideal amphiphilic and surface-active molecules and the mixed micelles have many advanced physicochemical properties in comparison of single-surfactant micelles, the miscellaneous aggregate structures for dendrimer-SDS mixture are also useful for the understanding of kinetic behavior of mixed micelles and lots of chemical and biological phenomena, such as the movement of membrane protein in the bilayer lipids and the penetration of cationic protein through cell membrane. Acknowledgment. We thank the Specialized Research Fund for the Doctoral Program of Higher Education (No.20093402110041) and the Young Teachers Research Foundation in Colleges and Universities of Anhui Province (No. 05010316) for financial support to this program. Supporting Information Available: Further information on H NMR and NOESY analysis of the dendrimer-SDS complexes. This material is available free of charge via the Internet at http://pubs.acs.org. 1

References and Notes

relatively rigid structure of dendritic polymers.80 When SDS globular micelle concentration increases to a high level, at which the micelles can interact with dendrimer surface, the aggregate structure in Scheme 1f is proposed (SDS/dendrimer ratio ) 516-1024). Finally, the supramolecular structures between dendrimers may form in the solution due to the further decrease of dendrimer diffusion coefficient in Figure 4 (Scheme 1g). 4. Conclusion The present study is concerned with the detailed interaction mechanism between dendrimer and surfactant. On the basis of NMR studies, different aggregate structures were proposed. 1H NMR titration results revealed the presence of fast-exchange/ slow-exchange transitions in the dendrimer-SDS aggregate structures when different amounts of SDS were added into the dendrimer solution. Diffusion and NOE measurements confirmed the formation of dendrimer-SDS inclusions, ion-dipole interaction-driven complexes, and dendrimer-SDS globular micelle supermolecular structures in D2O solutions. These

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