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Colloids and Surfaces A: Physicochem. Eng. Aspects 364 (2010) 49–54

Contents lists available at ScienceDirect

Colloids and Surfaces A: Physicochemical andEngineering Aspects

journa l homepage: www.e lsev ier .com/ locate /co lsur fa

omplexation between amine- and hydroxyl-terminated PAMAM dendrimersnd sodium dodecyl sulfate

hang Wanga, Evan Wyn-Jonesb, Kam Chiu Tamc,∗

Singapore-MIT Alliance, School of Mechanical and Aerospace Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore, SingaporeSchool of Computing Science and Engineering, University of Salford, Newton Building, Salford M5 4WT, United KingdomDepartment of Chemical Engineering, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada N2L 3G1

r t i c l e i n f o

rticle history:eceived 26 February 2010eceived in revised form 16 April 2010ccepted 21 April 2010vailable online 28 April 2010

eywords:endrimersurfactantsolymersnteractions

icrostructureight scattering

a b s t r a c t

Isothermal titration calorimetry (ITC), dynamic light scattering (DLS), electrophoretic mobility and trans-mission electronic microscopy (TEM) were employed to study the supramolecular complexation ofamine- (G3[EDA] PAMAM-NH2) and hydroxyl-terminated (G3[EDA]PAMAM-OH) PAMAM dendrimersinduced by the binding of anionic surfactant, sodium dodecyl sulfate (SDS). The binding was driven bythe electrostatic interaction between protonated amines on the dendrimer and SDS at pH ≤ 2. The amine-terminated PAMAM dendrimer was able to host more SDS molecules because it possessed more bindingsites compared to the hydroxyl-terminated system. The stoichiometry of binding suggested that SDS onlybinds to the amine groups on the outer rim of the dendrimers, i.e. the 3rd generation and the outmostlayer of the 2nd generation, the 32 amine groups within the inner layer of the 2nd generation cannotelectrostatically host SDS molecules owing to the strong steric hindrance. The binding induced the den-drimer/SDS supramolecular complexation via hydrophobic association between bound SDS molecules

itration calorimetryresulting in the formation of insoluble precipitates. The insoluble complex of amine-terminated PAMAMdendrimer persisted with further addition of SDS, whereas those of hydroxyl-terminated dendrimerresolubilized when SDS concentration exceeded 10 mM. With increasing SDS concentration, the den-drimer/SDS complex self-assembled into spherical aggregates that transformed into a highly ordered,hyper-branched conformation, where the branched structure appeared to be similar to the dendriticstructure of individual PAMAM dendrimer. This demonstrates the possibility of generating dendritic

ure b

supramolecular architect

. Introduction

Poly(amidoamine) (PAMAM) dendrimers have attractedncreasing attention in recent years because of their uniquetructure, interesting properties as well as their potential appli-ations in medicine, drug delivery, catalysis, gene therapy, andanoreactors [1–8]. PAMAM dendrimers are monodisperse, highlyranched polyelectrolytes with ammonium functional groups onhe surface (primary amine) and at the branch points in the interiortertiary amine). The PAMAM dendrimers can be hydrated andxpanded when protonated in aqueous medium where the degreef protonation depends on the pH [6–11]. In general, the charging

echanism of PAMAM dendrimers is described as a multi-step

rotonation; the primary amines on the surface protonate first atigher pH (∼8), whereas the tertiary amines within the interiorf the dendrimer molecules protonate at lower pH (∼3) [8]. Chen

∗ Corresponding author. Tel.: +1 519 888 4567; fax: +1 519 746 4979.E-mail address: mkctam@uwaterloo.ca (K.C. Tam).

927-7757/$ – see front matter © 2010 Elsevier B.V. All rights reserved.oi:10.1016/j.colsurfa.2010.04.029

y self-assembly .© 2010 Elsevier B.V. All rights reserved.

et al. also reported that at pH > 8.3, essentially all charges are onthe primary amines and further reduction in the pH led to theprotonation of tertiary amines within the core of the dendrimer[6].

The amphiphilic nature, well-defined size, shape and archi-tecture as well as the chargeable amine groups on the surfaceand interior of PAMAM dendrimers make them good host forsmall guest molecules, such as drugs and surfactants [12–16].The macromolecule/surfactant host–guest system is of great sci-entific and industrial importance because of its complex behaviorsand potential applications in pharmaceutical, cosmetic, agriculturalformulations and food processing [17–24]. A number of stud-ies have focused on the interaction and aggregation behaviorsbetween PAMAM dendrimers and surfactants in aqueous solution[11–16,25–34]. It was observed that the interaction is strongly

dependent on the nature of surfactant head groups, generationand terminal groups of dendrimers, as well as ionic strength andpH of the solution [11–16,29]. The interaction between PAMAMdendrimer and anionic surfactant is clearly observable becauseof the strong electrostatic attraction between protonated amines

5 Physic

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nd anionic surfactant head groups and takes place at a surfactantoncentration well below its critical micelle concentration. Signsf morphological transformation or supramolecular complexation,uch as increase in particle size, turbidity, changes in electromo-ive force, and precipitation were often observed in the coursef binding interaction [13–16,25,28,30–35]. Moreover, the assem-lies of PAMAM dendrimer/surfactant complexes were exploreds building blocks for well-defined nano- or micro-scale dendriticrchitecture, which has potential application in DNA transfec-ion and drug delivery [2,11,12,26,29,36]. However, a quantitativend molecular-level understanding on the nanostructure of theupramolecular assembly of PAMAM dendrimer/anionic surfactantystem is still lacking.

Previously, we have reported the complexation between amine-erminated PAMAM dendrimer and SDS in aqueous solutions ofarying pHs. We presents here a detailed and quantitative studyn the SDS induced supramolecular complexation of generation 3mine- and hydroxyl-terminated PAMAM dendrimer (designateds G3[EDA] PAMAM-NH2 and G3[EDA] PAMAM-OH, respectively)orroborated by isothermal titration calorimetric (ITC), dynamicight scattering (DLS) and transmission electron microscopic (TEM)

easurements. This study provides new insights on the bindingtoichiometry and binding mechanism, a molecular-level under-tanding on the structure of the supramolecular assembly, as wells a simple route to construct micro- to mesoscopic dendritic struc-ure by self-assembly of dendrimer and surfactant via physicalnteractions.

. Experimental

.1. Materials

The amine- and hydroxyl-terminated, generation 3AMAM dendrimers (designated as G3[EDA]PAMAM-NH2nd G3[EDA]PAMAM-OH, respectively), were purchased fromigma–Aldrich Chemical Co. (>99% purity) and used withouturther purification. G3[EDA]PAMAM-NH2 (Mw = 6909 g/mol)as 32 primary amines on the surface and 90 tertiary aminest the branch points within the core. It is fully protonated andnprotonated at pH ∼2 and ∼10, respectively, and in the pH rangef 7–8, only the primary amines on the outer most surface arerotonated. G3[EDA]PAMAM-OH (Mw = 6941 g/mol) possesses

dentical branching architecture as G3[EDA]PAMAM-NH2, wherehe surface functional groups comprise of 32 hydroxyl instead ofmine groups. It is also fully protonated at pH ∼ 2 and deprotonatedt pH > 9.

The anionic surfactant sodium dodecyl sulfate (SDS) wasbtained from BDH Lab Supplies (>99% purity) and used as received.

.2. Isothermal titration calorimetry

The microcalorimetric measurements were carried out usinghe Microcal isothermal titration calorimeter (ITC). This powerompensation, differential instrument was described in details by

iseman et al. [37,38]. It has a reference and a sample cell ofpproximately 1.35 ml and both cells are insulated by an adiabatichield. The titration was carried out at 25.0 ± 0.02 ◦C, by inject-ng 200 mM SDS solution from a 250 �l syringe into the sampleell filled with the aqueous solution of PAMAM dendrimer. Theyringe is tailored-made such that the tip acts as a blade-type stir-

er to ensure an optimum mixing efficiency at 400 rpm. The heatvolved or absorbed by each injection in the course of titration isirectly measured by the ITC unit, producing the raw heat signal,lso known as cell feedback (CFB). Integration of the each CFB giveshe differential enthalpy curve for the titration.

ochem. Eng. Aspects 364 (2010) 49–54

2.3. Dynamic light scattering

Dynamic light scattering (DLS) studies were conducted using theBrookhaven BI-200SM goniometer and BI-9000AT digital correlatorequipped with an argon-ion laser. The time correlation function ofthe scattered intensity G2(t), which is defined as G2(t) = I(t)I(t + �t)where I(t) is the intensity at time t and �t is the lag time, is ana-lyzed using the Inverse Laplace Transformation technique (REPESfor our case) to produce the distribution function of decay rates.Thus the apparent hydrodynamic radius Rh can be determined fromthe decay rate via the Stokes–Einstein equation, Rh = kTq2/6��� ,where k is the Boltzmann constant, q is the scattering vector(q = 4��sin(�/2)/�), where n is the refractive index of solvent, � isthe scattering angle and � is the wavelength of the incident laserlight in vacuum, � is the solvent viscosity, and � is the decay rate.Several measurements were performed for a sample to obtain anaverage hydrodynamic radius and the variation in the Rh valueswas found to be small.

The angular dependence (from 60◦ to 110◦ at 10◦ interval) ofrelaxation time distribution functions for the dendrimer/SDS mix-ture showed that the decay rates � exhibited a linear relationshipwith q2, confirming that the distribution functions were caused bythe translational diffusion of the particles.

2.4. Electrophoresis study

The electrophoretic mobility study was carried out using theBrookhaven Zeta PALS (phase analyzer light scattering). The ZetaPALS is an extension of laser electrophoretic light scattering (ELS),which measures the velocity of moving particles that scatter thelaser light. The zeta potential was calculated via the Smoluchowskimodel fitting of the mobility data, and thus the stability of thecomplex in the course of binding was determined.

2.5. Transmission electron microscope (TEM)

Transmission electron microscopic studies were conductedusing a JEOL JEM-2010 transmission electron microscope operat-ing at an accelerate voltage of 200 kV. The sample was preparedon a copper grid pre-coated with carbon and stained with osmiumtetraoxide (OsO4) to enhance the contrast between the assemblyand the background.

3. Results and discussion

The differential enthalpy curves obtained from titrating 200 mMSDS into aqueous solutions of G3[EDA]PAMAM-NH2 (closed sym-bols) and G3[EDA]PAMAM-OH (open symbols) with differentconcentrations ranging from 0.05 to 0.2 mM at pH 2, togetherwith the dilution curve of SDS, were plotted in Fig. 1. In agree-ment with our previous study [26], the sigmoidal enthalpy curvescorresponded to the site-to-site, uncooperative and instantaneousbinding of SDS molecules to protonated amine groups on PAMAMdendrimers driven by electrostatic attraction, which took placeat extremely low SDS concentration (<1 mM) without exhibit-ing a clearly marked critical aggregation concentration (CAC). Thebinding ceased when all positively charged amine groups wereoccupied by negatively charged SDS molecules, signaled by themerging of the titration curve and dilution curves at saturationconcentration (CS), representing the maximum uptake of SDS byprotonated PAMAM dendrimers. The saturation concentrations for

various concentrations of PAMAM dendrimers are listed in Table 1.It is evident that the amounts of bound SDS were proportionalto the concentration of dendrimers, indicating the stoichiomet-ric characteristic of the electrostatic site-to-site binding [26]. Theelectrostatic binding was exothermic and the negative enthalpy

C. Wang et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 364 (2010) 49–54 51

Fig. 1. Differential enthalpy versus concentration of SDS for fully protonated(c(G

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Fig. 2. Differential enthalpy versus sulfate/amine charge ratio for fully protonated(pH 2) amine- and hydroxyl-terminated PAMAM dendrimers at different con-

pH 2) amine- and hydroxyl-terminated PAMAM dendrimers at different con-entrations: (�) 0.2 mM G3[EDA]PAMAM-OH; (♦) 0.1 mM G3[EDA]PAMAM-OH;�) 0.05 mM G3[EDA]PAMAM-OH; (�) 0.2 mM G3[EDA]PAMAM-NH2; (�) 0.1 mM3[EDA]PAMAM-NH2; (�) 0.05 mM G3[EDA]PAMAM-NH2; (+) dilution curve of SDS.

as attributed to the formation of ion-pair between sulfate androtonated amine, which agrees with the observations in simi-

ar macromolecular host–guest systems such as DNA/surfactant,ntibiotic/serum albumin and peptite/phospholipid membraneystems [39–41]. The enthalpy profiles shown in Fig. 1 also demon-trated that:

(i) G3[EDA]PAMAM-NH2, which has 32 amine groups on the sur-face as active binding sites, was able to host more SDS moleculescompared to G3[EDA]PAMAM-OH (whose surface functionalgroups is hydroxyl) and hence are inert to SDS.

ii) The extent of binding interaction indicated by the value ofexothermic enthalpy for G3[EDA]PAMAM-NH2 (−10 kJ/mol)was stronger than that of G3[EDA]PAMAM-OH (−7 kJ/mol),where the protonated tertiary amines are located in the coreof the dendrimer and not readily accessible to SDS.

Fig. 2 shows the same enthalpy curves, plotted against theharge ratio of sulfate to amine groups, where the enthalpyurves obtained at different dendrimer concentrations fall onto

master curve showing that the dendrimer is saturated byDS at charge ratio ∼0.62 and ∼0.50 for G3[EDA]PAMAM-NH2nd G3[EDA]PAMAM-OH, respectively, suggesting that nearly 38%mine groups on G3[EDA]PAMAM-NH2 and 50% amine groupsn G3[EDA]PAMAM-OH were unable to bind SDS even thoughhey were protonated. The number of unbound amine groups

or individual dendrimer molecule was found to be identical formine- and hydroxyl-terminated dendrimer regardless of the sur-ace functional group, which was approximately 45 (38% of total22 amine groups for G3[EDA]PAMAM-NH2 and 50% of total 90

able 1aturation concentrations by SDS for amine- and hydroxyl-terminated PAMAM den-rimers at various concentrations.

Functional group ofPAMAM dendrimer

Concentration of PAMAMdendrimer (mM)

Saturation concentration(by SDS, mM)

Amine0.05 4.920.10 8.240.20 14.20

Hydroxyl0.05 2.990.10 5.060.20 7.60

centrations: (�) 0.2 mM G3[EDA]PAMAM-OH; (♦) 0.1 mM G3[EDA]PAMAM-OH;(�) 0.05 mM G3[EDA]PAMAM-OH; (�) 0.2 mM G3[EDA]PAMAM-NH2; (�) 0.1 mMG3[EDA]PAMAM-NH2; (�) 0.05 mM G3[EDA]PAMAM-NH2.

amine groups for G3[EDA]PAMAM-OH). Thus, we can deduce thatonly the amine groups on the outer rim of dendritic structure (i.e.the 3rd generation and the outer layer of the 2nd generation) wereelectrostatically bound to SDS molecules, whereas the 42 tertiaryamine groups within the inner core of the dendritic structure (innerlayer of the 2nd generation, 1st generation and zero generation)were not readily accessible and were unable to bind small guestmolecules, resulting from the strong steric hindrance caused bythe highly branched dendritic structure that is independent of thetype of surface functional groups.

Fig. 3 illustrates the phase behavior of 0.2 mM G3[EDA]PAMAM-NH2 and [EDA]PAMAM-OH in the course of the binding at pH2. The binding induced supramolecular complexation was clearlyvisible for both amine- and hydroxyl-terminated PAMAM den-drimers. The solution of G3[EDA]PAMAM-NH2 became slightlycloudy at SDS concentration as low as 1 mM, signaling the for-mation of the dendrimer/SDS complex driven by electrostaticattraction. The complex continued to evolve with higher quantityand larger size, resulting in a cloudy suspension at SDS concentra-tion of 5 mM, further addition of SDS resulted in the precipitationof the complex, which persisted with increasing SDS concentra-tion to as high as 18 mM. On the other hand, the phase behaviorof the G3[EDA]PAMAM-OH in the course of binding was generallyconsistent with that of G3[EDA]PAMAM-NH2, however the com-plexation signaled by the cloudiness of the solution took place athigher SDS concentration (>2 mM) because the number of bindingsites was reduced and the electrostatic interaction was weakened;moreover, the precipitated complex tended to resolubilize with fur-ther increase in SDS concentration (>10 mM), which is commonlyencountered in the oppositely charged polyelectrolyte/surfactantsystems, where the charge density of polyelectrolyte is sufficientlylow and the polyelectrolyte molecule can be stabilized in excessamounts of surfactant micelles [22–24].

To further elucidate the phase behaviors of the amine- andhydroxyl-terminated PAMAM dendrimers in the course of com-plexation with SDS, electrophoretic mobility measurements wereperformed and the results are shown in Fig. 4, where the zeta poten-tials of the dendrimer/SDS mixtures at pH 2 were plotted againstSDS concentration. The zeta potential of G3[EDA]PAMAM-NH and

2G3[EDA]PAMAM-OH in the absence of SDS was +27 and +18 mV,respectively because of the positively charged amine groups at pH2. The addition of SDS induces binding and consequent associationof multiple dendrimer molecules, resulting in a sharp increase of

52 C. Wang et al. / Colloids and Surfaces A: Physicochem. Eng. Aspects 364 (2010) 49–54

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ing the formation of dendrimer/SDS complexes are shown on eachfigure. The Rh of fully protonated G3[EDA]PAMAM-NH2 (Fig. 5a)and G3[EDA]PAMAM-OH (Fig. 5b) in the absence of SDS was3.4 and 2.3 nm, respectively, characterizing the individual den-

Fig. 3. Pictures depicting the different stages of complexation (various S

eta potential at the extremely low SDS regime. The zeta potentialseach the maxima, of +93 and +59 mV for G3[EDA]PAMAM-NH2 and3[EDA]PAMAM-OH, respectively at SDS ∼0.1 mM, which coin-ides with the strong exothermic binding enthalpies observedrom ITC experiments shown in Figs. 1 and 2. Further additionf negatively charged SDS molecules cancels out the positiveharge of amine groups and reduces the zeta potential of theomplex and consequently weakens the repulsive electrostaticorce that stabilizes the complex. For G3[EDA]PAMAM-OH, theeta potential decreases to +22 mV and the complex precipitateshen SDS concentration exceeded 12 mM; for G3[EDA]PAMAM-H2, the precipitation was observed at SDS concentration ∼18 mMt which the zeta potential decreased to +33 mV. Comparisonetween Figs. 1 and 4 shows that the reduction in the zeta poten-ial moderated at the region when the binding isotherm of theendrimer/SDS system merged with dilution curve of SDS/water.he SDS concentration for this phenomenon occurred at about0–15 and 15–20 mM of SDS for both amine- and hydroxyl-erminated dendrimers, respectively, which corresponded to thend of electrostatic binding. With further increase of SDS concen-ration, the zeta potential of G3[EDA]PAMAM-NH2/SDS complexecreased to the isoelectric point at SDS concentration ∼28 mMnd levels off, corresponding to the persistent precipitation event high SDS concentration; on the other hand, the zeta poten-ial of G3[EDA]PAMAM-OH/SDS complex decreased continuouslynd eventually exhibited a negative zeta potential when SDS con-entration exceeded ∼20 mM, signaling the resolubilization of the

recipitated complex.

Dynamic light scattering was performed to study the evo-ution of the particle size of the complex in the course ofinding, which provides a molecular-level understanding onhe mechanism and structural transformation upon complex-

ig. 4. Dependences of zeta potential on the SDS concentration in 0.2 mM PAMAMendrimer solutions at pH 2: (�) G3[EDA]PAMAM-OH; (�) G3[EDA]PAMAM-NH2.

centration) for 0.2 mM G3[EDA]PAMAM-NH2 and G3[EDA]PAMAM-OH.

ation. Previously, we studied the supramolecular assembly ofG3[EDA]PAMAM-NH2/SDS system at various pH conditions usinglight scattering, whereas in this paper we compared the complexa-tion behaviors between amine- and hydroxyl-terminated PAMAMdendrimers. The hydrodynamic radii (Rh) of G3[EDA]PAMAM-NH2and G3[EDA]PAMAM-OH at pH 2 were plotted against the SDSconcentration in Fig. 5a and b, respectively. Schematics illustrat-

Fig. 5. Dependences of hydrodynamic radius Rh on the SDS concentration in 0.2 mMPAMAM dendrimer solutions. (a) (filled circle) G3[EDA]PAMAM-NH2; (b) (open cir-cle) G3[EDA]PAMAM-OH.

Physicochem. Eng. Aspects 364 (2010) 49–54 53

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C. Wang et al. / Colloids and Surfaces A:

rimer molecule in aqueous solution. The slightly higher Rh for3[EDA]PAMAM-NH2 may be attributed to the additional 32 pro-

onated amine groups on its surface which swells the dendrimerore than that of G3[EDA]PAMAM-OH. Both dendrimers demon-

trated a significant increase of particle size upon the additionf SDS, characterizing the supramolecular complexation inducedy the electrostatic binding that was further enhanced by theydrophobic association between bound SDS molecules [26] Theh of G3[EDA]PAMAM-NH2 increased abruptly upon the first addi-ion of SDS (0.002 mM) followed by a progressive increase in size;hereas the Rh of G3[EDA]PAMAM-OH increased considerably

rom 4.4 to 54.7 nm only when the SDS concentration reached0.1 mM. This suggested that the absence of amine groups on the

urface of G3[EDA]PAMAM-OH (corresponding to a reduction inhe number of surface binding sites), weakened the overall elec-rostatic affinity between dendrimer and SDS, which delayed thenset of complexation to higher SDS concentration. The Rh ofoth dendrimers progressively increased to approximately 90 nmith further addition of SDS, corresponding to the consistent elec-

rostatic binding and continuous development of dendrimer/SDSomplex through intermolecular hydrophobic interaction. Whenhe SDS concentration was sufficiently high (>5 mM), the Rh of3[EDA]PAMAM-NH2 and G3[EDA]PAMAM-OH increased to 423.4nd 221.9 nm, respectively, corresponding to the precipitation ofhe complex as displayed in Fig. 3. In contrast to G3[EDA]PAMAM-H2, where the precipitation persisted at high SDS concentration

>20 mM), G3[EDA]PAMAM-OH exhibited a reduction in the parti-le size with further increase of SDS concentration (>10 mM) andhe dendrimer/SDS complex redispersed and the mixture becameransparent, which was a result of a structural reorganization ofhe complex in excess amount of free SDS micelles. Compared tohe amine-terminated PAMAM dendrimer, fewer SDS moleculesere electrostatically bound to G3[EDA]PAMAM-OH, which were

ocated in the interior of the dendrimer molecule, hence the bridg-ng of dendrimers by bound SDS aggregates was minimized. Whenhe SDS concentration was sufficiently high (well above the satura-ion concentration), free micelles were formed that stabilized theendrimer via electrostatic interaction, resulting in the redisper-ion/resolubilization of the complex. This agrees with our previoustudies on oppositely charged polymer/surfactant systems wherehe complex was also resolubilized when free surfactant micellestarted to form [23]. TEM measurements were performed to fur-her elucidate the morphological transformation of the PAMAMendrimer/SDS complex in the course of binding. The samplesere from the aqueous solutions of 0.2 mM G3[EDA]PAMAM-NH2ith SDS at different concentrations, representing different stages

f complexation. Fig. 6a and b depicted the TEM micrographs of.2 mM G3[EDA]PAMAM-NH2 in the presence of 1 and 10 mM SDS,espectively. At SDS concentration of 1 mM, the dendrimer and SDSolecules formed aggregates that were nearly spherical as shown

n the micrograph, corresponding to the slight cloudiness of theixture. The radii of the aggregates ranged from ∼10 to ∼70 nm,hich was generally consistent, however they were slightly lower

han the particle size obtained by DLS (∼90 nm), caused by thehrinkage of aggregates as the solvent evaporated during the sam-le preparation. As the SDS concentrated was increased to 10 mM,here massive precipitation of the dendrimer/SDS was observed,

he micrograph (Fig. 6b) showed that the complex evolved frommall spherical aggregates to a three-dimensional network confor-ation of length scale in the micron size, driven by a combination of

lectrostatic binding and hydrophobic association as discussed ear-

ier. It is interesting to note that the growth of the complex was notandom, but highly ordered and oriented towards the branches ofendrimer, leading to the formation of a hyper-branched complexhich resembles the tree-like architecture of individual dendrimerolecule, however, hundred times larger in size. This was com-

Fig. 6. TEM micrographs demonstrating the morphological transformation in thecourse of G3[EDA]PAMAM-NH2/SDS complexation. (a) 0.2 mM G3[EDA]PAMAM-NH2 with 1 mM SDS; (b) 0.2 mM G3[EDA]PAMAM-NH2 with 10 mM SDS.

pletely different from the complexation behaviors observed insystems consisting of linear polyelectrolyte and oppositely chargedsurfactant, where the conformation of the assembly correspondedto a random-coiled structure. Thus, we confirmed the possibilityof constructing supramolecular dendritic structure from micro-scopic to mesoscopic length scale in a controlled manner bydendrimer/surfactant assembly through physical interaction (elec-trostatic and hydrophobic interactions).

4. Conclusions

We observed strong electrostatic binding of SDS to amine-and hydroxyl-terminated PAMAM dendrimers, which induced thesupramolecular complexation through the hydrophobic associa-tion between bound SDS molecules. The binding stoichiometrysuggested that only the 3rd generation and outer layer of the 2ndgeneration amines for both dendrimers were able to host SDSmolecules via electrostatic interactions, whereas the 32 amineswithin the inner layer of the 2nd generation cannot bind SDSmolecules because of steric hindrance. A series of conformationaltransitions of the dendrimer/SDS supramolecular assembly wereobserved in the course of binding/complexation: from sphericalaggregation with a radius below 100 nm to precipitated three-dimensional network structure of micron size, that resolubilizedat higher SDS concentration (>10 mM) for hydroxyl-terminatedPAMAM dendrimer where the electrostatic interaction is not suf-

ficiently strong. For the first time, we observed the highly orderedevolution of the PAMAM dendrimer/SDS supramolecular assem-bly, leading to the formation of a mesoscopic and hyper-branchedstructure that is similar to the tree-like architecture of individualdendrimer molecule. This provides a new molecular-level, non-

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ovalent approach to control the size, shape and surface chemistryf dendritic structure using PAMAM dendrimer and oppositelyharged surfactants as building blocks.

cknowledgements

We are grateful for the financial support provided by Nanyangechnological University, Singapore-MIT Alliance and NSERC,anada.

eferences

[1] Y.H. Kim, O.W. Webster, J. Am. Chem. Soc. 112 (1990) 4592–4593.[2] K.M. Kitchens, M.E.H. El-Sayed, H. Ghandehari, Adv. Drug Deliv. Rev. 57 (2005)

2163–2176.[3] G.R. Newkome, C.N. Moorefield, G.R. Baker, A.L. Johnson, R.K. Behera, Angew.

Chem. Int. Ed. Engl. 30 (1991) 1176–1178.[4] A.M. Naylor, W.A. Goddard III, G.E. Kiefer, D.A. Tomalia, J. Am. Chem. Soc. 111

(1989) 2339–2341.[5] J. Haensler, F. Szoka, Bioconjug. Chem. 4 (1993) 372–379.[6] W. Chen, D.A. Tomalia, J.L. Thomas, Macromolecules 33 (2000) 9169–9172.[7] L. Sun, R.M. Crooks, J. Phys. Chem. B 106 (2002) 5864–5872.[8] D. Cakara, J. Kleimann, M. Borkovec, Macromolecules 36 (2003) 4201–

4207.[9] B. Rangarajan, L.S. Coons, A.B. Scranton, Biomaterials 17 (1996) 649–661.10] T.J. Prosa, B.J. Bauer, E.J. Amis, Macromolecules 34 (2001) 4897–4906.11] M.F. Ottaviani, F. Montalti, M. Romanelli, N.J. Turro, D.A. Tomalia, J. Phys. Chem.

B 100 (1996) 11033–11042.12] M.F. Ottaviani, N.J. Turro, S. Jockusch, D.A. Tomalia, Colloids Surf. A 115 (1996)

9–21.13] D.M. Watkins, Y. Sayed-Sweet, J.W. Klimash, N.J. Turro, D.A. Tomalia, Langmuir

13 (1997) 3136–3141.

14] V. Chechik, M. Zhao, R.M. Crooks, J. Am. Chem. Soc. 121 (1999) 4910–

4911.15] M.S. Bakshi, A. Kaura, J.D. Miller, V.K.J. Paruchuri, Colloid Interface Sci. 278

(2004) 472–477.16] M.S. Bakshi, A. Kaura, R.K. Mahajan, T. Toshimura, K. Esumi, Colloids Surf. A 246

(2004) 39–48.

[

[

[

ochem. Eng. Aspects 364 (2010) 49–54

17] E.D. Goddard, in: E.D. Goddard, K.P. Ananthapadmanabhan (Eds.), Interactionsof Surfactants with Polymers and Proteins, CRC Press, Boca Raton, FL, USA, 1993(chapter 4).

18] B. Erickson, S.C. DiMaggio, D.G. Mullen, C.V. Kelly, P.R. Leroueil, S.A. Berry, J.R.Baker Jr., B.G. Orr, M.M.B. Holl, Langmuir 24 (2008) 11003–11008.

19] K. Hayakawa, J.C. Kwak, J. Phys. Chem. 86 (1982) 3866–3870.20] J. Fundin, P. Hansson, W. Brown, I. Lidegran, Macromolecules 30 (1997)

1118–1126.21] D.M. Bloor, W.M.Z. Wan-Yunus, W.A. Wan-Badhi, L. Li, J.F. Holzwarth, E. Wyn-

Jones, Langmuir 11 (1995) 3395–3400.22] C. Wang, K.C. Tam, Langmuir 18 (2002) 6484–6490.23] C. Wang, K.C. Tam, J. Phys. Chem. B 108 (2004) 8976–8982.24] C. Wang, P. Ravi, K.C. Tam, Langmuir 22 (2006) 2930–2979.25] S. Jockusch, N.J. Turro, D.A. Tomalia, Macromolecules 28 (1995) 7416–7418.26] C. Wang, C.E. Wyn-Jones, J. Sidhu, K.C. Tam, Langmuir 23 (2007) 1635–1639.27] T.M. Hermans, M.A. Broeren, N. Gomopoulos, A.F. Smeijers, B. Mezari, E.N.M.

Van Leeuwen, M.R.J. Vos, P.C.M.M. Magusin, P.A.J. Hilbers, M.H.P. Van Gen-deren, N.A.J.M. Sommerdijk, G. Fytas, E.W. Meijer, J. Am. Chem. Soc. 129 (2007)15631–15638.

28] G. Caminati, N.J. Turro, D.A. Tomalia, J. Am. Chem. Soc. 112 (1990) 8515–8522.29] A.P.H.J. Schenning, C. Elissen-Roman, J. Weener, M.W.P.L. Baars, S.J. van der

Gaast, E.W. Meijer, J. Am. Chem. Soc. 120 (1998) 8199–8208.30] M. Miyazaki, K. Torigoe, K. Esumi, Langmuir 16 (2000) 1522–1528.31] S.M. Ghoreishi, Y. Li, J.F. Holzwarth, E. Khoshdel, J. Warr, D.M. Bloor, E. Wyn-

Jones, Langmuir 15 (1999) 1938–1944.32] K. Esumi, K. Kuwabara, T. Chiba, F. Kobayashi, H. Mizutani, K. Torigoe, Colloids

Surf. A 197 (2002) 141–146.33] H. Mizutani, K. Torigoe, K. Esumi, J. Colloid Interface Sci. 248 (2002) 493–

498.34] M.S. Bakshi, A. Kaura, Colloids Surf. A 244 (2004) 45–51.35] Y. Li, C.A. McMillan, D.M. Bloor, J. Penfold, J. Warr, J.F. Holzwarth, E. Wyn-Jones,

Langmuir 16 (2000) 7999–8004.36] S. Svenson, D.A. Tomalia, Adv. Drug Deliv. Rev. 57 (2005) 2106–2129.37] T. Wiseman, S. Williston, J.F. Brandts, L. Lin, Anal. Biochem. 179 (1989) 131–137.38] I. Jelesarov, H.R. Bosshard, J. Mol. Recognit. 12 (1999) 3–18.

39] S.J. Eastman, C. Siegel, J. Tousignant, A.E. Smith, S.H. Cheng, R.K. Scheule,

Biochim. Biophys. Acta 1325 (1997) 41–62.40] K. Tang, Y.M. Qin, A.H. Lin, X. Hu, G.L. Zou, J. Pharm. Biomed. Anal. 39 (2005)

404–410.41] R.P. Austin, P. Barton, A.M. Davis, R.E. Fessey, M.C. Wenlock, Pharm. Res. 22

(2005) 1649–1657.