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Liquid-like Ordering of Negatively Charged Poly(amidoamine) (PAMAM) Dendrimers in Solution Domenico Lombardo* CNR-IPCF, Istituto per i Processi Chimico Fisici, sez. Messina, C.da Papardo Salita Sperone s.n., I-98158 Messina, Italy ReceiVed December 23, 2008. ReVised Manuscript ReceiVed January 21, 2009 A structural investigation in water solution of the sodium carboxylate-terminated (generation G3.5) Tomalia-type poly(amidoamine) dendrimers has been performed by means of the small angle X-ray scattering (SAXS) technique. A long-range intermolecular interaction, revealed by the presence of sharp peaks in SAXS spectra, gives evidence of a considerable structural order in the system, even at low concentration of the dispersed phase. The experimental interdendrimer structure factor S(q) was analyzed in the framework of the Ornstein-Zernike integral equation by using the hypernetted chain approximation (HNCA) as closure relation. The effective interdendrimer interaction, modeled as a screened Coulombic plus hard-sphere repulsion potential, allows the estimation of the dendrimers’ effective surface charge Zeff. The present analysis strongly supports the findings that the effective intra- and interdendrimer charge interactions, as well as the dendrimer solution environment conditions, are crucial parameters for the modulation of the degree of structural organization in solution, suitable for a number of potential applications.
Introduction Dendrimers are highly branched macromolecules obtained by controlled, stepwise reaction sequences.1,2 Starting from a central core, it is possible to grow, through successive generations, dendritic structures with easily controllable molecular architecture.3 Their ability to be designed for specific uses, through suitable choice of the core molecule, interior region, and peripheral surface, makes dendrimers versatile systems for the study of molecular organization on size scales comparable to those of colloidal systems.4,5 One of the maior expected applications of dendrimers in the field of nanotechnology involves encapsulating guest molecules in their internal cavities.6 For this kind of application, fundamental information is needed regarding the determination of dendrimer spatial distribution structure, as well as investigation of the peculiar type of interactions that take place between the guest molecules and the particular end-groups employed. For this reason, most of the recent experimental7-12 and computer simulation13-19 investigations have been devoted mainly to the study of the density distribution inside the dendrimer as well as
to determination of the scaling law relating the number of monomers N with the dendrimer radius R.7 It is widely recognized that the chemical composition and branching architecture of the internal repeat units largely determine the morphology of the interior. On the other hand, the number and tunable nature of the surface groups largely influences the solution properties as well as certain relevant processes involved in molecular recognition and signal processing, or for binding various targeting or guest molecules. In this sense, an alternative key to understand the physical origin of the dense-core (or dense-shell) configurations assumed by the dendrimer lies, in fact, in the possibility of specific charge interactions within the macromolecular system.17,18 This tunable interaction, due to the presence of both internal and external chargeable groups, promises the possibility of controlling the dendrimer molecular conformation by varying the conditions of the solutions in a manner much like the polyelectrolyte systems. In this paper we discuss the results of a structural investigation in water solution of carboxylate-terminated generation G3.5 poly(amidoamine) (PAMAM) dendrimers by means of the small-
* E-mail:
[email protected]. (1) Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. Polym. J. 1985, 17, 117–132. (2) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A. Angew. Chem., Int. Ed. Engl. 1990, 29, 138–175. (3) Farin, D.; Advinir, D. Angew. Chem., Int. Ed. Engl. 1991, 30, 1379–1382. (4) (a) Tomalia, D. A. Chem. Today 2005, 23, 41–45. (b) Esfand, R.; Tomalia, D. A. Drug DiscoVery Today 2001, 6, 427–436. (5) (a) Burchard, W. AdV. Polym. Sci. 1999, 143, 113–195. (b) He, L.; Garamus, V. M.; Funari, S. S.; Malfois, M.; Willumeit, R.; Niemeyer, B. J. Phys. Chem B 2002, 106, 7596–7604. (c) Lafleche, F.; Durand, D.; Nicolai, T. Macromolecules 2003, 36, 1331–1340. (d) Lombardo, D.; Longo, A.; Darcy, R.; Mazzaglia, A. Langmuir 2004, 20, 1057–1064. (e) Lombardo, D.; Micali, N.; Villari, V.; Kiselev, M. A. Phys. ReV. E 2004, 70, 21402–21408. (f) Likos, C. N. Soft Matter 2006, 2, 478–498. (6) (a) Tomalia, D. A.; Naylor, A. M.; Goddard, A. M. Angew. Chem. 1990, 102, 119–157. (b) TomaliaD. A., FrechetJ. M. J., Eds. Dendrimers and other Dendritic Polymers; J. Wiley & Sons Ltd.: Chichester, 2001. (7) (a) Stechemesser, S.; Eimer, W. Macromolecules 1997, 30, 2204–2206. (b) Rathgeber, S.; Monkenbusch, M.; Kreitschmann, M.; Urban, V.; Brulet, A. J. Chem. Phys. 2002, 117, 4047–4062. (c) Prosa, T. J.; Bauer, B. J.; Amis, E. J.; Tomalia, D. A.; Scherrenberg, R. J. Polym. Sci. Part B 1997, 35, 2913–2924. (d) Rosenfeldt, S.; Dingenouts, N.; Ballauff, M.; Lindner, P.; Werner, N.; Vo¨gtle, F. Macromolecules 2002, 35, 8098–8105. (e) Mansfield, M. L.; Klushin, L. I. J. Phys. Chem. 1992, 96, 3994–3998. (f) Ballauff, M.; Likos, C. N. Angew. Chem. 2004, 116, 3060–3020. (g) Fritzinger, B.; Scheler, U. Macromol. Chem. Phys. 2005, 206, 1288–1291.
(8) (a) Scherrenberg, R.; Coussens, B.; van Vliet, P.; Edouard, G.; Brackman, J.; de Bebander, E.; Mortensen, K. Macromolecules 1998, 31, 456–461. (b) Ramzi, A.; Scherrenberg, R.; Brackman, J.; Joosten, J.; Mortensen, K. Macromolecules 1998, 31, 1621–1626. (9) Nisato, G.; Ivkov, R.; Amis, E. J. Macromolecules 1999, 32, 5895–5900. (10) (a) Micali, N.; Monsu Scolaro, L.; Romeo, A.; Lombardo, D.; Lesieur, P.; Mallamace, F. Phys. ReV. E 1998, 58, 6229–6235. (b) Mallamace, F.; Gambadauro, P.; Lesieur, P.; Lombardo, D.; Micali, N.; Romeo, A.; Monsu` Scolaro, L. J. Appl. Crystallogr. 2000, 33, 632–636. (c) Mallamace, F.; Canetta, E.; Lombardo, D.; Mazzaglia, A.; Romeo, A.; Monsu` Scolaro, L.; Maino, G. Physica A 2002, 304, 235–243. (11) Chen, W.-R.; Porcar, L.; Liu, Y.; Butler, P. D.; Magid, L. J. Macromolecules 2007, 40, 5887–5898. (12) de Gennes, P. G.; Hervet, H. J. Phys. Lett. Fr. 1983, 44, L351–L360. (13) Lascanec, R. L.; Muthukumar, M. Macromolecules 1990, 23, 2280–2288. (14) (a) Mansfield, M. L.; Klushin, L. I. J. Phys. Chem. 1992, 96, 3994. (b) Mansfield, M. L.; Klushin, L. I. Macromolecules 1993, 26, 4262–4268. (c) Mansfield, M. L. Polymer 1994, 35, 1827–1830. (15) Murrat, M.; Grest, G. S. Macromolecules 1996, 29, 1278–1285. (16) Boris, D.; Rubinstein, M. Macromolecules 1996, 29, 7251. (17) (a) Welch, P.; Muthukumar, M. Macromolecules 1998, 31, 5892–5897. (b) Terao, T.; Nakayama, T. Macromolecules 2004, 37, 4686–4694. (18) (a) Karatasos, K. Macromolecules 2008, 41, 1025–1033. (b) Blaak, R.; Lehmann, S.; Likos, C. N. Macromolecules 2008, 41, 4452–4458. (19) Paulo, P. M. R.; Canongia Lopes, J. N.; Costa, S. M. B. J. Phys. Chem. B 2007, 111, 10651–10664.
10.1021/la804234p CCC: $40.75 2009 American Chemical Society Published on Web 02/10/2009
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Figure 1. Small-angle X-ray scattering intensity profiles of water solution of G3.5 poly(amidoamine) dendrimers for different concentrations at 23 °C.
angle X-ray scattering (SAXS) technique. While from the experimental point of view the amine-terminated, and then positively charged, dendrimers have been the most investigated,8,9,11 in this work we point out the important role of the long-range ordering effects in water solution caused by the presence of negatively charged carboxylate terminal groups in the dendrimer. Our attempt to model the dendrimer interparticle interaction allows us to obtain important information on the dendrimers’ surface charge as well as counterion effects in the water environment.
at C ) 2.8 × 10-4 M. This indicates the presence of a long-range structural order in the system due to interparticle interaction in solution. Upon increasing the dendrimer concentration, the correlation peak becomes more pronounced and shifts toward larger scattering wavectors q. For a system composed of nearly monodisperse particles in solution, the SAXS scattering intensity I(q) can be expressed as a product of the form factor P(q), which contains information on the shape and dimension of the scattering particles, and the structure factor S(q), describing the interparticle interaction:20
Material and Methods
I(q) ) N(∆F)2 P(q)S(q)
PAMAM dendrimers of generation G3.5 (Mw ) 12 420 g/mol) were purchased from Sigma Aldrich Chemical Co. and consist of a tetrafunctional ethylenediamine core [>NCH2CH2N< ] and [-CH2CH2(CdO)NHCH2CH2N< ] spacers, terminated at the final generation with 64 sodium carboxylate terminal groups (COO-Na+) on average. The dendrimers were dispersed in deionized water, and the obtained solutions were filtered with Teflon filters (filter diameter D ) 0.02 µm). The solutions were also checked by dynamic light scattering prior to SAXS measurements to remove the presence of possible aggregates in the system. SAXS measurements were carried out at the D22 SAXS station of the LURE DCI synchrotron radiation facility (Orsay). The chosen angular range provided data from q ) 0.005 to 0.5 A-1 (q is the scattering vector equal to 4π sin θ/λ, where θ is half of the scattering angle and λ is the X-ray wavelength). The scattering intensities I(q) from the samples, detected by a gas-type linear detector, were corrected for the incident beam decay, sample thickness, and transmission. The background scattering from the solvent was also subtracted.
Results and Discussion In order to obtain valuable information about the structure and interaction of the investigated system, a set of SAXS measurements has been carried out in the range of polymer concentrations between C ) 2.75 × 10-5 and 5.6 × 10-3 M. Figure 1 shows the SAXS intensity profiles of G3.5 PAMAM dendrimers in water solution for the highest investigated concentrations. The SAXS intensity profiles clearly show the presence of a pronounced interference peak in the SAXS spectra starting from the sample
(1)
where N is the number density of the particles and ∆F ) (F F0) is the so-called “contrast” (i.e., the difference between the scattering length density of the particle F and that of the solvent F0). In the dilute region the interparticle interaction can be neglected (i.e., S(q) ≈ 1), so that the analysis of scattering intensity I(q) can furnish direct information on morphological features of the scattering particles (Figure 2A). Information about the dendrimer radius of gyration Rg in the low-concentration region has been obtained from the slope of the representation ln I(q) vs q2 in the so-called Guinier region (i.e., for qRg, 1), where the particle form factor can be expressed as P(q) ) P(0) exp(-q2Rg2/ 3). As shown in the inset of Figure 2A, the radii of gyration were obtained from the slope of the representation of ln I(q) vs q2. Results of the fitting furnish Rg ) 20.7, 19.2, and 20.2 Å for C ) 2.75 × 10-5, 5.6 × 10-5, and 1.1 × 10-4 M, respectively, as reported in Figure 2B. Experimental data have been analyzed also assuming dedrimers as uniform spheres of radius R. The corresponding form factor P(q) ) [3J1(qR)/(qR)]2 (where J1(x) ) [sin(x) - x cos(x)]/x2 is the first-order spherical Bessel function)20 has been used to fit our data in the concentration range 2.75 × 10-5 e c e 1.1 × 10-4 M, where interparticle interference effects are assumed to be negligible. We also assumed Gaussian size distribution during data fitting in order to take into proper account possible polydispersity in the dendrimer size (see Figure 2A). (20) (a) Feign L. A.; Svergun D. I. Structure Analysis by Small-Angle X-ray and Neutron Scattering; Plenum Press: New York, 1987. (b) Glatter O.; Kratky O. Small-Angle X-ray Scattering; Academic Press: London, 1982.
Ordering of PAMAM Dendrimers in Solution
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Figure 3. Analysis of the SAXS static structure factor S(q) in the dilute regime of the water solution of G3.5 poly(amidoamine) dendrimers.
Figure 2. (A) Analysis of the SAXS form factor for the water solution of G3.5 PAMAM dendrimers at C ) 0.056 mM. (B) Results obtained for the dendrimers dimension analysis as a function of particle concentration. The dot-dashed lines indicate the average values obtained for R and Rg.
The results of the form factor data analysis for all the studied concentrations are summarized in Figure 2B. Note that, at the higher concentrations (i.e., for C > 1.1 × 10-4 M), a possible source of uncertainty in the determination of the radius R is connected with the presence of the structure factor S(q) contribution to the SAXS spectra.21 The obtained results indicate that dendrimer radius is not sensitively influenced by the concentration and furnish average values of R ) 24.2 Å for the sphere radius and Rg ) 20.1 Å for the radius of gyration. In previous SAXS investigations in methanol solution, a dendrimer radius of gyration Rg ) 17.0 Å has been obtained10a for carboxyl-terminated dendrimers of the same kind as the one used in the present study. This difference in dendrimer dimension can be explained on the basis of the charge interaction of the dendrimer chains with polar solvent molecules. In this sense, the swelling effect is the consequence of the uptake of solvent molecules by the dendrimer macromolecules. The change in the dielectric constant from methanol ( ) 33) to water ( ) 78) causes, in fact, a modulation of the internal electrostatic force due to the presence of chargeable ammine internal groups and carboxylic external groups. Solvent effects on the dendrimer structural properties have been recently detected by Stechemesser and Eimer,7 who investigated the hydrodynamic properties of PAMAM dendrimers in different solvent conditions by holographic relaxation spectroscopy. They found a significant effect of swelling of the dendrimers when passing to good solvent (21) Analysis of the radius of gyration Rg has been performed up to the concentration C ) 1.1 × 10-4 M. For the higher concentrations the depletion in the SAXS profile in the low q region, due to the presence of the structure factor contribution, does not allow Rg to be obtained from SAXS data. On the other hand, information about the particle radius R at the higher concentrations can be retrieved in connection with the analysis of the structure factor S(q).
conditions for dendrimer molecules starting from generation G4. The effect of the solvent’s quality on the average dimensions of PAMAM dendrimers of generations G5 and G8 has also been investigated recently by small-angle neutron scattering (SANS) experiments.22 In that case the radius of gyration Rg of the G8 dendrimer decreases for the series of solvents D(CD2)mOD (with m ) 0, 1, 2, 4) by approximately 10% from m ) 0 to m ) 4 with decreasing solvent quality. As previously stated, the main macroscopic effect of the presence of chargeable carboxylate (COO-Na+) terminal groups is the observation of the structure factor peak in a wide concentrations range of the dilute regime (see Figure 1). This is a consequence a long-range ordering effect throughout the system caused by the electrostatic repulsive interaction that can be ascribed mainly to a partial ionization of the dendrimers’ surface groups. Analysis of the obtained structure factor S(q) for the sample at C ) 0.28 mM is presented in Figure 3. The static structure factor S(q) represented in the inset of Figure 3 is obtained by dividing the SAXS intensity profile of the system at concentration C ) 0.28 mM with the SAXS profile of the sample at C ) 0.065 mM, for which the contribution of only form factor P(q) is assumed. The presence of a well-defined peak in S(q) indicates that a sensitive electrostatic repulsion is still present despite the low concentration of the dispersed phase, thus confirming the long-range effect of the interparticle interaction. If we made the hypothesis that the system presents a liquid-like order in solution, it is known from the analysis of many simple liquids26 that the dimensionless product of the first interaction peak, qmax, and the mean “nearest neighbor” distance between particles, dave, is a constant quantity given by daveqmax ) k (where the constant k ) 7.2).23 This is near the value of k ) 1.22(2π) proposed for the arrangement of particles in a distorted face-centered cubic lattice.24 In this respect, from the value of qmax observed at the higher concentrations investigated, we can determine the average distance between dendrimers. The result of this analysis is reported in Figure 4. The plot shows the concentration dependence of the average interdendrimer distance for which a sensitive repulsion is still present between (22) Topp, A.; Bauer, B. J.; Tomalia, D. A.; Amis, E. J. Macromolecules 1999, 32, 7232–7237. (23) Waseda Y. The structure of Non-Crystalline Materials; McGraw-Hill: New York, 1980. (24) Guinier, A.; Fournet, G. Small Angle Scattering of X-Rays; John Wiley and Sons: London, 1955. (25) (a) Verwey E. J. W.; Overbeek J. T. G. Theory of the Stability of Lyophobic Colloids; Elsevier: Amsterdam, 1948. (b) Hunter R. J. Foundations of Colloid Science; Oxford University Press: NewYork, 1986; Vols. I- II. (26) Hansen J. P. and Mc Donald I. A. Theory of Simple Liquids; Academic Press: New-York, 1986.
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Figure 4. Analysis of the average interdendrimer distance dave computed from knowledge of the peak position qmax of the SAXS structure factor S(q) (the line is a guide for the eye). Concentration dependence of the Debye-Hukel screening constant is reported for comparison (inset).
dendrimers. The long-range nature of the interaction can be traced back to the variable screening efficiency of the Na+ counterions. In the inset of Figure 4, the concentration dependence of the Debye-Hukel screening constant is reported. This quantity, which takes into account the screening ability of the condensed couterions at the surface of the dendrimers, indicates the low screening efficiency at the high dilution needed to preserve the long-range influence of the interdendrimer electrostatic interaction. The peaks of the structure factor S(q) for the most concentrated solutions also furnish interesting information about the effective interparticle interaction potential. Recent studies on interdendrimer interactions in solution focused mainly on positively charged, amine-terminated dendrimers, with particular emphasis on the effects of the protonation of the amino end-groups upon the addition of acid.8,9,11 In this investigation, on the other hand, we focused our attention on the structural features of a dendrimer species that presents a negatively charged surface, with particular attention to the charge interaction effects in acid-free water solution. In terms of this interaction, the structure factor for a dispersed system of particles can be written as25
S(q) ) 1 +
dr ∫0∞ 4π2 FC[g(r) - 1] sin(qr) qr
(2)
where FC ) c/M is the particle number density (number of particles per unit volume). This last relation provides a way to connect the structure factor S(q) with the radial pair correlation function g(r) (i.e., the probability that two particles stay at distance r in the system). The relation (2) can be obtained by solving the Ornstein-Zernike integral equation (OZ) for the total correlation function:26
∫ c(r ′ )h|r - r′| d3r
h(r) ) c(r) + F0
(3)
The main advantage of this approach lies in the fact that the scattering cross section (in small-angle experiments) can be unambiguously written and computed once the equilibrium structural model of macro-ions and the inter-macro-ion interactions are specified. The solution of the OZ equation, in fact, strongly depends on the choice of the effective pair interparticles potential U(r) through the choice of the relevant structural parameters of the system. In our specific case, in order to obtain information about the interparticle interaction potential, the charged dendrimers have been approximated as inpenetrable spheres of radius R whose charge Ze is distributed on the surface. Those spheres are immersed in the uniform neutralizing
Figure 5. Analysis of the static structure factor S(q) of the carboxylateterminated G3.5 PAMAM system in water solution for three different concentrations. The experimental structure factor S(q) obtained from SAXS spectra is compared with the structure factor calculated by means of the adopted interparticle interaction model.
background of the solvent molecules, which participates with its dielectric constant ( ) 78 for water) and which produces also a screening effect in the system. According to this model, the repulsive potential between two identical spherical objects (macroions) of diameter σ ) 2R placed at a distance r (center-to-center distance) can be approximated as screened Coulombic potential by25
U(r) )
Z0e2
e-κ(r-σ) r 4πε(1 + κσ) 2
(4)
Here, κ ) (λDH)-1 ) (8πe2NaI/KBT 103)1/2 is the DebyeHuckel screening constant, which is determined, at a given temperature T, by the ionic strength I of the solvent (in mol/L) (where e is the unit of electron charge, KB the Boltzmann constant, and Na the Avogadro number). Moreover, a hard-sphere-type repulsive component for the potential has been adopted to represent the close-contact interdendrimer interaction. The OZ equation has been solved numerically by means of the hypernetted chain approximation (HNC)26,27 closure relation:
c(r) ) -
U(r) + h(r) - ln[h(r) - 1] kBT
(5)
In Figure 5, the numerical structure factor S(q) computed according to the adopted model is compared with the experimental structure factor from SAXS spectra for three different dendrimer concentrations. As shown in Figure 5, the adopted model reproduces quite satisfactorily the experimental results, with the same average dendrimer effective charge of Zeff ) 24.6 ( 2.5 (in unit of electron charge |e|). It is worth noticing that, in general, to have the interaction potential in a complete form, an additional term A in eq 4 is considered, due to a weak short-range van der Waals-London attractive contribution coming from interaction between particles in solution. This latter contribution is usually called the Hamaker interaction (A is the Hamaker constant), with magnitude of the (27) Belloni, L. In Neutron X-ray and Light Scattering; Lindner and Zemb, Eds.; Elsevier Science Publishers B.V.: Amsterdam, 1991.
Ordering of PAMAM Dendrimers in Solution
Figure 6. Concentration dependence of the rate of ionization Zeff/Zend for the water solution generation G3.5 poly(amidoamine) dendrimer. Concentration dependence of the Debye-Huckel length λDH (inset).
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charge of Zeff ) 12 ( 1.5e per dendrimer (i.e., degree of ionization near 19%). The obtained results indicate that the characteristics of the modifiable surface groups are responsible for much of the solution properties which are of fundamental importance for the relevant processes involved in molecular recognition and signal processing as well as for binding various targeting or guest molecules. For example, the difference in binding capacity between dendrimers species possessing different terminal groups has been explained by the different degrees of ionization of the species.28,29 This tunable interaction due to the charged (internal and external) groups plays a crucial role due to the possibility of controlling both intra- and intermolecular conformation by varying the solution conditions (such as solvent quality, pH, and ionic strength) and is expected to play an important role in determining to what extent the foreign molecules can be accommodated.30
Conclusions order of kBT. However, such a contribution in many systems, like ionic micellar solutions, colloidal solutions at low ionic strength, or the present dendrimer solution without salt addition can be considered negligible in comparison to the strong longrange Coulombic repulsive interaction (usually several kBT at contact).25 Thus, as far as the calculation of S(q) is concerned, the presence of the Hamaker interaction can be neglected, and only the effect of the double-layer repulsion must be considered. This last assumption relies also on the fact that, until now, no attractive interactions have been observed in similar systems, even with the addition of a given salt amount to the system.9 In Figure 6, the representation of the rate of ionization Zeff/Zend (i.e., number of average ionized end-groups Zeff per dendrimer over all available carboxylate endg-roups Zend) indicates a slow variation as a function of concentration. From our obtained results, we can deduce that the sodium carboxylate terminal groups of PAMAM generation G3.5 dendrimers in water solution are partially dissociated (COO-Na+). More specifically, an average number of 24 carboxylic groups (over the 64 total) per dendrimer realize this ionization (i.e., degree of ionization near 40%). The condensed counterions at the surface of the dendrimer not only preserve, with the neutralizing action of their charge compensation, the local electroneutrality within the dendrimer in solution but also realize a controlled screening of the long-range interdendrimer potential. In this respect, along with the increase in dendrimer concentration goes a corresponding decrease in the extent of double-layer interaction. This circumstance is evidenced in the inset of Figure 6, where the plot of the concentration dependence of the Debye-Hu¨ckel length λDH indicates the characteristic spatial range over which the decay of the particle correlations is expected. It is worth pointing out that a rather different result has been obtained in a SAXS investigation of half-integer PAMAM generation G3.5 in methanol solution.10a In that case, in fact, SAXS experiments in a wide range of concentrations revealed a very weak ionization coming from the dendrimer chargeable carboxylic end-groups, which was less than 10%. Moreover, preliminary results obtained for the study of the interparticle interactions in amine-terminated PAMAM dendrimers of the same generation as the one studied here indicated an effective average
We have presented the results of a small-angle X-ray scattering structural investigation in water solution of carboxyl-terminated generation G3.5 PAMAM dendrimers. The presence, even in the dilute regime, of a sharp interference peak in the SAXS spectra has been ascribed to the long-range intermolecular electrostatic interaction caused by the presence of chargeable moieties in the system. The experimental interdendrimer structure factor S(q), analyzed in the framework of the Ornstein-Zernike integral equation, allowed us to model interdendrimer interaction potential as well as to obtain important information about the dendrimer effective charge Zeff (degree of ionization). The obtained results point out the important role of the negatively charged dendrimer carboxylate surface groups in regulating, through the modulation of the electrostatic interaction, the main part of their structural properties in solution. The dendrimer charge interaction is expected, in fact, to play an important role in controlling the insertion of drug molecules within the internal dendrimer cavities.28 Carboxylate-terminated dendrimers showed in solution an enhanced charge activity and provided then an interesting alternative, with respect to the amine-terminated dendrimers, for the study of delivery processes in dendrimer-drug complexes. For example, the negatively charged carboxylic-terminated dendrimers presumably bind to positively charged regions and thus would most likely be removed by phosphate buffer. On the other hand, as charge effects manifest as a collective effect, to determine the exact dependence of the structural conformation of dendrimers on the ionic strength and the counterion condensation effect, more experimental and computational work should be performed. In this respect, further experiments are in progress in our laboratories in order to better clarify the role of the dendrimer charge in different solvent conditions (such as solvent quality, pH, ionic strength), as well as to investigate the relevant parameters which regulate the interactions with charged, lowmolecular-weight macromolecules. LA804234P (28) Chen, H.; Banaszak Holl, M.; Orr, B. G.; Majoros, I.; Clarkson, B. H. J Dent. Res. 2003, 82, 443–448. (29) Kofoed, J.; Reymond, J.-L. Curr. Opin. Chem. Biol. 2005, 9, 656–664. (30) (a) Cheng, Y.; Wu, Q.; Li, Y.; Xu, T. J. Phys. Chem. B 2008, 112, 8884– 8890. (b) Cheng, Y.; Li, Y.; Wu, Q.; Xu, T. J. Phys. Chem. B 2008, 112, 12674– 12680.
