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Size and shape assessment of organometallic gold(I) metallodendrimers through PGSE-NMR and molecular dynamics simulations
Inorganica Chimica Acta 380 (2012) 31–39
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Size and shape assessment of organometallic gold(I) metallodendrimers through PGSE-NMR and molecular dynamics simulations Francisco Corzana, Miguel Monge ⇑, Eva Sánchez-Forcada Departamento de Química, Universidad de La Rioja, Grupo de Síntesis Química de La Rioja, UA-CSIC, Complejo Científico-Tecnológico, 26004 Logroño, Spain
a r t i c l e
i n f o
Article history: Available online 8 October 2011 Young Investigator Award Special Issue Keywords: Gold Metallodendrimers 1 H PGSE NMR Molecular dynamics
a b s t r a c t The reactions of the amino-terminated PAMAM-dendrimers (generations 0–2) with Ph2PCH2OH in the appropriate molar ratios give rise to the dendritic phosphines PAMAM-GZ-(N(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)). Further reaction of phosphines 1–3 with one equivalent of [Au(C6F5)(tht)] (tht = tetrahydrothiophene) per P-donor site leads to metallodendrimers [{Au(C6F5)}2n {PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)). Phosphines 1–3 and metallodendrimers 4–6 have been characterized by 1H, 19F and 31P{1H} NMR spectroscopy and through IR spectroscopy. 1H PGSE NMR studies of the dendritic phosphines and the metallodendrimers permit the evaluation and comparison of the different molecular sizes through their corresponding hydrodynamic radius, depending on the dendrimer generation and on the coordination of the organometallic fragments [Au(C6F5)]. Molecular dynamics simulations allow the theoretical estimation of the macromolecular size through the calculation of the radius of gyration for each species and the calculation of the dendrimer flexibility. Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction Research on metal-containing highly-branched macromolecular architectures such as metallodendrimers has become a fascinating area of investigation [1,2]. This type of monodisperse nano-scale macromolecules displays intrinsic features like facile construction, tunable solubility and localized positioning of structural units compared to other functionalized polymers, which make them ideal systems for the characterization and for the development of new or enhanced properties and applications. Some of these potential applications have appeared in different fields. The most important advances have been carried out in the field of catalysis, in which metallodendrimers combine high loading of catalyst, homogeneous processing and straightforward separation of products and catalyst. Examples including Ni-, Cu-, Rh-, Pd- Ru-, Fe-, or Co-based dendritic catalysts, among others, have shown the performance of these systems [3]. Luminescent Ru-, Ir- or Lanthanide-based metallodendrimers have also been studied as potential chemical systems for light conversion, OLED devices, sensors or fluoroimmunoassays [4]. PAMAM-based Gd(III) dendritic contrast agents were found to be very effective in magnetic resonance imaging (MRI) [5]. Molecular batteries have also been designed from metallodendrimers containing Fe complexes that can provide robust redox activity [6].
⇑ Corresponding author. E-mail address: [email protected] (M. Monge). 0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2011.10.006
In most cases the characterization of these macromolecular large systems can be carried out using the standard spectroscopic techniques for molecular chemistry. Nevertheless, the use of other techniques is not only complementary, but can also provide very useful information. Thus, the size and shape of the metallodendrimers can be closely related to their intrinsic properties and, therefore, there is a need of combining different characterization techniques for a better knowledge of these macromolecules. In this sense, the size of dendritic molecules has been measured through different techniques such as Small Angle Neutron Scattering (SANS) [7], Small Angle X-ray Scattering (SAXS) [8], viscosimetry [7], mass spectrometry [9], or High Resolution Electron Microscopy (HREM) [10]. An alternative and powerful way of evaluating macromolecular size and shape is the use of Pulsed Field Gradient Spin-Echo (PGSE) NMR measurements, a method that allows measuring the molecular diffusion in solution which is related to the hydrodynamic radius through the Stokes–Einstein equation [11]. From a theoretical viewpoint, molecular dynamics (MD) simulations are a useful tool to describe the detailed dynamic properties of flexible and large systems in solution [12]. In particular, the combination of these computational calculations with experimental techniques, such as NMR, has been successfully applied to investigate the conformational behavior of a large variety of molecules [13]. If we focus on gold-containing metallodendrimers bearing the metal centers at the periphery, few examples have been reported if compared to other metals. The works by Rossell et al. [10] or
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Schmidbaur and co-workers [14] groups show that these hybrid homometallic (Au) or, to a less extent, gold-containing heterometallic dendrimers [15] are promising materials with potential applications in different fields, including their use as nanoparticle precursors or photoluminescent molecular nanomaterials. In this sense, some of us have recently studied the characterization and photoluminescent properties of octanuclear dendritic-like phosphine thiolate gold(I) complexes [16]. A clear advantage of Au(I) is its usually low coordination number that gives rise to linear environments what makes this metal ion very attractive for dendritic surface grafting. Among the ligands bonded to gold(I) the use of pentafluorophenyl ligands that together with aryl phosphines lead to stable [C6F5–Au–PR3] structural units has been extensively explored [17]. In this work, we describe the synthesis and characterization of generations 0, 1 and 2 PAMAM-modified dendrimers with aryl phosphines at the periphery PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)). We have also synthesized the corresponding organometallic metallodendrimers [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) by the coordination of [Au(C6F5)] fragments at the phosphine end groups. In the present study, the comparison of the experimental data obtained from PGSE-NMR, with those calculated using MD calculations, will be useful to validate our simulations. Thus, the validated trajectories will provide new insights into conformational behavior of the metallodendrimers and allow a better description of the structure–properties relationship. 2. Experimental 2.1. General remarks The compound [Au(C6F5)(tht)] [18] was synthesized by standard procedures reported in the literature. The starting materials Ph2PH, p-formaldehyde and PAMAMGZ-(NH2)n (Z = 0,1 and 2; ethylenediamine core) were purchased from Sigma Aldrich and used without further purification. Solvents used in the synthesis of new compounds were dried and distilled. 2.2. Instrumentation Infrared spectra were recorded in the 4000–200 cm1 range on a Nicolet Nexus FT-IR spectrophotometer, using Nujol mulls between polyethylene sheets. C, H, N analysis were carried out with a C.E. Instrument EA-1110 CHNS-O microanalyser. MALDI-TOF spectra were recorded in a Microflex MALDI-TOF Bruker spectrometer operating in the linear and reflector modes using dithranol as matrix. 31P{1H}, 19F and 1H NMR experiments were recorded on a Bruker ARX 300. PGSE-NMR experiments were recorded on a Bruker AVANCE 400 in d8-THF. 2.3. PGSE experiments 1
H PGSE measurements were carried out using the double stimulated echo pulse sequence (Double STE) [19] on a Bruker AVANCE 400 equipped with a BBI H-BB Z-GRD probe at 298 K without spinning. When this double stimulated echo pulse sequence is used, the dependence of the resonance intensity I on a constant waiting time and on a varied gradient strength G is described by the Eq. (1):
d 104 I ¼ I0 exp Dt ð2pc d GÞ2 D 3
ð1Þ
where I = intensity of the observed spin-echo, I0 = intensity of the spin-echo without gradients, Dt = diffusion coefficient, D = delay
between the midpoints of the gradients, d = length of the gradient pulse, and c = magnetogyric constant. The pulse sequence was composed of 90° pulses. The duration of the gradients (d) was 2 ms, the delay D was between 200 and 400 ms, depending on the sample, and the strength G was varied during the experiment. The spectra were acquired using 32 or 40 K points. The exponential plots of I versus G were fitted using a standard exponential algorithm implemented in TOPSPIN software. PGSE data were treated [20] using THF as internal standard in 2 mM samples at 298 K, and introducing in the Stokes–Einstein Eq. (3) the semiempirical estimation of the c factor, which can be obtained through Eq. (2) [21], derived from the microfriction theory proposed by Wirtz and co-workers [22] in which c is expressed as a function of the solute-to-solvent ratio of the radii.
c¼
6 v Þ2:234 1 þ 0:695ðrsol rH
Dt ¼
kT crH gp
ð2Þ ð3Þ
Using the experimentally measured diffusion coefficients Dt of the sample and the internal standard, and through the Stokes– Einstein Eq. (3), an accurate value of the hydrodynamic radius rH can be obtained in each case [20]. 2.4. Molecular dynamics (MD) simulations Molecular dynamics (MD) simulations were performed with HYPERCHEM 7.5 package, implemented with AMBER99 force field [23]. All the simulations were carried out at 300 K and using the appropriate dielectric constant to simulate the solvent. No cut-offs were used for the non-boding interactions. The timestep was adjusted to 1 fs and the simulation lengths to 10 ns to ensure an adequate sampling of the conformations present in solution. The radius of gyration (in nm) was calculated from the different trajectories following this expression (4):
P mi r2 R2g ¼ P i mi
ð4Þ
where mi is the mass of the ith atom in the particle and ri is the distance from the center of mass to the ith particle. 2.5. Synthesis 2.5.1. General procedure for the preparation of PAMAM-GZ-(N(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) To a paraformaldehyde suspension (0.087 g, 2.87 mmol) in 10 mL of distilled methanol under Ar atmosphere, diphenylphosphine (0.5 mL, 2.87 mmol) was added. This suspension was heated under reflux for 3 h. After cooling down the solution, PAMAM-GZ-(NH2)n dendrimer (0.186 g, 0.36 mmol for Z = 0; 0.257 g, 0.18 mmol for Z = 1 or 0.292 g, 0.09 mmol for Z = 2) was added. The reaction mixture was stirred for 1 h and 15 mL of toluene were then added, following the reaction stirring for 12 h at room temperature and 3 h under reflux (110 °C). Evaporation of the solvents under reduced pressure gave rise to the dendritic phosphines PAMAM-GZ(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) in quantitative yields as oils. Anal. Calc. for (C126H136N10O4P8) (1): C, 71.98; H, 6.52; N, 6.66. Found: C, 71.70; H, 6.47; N, 6.70%. Anal. Calc. for (C270H304N26O12P6) (2): C, 70.48; H, 6.69; N, 7.91. Found: C, 70.52; H, 6.61; N, 7.85%. Anal. Calc. for (C558H640N58O28P32) (3): C, 69.82; H, 6.72; N, 8.46. Found: C, 69.72; H, 6.51; N, 8.46%. 1H NMR (300 MHz, CDCl3) for 1, d: 7.54–7.32 (m, Ph rings), 3.62 (m, N–CH2– P), 3.21 (m, NH–CH2–CH2), 2.98 (m, N–CH2–CH2), 2.59 (m, CH2– CH2–N), 2.41 (m, N–CH2–CH2) and 2.00 ppm (s, N–CH2–CH2–N); 2, d: 7.34–7.25 (m, Ph rings), 3.53 (m, N–CH2–P), 3.11 (m, NH–CH2–CH2),
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Scheme 1. Synthesis of dendritic phosphines PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)).
2.89 (m, N–CH2–CH2), 2.63 (m, CH2–CH2–N), 2.50 (m, N–CH2–CH2) and 2.27 ppm (s, N–CH2–CH2–N) and 3, d: 7.33–7.23 (m, Ph rings), 3.53 (m, N–CH2–P), 3.16 (m, NH–CH2–CH2), 2.89 (m, N–CH2–CH2), 2.70 (m, CH2– CH2–N), 2.53 (m, N–CH2–CH2) and 2.29 ppm (s, N–CH2–CH2–N).
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P{1H} NMR (121 MHz, CDCl3) for 1, d: 28.3 ppm; 2, d: 28.5 ppm and 3, d: 28.5 ppm. MS (MALDI+) m/z (%) = 2165.6 [M+4O+H]+ (1); m/z (%) = 4856,3 [M+16O+H]+ (2) and m/z (%) = 9620.9 [M+Na]+ (3).
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Scheme 2. Synthesis of complexes [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)).
Fig. 1. 1H NMR spectrum of metallodendrimer [{Au(C6F5)}32{PAMAM-GZ-(N-(CH2PPh2)2)16}] (6).
2.5.2. General procedure for the preparation of [{Au(C6F5)}2n{PAMAMGZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) To a dichloromethane solution (15 mL) of ligand (PAMAMGZ-(CH2PPh2)2)n (0.113 g, 0.062 mmol for Z = 0; 0.244 g, 0.053 mmol for Z = 1 or 0.249 g, 0.026 mmol for Z = 2) was added the organometallic precursor [Au(C6F5)(tht)] (0.220 g, 0.490 mmol for Z = 0; 0.380 g, 0.850 mmol for Z = 1 or 0.375 g, 0.831 mmol for Z = 2, respectively). After stirring 24 h, the solvent was evaporated under vacuum to ca. 5 mL. Addition of n-hexane (20 mL) gave rise to
complexes [{Au(C6F5)}2n{(PAMAM-GZ-(CH2PPh2)2)n}] (Z = 0, n = 4, 78% yield (4), Z = 1, n = 8, 76% yield (5) and Z = 2, n = 16, 82% yield (6)) as white solids. Anal. Calc. for (C174H136Au8F40N10O4P8) (4): C, 41.68; H, 2.73; N, 2.79. Found: C, 41.83; H, 2.79; N, 2.88%. Anal. Calc. for (C366H304Au16F80N26O12P16) (5): C, 42.16; H, 2.94; N, 3.49. Found: C, 42.08; H, 2.89; N, 3.51%. Anal. Calc. for (C750H640Au32F160N58O28P32) (6): C, 42.40; H, 3.04; N, 3.82. Found: C, 43.05; H, 3.22; N, 4.21%. 1H NMR (300 MHz, CDCl3) for 4, d: 7.68–7.38 (m, Ph rings), 4.33 (m, N–CH2–P), 2.98 ppm (broad m, NH–CH2–CH2 and CH2–CH2– N), 2.62–2.10 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and
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N–CH2–CH2–N); 5, d: 7.69–7.36 (m, Ph rings), 4.33 (m, N–CH2–P), 3.03 ppm (broad m, NH–CH2–CH2 and CH2–CH2–N), 2.52– 2.00 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and N–CH2–CH2– N) and 6, d: 7.67–7.35 (m, Ph rings), 4.36 (m, N–CH2–P), 3.12 ppm (broad m, NH–CH2–CH2), 2.99 ppm (broad m, CH2–CH2–N), 2.52– 2.00 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and N–CH2–CH2– N). 19F NMR (283 MHz, CDCl3) for 4, d: 162.0 (m, 16F, Fm), 157.9 (m, 8F, Fp) and 115.6 ppm (m, 16F, Fo); for 5, d: 162.1 (m, 32F, Fm), 158.1 (m, 16F, Fp) and 115.55 ppm (m, 32F, Fo) and 6, d: 162.1 (m, 64F, Fm), 158.1 (m, 32F, Fp) and 115.5 ppm (m, 64F, Fo). 31P{1H} NMR (121 MHz, CDCl3) for 4, d: 26.7 ppm; 5, d: 26.7 ppm and 6, d: 26.7 ppm. MS (MALDI+) m/z (%) = 5014.3 [M+H]+ (4); m/z (%) = 10429.0 [M+H]+ (5) and m/z (%) = 10624.0 [M+2H]2+ (6). IR: m = 1658 m(C–N); 1546 m(N–H); 1502, 955, 793 cm1 m(Au–C6F5) (4); 1659 m(C–N); 1546 m(N–H); 1505, 955, 789 cm1 m(Au–C6F5) (5); 1650 m(C–N); 1543 m(N–H); 1503, 958, 793 cm1 m(Au–C6F5) (6).
Table 1 Diffusion Coefficients Dt (1010 m2 s1) and hydrodynamic radii rH(nm) for PAMAMNH2 dendrimers P-donor ligands 1–3 and complexes 4–6.
PAMAM-G0-(NH2)4 PAMAM-G1-(NH2)8 PAMAM-G2-(NH2)16 PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0-(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2-(N-(CH2PPh2)2)16}] 6
Dt
rH
Ref.
5.86 3.77 3.00 4.79 3.14 2.55 3.73 2.63 2.05
0.67 1.04 1.30 0.83 1.29 1.59 1.04 1.35 1.68
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3. Results and discussion 3.1. Synthesis and characterization The PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) dendritic P-donor ligands were prepared following a modification of an already reported synthesis of P-donor poly(propileneimine) dendrimers [3c]. Thus, addition of the amino terminated PAMAM-GZ-(NH2)n (Z = 0, n = 4, Z = 1, n = 8 and Z = 2, n = 16) dendrimers to the corresponding amount of Ph2PCH2OH (two equivalents of phosphine per amine group) gives rise to phosphino-terminated dendrimer ligands bearing 8 (1), 16 (2) or 32 (3) Ph2P end-groups (see Scheme 1). The 31P{1H} NMR of these P-donor groups at the periphery of the PAMAM dendrimers is similar for the three generations, displaying a singlet at 28.3 (1), 28.5 (2), 28.5 ppm (3), respectively (see Scheme 1). Complexes [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) have been synthesized by reaction of the multidentate ligands 1–3 with the [Au(C6F5)(tht)] (tht = tetrahydrothiophene) precursor in 1:8 (4), 1:16 (5) and 1:32 (6) molar ratios, respectively (see Scheme 2) leading to complexes 4–6 in quantitative yields by displacement of the labile ligand tht. The 31P{1H} NMR spectra of these complexes display a singlet at 26.7 (4), 26.7 (5), 26.5 ppm (6), respectively, showing a large shift downfield with respect to the free ligands. The proton signals arising from the dendrimer skeleton are observed in the 1H NMR spectra in each case and they are also shifted downfield when compared to those of the free ligand. The corresponding assignment of the proton signals in the 1H NMR spectrum has been carried out following the scheme on Fig. 1 (see Section 2). Their IR spectra show absorptions arising from the Au–C6F5 vibrations at 1502, 955, 793 (4), 1505, 955, 789 (5), 1503, 958, 793 cm1 (6), respectively. 3.2. PGSE-NMR studies The use of the PGSE-NMR technique permits an evaluation of the self-diffusion coefficient Dt for phosphino dendrimers 1–3 and the corresponding organometallic Au(I) metallodendrimers 4–6 in 0.5 mL of 2 mM d8-THF solutions at 298 K. Subsequently, the evaluation of the molecular size through the hydrodynamic radius rH can be carried out by the use of the Stokes–Einstein equation. The results are given in Table 1 (see Section 2 for details), including the diffusion coefficients Dt and hydrodynamic radius rH for the dendritic phosphines 1–3 and for the (pentafluorophenyl)phosphinogold(I) metallodendrimers 4–6. In Fig. 2 the sections of 1H PGSE NMR spectra in d8-THF for metallodendrimer 5 are shown. As it can be observed, the resonance intensities of the P–CH2–N protons
Fig. 2. Sections of 1H PGSE NMR spectra in d8-THF for complex [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5. The resonance intensities of the P–CH2–N protons and those of the solvent decrease upon increasing the pulsed-field gradient. (The P– CH2–N signal is a broad signal without resolved multiplicities).
from the metallodendrimer periphery and O–CH2– protons from the non-deuterated THF solvent decrease upon increasing the pulsed-field gradient. The P–CH2–N signal is a broad signal without resolved multiplicities. In Fig. 3, we represent the typical plot of all the observed 1H signal intensity changes obtained through the PGSE data in two sets (dendritic phosphines and metallodendrimers), representing ln(I/ I0), as a function of the square of the increasing gradient strengths G2, following the equation given in the figure. Molecules possessing larger sizes will diffuse more slowly than smaller ones, leading to smaller slopes. As it can be seen in Table 1, larger Dt coefficients are obtained for the PAMAM-GZ-(N-(CH2PPh2)2)n ligands 1–3 when compared with the corresponding metallodendrimers [Au2n(C6F5)2n {PAMAM-GZ-(N-(CH2PPh2)2)n}] 4–6, which is, as expected, in agreement with the smaller size of the phosphines at each generation. The hydrodynamic radii rH is then slightly larger for metallodendrimers 4 (1.04 nm), 5 (1.35 nm) and 6 (1.68 nm) than the ones obtained for dendrimer ligands 1 (0.83 nm), 2 (1.29 nm) and 3 (1.59 nm), respectively. If we represent the hydrodynamic radii versus the dendritic generation, we observe an almost parallel growth of the dendrimer ligands and the metallodendrimer, although a larger size expansion of the metallodendrimer is observed when the [Au(C6F5)] groups are bonded to the smaller dendritic phosphine 1 (see Fig. 4). This result is also expected since the contribution of the organometallic periphery to the metallodendrimer size is larger in the smallest metallodendrimer 4. It is also worth mentioning that the results obtained here are comparable to PGSE-NMR measurements of the self-diffusion coefficients (Dt) and hydrodynamic radii (rH) of the dendrimer precursors
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Fig. 3. Plots of 1H ln(I/I0) vs. arbitrary units proportional to the square of the gradient amplitude on dendrimers 1–3 (top) and metallodendrimers 4–6 (bottom). The larger the dendrimer (or metallodendrimer) is, the smaller the value of the absolute slope becomes.
PAMAM-GZ-(NH2)n (Z = 0, n = 4; Z = 1, n = 8 and Z = 2, n = 16) although they are measured under different experimental conditions [24] (see Table 1). 3.3. Molecular dynamics (MD) simulations In view of the interesting results obtained through PGSE-NMR measurements for the size assessment of the organometallic Au(I) metallodendrimers and their corresponding dendritic phosphines precursors, we have carried out molecular dynamics (MD) theoretical studies in order to gain insight about the size and shape of this nanometric size molecular systems. We have estimated the radius of gyration (rG) of the phosphines 1–3 and the metallodendrimers 4–6 in order to compare them with the hydrodynamic radii experimentally measured. In a second step, we have analyzed the MD results in order to estimate the shape of the
metallodendrimers by the superposition of several conformations (frames) and by the analysis of the contraction/expansion capabilities of the different conformations that the dendrimers and metallodendrimers can adopt through the dynamics process. Before analyzing the obtained results for comparison with the experimental ones we have validated our method of calculation. Since the use of force fields are not specifically designed for the analysis of organometallic systems, we have first checked several structural parameters of the organometallic units coordinated at the periphery of the metallodendrimers during the dynamics. In Fig. 5, we can observe that the P–Au–C angle (ca. 180°) and the Au–P (ca. 2.5 Å) and Au–C (ca. 2.2 Å) distances are stable through the simulation and closed to the experimental ones obtained in the X-ray structure analysis of the molecular analog [Au4R4 {(Ph2PCH2)2NCH2CH2N(CH2PPh2)2}] (P–Au–C: 174.7–175.8°, Au–P 2.28 Å and Au–C 2.05 Å) [16a]. Unfortunately, the use of classical
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Fig. 4. Graphical representation of the hydrodynamic radii (rH) obtained for the dendritic phosphine ligands 1–3 (black line) and for the gold(I) metallodendrimers 4–6 (red line) as a function of the generation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5. Time series monitoring the P–Au–C angle and the Au–P and Au–C distances in the 10 ns MD simulations.
MD calculations allows including hundreds or thousands of atoms in the models but it does not allow analyzing the dispersive component of the possible aurophilic interactions present in these
37
systems. However, since the overall size of the metallodendrimers would not be much affected by the presence or not of aurophilic contacts and since the previously commented tetranuclear structure does not show aurophilic interactions even for C6F5–Au–P units in parallel disposition, we think that the MD calculations can give a nice description of these very large molecules. Fig. 6 depicts the superposition of several conformations of dendritic phosphines 1–3. With this representation we can assume an almost spherical shape for these systems. The analysis of the radii of gyration provides interesting conclusions. First, if we take into account the equations for the estimation of the radius of gyration and the hydrodynamic radius, the obtained rG for dendrimers 1–3 and metallodendrimers 4–6 would be smaller than the corresponding rH ones, since the experimental rH values take into account the structure adopted by the dendrimers and metallodendrimers in the presence of solvent molecules (see Section 2). The rG and rH values obtained for dendrimers 1–3 and metallodendrimers 4–6 are shown in Table 2. As expected, in all cases the rG is smaller than the corresponding rH. If we represent the dendrimer (or metallodendrimer) radii versus the studied species with increasing size we observe the same trend, which is that both the rH and the rG increase when going from the dendrimer to the corresponding metallodendrimer or when increasing the generation (Fig. 7). We can also analyze the role of the solvent in the size of these macromolecular systems since the MD calculations are carried out in implicit solvent (the dielectric constant is taken into account but not the volume and surface of solvent molecules) and the experimental PGSE measurements include the solvent influence in the obtained rH values. If we observe the results in Fig. 7, we can see that the rH and rG values are closer in the case of 0th generation, that is dendrimer 1 and metallodendrimer 4, but they differ for generations 1 (2 and 5) and 2 (3 and 6). This trend could be interpreted taking into account the ability of the THF molecules for interacting with increasing generations of dendrimers. Thus, while a peripheric interaction between the solvent molecules would be expected for the smaller dendrimers 1 and 4, a possible interaction of the solvent molecules with the functional groups of the inner cavities of the higher generation dendrimers (generations 1 and 2), acting as a guest molecule, would be proposed, leading to larger differences between the theoretically predicted rG values and the experimentally obtained rH ones. This result is also in agreement with previously PGSE-NMR studies of dendrons in THF in which the authors propose the swelling of the dendron molecules [24]. The molecular dynamics simulations carried out for macromolecular systems 1–6 also provide interesting results regarding the flexibility of these nanometric size systems. We have evaluated the percentage of dendrimer expansion and contraction for each dynamics by computing the larger (rGmax) and smaller (rGmin) radius of gyration for each dendritic molecule throughout the trajectory. The results are depicted in Table 3 and Fig. 8. As it can be observed, all the dendrimers and metallodendrimers display a high degree of flexibility as it is observed in the percentage of contraction and expansion of the smallest and largest conformation, respectively. In the case of the dendritic phosphines 1–3, the % of expansion increases with the increase in the generation while the % of contraction increases when going from generation 0 (28.57%) to 1st generation (39.80%), but is almost the same for 2nd generation (39.69%). In the case of the metallodendrimers 4– 6, we observe a different trend, showing an increase in the degree of contraction with the increase of the generation and different values without a clear tendency for the % of expansion with respect to the dendrimer generation. Finally, in view of the percentage values of contraction and expansion, we can conclude that the metallodendrimers 4–6 are as flexible as their precursor phosphines 1–3.
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Fig. 6. Superimposition of different frames randomly taken from the 10 ns MD simulations for 1 (A), 2 (B) and 3 (C).
Table 2 Comparison between hydrodynamic radius (rH, nm) and calculated radius of gyration (rG, nm) for P-donor ligands 1–3 and complexes 4–6.
PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0-(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2-(N-(CH2PPh2)2)16}] 6
rH (nm)
rG (nm)
0.83 1.29 1.59 1.04 1.35 1.68
0.77 1.03 1.31 0.92 1.12 1.40
Fig. 7. Hydrodynamic radii (rH) and radii of gyration (rG) for all dendritic species (1– 6) with increasing size.
Table 3 rG, rGmax and rGmin values and % of size expansion and contraction for compounds 1–6 obtained from the MD simulations.
PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2(N-(CH2PPh2)2)16}] 6
rG (nm)
% Expansion (rGmax) (nm)
% Contraction (rGmin) (nm)
0.77 1.03 1.31 0.92
7.79 (0.83) 36.89 (1.41) 54.43 (2.01) 4.34 (0.96)
28.57 39.80 39.69 43.48
1.12
27.68 (1.43)
51.78 (0.54)
1.40
22.85 (1.72)
53.57 (0.65)
(0.55) (0.62) (0.79) (0.52)
Fig. 8. Percentage of contraction and expansion taking into account the size of the smallest and largest conformation for each case.
F. Corzana et al. / Inorganica Chimica Acta 380 (2012) 31–39
4. Conclusions We have carried out a combined experimental and theoretical study by the use of 1H PGSE spectroscopy and molecular dynamics simulations. This methodology has allowed us to gain insight about the size and the shape of dendritic phosphines and metallodendrimers of nanometer size. These molecular nanosystems are of spherical shape and display a high degree of flexibility. In addition, the larger increase of the hydrodynamic radius in tetrahydrofuran with respect to the theoretical radius of gyration calculated in implicit solvent could be in agreement with a dendrimer swelling in this solvent. Acknowledgements The D.G.I. (MEC)/FEDER (CTQ2010-20500-C02-02) and European Commission, POCTEFA (METNANO, EFA 17/08) Projects are acknowledged for financial support. E. Sánchez-Forcada thanks the C.S.I.C. for a JAE-Predoc Grant. Appendix A. Supplementary data
[5] [6] [7] [8] [9] [10] [11]
[12]
[13]
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ica.2011.10.006. References [1] S.-H. Hwang, C.D. Schreiner, C.N. Moorefield, G.R. Newkome, N. J. Chem. 31 (2007) 1192. [2] B.J. Ravoo, Dalton Trans. (2008) 1533. [3] See for example: (a) A.W. Kleij, R.A. Grossage, R.J.M.K. Gebbink, N. Brinkmann, E.J. Reijerse, U. Kragl, M. Lutz, A.L. Spek, G. van Koten, J. Am. Chem. Soc. 122 (2000) 12112; (b) H.-F. Chow, C.C. Mak, J. Org. Chem. 62 (1997) 5116; (c) M.T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. Int. Ed. Engl. 36 (1997) 1526; (d) D. de Groot, J.N.H. Reek, P.C.J. Kamer, P.W.N.M. van Leeuwen, Eur. J. Org. Chem. (2002) 1085; (e) S. Gatard, S. Nlate, E. Cloutet, G. Bravic, J.-C. Blais, D. Astruc, Angew. Chem., Int. Ed. 42 (2003) 452; (f) V. Maraval, R. Laurent, A.-M. Caminade, J.-P. Majoral, Organometallics 19 (2000) 4025; (g) S. Rigaut, M.-H. Delville, D. Astruc, J. Am. Chem. Soc. 119 (1997) 11132; (h) R. Breinbauer, E.N. Jacobsen, Angew. Chem., Int. Ed. 39 (2000) 3604. [4] See for example: (a) S. Campagna, S. Serroni, S. Bodige, F.M. MacDonnell, Inorg. Chem. 38 (1999) 692;
[14] [15] [16]
[17] [18] [19] [20] [21] [22] [23] [24]
39
(b) G. Bergamimi, C. Saudan, P. Ceroni, M. Maestri, V. Balzani, M. Gorka, S.-K. Lee, J. van Heyst, F. Vögtle, J. Am. Chem. Soc. 126 (2005) 16466; (c) T. Tsuzuki, N. Shirasawa, T. Suzuki, S. Tokito, Jpn. J. Appl. Phys. Part I 44 (2005) 4151; (d) F. Vögtle, M. Gorka, V. Vicinelli, P. Ceroni, M. Maestri, V. Balzani, ChemPhysChem 2 (2002) 769; (e) U. Hahn, M. Gorka, F. Vögtle, V. Vicinelli, P. Ceroni, M. Maestri, V. Balzani, Angew. Chem., Int. Ed. 41 (2002) 3595;. f. E.C. Wiener, M.W. Brechbiel, H. Brothers, R.L. Magin, O.A. Gansow, D.A. Tomalia, P.C. Lauterbur, Magn. Reson. Med. 31 (1994) 1. S. Nlate, J. Ruiz, V. Sartor, R. Navarro, J.-C. Blais, D. Astruc, Chem. Eur. J. 6 (2000) 2544. R. Scherrenberg, B. Coussens, P. van Vliet, G. Edouard, J. Brackman, E. de Brabender, Macromolecules 31 (1998) 456. B. Huang, A.R. Hirst, D.K. Smith, V. Castelletto, I.W. Hamley, J. Am. Chem. Soc. 127 (2005) 7130. F.F. Fan, C.L. Mazzitelli, J.S. Brodbelt, A.J. Bard, Anal. Chem. 77 (2005) 4413. O. Rossell, M. Seco, A.-M. Caminade, J.-P. Majoral, Gold Bull. 34 (2001) 88. See for example: (a) A. Macchioni, G. Ciancaleoni, C. Zuccaccia, D. Zuccaccia, Chem. Soc. Rev. 37 (2008) 479; (b) D. Zuccaccia, L. Busetto, M.C. Cassani, A. Macchioni, R. Mazzoni, Organometallics 25 (2006) 2201; (c) Y. Cohen, L. Avram, L. Frish, Angew. Chem., Int. Ed. 44 (2005) 520. (a) T.E. Cheatham, P.A. Kollman, Ann. Rev. Phys. Chem. 51 (2000) 435; (b) T. Schlick, Molecular Modeling and Simulation: An Interdisciplinary Guide, Springer, New York, 2010. See for example: (a) F. Corzana, J.H. Busto, G. Jimenez-Oses, M. Garcia de Luis, J.L. Asensio, J. Jimenez-Barbero, J.M. Peregrina, A. Avenoza, J. Am. Chem. Soc. 129 (2007) 9458; (b) Z. Zhang, S.A. McCallum, J. Xie, L. Nieto, F. Corzana, J. Jimenez-Barbero, M. Chen, J. Liu, R.J. Linhardt, J. Am. Chem. Soc. 130 (2008) 12998; (c) T. Vacas, F. Corzana, G. Jimenez-Oses, C. Gonzalez, A.M. Gomez, A. Bastida, J. Revuelta, J.L. Asensio, J. Am. Chem. Soc. 132 (2010) 12074. P. Lange, A. Schier, H. Schmidbaur, Inorg. Chem. 35 (1996) 637. I. Angurell, O. Rossell, M. Seco, Chem. Eur. J. 15 (2009) 2932. (a) E.J. Fernández, A. Laguna, M. Monge, M. Montiel, M.E. Olmos, J. Pérez, E. Sánchez-Forcada, Dalton Trans. (2009) 474; (b) E.J. Fernández, A. Laguna, J.M. López-de-Luzuriaga, M. Monge, E. Sánchez-Forcada, Dalton Trans. 40 (2011) 3287; (c) E.J. Fernández, A. Laguna, J.M. López-de-Luzuriaga, M. Monge, M. Montiel, M.E. Olmos, R.C. Puelles, E. Sánchez-Forcada, Eur. J. Inorg. Chem. (2007) 4001. E.J. Fernández, A. Laguna, M.E. Olmos, Coord. Chem. Rev. 252 (2008) 1630. R. Usón, A. Laguna, J. Vicente, J. Chem. Soc., Chem. Commun. (1976) 353. A.A. Khrapitchev, P.T. Callaghan, J. Magn. Res. 152 (2001) 259. D. Zuccaccia, A. Macchioni, Organometallics 24 (2005) 3476. (a) H.-C. Chen, S.-H. Chen, J. Phys. Chem. 88 (1984) 5118; (b) J. Espinosa, J.G. de la Torre, J. Phys. Chem. 91 (1987) 3612. (a) A. Gierer, K. Wirtz, Z. Naturforsch. Teil A 8 (1953) 522; (b) A. Spernol, K. Wirtz, Z. Naturforsch. Teil A 8 (1953) 532. T.E. Cheatham III, P. Cieplak, P.A. Kollman, J. Biomol. Struct. Dyn. 16 (1999) 845. B. Fritzinger, U. Scheler, Macromol. Chem. Phys. 206 (2005) 1288.
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Size and shape assessment of organometallic gold(I) metallodendrimers through PGSE-NMR and molecular dynamics simulations Francisco Corzana, Miguel Monge ⇑, Eva Sánchez-Forcada Departamento de Química, Universidad de La Rioja, Grupo de Síntesis Química de La Rioja, UA-CSIC, Complejo Científico-Tecnológico, 26004 Logroño, Spain
a r t i c l e
i n f o
Article history: Available online 8 October 2011 Young Investigator Award Special Issue Keywords: Gold Metallodendrimers 1 H PGSE NMR Molecular dynamics
a b s t r a c t The reactions of the amino-terminated PAMAM-dendrimers (generations 0–2) with Ph2PCH2OH in the appropriate molar ratios give rise to the dendritic phosphines PAMAM-GZ-(N(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)). Further reaction of phosphines 1–3 with one equivalent of [Au(C6F5)(tht)] (tht = tetrahydrothiophene) per P-donor site leads to metallodendrimers [{Au(C6F5)}2n {PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)). Phosphines 1–3 and metallodendrimers 4–6 have been characterized by 1H, 19F and 31P{1H} NMR spectroscopy and through IR spectroscopy. 1H PGSE NMR studies of the dendritic phosphines and the metallodendrimers permit the evaluation and comparison of the different molecular sizes through their corresponding hydrodynamic radius, depending on the dendrimer generation and on the coordination of the organometallic fragments [Au(C6F5)]. Molecular dynamics simulations allow the theoretical estimation of the macromolecular size through the calculation of the radius of gyration for each species and the calculation of the dendrimer flexibility. Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction Research on metal-containing highly-branched macromolecular architectures such as metallodendrimers has become a fascinating area of investigation [1,2]. This type of monodisperse nano-scale macromolecules displays intrinsic features like facile construction, tunable solubility and localized positioning of structural units compared to other functionalized polymers, which make them ideal systems for the characterization and for the development of new or enhanced properties and applications. Some of these potential applications have appeared in different fields. The most important advances have been carried out in the field of catalysis, in which metallodendrimers combine high loading of catalyst, homogeneous processing and straightforward separation of products and catalyst. Examples including Ni-, Cu-, Rh-, Pd- Ru-, Fe-, or Co-based dendritic catalysts, among others, have shown the performance of these systems [3]. Luminescent Ru-, Ir- or Lanthanide-based metallodendrimers have also been studied as potential chemical systems for light conversion, OLED devices, sensors or fluoroimmunoassays [4]. PAMAM-based Gd(III) dendritic contrast agents were found to be very effective in magnetic resonance imaging (MRI) [5]. Molecular batteries have also been designed from metallodendrimers containing Fe complexes that can provide robust redox activity [6].
⇑ Corresponding author. E-mail address: [email protected] (M. Monge). 0020-1693/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2011.10.006
In most cases the characterization of these macromolecular large systems can be carried out using the standard spectroscopic techniques for molecular chemistry. Nevertheless, the use of other techniques is not only complementary, but can also provide very useful information. Thus, the size and shape of the metallodendrimers can be closely related to their intrinsic properties and, therefore, there is a need of combining different characterization techniques for a better knowledge of these macromolecules. In this sense, the size of dendritic molecules has been measured through different techniques such as Small Angle Neutron Scattering (SANS) [7], Small Angle X-ray Scattering (SAXS) [8], viscosimetry [7], mass spectrometry [9], or High Resolution Electron Microscopy (HREM) [10]. An alternative and powerful way of evaluating macromolecular size and shape is the use of Pulsed Field Gradient Spin-Echo (PGSE) NMR measurements, a method that allows measuring the molecular diffusion in solution which is related to the hydrodynamic radius through the Stokes–Einstein equation [11]. From a theoretical viewpoint, molecular dynamics (MD) simulations are a useful tool to describe the detailed dynamic properties of flexible and large systems in solution [12]. In particular, the combination of these computational calculations with experimental techniques, such as NMR, has been successfully applied to investigate the conformational behavior of a large variety of molecules [13]. If we focus on gold-containing metallodendrimers bearing the metal centers at the periphery, few examples have been reported if compared to other metals. The works by Rossell et al. [10] or
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Schmidbaur and co-workers [14] groups show that these hybrid homometallic (Au) or, to a less extent, gold-containing heterometallic dendrimers [15] are promising materials with potential applications in different fields, including their use as nanoparticle precursors or photoluminescent molecular nanomaterials. In this sense, some of us have recently studied the characterization and photoluminescent properties of octanuclear dendritic-like phosphine thiolate gold(I) complexes [16]. A clear advantage of Au(I) is its usually low coordination number that gives rise to linear environments what makes this metal ion very attractive for dendritic surface grafting. Among the ligands bonded to gold(I) the use of pentafluorophenyl ligands that together with aryl phosphines lead to stable [C6F5–Au–PR3] structural units has been extensively explored [17]. In this work, we describe the synthesis and characterization of generations 0, 1 and 2 PAMAM-modified dendrimers with aryl phosphines at the periphery PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)). We have also synthesized the corresponding organometallic metallodendrimers [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) by the coordination of [Au(C6F5)] fragments at the phosphine end groups. In the present study, the comparison of the experimental data obtained from PGSE-NMR, with those calculated using MD calculations, will be useful to validate our simulations. Thus, the validated trajectories will provide new insights into conformational behavior of the metallodendrimers and allow a better description of the structure–properties relationship. 2. Experimental 2.1. General remarks The compound [Au(C6F5)(tht)] [18] was synthesized by standard procedures reported in the literature. The starting materials Ph2PH, p-formaldehyde and PAMAMGZ-(NH2)n (Z = 0,1 and 2; ethylenediamine core) were purchased from Sigma Aldrich and used without further purification. Solvents used in the synthesis of new compounds were dried and distilled. 2.2. Instrumentation Infrared spectra were recorded in the 4000–200 cm1 range on a Nicolet Nexus FT-IR spectrophotometer, using Nujol mulls between polyethylene sheets. C, H, N analysis were carried out with a C.E. Instrument EA-1110 CHNS-O microanalyser. MALDI-TOF spectra were recorded in a Microflex MALDI-TOF Bruker spectrometer operating in the linear and reflector modes using dithranol as matrix. 31P{1H}, 19F and 1H NMR experiments were recorded on a Bruker ARX 300. PGSE-NMR experiments were recorded on a Bruker AVANCE 400 in d8-THF. 2.3. PGSE experiments 1
H PGSE measurements were carried out using the double stimulated echo pulse sequence (Double STE) [19] on a Bruker AVANCE 400 equipped with a BBI H-BB Z-GRD probe at 298 K without spinning. When this double stimulated echo pulse sequence is used, the dependence of the resonance intensity I on a constant waiting time and on a varied gradient strength G is described by the Eq. (1):
d 104 I ¼ I0 exp Dt ð2pc d GÞ2 D 3
ð1Þ
where I = intensity of the observed spin-echo, I0 = intensity of the spin-echo without gradients, Dt = diffusion coefficient, D = delay
between the midpoints of the gradients, d = length of the gradient pulse, and c = magnetogyric constant. The pulse sequence was composed of 90° pulses. The duration of the gradients (d) was 2 ms, the delay D was between 200 and 400 ms, depending on the sample, and the strength G was varied during the experiment. The spectra were acquired using 32 or 40 K points. The exponential plots of I versus G were fitted using a standard exponential algorithm implemented in TOPSPIN software. PGSE data were treated [20] using THF as internal standard in 2 mM samples at 298 K, and introducing in the Stokes–Einstein Eq. (3) the semiempirical estimation of the c factor, which can be obtained through Eq. (2) [21], derived from the microfriction theory proposed by Wirtz and co-workers [22] in which c is expressed as a function of the solute-to-solvent ratio of the radii.
c¼
6 v Þ2:234 1 þ 0:695ðrsol rH
Dt ¼
kT crH gp
ð2Þ ð3Þ
Using the experimentally measured diffusion coefficients Dt of the sample and the internal standard, and through the Stokes– Einstein Eq. (3), an accurate value of the hydrodynamic radius rH can be obtained in each case [20]. 2.4. Molecular dynamics (MD) simulations Molecular dynamics (MD) simulations were performed with HYPERCHEM 7.5 package, implemented with AMBER99 force field [23]. All the simulations were carried out at 300 K and using the appropriate dielectric constant to simulate the solvent. No cut-offs were used for the non-boding interactions. The timestep was adjusted to 1 fs and the simulation lengths to 10 ns to ensure an adequate sampling of the conformations present in solution. The radius of gyration (in nm) was calculated from the different trajectories following this expression (4):
P mi r2 R2g ¼ P i mi
ð4Þ
where mi is the mass of the ith atom in the particle and ri is the distance from the center of mass to the ith particle. 2.5. Synthesis 2.5.1. General procedure for the preparation of PAMAM-GZ-(N(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) To a paraformaldehyde suspension (0.087 g, 2.87 mmol) in 10 mL of distilled methanol under Ar atmosphere, diphenylphosphine (0.5 mL, 2.87 mmol) was added. This suspension was heated under reflux for 3 h. After cooling down the solution, PAMAM-GZ-(NH2)n dendrimer (0.186 g, 0.36 mmol for Z = 0; 0.257 g, 0.18 mmol for Z = 1 or 0.292 g, 0.09 mmol for Z = 2) was added. The reaction mixture was stirred for 1 h and 15 mL of toluene were then added, following the reaction stirring for 12 h at room temperature and 3 h under reflux (110 °C). Evaporation of the solvents under reduced pressure gave rise to the dendritic phosphines PAMAM-GZ(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) in quantitative yields as oils. Anal. Calc. for (C126H136N10O4P8) (1): C, 71.98; H, 6.52; N, 6.66. Found: C, 71.70; H, 6.47; N, 6.70%. Anal. Calc. for (C270H304N26O12P6) (2): C, 70.48; H, 6.69; N, 7.91. Found: C, 70.52; H, 6.61; N, 7.85%. Anal. Calc. for (C558H640N58O28P32) (3): C, 69.82; H, 6.72; N, 8.46. Found: C, 69.72; H, 6.51; N, 8.46%. 1H NMR (300 MHz, CDCl3) for 1, d: 7.54–7.32 (m, Ph rings), 3.62 (m, N–CH2– P), 3.21 (m, NH–CH2–CH2), 2.98 (m, N–CH2–CH2), 2.59 (m, CH2– CH2–N), 2.41 (m, N–CH2–CH2) and 2.00 ppm (s, N–CH2–CH2–N); 2, d: 7.34–7.25 (m, Ph rings), 3.53 (m, N–CH2–P), 3.11 (m, NH–CH2–CH2),
F. Corzana et al. / Inorganica Chimica Acta 380 (2012) 31–39
33
Scheme 1. Synthesis of dendritic phosphines PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)).
2.89 (m, N–CH2–CH2), 2.63 (m, CH2–CH2–N), 2.50 (m, N–CH2–CH2) and 2.27 ppm (s, N–CH2–CH2–N) and 3, d: 7.33–7.23 (m, Ph rings), 3.53 (m, N–CH2–P), 3.16 (m, NH–CH2–CH2), 2.89 (m, N–CH2–CH2), 2.70 (m, CH2– CH2–N), 2.53 (m, N–CH2–CH2) and 2.29 ppm (s, N–CH2–CH2–N).
31
P{1H} NMR (121 MHz, CDCl3) for 1, d: 28.3 ppm; 2, d: 28.5 ppm and 3, d: 28.5 ppm. MS (MALDI+) m/z (%) = 2165.6 [M+4O+H]+ (1); m/z (%) = 4856,3 [M+16O+H]+ (2) and m/z (%) = 9620.9 [M+Na]+ (3).
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Scheme 2. Synthesis of complexes [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)).
Fig. 1. 1H NMR spectrum of metallodendrimer [{Au(C6F5)}32{PAMAM-GZ-(N-(CH2PPh2)2)16}] (6).
2.5.2. General procedure for the preparation of [{Au(C6F5)}2n{PAMAMGZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) To a dichloromethane solution (15 mL) of ligand (PAMAMGZ-(CH2PPh2)2)n (0.113 g, 0.062 mmol for Z = 0; 0.244 g, 0.053 mmol for Z = 1 or 0.249 g, 0.026 mmol for Z = 2) was added the organometallic precursor [Au(C6F5)(tht)] (0.220 g, 0.490 mmol for Z = 0; 0.380 g, 0.850 mmol for Z = 1 or 0.375 g, 0.831 mmol for Z = 2, respectively). After stirring 24 h, the solvent was evaporated under vacuum to ca. 5 mL. Addition of n-hexane (20 mL) gave rise to
complexes [{Au(C6F5)}2n{(PAMAM-GZ-(CH2PPh2)2)n}] (Z = 0, n = 4, 78% yield (4), Z = 1, n = 8, 76% yield (5) and Z = 2, n = 16, 82% yield (6)) as white solids. Anal. Calc. for (C174H136Au8F40N10O4P8) (4): C, 41.68; H, 2.73; N, 2.79. Found: C, 41.83; H, 2.79; N, 2.88%. Anal. Calc. for (C366H304Au16F80N26O12P16) (5): C, 42.16; H, 2.94; N, 3.49. Found: C, 42.08; H, 2.89; N, 3.51%. Anal. Calc. for (C750H640Au32F160N58O28P32) (6): C, 42.40; H, 3.04; N, 3.82. Found: C, 43.05; H, 3.22; N, 4.21%. 1H NMR (300 MHz, CDCl3) for 4, d: 7.68–7.38 (m, Ph rings), 4.33 (m, N–CH2–P), 2.98 ppm (broad m, NH–CH2–CH2 and CH2–CH2– N), 2.62–2.10 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and
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N–CH2–CH2–N); 5, d: 7.69–7.36 (m, Ph rings), 4.33 (m, N–CH2–P), 3.03 ppm (broad m, NH–CH2–CH2 and CH2–CH2–N), 2.52– 2.00 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and N–CH2–CH2– N) and 6, d: 7.67–7.35 (m, Ph rings), 4.36 (m, N–CH2–P), 3.12 ppm (broad m, NH–CH2–CH2), 2.99 ppm (broad m, CH2–CH2–N), 2.52– 2.00 ppm (broad signal, N–CH2–CH2, N–CH2–CH2 and N–CH2–CH2– N). 19F NMR (283 MHz, CDCl3) for 4, d: 162.0 (m, 16F, Fm), 157.9 (m, 8F, Fp) and 115.6 ppm (m, 16F, Fo); for 5, d: 162.1 (m, 32F, Fm), 158.1 (m, 16F, Fp) and 115.55 ppm (m, 32F, Fo) and 6, d: 162.1 (m, 64F, Fm), 158.1 (m, 32F, Fp) and 115.5 ppm (m, 64F, Fo). 31P{1H} NMR (121 MHz, CDCl3) for 4, d: 26.7 ppm; 5, d: 26.7 ppm and 6, d: 26.7 ppm. MS (MALDI+) m/z (%) = 5014.3 [M+H]+ (4); m/z (%) = 10429.0 [M+H]+ (5) and m/z (%) = 10624.0 [M+2H]2+ (6). IR: m = 1658 m(C–N); 1546 m(N–H); 1502, 955, 793 cm1 m(Au–C6F5) (4); 1659 m(C–N); 1546 m(N–H); 1505, 955, 789 cm1 m(Au–C6F5) (5); 1650 m(C–N); 1543 m(N–H); 1503, 958, 793 cm1 m(Au–C6F5) (6).
Table 1 Diffusion Coefficients Dt (1010 m2 s1) and hydrodynamic radii rH(nm) for PAMAMNH2 dendrimers P-donor ligands 1–3 and complexes 4–6.
PAMAM-G0-(NH2)4 PAMAM-G1-(NH2)8 PAMAM-G2-(NH2)16 PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0-(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2-(N-(CH2PPh2)2)16}] 6
Dt
rH
Ref.
5.86 3.77 3.00 4.79 3.14 2.55 3.73 2.63 2.05
0.67 1.04 1.30 0.83 1.29 1.59 1.04 1.35 1.68
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3. Results and discussion 3.1. Synthesis and characterization The PAMAM-GZ-(N-(CH2PPh2)2)n (Z = 0, n = 4 (1), Z = 1, n = 8 (2) and Z = 2, n = 16 (3)) dendritic P-donor ligands were prepared following a modification of an already reported synthesis of P-donor poly(propileneimine) dendrimers [3c]. Thus, addition of the amino terminated PAMAM-GZ-(NH2)n (Z = 0, n = 4, Z = 1, n = 8 and Z = 2, n = 16) dendrimers to the corresponding amount of Ph2PCH2OH (two equivalents of phosphine per amine group) gives rise to phosphino-terminated dendrimer ligands bearing 8 (1), 16 (2) or 32 (3) Ph2P end-groups (see Scheme 1). The 31P{1H} NMR of these P-donor groups at the periphery of the PAMAM dendrimers is similar for the three generations, displaying a singlet at 28.3 (1), 28.5 (2), 28.5 ppm (3), respectively (see Scheme 1). Complexes [{Au(C6F5)}2n{PAMAM-GZ-(N-(CH2PPh2)2)n}] (Z = 0, n = 4 (4), Z = 1, n = 8 (5) and Z = 2, n = 16 (6)) have been synthesized by reaction of the multidentate ligands 1–3 with the [Au(C6F5)(tht)] (tht = tetrahydrothiophene) precursor in 1:8 (4), 1:16 (5) and 1:32 (6) molar ratios, respectively (see Scheme 2) leading to complexes 4–6 in quantitative yields by displacement of the labile ligand tht. The 31P{1H} NMR spectra of these complexes display a singlet at 26.7 (4), 26.7 (5), 26.5 ppm (6), respectively, showing a large shift downfield with respect to the free ligands. The proton signals arising from the dendrimer skeleton are observed in the 1H NMR spectra in each case and they are also shifted downfield when compared to those of the free ligand. The corresponding assignment of the proton signals in the 1H NMR spectrum has been carried out following the scheme on Fig. 1 (see Section 2). Their IR spectra show absorptions arising from the Au–C6F5 vibrations at 1502, 955, 793 (4), 1505, 955, 789 (5), 1503, 958, 793 cm1 (6), respectively. 3.2. PGSE-NMR studies The use of the PGSE-NMR technique permits an evaluation of the self-diffusion coefficient Dt for phosphino dendrimers 1–3 and the corresponding organometallic Au(I) metallodendrimers 4–6 in 0.5 mL of 2 mM d8-THF solutions at 298 K. Subsequently, the evaluation of the molecular size through the hydrodynamic radius rH can be carried out by the use of the Stokes–Einstein equation. The results are given in Table 1 (see Section 2 for details), including the diffusion coefficients Dt and hydrodynamic radius rH for the dendritic phosphines 1–3 and for the (pentafluorophenyl)phosphinogold(I) metallodendrimers 4–6. In Fig. 2 the sections of 1H PGSE NMR spectra in d8-THF for metallodendrimer 5 are shown. As it can be observed, the resonance intensities of the P–CH2–N protons
Fig. 2. Sections of 1H PGSE NMR spectra in d8-THF for complex [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5. The resonance intensities of the P–CH2–N protons and those of the solvent decrease upon increasing the pulsed-field gradient. (The P– CH2–N signal is a broad signal without resolved multiplicities).
from the metallodendrimer periphery and O–CH2– protons from the non-deuterated THF solvent decrease upon increasing the pulsed-field gradient. The P–CH2–N signal is a broad signal without resolved multiplicities. In Fig. 3, we represent the typical plot of all the observed 1H signal intensity changes obtained through the PGSE data in two sets (dendritic phosphines and metallodendrimers), representing ln(I/ I0), as a function of the square of the increasing gradient strengths G2, following the equation given in the figure. Molecules possessing larger sizes will diffuse more slowly than smaller ones, leading to smaller slopes. As it can be seen in Table 1, larger Dt coefficients are obtained for the PAMAM-GZ-(N-(CH2PPh2)2)n ligands 1–3 when compared with the corresponding metallodendrimers [Au2n(C6F5)2n {PAMAM-GZ-(N-(CH2PPh2)2)n}] 4–6, which is, as expected, in agreement with the smaller size of the phosphines at each generation. The hydrodynamic radii rH is then slightly larger for metallodendrimers 4 (1.04 nm), 5 (1.35 nm) and 6 (1.68 nm) than the ones obtained for dendrimer ligands 1 (0.83 nm), 2 (1.29 nm) and 3 (1.59 nm), respectively. If we represent the hydrodynamic radii versus the dendritic generation, we observe an almost parallel growth of the dendrimer ligands and the metallodendrimer, although a larger size expansion of the metallodendrimer is observed when the [Au(C6F5)] groups are bonded to the smaller dendritic phosphine 1 (see Fig. 4). This result is also expected since the contribution of the organometallic periphery to the metallodendrimer size is larger in the smallest metallodendrimer 4. It is also worth mentioning that the results obtained here are comparable to PGSE-NMR measurements of the self-diffusion coefficients (Dt) and hydrodynamic radii (rH) of the dendrimer precursors
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Fig. 3. Plots of 1H ln(I/I0) vs. arbitrary units proportional to the square of the gradient amplitude on dendrimers 1–3 (top) and metallodendrimers 4–6 (bottom). The larger the dendrimer (or metallodendrimer) is, the smaller the value of the absolute slope becomes.
PAMAM-GZ-(NH2)n (Z = 0, n = 4; Z = 1, n = 8 and Z = 2, n = 16) although they are measured under different experimental conditions [24] (see Table 1). 3.3. Molecular dynamics (MD) simulations In view of the interesting results obtained through PGSE-NMR measurements for the size assessment of the organometallic Au(I) metallodendrimers and their corresponding dendritic phosphines precursors, we have carried out molecular dynamics (MD) theoretical studies in order to gain insight about the size and shape of this nanometric size molecular systems. We have estimated the radius of gyration (rG) of the phosphines 1–3 and the metallodendrimers 4–6 in order to compare them with the hydrodynamic radii experimentally measured. In a second step, we have analyzed the MD results in order to estimate the shape of the
metallodendrimers by the superposition of several conformations (frames) and by the analysis of the contraction/expansion capabilities of the different conformations that the dendrimers and metallodendrimers can adopt through the dynamics process. Before analyzing the obtained results for comparison with the experimental ones we have validated our method of calculation. Since the use of force fields are not specifically designed for the analysis of organometallic systems, we have first checked several structural parameters of the organometallic units coordinated at the periphery of the metallodendrimers during the dynamics. In Fig. 5, we can observe that the P–Au–C angle (ca. 180°) and the Au–P (ca. 2.5 Å) and Au–C (ca. 2.2 Å) distances are stable through the simulation and closed to the experimental ones obtained in the X-ray structure analysis of the molecular analog [Au4R4 {(Ph2PCH2)2NCH2CH2N(CH2PPh2)2}] (P–Au–C: 174.7–175.8°, Au–P 2.28 Å and Au–C 2.05 Å) [16a]. Unfortunately, the use of classical
F. Corzana et al. / Inorganica Chimica Acta 380 (2012) 31–39
Fig. 4. Graphical representation of the hydrodynamic radii (rH) obtained for the dendritic phosphine ligands 1–3 (black line) and for the gold(I) metallodendrimers 4–6 (red line) as a function of the generation. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 5. Time series monitoring the P–Au–C angle and the Au–P and Au–C distances in the 10 ns MD simulations.
MD calculations allows including hundreds or thousands of atoms in the models but it does not allow analyzing the dispersive component of the possible aurophilic interactions present in these
37
systems. However, since the overall size of the metallodendrimers would not be much affected by the presence or not of aurophilic contacts and since the previously commented tetranuclear structure does not show aurophilic interactions even for C6F5–Au–P units in parallel disposition, we think that the MD calculations can give a nice description of these very large molecules. Fig. 6 depicts the superposition of several conformations of dendritic phosphines 1–3. With this representation we can assume an almost spherical shape for these systems. The analysis of the radii of gyration provides interesting conclusions. First, if we take into account the equations for the estimation of the radius of gyration and the hydrodynamic radius, the obtained rG for dendrimers 1–3 and metallodendrimers 4–6 would be smaller than the corresponding rH ones, since the experimental rH values take into account the structure adopted by the dendrimers and metallodendrimers in the presence of solvent molecules (see Section 2). The rG and rH values obtained for dendrimers 1–3 and metallodendrimers 4–6 are shown in Table 2. As expected, in all cases the rG is smaller than the corresponding rH. If we represent the dendrimer (or metallodendrimer) radii versus the studied species with increasing size we observe the same trend, which is that both the rH and the rG increase when going from the dendrimer to the corresponding metallodendrimer or when increasing the generation (Fig. 7). We can also analyze the role of the solvent in the size of these macromolecular systems since the MD calculations are carried out in implicit solvent (the dielectric constant is taken into account but not the volume and surface of solvent molecules) and the experimental PGSE measurements include the solvent influence in the obtained rH values. If we observe the results in Fig. 7, we can see that the rH and rG values are closer in the case of 0th generation, that is dendrimer 1 and metallodendrimer 4, but they differ for generations 1 (2 and 5) and 2 (3 and 6). This trend could be interpreted taking into account the ability of the THF molecules for interacting with increasing generations of dendrimers. Thus, while a peripheric interaction between the solvent molecules would be expected for the smaller dendrimers 1 and 4, a possible interaction of the solvent molecules with the functional groups of the inner cavities of the higher generation dendrimers (generations 1 and 2), acting as a guest molecule, would be proposed, leading to larger differences between the theoretically predicted rG values and the experimentally obtained rH ones. This result is also in agreement with previously PGSE-NMR studies of dendrons in THF in which the authors propose the swelling of the dendron molecules [24]. The molecular dynamics simulations carried out for macromolecular systems 1–6 also provide interesting results regarding the flexibility of these nanometric size systems. We have evaluated the percentage of dendrimer expansion and contraction for each dynamics by computing the larger (rGmax) and smaller (rGmin) radius of gyration for each dendritic molecule throughout the trajectory. The results are depicted in Table 3 and Fig. 8. As it can be observed, all the dendrimers and metallodendrimers display a high degree of flexibility as it is observed in the percentage of contraction and expansion of the smallest and largest conformation, respectively. In the case of the dendritic phosphines 1–3, the % of expansion increases with the increase in the generation while the % of contraction increases when going from generation 0 (28.57%) to 1st generation (39.80%), but is almost the same for 2nd generation (39.69%). In the case of the metallodendrimers 4– 6, we observe a different trend, showing an increase in the degree of contraction with the increase of the generation and different values without a clear tendency for the % of expansion with respect to the dendrimer generation. Finally, in view of the percentage values of contraction and expansion, we can conclude that the metallodendrimers 4–6 are as flexible as their precursor phosphines 1–3.
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Fig. 6. Superimposition of different frames randomly taken from the 10 ns MD simulations for 1 (A), 2 (B) and 3 (C).
Table 2 Comparison between hydrodynamic radius (rH, nm) and calculated radius of gyration (rG, nm) for P-donor ligands 1–3 and complexes 4–6.
PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0-(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1-(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2-(N-(CH2PPh2)2)16}] 6
rH (nm)
rG (nm)
0.83 1.29 1.59 1.04 1.35 1.68
0.77 1.03 1.31 0.92 1.12 1.40
Fig. 7. Hydrodynamic radii (rH) and radii of gyration (rG) for all dendritic species (1– 6) with increasing size.
Table 3 rG, rGmax and rGmin values and % of size expansion and contraction for compounds 1–6 obtained from the MD simulations.
PAMAM-G0-(N-(CH2PPh2)2)4 1 PAMAM-G1-(N-(CH2PPh2)2)8 2 PAMAM-G2-(N-(CH2PPh2)2)16 3 [{Au(C6F5)}8{PAMAM-G0(N-(CH2PPh2)2)4}] 4 [{Au(C6F5)}16{PAMAM-G1(N-(CH2PPh2)2)8}] 5 [{Au(C6F5)}32{PAMAM-G2(N-(CH2PPh2)2)16}] 6
rG (nm)
% Expansion (rGmax) (nm)
% Contraction (rGmin) (nm)
0.77 1.03 1.31 0.92
7.79 (0.83) 36.89 (1.41) 54.43 (2.01) 4.34 (0.96)
28.57 39.80 39.69 43.48
1.12
27.68 (1.43)
51.78 (0.54)
1.40
22.85 (1.72)
53.57 (0.65)
(0.55) (0.62) (0.79) (0.52)
Fig. 8. Percentage of contraction and expansion taking into account the size of the smallest and largest conformation for each case.
F. Corzana et al. / Inorganica Chimica Acta 380 (2012) 31–39
4. Conclusions We have carried out a combined experimental and theoretical study by the use of 1H PGSE spectroscopy and molecular dynamics simulations. This methodology has allowed us to gain insight about the size and the shape of dendritic phosphines and metallodendrimers of nanometer size. These molecular nanosystems are of spherical shape and display a high degree of flexibility. In addition, the larger increase of the hydrodynamic radius in tetrahydrofuran with respect to the theoretical radius of gyration calculated in implicit solvent could be in agreement with a dendrimer swelling in this solvent. Acknowledgements The D.G.I. (MEC)/FEDER (CTQ2010-20500-C02-02) and European Commission, POCTEFA (METNANO, EFA 17/08) Projects are acknowledged for financial support. E. Sánchez-Forcada thanks the C.S.I.C. for a JAE-Predoc Grant. Appendix A. Supplementary data
[5] [6] [7] [8] [9] [10] [11]
[12]
[13]
Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.ica.2011.10.006. References [1] S.-H. Hwang, C.D. Schreiner, C.N. Moorefield, G.R. Newkome, N. J. Chem. 31 (2007) 1192. [2] B.J. Ravoo, Dalton Trans. (2008) 1533. [3] See for example: (a) A.W. Kleij, R.A. Grossage, R.J.M.K. Gebbink, N. Brinkmann, E.J. Reijerse, U. Kragl, M. Lutz, A.L. Spek, G. van Koten, J. Am. Chem. Soc. 122 (2000) 12112; (b) H.-F. Chow, C.C. Mak, J. Org. Chem. 62 (1997) 5116; (c) M.T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. Int. Ed. Engl. 36 (1997) 1526; (d) D. de Groot, J.N.H. Reek, P.C.J. Kamer, P.W.N.M. van Leeuwen, Eur. J. Org. Chem. (2002) 1085; (e) S. Gatard, S. Nlate, E. Cloutet, G. Bravic, J.-C. Blais, D. Astruc, Angew. Chem., Int. Ed. 42 (2003) 452; (f) V. Maraval, R. Laurent, A.-M. Caminade, J.-P. Majoral, Organometallics 19 (2000) 4025; (g) S. Rigaut, M.-H. Delville, D. Astruc, J. Am. Chem. Soc. 119 (1997) 11132; (h) R. Breinbauer, E.N. Jacobsen, Angew. Chem., Int. Ed. 39 (2000) 3604. [4] See for example: (a) S. Campagna, S. Serroni, S. Bodige, F.M. MacDonnell, Inorg. Chem. 38 (1999) 692;
[14] [15] [16]
[17] [18] [19] [20] [21] [22] [23] [24]
39
(b) G. Bergamimi, C. Saudan, P. Ceroni, M. Maestri, V. Balzani, M. Gorka, S.-K. Lee, J. van Heyst, F. Vögtle, J. Am. Chem. Soc. 126 (2005) 16466; (c) T. Tsuzuki, N. Shirasawa, T. Suzuki, S. Tokito, Jpn. J. Appl. Phys. Part I 44 (2005) 4151; (d) F. Vögtle, M. Gorka, V. Vicinelli, P. Ceroni, M. Maestri, V. Balzani, ChemPhysChem 2 (2002) 769; (e) U. Hahn, M. Gorka, F. Vögtle, V. Vicinelli, P. Ceroni, M. Maestri, V. Balzani, Angew. Chem., Int. Ed. 41 (2002) 3595;. f. E.C. Wiener, M.W. Brechbiel, H. Brothers, R.L. Magin, O.A. Gansow, D.A. Tomalia, P.C. Lauterbur, Magn. Reson. Med. 31 (1994) 1. S. Nlate, J. Ruiz, V. Sartor, R. Navarro, J.-C. Blais, D. Astruc, Chem. Eur. J. 6 (2000) 2544. R. Scherrenberg, B. Coussens, P. van Vliet, G. Edouard, J. Brackman, E. de Brabender, Macromolecules 31 (1998) 456. B. Huang, A.R. Hirst, D.K. Smith, V. Castelletto, I.W. Hamley, J. Am. Chem. Soc. 127 (2005) 7130. F.F. Fan, C.L. Mazzitelli, J.S. Brodbelt, A.J. Bard, Anal. Chem. 77 (2005) 4413. O. Rossell, M. Seco, A.-M. Caminade, J.-P. Majoral, Gold Bull. 34 (2001) 88. See for example: (a) A. Macchioni, G. Ciancaleoni, C. Zuccaccia, D. Zuccaccia, Chem. Soc. Rev. 37 (2008) 479; (b) D. Zuccaccia, L. Busetto, M.C. Cassani, A. Macchioni, R. Mazzoni, Organometallics 25 (2006) 2201; (c) Y. Cohen, L. Avram, L. Frish, Angew. Chem., Int. Ed. 44 (2005) 520. (a) T.E. Cheatham, P.A. Kollman, Ann. Rev. Phys. Chem. 51 (2000) 435; (b) T. Schlick, Molecular Modeling and Simulation: An Interdisciplinary Guide, Springer, New York, 2010. See for example: (a) F. Corzana, J.H. Busto, G. Jimenez-Oses, M. Garcia de Luis, J.L. Asensio, J. Jimenez-Barbero, J.M. Peregrina, A. Avenoza, J. Am. Chem. Soc. 129 (2007) 9458; (b) Z. Zhang, S.A. McCallum, J. Xie, L. Nieto, F. Corzana, J. Jimenez-Barbero, M. Chen, J. Liu, R.J. Linhardt, J. Am. Chem. Soc. 130 (2008) 12998; (c) T. Vacas, F. Corzana, G. Jimenez-Oses, C. Gonzalez, A.M. Gomez, A. Bastida, J. Revuelta, J.L. Asensio, J. Am. Chem. Soc. 132 (2010) 12074. P. Lange, A. Schier, H. Schmidbaur, Inorg. Chem. 35 (1996) 637. I. Angurell, O. Rossell, M. Seco, Chem. Eur. J. 15 (2009) 2932. (a) E.J. Fernández, A. Laguna, M. Monge, M. Montiel, M.E. Olmos, J. Pérez, E. Sánchez-Forcada, Dalton Trans. (2009) 474; (b) E.J. Fernández, A. Laguna, J.M. López-de-Luzuriaga, M. Monge, E. Sánchez-Forcada, Dalton Trans. 40 (2011) 3287; (c) E.J. Fernández, A. Laguna, J.M. López-de-Luzuriaga, M. Monge, M. Montiel, M.E. Olmos, R.C. Puelles, E. Sánchez-Forcada, Eur. J. Inorg. Chem. (2007) 4001. E.J. Fernández, A. Laguna, M.E. Olmos, Coord. Chem. Rev. 252 (2008) 1630. R. Usón, A. Laguna, J. Vicente, J. Chem. Soc., Chem. Commun. (1976) 353. A.A. Khrapitchev, P.T. Callaghan, J. Magn. Res. 152 (2001) 259. D. Zuccaccia, A. Macchioni, Organometallics 24 (2005) 3476. (a) H.-C. Chen, S.-H. Chen, J. Phys. Chem. 88 (1984) 5118; (b) J. Espinosa, J.G. de la Torre, J. Phys. Chem. 91 (1987) 3612. (a) A. Gierer, K. Wirtz, Z. Naturforsch. Teil A 8 (1953) 522; (b) A. Spernol, K. Wirtz, Z. Naturforsch. Teil A 8 (1953) 532. T.E. Cheatham III, P. Cieplak, P.A. Kollman, J. Biomol. Struct. Dyn. 16 (1999) 845. B. Fritzinger, U. Scheler, Macromol. Chem. Phys. 206 (2005) 1288.