Anion Receptor Electrochemical Sensing Properties of Poly

Organometallics 2009, 28, 727–733

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Anion Receptor Electrochemical Sensing Properties of Poly(propyleneimine) Dendrimers with Ferrocenylamidoalkyl Terminal Groups Raul Villoslada,† Beatriz Alonso,*,† Carmen M. Casado,*,† Pilar Garcı´a-Armada,‡ and Jose´ Losada*,‡ Departamento de Quı´mica Inorga´nica, Facultad de Ciencias, UniVersidad Auto´noma de Madrid, Cantoblanco 28049-Madrid, Spain, and Departamento de Ingenierı´a Quı´mica Industrial, Escuela Te´cnica Superior de Ingenieros Industriales, UniVersidad Polite´cnica de Madrid, 28006-Madrid, Spain ReceiVed July 23, 2008

A novel family of dendrimers with amidoferrocenyl units attached to diaminobutane-based poly(propyleneimine) surfaces through alkyl chains, DAB-dend-[NHCO(CH2)10HNCOFc]x (3-6: x ) 4, 8, 16, 32), Fc ) [η5-C5H5]Fe[η5-C5H4], has been prepared by reaction of the novel functionalized ferrocenyl derivative [η5-C5H5]Fe[η5-C5H4CONH(CH2)10COF] (2) with the corresponding amine dendrimers. Characterization of the synthesized dendrimers by 1H and 13C{1H} NMR and IR spectroscopy and mass spectrometry supports their assigned structures. The redox activity of the ferrocenyl centers in 3-6 has been characterized by cyclic voltammetry. These compounds showed electrochemical responses to the anions not only in organic solvents but also immobilized onto electrode surfaces in organic and aqueous media. Selective recognition for H2PO4- over other anions was observed. Introduction 1

The chemistry of ferrocene derivatives has been at the forefront of attention over the last 25 years regarding the development of redox-active supramolecules with advanced materials applications. There is also currently a considerable interest in producing multifunctional organometallic dendritic architectures2 bearing redox-active moieties. Within this context, the development of dendrimers bearing pendent ferrocenyl units is a burgeoning field of study. In addition, the development of molecule-based ion sensors has been a pivotal issue currently receiving considerable attention, and the recognition and sensing of anionic analytes has emerged as a key research theme within the generalized area of supramolecular chemistry.3 Among numerous methodologies, the exploitation of organometallic fragments incorporated with redox transductions as a reporter seems to be a very promising one.4 An especially interesting approach for the * To whom correspondence should be addressed. E-mail: beatriz.alonso@ uam.es; [email protected]; [email protected]. † Universidad Auto´noma de Madrid. ‡ Universidad Polite´cnica de Madrid. (1) Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Materials Science; Togni, A., Hayashi, T., Eds.; VCH: Weinheim, Germany, 1995. (2) (a) Newkome, G. R.; Moorefield, C. N.; Vo¨gtle, F., Dendrimers and Dendrons. Concept, Synthesis and Application; Wiley-VCH: Weinheim, Germany, 2001. (b) Freche´t, J. M. J.; Tomalia, D. A., Eds.; Dendrimers and Other Dendritic Polymers; VCH: Weinheim, Germany, 2002. (c) Dendrimers and Nanosciences; Astruc, D., Guest Ed.; Elsevier: Paris, 2003; Vol 6, Issues 8-10. (d) Vo¨gtle, F.; Gestermann, S.; Hesse, R.; Schwierz, H.; Windisch, B. Prog. Polym. Sci. 2000, 25, 987. (e) Grayson, S. M.; Frechet, J. M. J. Chem. ReV. 2001, 101, 3819. (f) Chase, P. A.; Klein Gebbink, R. J. M.; van Koten, G. J. Organomet. Chem. 2004, 689, 4016. (g) Caminade, A.-M.; Majoral, J.-P. Coord. Chem. ReV. 2005, 249, 1917. (h) Astruc, A.; Lu, F.; Ruiz Aranzaes, J. Angew. Chem., Int. Ed. 2005, 44, 7852. (3) ComprehensiVe Supramolecular Chemistry; Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F., Suslick, K. S., Eds.; Pergamon: Oxford, 1996.

preparation of electrochemical sensory devices is the immobilization of redox-responsive receptor systems on electrode surfaces.5 One objective of our research is to study the ion recognition properties of organometallic derivatives containing ferrocene or cobaltocene units,6,7 not only in solution but also confined onto electrode surfaces. Although diaminobutane-based dendrimers with alkyl chains have been described,8 there have been no reports on such derivatives containing ferrocenylalkyl units. (4) (a) Beer, P. D.; Gale, P. A.; Chen, G. Z. J. Chem. Soc., Dalton Trans. 1999, 1897. (b) Collinson, S. R.; Gelbrich, T.; Hursthouse, M. B.; Tucker, J. H. R. Chem. Commun. 2001, 555. (c) Plenio, H.; Aberle, C. Angew. Chem., Int. Ed. 1998, 37, 1397. (d) Labande, A.; Ruiz, J.; Astruc, D. J. Am. Chem. Soc. 2002, 124, 1782. (e) Bucher, C.; Devillers, C. H.; Moutet, J.C.; Pe´caut, J.; Royal, G.; Saint-Aman, E.; Thomas, F. Dalton Trans. 2005, 3620. (f) Reynes, O.; Moutet, J.-C.; Pecaut, J.; Royal, G.; Saint-Aman, E. New J. Chem. 2002, 26, 9. (g) Oto´n, F.; Espinosa, A.; Ta´rraga, A.; Molina, P. Organometallics 2007, 26, 6234. (5) (a) Casado, C. M.; Cuadrado, I.; Alonso, B.; Mora´n, M.; Losada, J. J. Electroanal. Chem. 1999, 463, 87. (b) del Peso, I.; Alonso, B.; Lobete, F.; Casado, C. M.; Cuadrado, I.; Losada, J. Inorg. Chem. Commun. 2002, 288. (c) Reynes, O.; Gulon, T.; Moutet, J.-C.; Royal, G.; Saint-Aman, E. J. Organomet. Chem. 2002, 656, 116. (d) Reynes, O.; Moutet, J.-C.; Royal, G.; Saint-Aman, E. Electrochim. Acta 2004, 49, 3727. (6) (a) Cuadrado, I.; Mora´n, M.; Losada, J.; Casado, C. M.; Pascual, C.; Alonso, B.; Lobete, F. In AdVances in Dendritic Macromolecules; Newkome, G. R., Ed.; JAI Press: Greenwich, CT, 1996; Vol. 3, p 151. (b) Alonso, B.; Casado, C. M.; Cuadrado, I.; Mora´n, M.; Kaifer, A. E. Chem. Commun. 2002, 1778. (c) Gonza´lez, B.; Alonso, B.; Losada, J.; Garcı´aArmada, M. P.; Casado, C. M. Organometallics 2006, 25, 3558. (7) For other examples on ferrocenyl dendrimers as anion receptors, see (a) Valerio, C.; Fillaut, J.-L.; Ruiz, J.; Guittard, J.; Blais, J.-C.; Astruc, D. J. Am. Chem. Soc. 1997, 119, 2588. (b) Valerio, C.; Alonso, E.; Ruiz, J.; Blais, J.-C.; Astruc, D. Angew. Chem., Int. Ed. Engl. 1999, 38, 1747. (c) Daniel, M.-C.; Ruiz, J.; Blais, J. C.; Daro, N.; Astruc, D. Chem.;Eur. J. 2003, 9, 4371. (d) Astruc, D.; Daniel, M.-C.; Ruiz, J. Chem. Commun. 2004, 2637. (e) Daniel, M.-C.; Ruiz, J.; Nlate, S.; Astruc, D. J. Inorg. Organomet. Polym. Mater. 2005, 15, 107. (f) Ornelas, C.; Ruiz, J.; Cloutet, E.; Alves, S.; Astruc, D. Angew. Chem., Int. Ed. 2006, 45, 1. (g) Ornelas, C.; Ruiz, J.; Cloutet, E.; Alves, S.; Astruc, D. Angew. Chem., Int. Ed. 2007, 46, 872. (h) Astruc, D.; Daniel, M.-C.; Ruiz, J. Top. Organomet. Chem. 2006, 20, 121.

10.1021/om8007019 CCC: $40.75  2009 American Chemical Society Publication on Web 01/05/2009

728 Organometallics, Vol. 28, No. 3, 2009 Scheme 1. Synthesis of Organometallic Fragments 1 and 2

Villoslada et al. Scheme 2. Synthesis of Dendrimers 3-6

Chart 1

With this in mind and as a continuation of our search for new macromolecules that could be used to modify electrodes with films within which the amidoferrocenyl units are accessible hosts to interact with anionic guests, herein we report on the synthesis and characterization of a new family of dendrimers with large and flexible ferrocenylamidoalkyl chains at the periphery as well as their exploitation in the construction of robust modified electrodes with sensing properties toward dihydrogenphosphate anion.

Results and Discussion The ferrocenyl unit has been incorporated in many dendritic architectures. A commonly used intermediate in the synthesis of these systems is chlorocarbonylferrocene, but it presents some major drawbacks as moisture sensitivity and thermal and photochemical instability. To circumvent these difficulties, we have investigated the use of the corresponding acid fluorides as synthetic intermediates in the amidation procedures for the preparation of the new dendrimers. We report here the synthesis of derivatives ferrocenylamidoundecanoic acid (1) and ferrocenylamidoundecanoic acid fluoride (2) and the application of the intermediate 2 to the synthesis of diamide dendrimers 3-6. Synthesis and Characterization of Dendrimers. The key starting step in the preparation of the new family of dendrimers is the previous synthesis and purification of the organometallic derivatives [η5-C5H5]Fe[η5-C5H4CONH(CH2)10COOH] (1) and [η5-C5H5]Fe[η5-C5H4CONH(CH2)10COF] (2). The reaction of equimolar amounts of fluorocarbonylferrocene9 and 11-aminoundecanoic acid in THF, at 30 °C and under an argon atmosphere affords, after workup, the functionalized monomer 1 (Scheme 1), as an orange solid. Reaction of 1 with cyanuric fluoride and pyridine in dichloromethane at 0 °C provides the (8) See, for example,(a) Schenning, A. P. H. J.; Elissen-Roman, C.; Weener, J.-W.; Baars, M. W. P. L.; van der Gaast, S. J.; Meijer, E. W, J. Am. Chem. Soc. 1998, 120, 8199. (b) Stephan, H.; Spies, H.; Johannsen, B.; Klein, L.; Vo¨gtle, F. Chem. Commun. 1999, 1875. (9) Gallow, T. H.; Rodrigo, J.; Cleary, K.; Cooke, G.; Rotello, V. M. J. Org. Chem. 1999, 64, 3745.

acid fluoride 2 reproducibly as an orange solid in 80% yield (Scheme 1). Generation of the acid fluoride occurs under mild conditions. The ferrocenylamidoalkyl dendrimers 3-6 have been obtained by treatment of the first four generations of diaminobutanebased poly(propyleneimine) dendrimers DAB-dend-(NH2)x (x ) 4, 8, 16, and 32) with an excess of the organometallic fragment 2 in dichloromethane solution at 30 °C (Scheme 2 and Chart 1). The condensation reactions were completed within 7 days for the first generation, whereas approximately 13 days was needed using the fourth generation, as indicated by the 1H NMR of the reaction mixture, which showed the disappearance of the -NH2 signals of the starting dendritic polyamines around 1.3 ppm and the appearance of a new signal in the 6-7 ppm range due to the new alkylamide group. After the appropriate workup, the products were purified by washing several times with acetonitrile. Dendrimers 3-6 were isolated as air-stable orange to brown solids. The structures of 1, 2, and the ferrocenylamidoalkyl dendrimers 3-6 have been established on the basis of 1H and 13C NMR spectra and were corroborated by mass spectrometry. The

Ferrocenylamidoalkyl Dendrimers as Anion Receptors

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Table 1. Electrochemical Data for 3-6 before and after Titration of [n-Bu4N][H2PO4] solutiona 3 4 5 6

modified electrodeb

E0

E0(free)

∆Ep/mVc

0.63 0.63 0.60 0.62

0.60 0.58 0.58 0.56

256 260 296 284

a NPV data measured in CH2Cl2/0.1 M TBAH at a Cglassy disk electrode. b CV data measured in CH2Cl2/0.1 M TBAH at a Cglassy disk electrode. Γ ∼ 2.5 × 1010 molFc/cm2. c OSWV data. ∆Ep ) Ep([H2PO4]- ) 6 × 10-5 M) - Ep([H2PO4]- ) 0).

1

H NMR spectra of 1 and 2 (see Figure S1 in the Supporting Information (SI)) show in both cases the pattern of resonances in the range 4.7-4.2 ppm characteristic of the unsubstituted and substituted cyclopentadienyl ligands in the ferrocenyl moieties, one apparent quartet corresponding to the β protons of the acid, and fluoride groups centered at 3.4 ppm; the proton resonances due to the alkyl chain are shown in the range 1.3-1.7 ppm, and the ferrocenylamide proton resonance is shown at 5.7 ppm. In the 1H NMR spectrum of 1, a triplet centered at 2.35 ppm for the R protons of the acid group is shown. This signal disappears when 1 is fluorated, and the corresponding methylene signal appears to be low field shifted at 2.5 ppm and split into two due to the coupling to the fluorine atom. In the 1H NMR spectra of dendrimers 3-6, key signals arising from the peripheral ferrocenyl groups are observed in the range 4.7-4.2 ppm, and those corresponding to the poly(propyleneimine) dendritic framework and the alkyl chain appear around 3.4, 2.5, 2.3, 2.1, 1.6, and 1.3 ppm. The complete amidation of the dendrimer peripheral amine groups was supported by the appearance, in the 1H NMR spectra, of a new signal in the 6.0-6.7 ppm range due to the alkylamide group, as well as by the integration ratios of the different protons, which are in agreement with the expected structures. The assignment of the peaks corresponding to the methylene carbons for 1 and 2 in the 13C NMR spectrum has been confirmed by heteronuclear single quantum coherence (HSQC) (see Figure S2 in the SI). The structures of 1 and 2 and dendrimers 3-6 were corroborated by mass spectrometry (liquid secondary ion mass spectrometry (L-SIMS) or matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF)). The main peaks in the spectra of 1 and 2 are singly charged molecular ions at m/z 413.2 and 415.2 (L-SIMS), respectively, which correspond to the correct molecular mass. In the L-SIMS mass spectrum of the first-generation dendrimer 3 and MALDI-TOF mass spectrum of the second-generation 4, the molecular protonated ion peaks at m/z 1898.7 and m/z 8012.9 are detectable. MALDITOF mass spectra of the third- and fourth-generation dendrimers (Figure 1) showed dominant peaks at m/z 8012.9 and m/z 4007.3 for 5, and m/z 16163 and m/z 8081 for 6, with isotopic patterns matching exactly the calculated values for the protonated and doubly protonated dendrimers. Electrochemical Behavior. The electrochemical behavior of the synthesized ferrocenylamidoalkyl dendrimers 3-6 has been investigated by cyclic voltammetry (CV) and normal pulse voltammetry (NPV) of the materials in homogeneous solution, as well as confined to electrode surfaces (i.e., where the dendrimers serve as electrode modifiers). For all generations of this dendritic family, a single redox process is observed in CH2Cl2 with a formal potential of about 0.60 V versus saturated calomel electrode (SCE) (see Table 1). The fact that only a single redox process is observed indicates that the 4, 8, 16, and

32 ferrocenyl units in 3, 4, 5, and 6, respectively, are seemingly identical and sufficiently remote from one another to render the electrostatic factor negligible.10 It is worth noting that the redox behavior of the dendrimers is marked by changes in solubility with the change in the oxidation state of the ferrocene units on the dendritic surface. It can be observed that anodic waves showed a typical diffusional shape, whereas cathodic waves showed a stripping shape, indicating that the dendrimers adsorb onto the electrode during oxidation and desorb partially during reduction with some strongly adsorbed dendrimer remaining on the electrode surface. On other hand, the redox behavior of the dendrimers in solution is sensitive to the dendrimer generation. In order to check the evolution of this dendritic effect on the voltammetric response, cyclic voltammograms of solutions of these polymetallic species in CH2Cl2 containing nearly the same molar amount of ferrocene units in all cases, were obtained. It is observed that the cathodic stripping wave increased in magnitude as the number of peripheral amide linked ferrocene moieties per dendritic molecule increased (i.e., as the generation increased). This behavior is very similar to that previously observed for the analogous ferrocenyl dendrimers DAB-dend(NHCOFc)x.11,12 Because of the deposition of the oxidized dendrimers on the electrode surface, the formal potential values (E0) of the ferrocene-functionalized dendrimers 3-6 (see Table 1) were determined by using NPV. A valuable feature of these organometallic dendrimers is their ability to modify electrodes, resulting in electroactive material that remains persistently attached to the electrode surface. The deposition of the dendrimers can be carried out onto Pt or glassy carbon (GC) electrodes, and presumably other materials, by a simple soaking procedure (i.e., no applied potential), by controlled potential electrolysis at 0.75 V or by repeated cycling between +0.4 and 0.9 V versus SCE in degassed solutions of the dendrimer in CH2Cl2. Thus, in the last two cases the amount of electrodeposited material can be controlled through the time interval during which the potential was held fixed or the number of scans. The redox behavior of films of the dendrimers electrodeposited onto electrode surfaces was studied by CV in fresh CH2Cl2 solutions containing only the supporting electrolyte. In all cases, a well-defined symmetrical oxidation-reduction wave corresponding to the ferrocene/ferricinium couple is observed, with a formal potential value E0 of about 0.60 V. The wave shape is typical of a surface-confined reversible couple with the expected linear relationship of peak current to potential sweep rate, V, for values up to 500 mVs-1.13 The voltammetric response of a film of dendrimer 6 is shown in Figure 2, curve a, as a representative example. The peak-to-peak separation values (∆Epk) were typically small (40 mV) at 50 mVs-1, and for sweep rates below 20 mVs-1 the splitting was virtually zero. However for higher sweep rates, ∆Epk values tended to increase. These observations indicate that, for sweep rates below about 500 mVs-1, these films exhibit rapid electron and charge-transfer kinetics. ∆Epk increases with film thickness; however, at low coverages it remains equal to 60 mV over the sweep rate range (10) Flanagan, J. B.; Margel, S.; Bard, A. J.; Anson, F. C. J. Am. Chem. Soc. 1978, 100, 4248. (11) Cuadrado, I.; Mora´n, M.; Casado, C. M.; Alonso, B.; Lobete, F.; Garcı´a, B.; Ibisate, M.; Losada, J. Organometallics 1996, 15, 5278. (12) Takada, K.; Dı´az, D. J.; Abrun˜a, H.; Cuadrado, I.; Casado, C. M.; Alonso, B.; Mora´n, M.; Losada, J. J. Am. Chem. Soc. 1997, 119, 10763. (13) (a) Abrun˜a, H. D. In ElectroresponsiVe Molecular and Polymeric Systems; Skotheim, T. A., Ed.; Dekker: New York, 1998 ; Vol. 1, p 97. (b) Murray, R. W. In Molecular Desing of Electrode Surfaces; Murray, R. W., Ed.; Techniques of Chemistry XXII; Wiley: New York, 1992; p 1.

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Figure 1. MALDI-TOF mass spectra of dendrimers 5 (A) and 6 (B).

of 200-500 mVs-1. One of the most remarkable features of electrodes modified with films of these dendrimers is that they are extremely durable and reproducible. In fact, the shape of the features in the cyclic voltammograms is independent of the scan rate from 5 to 1000 mVs-1, and repeated scanning in CH2Cl2 electrolyte solutions did not change the voltammograms, demonstrating that films of different generations are stable to electrochemical cycling. Likewise, after standing in air for several weeks, the redox response was practically unchanged with no loss of electroactivity. The high stability of these surface-confined ferrocenylamidoalkyl dendrimer films contrasts with the behavior of electrodes modified with electrodeposited films of dendrimers containing ferrocenyl amido groups directly attached to the DAB framework, which are not durable enough to be used for electrochemical sensing. This is an important

observation since the applications of modified electrodes require extensive redox cycling. Anion Sensing Properties. The electrochemical response of 3 in CH2Cl2/tetra-n-butylammonium hexafluorophosphate (TBAH) solution is strongly affected by the addition of increasing amounts of H2PO4- anion. The CV curves exhibit a “two-wave” behavior. A progressive decrease of the initial Fc/Fc+ wave is observed along with the growth at less positive potentials of a new peaks system (Figure 3). In the presence of an excess of [n-Bu4N][H2PO4], the cathodic response of the dendrimers is characterized by an intense and spikey peak. This stripping peak is due to the reduction and desorption of ion pairs, Dendx+ xH2PO4-, that precipitate onto the electrode surface during the positive scan.

Ferrocenylamidoalkyl Dendrimers as Anion Receptors

Figure 2. CV of a GC electrode modified with a film of dendrimer 6, measured in CH2Cl2/TBAH at 100 mV s-1 (Γ ) 2.3 × 10-10 mol Fc cm-1) in the absence (a) and presence of [n-Bu4N][H2PO4] (b) 2 × 10-5 M, (c) 3 × 10-5 M, and (d) 4 × 10-5 M. Inset: OSWV curves in the absence (a) and presence of [n-Bu4N][H2PO4] (b) 10-5 M, (c) 5 × 10-5 M, and (d) 10-4 M.

Figure 3. CV of dendrimer 3 (10-4 M) in the absence (a) and presence of [n-Bu4N][H2PO4] (b) 0.6 equiv, (c) 1.75 equiv, and (d) 2.25 equiv. Recorded in CH2Cl2/0.1 M TBAH, at 100 mV s-1, working electrode GC vs SCE.

A “two-wave” behavior was also observed in the CV curves for electrodes modified with dendrimer films. A new redox peak couple merges at the expense of the original one at less positive potentials (Figure 2, curves b-d). Moreover a significant decrease in the electroactivity of the films is observed, even at low [n-Bu4N][H2PO4] concentrations, and the intensity of the electrochemical response of the film is depressed. The loss of electroactivity can be attributed to the doping of the films, which is responsible for a restricted transport of counterions due to the formation of strong ion-pairs. This leads to a decrease in the rate of charge propagation which is controlled by counterion diffusivity in the films and ion-trapping effects. A similar electrochemical behavior due to the counteranion effects has been previously reported for electrodes modified with films of polymers containing ferrocene units.14 The two-wave behavior observed both in solution as well as in the modified electrodes can be attributed to a large increase in the association constants on oxidation,15 due to the establishment of strong electrostatic interactions between H2PO4- and the oxidized ferricinium. In our case, the dendrimers studied

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are potentially capable of coordinating and recognizing anionic guests via the cooperative forces of NH-anion hydrogen bonding interactions in the neutral state and electrostatic interactions with the positively charged ferricinium centers, in a similar manner as well-known receptors containing amide NH groups.16 Thus, it can be assumed that the effect of the synergy between the H-bonding and the electrostatic interactions is enhanced by the dendritic structure, which improves the electrochemical sensing properties toward the dihydrogenphosphate anion. The sensing properties of the dendrimer films toward various anions have been also examined from Osteryoung square-wave voltammetry (OSWV) experiments. Well-behaved OSWV curves are obtained in the absence and in the presence of [n-Bu4N][H2PO4] in TBAH/CH2Cl2 solutions (Figure 2, inset). In dihydrogenphosphate-free solution, a peak corresponding to the Fc/Fc+ redox couple is observed at Ep ) 0.62 V. As in the CV experiments, in the presence of increasing amounts of [n-Bu4N][H2PO4], a new peak appears at a less positive potential with a concomitant decrease in the intensity of the initial peak, which disappears after the addition of at least 10-4 M [n-Bu4N][H2PO4]. The potential of this second peak is progressively shifted to less positive potentials with increasing amounts of dihydrogenphosphate. The binding of anions effectively stabilizes the positive charge of the oxidized film, shifting the redox potential (Ep) of the Fc/Fc+ system to less positive values until the potential peak reaches a constant value. This behavior is in accordance with the increase of the effective electron density on the redox center due to the binding of the H2PO4anion, which makes the oxidation easier. The intensity of the OSWV peaks is somewhat depressed in the presence of H2PO4ions, even at low concentrations. This lost of electroactivity is a consequence of the aforementioned ion trapping effects. Analysis of the OSWV curves for electrodes modified with the films of dendrimers as a function of the [n-Bu4N][H2PO4] concentration allows calibration graphs to be established. The intensity of the anodic peak, ipa of the original wave decreases continuously in the presence of H2PO4-. This decrease parallels the negative potential shift of the new peak corresponding to the formation of the ferricinium-ion pairs. The cathodic shift of the new ferrocene OSWV oxidation wave, ∆Ep (peak-to-peak separation), increases with the anion concentration (Figure S3A-C in the SI). Increasing values of ∆Ep can be measured in the [n-Bu4N][H2PO4] concentration range of 20-70 µM. It can be observed that higher shifts were obtained using the higher generations of the dendrimers (5 and 6) in electrodes modified with films of nearly the same ferrocene units coverage. Analysis of the intensity of the initial OSWV peak also allows amperometric titration curves to be drawn (Figure S3D-F in the SI) that present low and high limits of detection of 10 and 50 µM in H2PO4-, respectively. For electrodes prepared with a similar coverage of redox groups, lower ip values were obtained (14) (a) Alonso, B.; Garcı´a-Armada, P.; Losada, J.; Cuadrado, I.; Gonza´lez, B.; Casado, C. M. Biosens. Bioelectron. 2004, 19, 1617. (b) Berduque, A.; Herzog, G.; Watson, Y. E.; Arrigan, D. W. N.; Moutet, J.C.; Reynes, O.; Royal, G.; Saint-Aman, E. Electroanalysis 2005, 17, 392. (c) Reynes, O.; Royal, G.; Chaıˆnet, E.; Moutet, J.-C.; Saint-Aman, E. Electroanalysis 2003, 15, 65. (15) Miller, S. R.; Gustowski, D. A.; Chen, Z. H.; Gokel, G. W.; Echegoyen, L.; Kaifer, A. E. Anal. Chem. 1988, 60, 2021. (16) (a) Beer, P. D. Chem. Commun. 1996, 689. (b) Beer, P. D. AdV. Inorg. Chem. 1992, 79. (c) Beer, P. D.; Hazlewood, C.; Hesek, D.; Hodacova, J.; Stokes, S. E. J. Chem. Soc., Dalton Trans. 1993, 1327. (d) Beer, P. D.; Chen, Z.; Goulden, A. J.; Graydon, A.; Stokes, S. E.; Wear, T. J. Chem. Soc. Chem. Commun. 1993, 1834. (e) Beer, P. D. Acc. Chem. Res. 1998, 31, 71.

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Figure 4. OSWV curves for a GC electrode modified with dendrimer 3 measured in CH2Cl2/0.1 M TBAH in the absence (a) and presence of [n-Bu4N][HSO4] (b) 5 × 10-6 M, (c) 10-5 M, (d) 5 × 10-5 M, and (e) 10-4 M. Inset: ∆E vs [HSO4-].

Figure 6. OSWV oxidation peak currents for a film of dendrimer 3 on a GC electrode versus KH2PO4 (A) and versus Na2ATP (B), measured in H2O/0.1 M LiClO4.

Figure 5. OSWV curves for a GC electrode modified with dendrimer 6 measured in CH2Cl2/0.1 M TBAH, in the absence (a) and presence of 4 × 10-5 M [n-Bu4N][HSO4] (b), 4 × 10-5 M [n-Bu4N][HSO4] + 4 × 10-5 M [n-Bu4N][H2PO4] (c), and 4 × 10-5 M HSO4- + 8 × 10-5 M [n-Bu4N][H2PO4] (d).

using electrodes modified with higher generation dendrimers films. This fact is probably due to a larger loss of electroactivity caused by stronger ion-film interactions. From these results, it can be concluded that the strength of the hydrogen-bonding and electrostatic interactions between the amidoferrocene groups and the anions depends on the topological characteristics and concentration effects. It is likely that, in the layers of the dendrimers deposited onto the electrode surface, the alkyl organometallic units form cavities and channels that are responsible of the establishment of stronger interactions as the dendrimer generation increases. As a representative example, it can be seen in Figure S4A-C in the SI that, for electrodes modified with films of dendrimer 4, the low limit of detection (5 µM) is independent of the apparent surface coverage, Γ, in the range 1.5 × 10-10 to 6.3 × 10-10 mol cm-2. In contrast, the high limit of detection depends on the number of amidoferrocenyl groups in the film. It varies from 50 µM (Γ ) 1.5 × 10-10 mol cm-2) to 500 µM (Γ ) 6.3 × 10-10 mol cm-2). Similar results are obtained in the titration curves based on ∆Ep measurements of the negative shift of the new ferrocene oxidation peak (Figure S4D-F in the SI). The sensing properties were further studied by analyzing OSWV response of dendrimer 6 films (Γ ) 2.78 × 10-10 mol cm-2) in the presence of other anions. The addition of increasing

amounts of [n-Bu4N][HSO4] leads only to a progressive shift of the potential of the Fc/Fc+ peak without the growth of a new redox wave (Figure 4). This behavior can be linked to a weaker anion-ligand interaction following the oxidation of the ferrocene groups.5c,d Increasing values of ∆E can be measured in the HSO4- concentration range from 5 × 10-6 to 10-4 M. Competitive experiments in the presence of H2PO4-, HSO4-, Cl- and Br- anions allow one o confirm the selectivity of the sensors.5d,14c When the modified electrode is exposed to a solution containing [n-Bu4N][H2PO4] and [n-Bu4N][HSO4] both at concentration 4 × 10-5 M, the cathodic perturbations observed in the OSWV curves are approximately the same as that induced by the H2PO4- alone (Figure 5). The electrochemical response of electrodes modified with the surveyed dendrimers were also tested in water. Figure 6 shows the variation of the intensity of the Fc/Fc+ peak at an electrode modified with a dendrimer 3 film (Γ ) 1.7 × 10-10 mol cm-2) as a function of increasing concentrations of KH2PO4 or Na2 ATP. As observed, decreasing values of ip can be measured until a constant value of 1000 µM is reached.

Conclusions A new family of dendrimers containing ferrocenyl units attached to poly(propyleneimine) frameworks through diamido aliphatic chains have been synthesized and characterized. Electrochemical investigations of the new ferrocenylamidoalkyl dendrimers show their ability to recognize and sense anionic species. Robust modified electrodes can be successfully prepared with the dendrimers by different procedures. Their voltammetric response is also sensitive to the presence and concentration of anions in both organic and aqueous media. Furthermore, sensor sensitivity toward the anions depends on the film thickness.

Experimental Section Materials and Equipment. All reactions were performed under an inert atmosphere (prepurified N2 or Ar) using standard Schlenk techniques. Solvents were dried by standard procedures over the

Ferrocenylamidoalkyl Dendrimers as Anion Receptors appropriate drying agents and distilled immediately prior to use. Fluorocarbonylferrocene9 was prepared according to published procedures. Commercially available ferrocenecarboxylic acid, 11aminoundecanoic acid, cyanuric fluoride, pyridine, and the dendritic polyamines DAB-dend-(NH2)x (x ) 4, 8, 16, and 32) were used for the preparations. These compounds were used without further purification. NMR spectra were recorded on a Bruker AMX-300 spectrometer. The MALDI-TOF mass spectra were obtained using a Reflex III (Bruker) mass spectrometer equipped with a nitrogen laser emitting at 337 nm. The matrix was ditranol. Elemental analyses were performed by the Microanalytical Laboratory, Universidad Auto´noma de Madrid, Madrid, Spain. Electrochemical Measurements. CV experiments were performed on a BAS CV-50W potentiostat. CH2Cl2 (spectrograde) for electrochemical measurements was freshly distilled from calcium hydride under nitrogen. The supporting electrolyte was TBAH that was purchased from Fluka and was purified by recrystallization from ethanol and dried under vacuum at 60 °C. In aqueous solution, LiClO4 (Aldrich) was used as the supporting electrolyte. The supporting electrolyte concentration was typically 0.1 M. A conventional sample cell operating under an atmosphere of prepurified nitrogen was used for CV. All CV experiments were performed using either a platinum-disk working electrode (A ) 0.020 cm2) or a GC-disk working electrode (A ) 0.070 cm2), each of which was polished prior to use with either 0.05 µm alumina/ water slurry or 1 µm diamond paste (Buehler) and rinsed thoroughly with purified water and acetone. All potentials are referenced to the SCE. A coiled platinum wire was used as a counter electrode. Solutions for CV were typically 1.0 mM in the redox active species and were deoxygenated by purging with prepurified nitrogen. No iR compensation was used. OSWV was done with a step potential of 4 mV, a square wave frequency of 15 Hz, and a square wave amplitude of 25 mV. [n-Bu4N][HSO4] (Sigma), [n-Bu4N][H2PO4] (Aldrich), [n-Bu4N][Cl] (Fluka), [n-Bu4N][Br] (Fluka), [Na]2[ATP] (Fluka), and [K][H2PO4] (Fluka) were used as received. Synthesis of 1. Fluorocarbonylferrocene (1.67 g, 6 mmol) were dissolved in anhydrous tetrahydrofuran (THF) under nitrogen atmosphere. Then 11-aminoundecanoic acid (1.45 g, 7 mmol) was added. The reaction mixture was stirred at 30 °C for 5 days while argon was bubbled in order to eliminate the hydrofluoric acid byproduct. Once the 11-aminoundecanoic acid in excess had been removed, the solvent was evaporated under vacuum, and the resulting residue was dissolved in dichloromethane and cooled to -20 °C. A yellow solid of pure 1 was isolated. Yield: 2.97 g (60%). Anal. Calc (found) for C22H31O3NFe: C, 63.94 (64.03); H, 7.50 (7.43). 1H NMR (CDCl3 300 MHz): 1.31 (m, 12H, CH2), 1.59 (m, 4H, CH2), 2.35 (t, 2H, CH2COOH), 3.36 (dt, 2H, CH2NH), 4.20 (s, 5H, C5H5), 4.33 (t, 2H, C5H4), 4.65 (t, 2H, C5H4), 5.68 (m, 1H, CONH). 13C{1H} NMR (DMSO-d6, 75.43 MHz): δ 25.36, 27.36, 29.41, 29.60, 29.72, 29.74, 29.87, 30.36, 39.49 (CH2), 34.52 (CH2COOH), 68.96, 70.61, 77.84 (C5H4), 70.11 (C5H5), 169.46 (CONH), 175.37 (COOH). MS (L-SIMS): m/z 413.2 (M+). Synthesis of 2. A suspension of compound 1 (1.40 g, 0.72 mmol) and pyridine (0.12 g, 1.51 mmol) in dry dichloromethane (60 mL) was cooled to 0 °C under an argon atmosphere. To this solution cyanuric fluoride (0.10 g, 0.74 mmol) was added, and the mixture was stirred for 2 h. A copper color was observed. Crushed ice/ water (40 g) was then added, the suspension was filtered, and the organic layer was separated and washed with cold water. The organic layer was then dried over anhydrous MgSO4 and filtered. Solvent removal from the filtrate affords 2 as a dark orange crystalline solid. Yield: 1.27 g (91%). Anal. Calc (found) for C22H30O2NFFe: C, 63.63 (63.90); H, 7.23 (7.33). 1H NMR (CDCl3 300 MHz): 1.31 (m, 12H, CH2), 1.67 (m, 4H, CH2), 2.49 (td, 2H, CH2COF), 3.36 (dt, 2H, CH2NH), 4.19 (s, 5H, C5H5), 4.33 (t, 2H, C5H4), 4.65 (t, 2H, C5H4), 5.65 (m, 1H, CONH). 13C{1H} NMR (DMSO-d6, 75.43 MHz): δ 24.23, 27.35, 28.84, 29.37, 29.64, 29.69,

Organometallics, Vol. 28, No. 3, 2009 733 29.82, 30.36, 39.49 (CH2), 32.19 (CH2COF), 68.96, 70.61, 77.84 (C5H4), 70.10 (C5H5), 169.46 (CONH), 164.80 (COF). MS (L-SIMS): m/z 415.2 (M+). Synthesis of Dendrimers 3-6. The representative procedure for the reaction of 2 with dendritic amines is as follows: 2 (1.1 equiv for dendritic amine) was dissolved in anhydrous dichloromethane at 30 °C under argon atmosphere. The dendritic amine (1 equiv) in dichloromethane was slowly added and stirred for several days while bubbling argon. The solvent was removed, and the residue was washed several times with CH3CN at 35 °C to give the corresponding ferrocenyl dendrimers. Synthesis of Dendrimer 3. The contents were stirred at 30 °C for 7 days to give 0.08 g of the product (14%). 1H NMR (CDCl3 300 MHz): 1.31 (m, 52H, CH2), 1.62 (m, 24H, CH2CH2NH), 2.15 (t, 8H, CH2CONH), 2.30-2.50 (m, 12H, CH2N) 3.20-3.45 (m, 16H, CH2NHCO), 4.19 (s, 20H, C5H5), 4.32 (t, 8H, C5H4), 4.70 (t, 8H, C5H4), 6.05 (m, 4H, CH2NHCOCH2) 6.76 (m, 4H, CH2NHCOFc). 13 C{1H} NMR (CDCl3, 75.43 MHz): δ 26.35, 26.27 (NCH2CH2) 29.84, 29.78, 29.70, 29.67 (CH2CH2CH2), 30.36 (CH2CH2NHCO), 37.18 (CH2CH2NHCO), 40.06 (CH2CONH), 52.39 (CH2NCH2), 68.52, 70.69, (C5H4), 70.11 (C5H5), 170.57 (NHCOFc), 173.85 (NHCOCH2). MS (L-SIMS): m/z 1898.7 (M + H)+. Synthesis of Dendrimer 4. The contents were stirred at 30 °C for 9 days to give 0.15 g of the product (30%). 1H NMR (CDCl3 300 MHz): 1.15- 1.40 (m, 104H, CH2), 1.65- 1.75 (m, 48H, CH2CH2NH), 2.18 (t, 16H, CH2CONH), 2.40- 2.70 (m, 24H, CH2N) 3.13- 3.45 (m, 32H, CH2NHCO), 4.19 (s, 40H, C5H5), 4.31 (t, 16H, C5H4), 4.73 (t, 16H, C5H4), 6.26 (m, 8H, CH2NHCOCH2) 7.28 (m, 8H, CH2NHCOFc). 13C{1H} NMR (CDCl3, 75.43 MHz): δ 27.40, 26.32 (NCH2CH2) 29.84, 29.77 (CH2CH2CH2), 30.39 (CH2CH2NHCO), 37.18 (CH2CH2NHCO), 40.05 (CH2CONH), 52.39 (CH2NCH2), 68.58, 70.70, (C5H4), 70.12 (C5H5), 170.65 (NHCOFc), 173.85 (NHCOCH2). MS (MALDI-TOF): m/z 3936.8 (M + H)+. Synthesis of Dendrimer 5. The contents were stirred at 30 °C for 11 days to give 0.07 g of the product (15%). 1H NMR (CDCl3 300 MHz): 1.27 (m, 208H, CH2), 1.58 (m, 96H, CH2CH2NH), 2.19 (t, 32H, CH2CONH), 2.31- 2.52 (m, 48H, CH2N) 3.23- 3.32 (m, 64H, CH2NHCO), 4.19 (s, 80H, C5H5), 4.31 (t, 32H, C5H4), 4.75 (t, 32H, C5H4), 6.45 (m, 16H, CH2NHCOCH2) 7.38 (m, 16H, CH2NHCOFc). 13 C{1H} NMR (CDCl3, 75.43 MHz): δ 27.44, 26.35 (NCH2CH2) 29.83 (CH2CH2CH2), 30.41 (CH2CH2NHCO), 37.18 (CH2CH2NHCO), 40.08 (CH2CONH), 52.39 (CH2NCH2), 68.64, 70.71, (C5H4), 70.13 (C5H5), 170.65 (NHCOFc), 173.85 (NHCOCH2). MS (MALDI-TOF): m/z 8012.9 (M + H)+, 4007.3 (M + 2H)2+. Synthesis of Dendrimer 6. The contents were stirred at 30 °C for 13 days to give 0.05 g of the product (20%). 1H NMR (CDCl3 300 MHz): 1.28 (m, 416H, CH2), 1.61 (m, 192H, CH2CH2NH), 2.20 (t, 64H, CH2CONH), 2.70-2.30 (m, 96H, CH2N) 3.35-3.37 (m, 128H, CH2NHCO), 4.21 (s, 160H, C5H5), 4.34 (t, 64H, C5H4), 4.80 (t, 64H, C5H4), 6.70 (m, 32H, CH2NHCOCH2) 7.61 (m, 32H, CH2NHCOFc). 13C{1H} NMR (CDCl3, 75.43 MHz): δ 27.51, 26.40 (NCH2CH2) 29.86 (CH2CH2CH2), 30.44 (CH2CH2NHCO), 36.96 (CH2CH2NHCO), 40.12 (CH2CONH), 51.69 (CH2NCH2), 68.70, 70.72, (C5H4), 70.13 (C5H5), 170.80 (NHCOFc), 174.39 (NHCOCH2). MS (MALDI-TOF): m/z 16163 (M + H)+, 8081 (M + 2H)2+.

Acknowledgment. We thank the Consejerı´a de Educacio´n, Comunidad de Madrid (S-0505/PPQ-0328) for the financial support of this research. Supporting Information Available: NMR spectra of organometallic fragments 1 and 2, and graphs showing the cathodic shift of the new ferrocene OSWV oxidation wave. This material is available free of charge via the Internet at http://pubs.acs.org. OM8007019