A polyazacyclophane containing two biphenyl subunits as a versatile cation and anion receptor

Journal of Supramolecular Chemistry 2 (2002) 107–114

A Polyazacyclophane Containing Two Biphenyl Subunits as a Versatile Cation and Anion Receptor Pilar Dı´az,a Antonio Dome´nech,b Enrique Garcı´a-Espan˜a,a,* Laura Lo´pez,c Santiago V. Luis,c,* Juan Miravet, Manuel Querolc and Patricia Solera a

Departamento de Quı´mica Inorga´nica,Instituto de Ciencia Molecular, Universidad de Valencia, C/ Dr. Moliner 50, 46100 Burjassot, Valencia, Spain b Departamento de Quı´mica Analı´tica, Universidad de Valencia, C/ Dr. Moliner 50, 46100 Burjassot, Valencia, Spain c Departamento de Quı´mica Inorga´nica y Orga´nica, Universitat Jaume I, 12080 Castello´n, Spain

Dedicated to Professor J. L. Atwood on the occasion of his 60th birthday

Abstract—The synthesis, protonation behaviour and coordination capabilities towards Cu2+, Zn2+ and towards the nucleotides ATP and ADP of a cyclophane ditopic receptor 2,6,10,23,27,31-hexaaza[11,11](2,20 )biphenylophane containing two 2,20 -biphenylene spacers linked to the ends of 1,5,9-triazanonane chains are presented. # 2003 Elsevier Ltd. All rights reserved.

Introduction Well-organized natural or synthetic molecular receptors are at the heart of supramolecular chemistry.1 Polyazacyclophanes represent an interesting category of synthetic receptors, as they combine the donor and acidbase properties of polyazamacrocycles with those provided by the aromatic subunit.2 The aromatic fragments can play several roles in determining the final properties of polyazacyclophanes: (i) they can afford some degrees of preorganization to the macrocycle, (ii) they introduce hydrophobic regions in the molecule that are important for solvation-desolvation processes, for instance, and (iii) can contribute to the recognition process through specific interactions such as solvophobic, p-cation or p–p interactions. In the last years we have been involved in the design, synthesis and study of the coordination capabilities of several families of receptors of this class.3 A fine tuning of the desired features in cyclophane receptors can be achieved both through the modification of the nature of the polyamine chain or through the use of different aromatic fragments. In this respect, a

Keywords: Polyazacyclophanes; Biphenyl; Synthesis; Cu2+ and Zn2+ coordination; ATP; ADP. *Corresponding author. Tel.: +34-6-398-3001; fax: +34-6-386-4322; e-mail: enrique.garcia- [email protected] 1472-7862/01/$ - see front matter # 2003 Elsevier Ltd. All rights reserved. PII: S1472-7862(02)00086-2

further step in the evolution of these receptors may be the introduction of dynamic features which might modulate the activity and coordination capabilities of those systems. The substitution of the original benzene fragment in L1 by a biphenyl subunit (L2) represents the more simple approach, and we have shown how simple polyazabiphenylophanes possess interesting properties as receptors,4 in good agreement with previous studies on related biphenyl crown ethers.5 Only a few reports can be found in which the oxygen atoms in the crown have been substituted by nitrogen donors.6 Here we report on the preparation and study of cyclophane L3 containing two biphenyl fragments. The introduction of two biphenyl subunits can have some important consequences on the final properties of the receptor (Chart 1). Indeed, compounds such as L3 should have a ditopic character whose activity would be regulated by the dynamic properties of the biphenyl moieties. The nature of the polyamine chains present in L3, in which three nitrogen atoms are separated by two propylenic spacers, has been designed in order to obtain a receptor able to interact with both anions and cations.

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presence of two well separated binding sites in correspondence with the classical distribution observed for ditopic receptors.13 Only for higher protonation degrees electrostatic repulsion between the two charged sites becomes important. The 1H and 13C NMR spectra for the free ligand L3 at basic pH show the presence of a four-fold symmetry, and the benzylic protons appear in the 1H spectrum as a singlet at 3.5 ppm, pointing out that conformational exchange is relatively fast on the NMR time scale. Upon full protonation, significant changes occur in the spectra. The most prominent feature is the splitting of the different signals in the proton NMR spectrum. Thus, for instance, two well separated signals at 1.6–1.8 ppm are observed for the central methylene groups of the propylenic subunits, and the benzylic protons appear as an AB system at ca. 4.0 and 4.6 ppm (J=13 Hz). Those data reveal that an important rigidification occurs at acidic pH values.4 Clearly, the transition state for the conformational interconversion at the biphenyl moiety requires an unfavorable approximation of the protonated nitrogen atoms. As a matter of fact, the presence of a slow exchange, on the NMR time scale, is observed even for lower protonation degrees. At pH=7, where L3 will be in its tetraprotonated form, an AB system is also observed for the benzylic protons (3.95 and 4.15, J=13 Hz) (Fig. 1).

Chart 1.

Results and discussion Acid-base behavior The protonation constants of L3 have been determined by pH-metric titration in aqueous solution at 0.15 mol dm3 NaCl at 298.1 K. The results are gathered in Table 1 together with those we have measured for the related cyclophane L1.7 As can be seen in Table 1, the stepwise protonation constants can be arranged in three groups of two constants each; the first two constants are very large and compare well with the first protonation constants of other polyazamacrocycles, including L1. The second group of constants presents values around 8 logarithmic units, and the values of the constants in the third group, although lower, are still relatively high in correspondence with the presence of the propylenic spacers between the amino groups. The second constant for L1 falls within the range observed for the second group in compound L3, while the third constant for L1 is higher than the values obtained for the third group of constants (log KH5L, log KH6L) in L3. These data suggest the Table 1. Logarithms of the stepwise protonation constants for L3 determined at 298.1 K in 0.15 mol dm3 NaCl and for L1 taken from ref 12 Reaction L+H=HLa HL+H=H2L H2L+H=H3L H3L+H=H4L H4L+H=H5L H5L+H=H6L log
c a

L3

L1

10.65(2)b 10.47(2) 8.56(4) 7.80(4) 5.35(5) 4.25(5) 47.1

10.13 8.34 6.8

25.3

Charges omitted for clarity. Figures in parentheses are standard deviations in the last significant figure. c
=[HjL]/ [L] [H]j. b

In this case, however, the central methylene groups of the propylenic subunits appear as a broad singlet. Cu2+ and Zn2+ coordination. In order to study the ability of L3 as a metal ion receptor, the association constants with Zn2+ and Cu2+ were determined potentiometrically in 0.15 mol dm3 NaCl aqueous solution at 298.1 K (Table 2). Compound L3 forms both with Cu2+ and Zn2+ mononuclear species of stoichiometry ML2+, ML(OH)+ and the protonated species MHnL(n+2)+ with protonation degrees n=1–3. Also, in both systems several binuclear species are detected. If we focus our discussion firstly in the mononuclear species several aspects deserve some comment. Thus, it is noteworthy that although the stability constant for the ML2+ species of Cu2+ is higher than for Zn2+, the difference between them (
log K=1.3) is rather small in comparison with the results found in other systems. For instance, the log K values reported in the literature for the interaction of the triamine 1,5,9-triazanonane (4a) with Cu2+ and Zn2+ are 14.6 and 7.92 respectively (
log K=6.7).14 These results suggest that the dynamic behavior of ligand L3 allows for a better fitting to the coordination requirements of Zn2+ which does not present crystal field stabilisation. A somewhat related situation can be also found in the polyaza[n]paracyclophane L1, for which a
log K value of 2.6 is observed. The absolute values for log KML suggest a participation of the two polyamine chains of L3 in the co-ordination to the metal cation. The log KML values, in particular

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Figure 1. 1H NMR spectrum of L3 recorded at pH 7. Table 2. Logarithms of the stability constants for the formation of Cu2+ and Zn2+ complexes of the ligands L3 and L1 a

Reaction

L 2+

Cu M+L=ML ML+H=MHL MHL+H=MH2L MH2L+H=MH3L MHL+2H=MH3L ML+H2O=ML(OH) +H ML(OH)+H2O=ML (OH)2+H 2M+ L=M2L ML+M=M2L 2M+L+H2O=M2L (OH)+H+ 2M+L+2H2O=M2L (OH)2+2H+

16.0(1)b 8.7(1) 7.10(2) 4.4(1) 11.5(1) 10.1(1)

3

L 2+

Cu

Zn2+

14.68(7) 7.80(7)

7.97(2) 6.93(2)

5.36(2)

13.01(5) 8.56(7)

8.50(3)

8.59(2)

9.81(3)

10.02(2)

Zn

2+

1

24.34(5) 8.34(5) 10.64(9) 6.2(1)

1.72(9)

a

Charges omitted for clarity. Numbers in parentheses are standard deviations in the last significant figure. b

for Zn2+, are higher than those found with triamine L4 (
log K=1.4 for Cu2+ and
log K=6.8 for Zn2+). When the complexes formed with a tetraamine such as 1, 5, 9, 13-tetraazatridecane (L9) are considered, the log K values continue being much higher for the complex [ZnL3]2+ while those for the Cu2+ complexes are comparable (see Chart 2). This indicates that, in the case of Cu2+, an increase in the number of coordinated nitrogen atoms brings along a simultaneous increase of the steric and/or torsional energy. The high values of the protonation constants for the complexes are indicative of the presence of noncoordinating nitrogen atoms in both cases.

Chart 2.

An interesting feature is the formation of monohydroxylated species in both systems, which, in the case of Zn2+ are formed at relatively low pH values (log Ka=8.6). In Figure 2 the distribution diagrams for the systems Cu2+-L3 and Zn2+- L3 calculated for molar ratio metal:ligand 2:1 are shown. It deserves to be mentioned that the Cu2L complex is the main species in solution between pH values 5 and 9. Above this pH value a dihydroxylated binuclear species predominates. In the case of Zn2+ binuclear species do not predominate until pH 7, and the complexes formed would be already monohydroxylated. A dihydroxylated binuclear species predominates at the same pH values than for Cu2+. Most likely, these data support the fact that the involvement of both polyamine chains in the coordination to a single copper ion is less favored than in the case of Zn2+. Therefore, binuclear complexes are more readily formed in the case of Cu2+. The generation of Zn2L(OH)3+ species at physiological pH values can be of interest for the use of this system as a minimalist model of hydrolytic enzymes. Electrochemical studies. The redox chemistry of copper complexes with macrocyclic receptors has been extensively studied and the influence of a variety of factors on the Cu2+/Cu+ redox potential systematically analysed.15 As a consequence, different empirical correlations between the redox potential and electronic and structural parameters have been put forward.16,17 Studies performed by Schroeder and Rorabacher et al. on open-chain and macrocyclic polyamine and polythiaether complexes of copper in aqueous solution indicated the existence of a significant increase in the redox

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Figure 2. Distribution diagrams for the systems Cu2+-L3 (A) and Zn2+-L3 (B). [M]=2103 mol dm3, L3=1103 mol dm3.

potential of the Cu2+/Cu+ couple when sulfur atoms were replacing nitrogen atoms. However, this behavior is due to a lowering in the stability of Cu2+ complexes rather than to a stabilization of the Cu+ complexes.18,19 N-Permethylation of macrocyclic polyamines also produces a relative stabilization of the Cu+ complexes; the enhancement in hydrophobicity induced by the methyl groups being considered the most relevant factor for such stabilization.20,21 Polyazamacrocyclic receptors containing benzene,22 durene,23 or thiophene24 spacers were found to form stable Cu2+ and Cu+ complexes in aqueous media, the stabilisation of Cu+ complexes towards disproportionation into Cu2+ and Cu being attributed to the increase in hydrophobicity afforded by the aromatic spacer. Another factor that affects Cu+ stabilisation is the formation of ternary complexes. In the case of polyaza[n]cyclophanes the introduction of an exogen polyphosphate ligand yielded a destabilisation of the Cu+ oxidation state in the mixed complex.25 In other studies, Saphier et al.26 attributed the stabilization of Cu+ polyazacyclophane complexes to the existence of d–p interactions between the copper d-orbitals and the aromatic p-system. In this context, polyazacyclophanes containing biphenyl subunits offer the opportunity to study the relative influence of the electronic, steric, and solvation factors affecting the redox chemistry of the complexes formed by copper with macrocyclic polyamines. In solutions containing Cu2+ and L3 in 2:1 and 1:1 molar ratios at neutral and alkaline pH values, where the complex species predominate, the voltammetric response is similar in both molar ratios and strongly dependent on the potential scan rate. As shown in Figure 3a, the cyclic voltammograms at low scan rates (v < 200 mV/s) show a single cathodic peak at 0.10 V (C1) coupled with an anodic one at +0.06 V (A1). On increasing the potential scan rate, the peak C1 is cathodically shifted and lowered while a second reduction peak (C2) appears at more negative potentials. At relatively high scan rates (v > 2000 mV/s) (see Fig. 3b), the C2 peak replaces almost entirely the C1 peak. On increasing the potential scan rate, the peak A1 is anodically shifted, whereas a second anodic peak, A2,

Figure 3. Initial cathodic scan (CVs) at GCE for a Cu(NO3)2.4H2O (7.0104 mol dm3)+L3 (2.55103 mol dm3) at pH=9.5. (a) v=20 mVs1, (b) 2000 mV s1. I=0.15 mol dm3 NaClO4.

appears at more negative potentials than A1 (0.13 V). The anodic to cathodic peak current ratio approaches at low scan rates approaches a value of one for peaks A1 and C1, while at high scan rates this ratio gets for A2/C2 peaks close to 0.5. The described electrochemistry is essentially unchanged in the pH range 7–11. A possible scheme for the reduction of Cu2+ complexes involves an initial one-electron reduction (n=1, 2), 3  CuII nL þe

I 3 !  Cun L

ð1Þ

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superimposed with a two-electron reduction, possibly preceded by ligand loss, 3  CuII n L þ 2n e

3 !  n Cu þ L

ð2Þ

Although the observed electrochemical response for peaks C1/A1 approaches that of a single one-electron transfer, the large peak to peak potential separation and the peak potential shifts on scan rate suggest a more complicated electrochemical pathway, involving a relatively slow reaction presumably a ligand re-organization or even a ligand loss preceding the charge transfer step. As a result, the process described by eq 1 is operative at relatively low scan rates, while the process eq 2 prevails at relatively high scan rates. This situation parallels that reported for the electrochemical reduction of Cu2+ in uncomplexing media, in which pre- and post-electron transfer deaquation and/or hydrolysis reactions condition the overall electrochemical behavior.2730 The subsequent anodic steps A1 and A2 appear to involve one-electron processes as suggested by the anodic to cathodic peak ratios. These peaks can be attributed to the oxidation of different Cu(I) species formed through the process eq 1 and via comproportionation reactions following the process represented by eq 3:  3 3 CuII n L þ n Cu þ L

3 !  2 Cun L


0

ð3Þ

Accordingly, at high scan rates two anodic processes, corresponding to the one-electron oxidation of CuInL and (CuInL)0 appear. All these data denote that there is a relatively high stabilisation of the intermediate Cu+ oxidation state towards disproportionation into Cu2+ and Cu upon complexation with L3. As can be seen in Figure 4, on extending the potential range toward values more negative than 1.0 V, a prominent cathodic peak appears near to 1.2 V (C3), while an additional anodic peak (A3) appears at +0.15 V. Peak C3 can be assigned to the reduction of the biphenyl groups through successive electron/proton transfers resulting in the formation of dihydroderivatives, Lrd.3133 Then, the peak A3 must correspond to the oxidation of CuInLrd complexes electrochemically rd species. generated to CuII nL

Figure 4. CVs at the GCE for a Cu(NO3)2.4H2O (3.0104 mol dm3)+L3 (1.08103 mol dm3) at pH=10.0. Potential scan initiated at 0.0 V; cathodic scan (continuous line), anodic scan (dotted line).

geometries usually associated with Cu+ and Cu2+ complexes. Cu2+-polyamine complexes show a clear preference for square-planar coordination geometries, as deduced from ESR data.36,37 In contrast, it is well known that Cu+ complexes prefer the tetrahedral geometry. As described in the literature,3841 the stabilization of Cu+ complexes with such ligands towards their disproportionation into Cu2+ ones and Cu presumably results from the possibility of adopting favorable pseudotetrahedral geometries. Thus, electrochemical data are in good agreement with potentiometric data obtained for Zn2+ and Cu2+ complexes of receptor L3, and seem to suggest that the coordination of this polyamine to the metal center is more favorable when tetrahedral or pseudotetrahedral geometries are involved, whilst square-planar geometries are not favored, most likely because the associated increase in unfavorable steric and torsional energies. Other factors such as the hydrophobicity provided by the presence of the four aromatic rings or an increase in the d–p interactions can also contribute, however, to this stabilization of Cu+–L3 complexes.

As shown in Figure 4, prolongation of the potential scan in the positive direction provides a prominent anodic wave near to +0.90 V (A4) followed, in the subsequent cathodic scan, by reduction peaks at 0.0 V (C4) and 0.15 (C1), and by peak A1 in the consecutive anodic scan. The anodic peak A4 must correspond to the electrochemical oxidation of aromatic subunit that can be described in terms of electron transfer steps coupled with the water attack to form quinone derivatives.31,34,35

A variety of factors can also determine the larger stabilization of Cu+ complexes observed for Lox and Lrd forms of the macrocycle L3, but, most likely, an improvement in the ability to adopt tetrahedral coordination geometries must be considered as an essential factor.

The peak C4 must correspond to the one-electron reduction of a Cu2+ complex of any oxidized form of the ligand, Lox. In order to rationalize the stabilization of the Cu+ oxidation state upon complexation by Lrd and Lox, we need to take into account the different

In Table 3 are presented the cumulative stability constants for the interaction of L3 with ATP and ADP (entries 1–8). Adduct species with protonation degrees varying from 1 to 7 for ADP and 2 to 8 for ATP are formed. Particularly in the case of ATP, these adducts

Nucleotide interaction. The large protonation constants displayed by L3 make this receptor prone to interact in its protonated forms with anionic species through salt bridge and hydrogen bond formation.

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are the predominating species in all the pH range studied (2.5–11.0). In order to better interpret the chemical meaning of these parameters the cumulative constants have to be translated into stepwise constant representative of the equilibria actually occurring in solution. Thus, taking into account the basicity constants of both receptor and substrates the relevant constants shown at the bottom of Table 3 have been calculated (entries 9–19). Depending on the pH range some species can be unambiguously associated with a given stepwise constant. For instance, for the system ADP-L3 above pH 8 the species HAL, H2AL and H3AL can be defined as being formed by the interaction of the fully deprotonated nucleotide and the mono-, di- and triporotonated receptor, respectively (entries 9–11). For the system ATP-L3 a similar pattern can be derived above pH 8 in correspondence with the formation of the species HiAL (i=1–4). Below pH=8 the analysis becomes more complicated since differently protonated forms of the receptor and substrate can be involved in the formation of a given adduct species. For instance, formation of the H4AL species in the case of ADP can be ascribed to the reactions indicated in entries 12 and 13 with values of the stability constants of 3.3 and 4.9 logarithmic units or, most likely, to a mixture of these two situations with percentages of participation of both equilibria which will depend on pH. For the ATP-L3 system a similar situation will happen with the formation of the H7LA species which can be ascribed to the reactions included in entries 17 and 18. Therefore, to better understand the magnitude of the interaction and to better interpret selectivity patterns it is very useful to apply the concept of conditional constants. Such constants are defined as the quotient, at a given pH value, between the overall

Table 3. Cumulative and stepwise formation constants of ADP-(L3) and ATP-( L3) adducts (0.15 mol dm3 NaCl at 298.1 K) Entry

Equilibrium

Log K (A=ADP3-) Log K ( A=ATP4-)

1 2 3 4 5 6 7 8

A+H+L=HALa A+2H+L=H2AL A+3H+L=H3AL A+4H+L=H4AL A+5H+L=H5AL A+6H+L=H6AL A+7H+L=H7AL A+8H+L=H8AL

14.35(3)b 24.84(2) 33.24(3) 40.79(3) 47.31(2) 52.13(3) 56.56(3)

— 25.44(6) 35.36(5) 43.49(5) 50.89(5) 56.60(5) 61.09(5) 65.07(5)

9 10 11 12* 13* 14 15* 16* 17* 18* 19

A+ HL=HAL A+ H2L=H2AL A+H3L=H3AL A+H4L=H4AL HA+H3L=H4AL HA+H4L=H5AL HA+H5L=H6AL H2A+H4L=H6LA HA+H6L=H7LA H2A+H5L=H7LA H2A+H6L=H8LA

3.9 3.7 3.6 3.3 4.9 3.6 3.0 4.6 3.2 3.7

— 4.3 5.7 6.0

amount of complexed species and the overall amounts of free receptor and substrate, independently of their protonation degrees.42 Figure 5 shows a plot of these constants for the systems ATP-L3 and ADP-L3 ([ATP]=[ADP]=[L3]=103 mol dm3). The analysis of such a plot allows one to discard for the system ADP-L3 any constant with values higher than 4 (entries 13 and 16). However, in the system ATP-L3 it seems to indicate that both the equilibia in entries 17 and 18 might actually be involved in the formation of H7LA. A second aspect that can be properly deduced from Figure 5 is selectivity. Receptor L3 complexes selectivity ATP over ADP in a large pH range, particularly in neutral and acidic pH values. The selectivity reaches its highest values at acidic pH and while at pH 8 the selectivity ATP/ADP is 158 (selectivity=Keff[ATP-L3]/Keff [ADP-L3]), at pH 2.0 this value reaches six orders of magnitude. 1 H NMR spectra performed at pH 7 do not reveal significant shifts of either the signals of the adenine fragment of ATP or of those of the biphenyl fragment suggesting that p–p stacking would not be significantly contributing to the stabilization of the adducts. Therefore, those results may be interpreted on the basis of a very nice match between the size of the receptor and the tripolyphospate chain, which might be interacting through all its three phosphate groups with the polyammonium sites (see figure in graphical abstract).

Experimental Synthesis of 2,6,10,23,27,31-hexaaza[11,11](2, 20 )biphenylophane (L3) Compound L3 was prepared according to the modification of the general Richman-Atkins procedure that we have been using for the preparation of different polyazacyclophanes and that is shown in Scheme 1.7

7.0 7.4 7.6 8.0 7.7

a

Charges omitted for clarity. Figures in parentheses are standard deviations in the last significant figure. b

Figure 5. Plot of the conditional constant versus pH for the systems ATP-(L3) and ADP-(L3) ([ATP]=[ADP]=[L3]=103 mol dm3).

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Scheme 1. (i) TsCl, DMF; (ii) CH3CN, K3CO3, (iii) Na/Hg, NaH2PO4/KHCO3; MeOH/THF.

A solution of 2,20 -bis(bromomethyl)biphenyl (5) (0.442 g, 1.3 mmol) in dry CH3CN (50 mL) was added dropwise to a suspension of the pertosylated 1, 5, 9-triazanonane (4) (0.772 g, 1.3 mmol) and K2CO3 anhydrous in excess in 50 mL of dry CH3CN. As a result, a mixture of the tosylated macrocyles 6 and 7 was obtained, being 6 the major product (41% after chromatographic purification). Detosylation of 6 (3 mmol) was carried out by using Na/Hg (4.5%, 30 g) in MeOH/THF (160/40 v/v) buffered with Na2HPO4/KHCO3. In this way, after chromatographic purification in silica-gel using MeOH/ NH3 as the eluent, the expected macrocycle L3 was obtained as its hexahydrobromide salt in 63% yield. 1H RMN (d ppm), 1.48–1.52 (m, 6H), 2.18–2.61 (m, 16H), 3.34 (d, J=12 Hz, 4H), 3.53 (d, J=12 Hz, 4H), 6.94 (d, J=6 Hz, 2H), 7.1 (t, J=9 Hz, 2H), 7.18 (t, J=9 Hz, 2H), 7.41 (d, J=6 Hz, 2H). 13C NMR (d ppm), 28.0, 48.3, 49.3, 51.6, 125.8, 127.0, 129.4, 129.7, 137.7, 139.6. calcd for C40H54N6.6HBr: C, 43.50, H, 5.48, N, 7.61; found, C, 43.5, H, 5.5, N, 7.6. Potentiometric measurements. All pH-metric measurements (pH=log [H+]) were carried out in 0.15 mol dm3 NaCl solutions at 298.1  0.1 K, by using the equipment and the methodology that has been already described.8 The system was calibrated as a hydrogen concentration probe by titrating known amounts of HCl with CO2-free NaOH solutions and determining the equivalent point by Gran’s method9 which allows one to determine the standard potential E and the ionic product of water (pKw=13.73(1) in NaCl, at 298.1  0.1 K). At least three measurements (about 100 data points each one) were performed for each system in the pH ranges 2.5–10.5. In all experiments the ligand concentration [L] was about 1103 mol dm3. In the metal complexation studies meta:ligand ratios varying from 2:1 to 1:2 were used and in the complexation experiments with ATP and ADP, the nucleotide (A) concentration was varied in the range [L]  [A]  2[L]. The computer program HYPERQUAD10 was used to calculate the equilibrium constants from e.m.f. data.

Electrochemistry. Cyclic voltammograms (CVs) were performed with a BAS CV50-W obtained in a three-electrode cell with a glassy carbon working electrode, a platinum wire auxiliary electrode and a AgCl/Ag reference electrode. Linear potential scan voltammograms (LSVs) and differential pulse voltammograms (DPVs) were performed with a Metrohm E506 polarecord. Electrochemical experiments were performed under argon atmosphere in solutions of Cu(NO3)2 in doubly distilled water. NaClO4 0.15 mol dm3 was used as supporting electrolyte, the pH being adjusted to the required value by adding the appropriate amounts of HClO4 and/or NaOH. NMR measurements. The 1H and 13C NMR spectra were recorded on Varian UNITY 300 and UNITY 400 spectrometers, operating at 299.95 and 399.95 MHz for 1 H and at 75.43 and 100.58 MHz for 13C respectively. The spectra were obtained at room temperature in D2O or CDCl3 solutions. For the 13C NMR spectra dioxane was used as a reference standard (dC=67.4 ppm) and for the 1H spectra the solvent signal. A variable temperature accessory regulated the probe temperature. Adjustments to the desired pH were made using drops of HCl or NaOH solutions The pH was calculated from the measured pD values using the correlation, pH=pD0.4.11

Acknowledgements We are indebted to CICYT (BQU200-1424) for financial support.

References and notes 1. See for instance: Lehn, J.-M. Supramolecular Chemistry, Concepts and Perspectives; VCH: Weinheim, 1995. Steed, J. W.; Atwood, J. L. Supramolecular Chemistry; John Wiley & Sons, Ltd: New York, 2000.

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