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Anal. Chem. 1988, 6 0 , 2021-2024
Rationalization of the Unusual Electrochemical Behavior Observed in Lariat Ethers and Other Reducible Macrocyclic Systems Steven R. Miller, Deborah A. Gustowski, Zhi-hong Chen, George W. Gokel,* Luis Echegoyen,* and Angel E. Kaifer* Department of Chemistry, University of Miami, Coral Gables, Florida 33124
Upon the addltion of cations, the observed electrochemical behavior of crown ether compounds containing or bearing reduclble functions sometlmes exhlblts two waves or sometimes a single wave that is shlfted in position relative to the orlginai redox couple. The type of eiectrochemlcalbehavior observed depends upon the binding (stablilty) constant (K,) for the neutral ilgand-catlon Interaction and the binding constant ( K S E )for the reduced ligand-cation Interaction. A computer-based, digltal simulation scheme has been devised that leads one to the conclusion that two dlstlnct waves will be observed only when the lnltlai catlon binding constant is large and that a shifted wave will result from weaker catlonmacrocycle Interactlons. Of speclai signlflcance Is the fact ) that the cation blnding enhancement ( K S E / K s calculated from the E o values measured from the two dlstlnct waves will generally be In error for cases In which K , for the neutral Ilgand-catlon Interaction falls in the range 1-10.. For ligands in thls blndlng range, the digital simulation procedures reported here appear to be particularly useful for the anaiysls of the voilammetrlc data.
The electrochemical behavior of lariat ethers and other macrocyclic systems is now reasonably well-known and certainly widely studied (1-8). Several years ago, when we first observed the two-wave behavior of reduced lariat ethers in the presence of cations, we were surprised to see two distinct waves rather than a shift in position of the original wave. Although Tsukube (6),Saji (3,and Cooper (9)have all studied the electrochemical behavior of systems related to ours, only Saji (7) has observed two resolved electrochemical waves corresponding to complexed and uncomplexed macrorings. Unlike what we observed, Cooper (9) and Tsukube (6) observed a single wave that shifts when the amount of cation is increased. We show here that application of the analysis we used to obtain cation binding enhancements for electrochemically reduced systems is inappropriate for systems not exhibiting two redox couples. In fact, there are several possible combinations of binding constants and enhancements that lead to distinctly different behavior. We have used the technique of digital simulation (10, 11) and developed a program that can be used to obtain true cation binding enhancements under a variety of conditions.
EXPERIMENTAL SECTION Materials. Two ligands were chosen for study. They are N-(2-nitrobenzyl)aza-15-crown-5, 1 (2), and 2-((2-nitrophenoxy)methyl)-15-crown-5,2(1). Details of the syntheses, purification, and electrochemical behavior for these compounds are available in the references cited. Acetonitrile (Alfa) was distilled from CaH2 and PzOs. All solutions were prepared under an atmosphere of dry N2. Tetrabutylammonium perchlorate (TBAP, Fluka) was recrystallized twice from EtOAc and stored in a desiccator. Sodium perchlorate i)
0003-2700/88/0360-2021$01.50/0
1
2
was recrystallized from deionized water and dried in a vacuum oven at 100 "C for 24 h. Cyclic Voltammetry Experiments. The electrochemical experiments were performed at 25 "C under N2 in MeCN 0.1 M in TBAP. The electroactive species was present in millimolar concentrations. Glassy carbon was used as the working electrode (0.080 cm2)and a Pt wire as the counterelectrode. E" values are reported vs the sodium saturated calomel electrode (SSCE). The measurements were done on a Bioanalytical Systems (Model 100) electrochemical analyzer equipped with IR compensation and recorded on a Houston Instruments DMP-40 plotter. Digital Simulations. The digital simulation method used for our studies was based on previous reports by Feldberg (IO,11) and Evans and Xie (12). Calculations were based on several assumptions commonly made when Feldberg's method is applied, namely: (i) The chemical and electrochemicalprocesses are fast on the experimental time scale and all equilibria are therefore maintained. (ii) All of the species diffuse at the same rate. (iii) The concentration profiles are approximated by a series of thin layers in the solution with mass transfers occurring from one layer to another by diffusion. (iv) The electrode surface is planar. The following values were entered for each simulation: (i) the (ii) the binding constant of binding constant of the ligand (Ks); the reduced ligand (KsE);(iii) the starting potential relative to the free ligand redox potential (E,"'); (iv) the switching potential relative to the free ligand potential, (v) the concentration of the ligand; and (vi) the concentration of the cation. One electron was transferred in the electrode reactions and the scan step size was 2 mV. Each cycle of the simulation consists of the following steps: (i) establish the chemical equilibria in all of the diffusion layers (the chemical equilibria used in the simulation are shown in Scheme I); (ii) approximate the diffusion out to layer 4.2k1/2where k is the number of iterations calculated; (iii) reestablish the chemical and electrochemical equilibria at the surface and calculate the current from the surface flux;and (iv) increment the potential and return to step i. The program was written in Fortran 77 and compiled with the Microsoft Fortran Compiler (v. 3.31). It was run on an IBM-PC computer equipped with an 8087 numeric coprocessor. The program sources will be made available upon request.
RESULTS AND DISCUSSION In principle, switching between binding states can be classed broadly into two categories, binary and incremental. The binary case refers to the situation in which there is no affinity between cation and the neutral ligand, but an interaction occurs when the ligand is reduced. The incremental case refers to all situations in which a finite binding interaction is observed between cation and ligand and this interaction strengthens upon reduction of the ligand. Incremental behavior is more suitable for rapid interconversions of molecular 0 1988 American Chemical Society
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ANALYTICAL CHEMISTRY, VOL. 60, NO. 19, OCTOBER 1, 1988 SIMULATION
EXPERIMENT
r"
A
2OPAl
/
,'
F
:i
L'
% /
E
/---'
-
--__\/ -10
00
-135
0.0
-1.0
-1.35
Flgure 1. Experimental and simulated cyclic voltammograms for N-(2-nitrobenzyl)aza-15-crown-5 in the presence of varying amounts of NaCIO,: (A-E) experimental voltammograms, (Fa) simulated voltammograms; (A, F) 0.0 equiv, (B, 0 )0.25 equiv, (C, H) 0.50 equlv, (D, I ) 0.75 equiv, and (E, J) 1.0 equiv of NaCIO,; scan rate, 100 mV s-1.
Scheme I LIGAND
+
e-
'
EP
L
It [LIGAND*M]++
[LIGAND]-
J
It
e-.
EP
+ L1GAND.M
structure due to kinetic availability of the bound species in both binding states. Conversely, in the binary case, the off or zero state corresponds to an unbound state so that the rate of switching is, a t best, limited by diffusion. In previous studies (1-3) we have characterized the electrochemical behavior of reducible lariat ethers by using Scheme I shown below. Simulation of the Electrochemical Behavior of Systems with Large Neutral Binding. We chose N-(2-nitrobenzyl)aza-15-crown-5, 1, because it clearly exhibits incremental electrochemical behavior. In the absence of any added cation, a single redox wave is observed (see Figure 1A). The small prewave in this voltammogram is due to leakage of sodium ion from the reference electrode. Addition of substoichiometric amounts of Na+ resulted in the clear observation of a second redox couple at a more positive potential (Figure 1B-D).The new wave was proportional in intensity to the amount of added cation (Figure 1E). Only the new redox couple was observed when a full equivalent of Na+ was present (Figure 1E). Further addition of Na+ did not alter the appearance of the voltammogram. We determined Ks for 1 in MeCN by using a potentiometric titration method that we reported recently (13). The value is 24550. Using this Ks value with a binding enhancement factor of 30000 resulted
6
0.0
-1.0
-1.5
0.0
-1.0
-1.5
Flgure 2. Simulated voltammograms calculated for K,IK, = 10 000 and 0.5 equiv of cation: (A) K , = 1000, (B) K , = 500, K , = 100, (D) K , = 50, (E) K s = 10, (F) K s = 5, (G)K , = 1, (H) K, = 0.1.
(4
in the digital simulations shown in Figures 1F-J. Note that the agreement between experiment and simulation is excellent in each case. It is interesting to note than the binding enhancement factor used in these simulations (30000)is slightly larger than that determined by using eq 1 (24950, see below). This corresponds to a difference of 0.005 V from the experimental observation and is clearly within the error of voltammetric experiments. In this case, Ks for the neutral ligand is quite large, and the agreement between experiment and simulation is excellent. In order to demonstrate that the redox wave observed when 1 equiv of Na+ was added actually represents the complex, we added NaC104 until 20 equiv was present. The fact that Eo for this wave remains at 0.90 V indicates that the new wave represents the complex. Indeed, these results were simulated satisfactorily by our program. The enhancement value can correctly be determined by using eq 1, shown below, as we have done in the past. KsE/Ks = exp[-nF(Efo - E,")/RT] (1) Simulation of the Electrochemical Behavior of Systems with Intermediate Neutral Binding. We investigated the effect of an intermediate Ks value on the hypothetical electrochemical behavior while keeping an enhancement factor = 10 000). The electrochemical behavior constant (&E/& varies considerably in this case as shown in Figure 2. The simulated voltammograms shown in Figure 2 range in K s values from 1000 to 0.1. When Ks is large, the two-wave behavior observed for 1 is apparent. As Ks diminishes, the two waves merge until (Figure 2g) a single wave is observed. The transition from two to one voltammetric waves is preceded by a decrease in the observed potential difference between the two couples. This decrease is not obvious in Figure 2 except where two waves are clearly merging into one. The deviation of the measured enhancement from the calculated enhancement is demonstrated by the results plotted in Figure 3. The graph shows that as the value of Ks decreases, the observed enhancement value increasingly deviates from the constant, actual factor of 10 000 (the line through the diamonds). The point where the lines end for the lower values of Ks is where the two waves are no longer resolved
ANALYTICAL CHEMISTRY, VOL. 60, NO. 19, OCTOBER 1, 1988
2 7
W-DKse/Ks e---oKse/ks
4-
= 1000
250
I
4 Kse/Ks = f 0000 T -V Kse/Ks = 25000
= 500
i
.-.
... . ..... ... .. ...... .. ..
0
...
,
.. ....
K ~ = o . Cclcbloied ~
5
IO
15
20
Ecu d e - : s
5 11
,
1
, 2
.-
----. 5
4
3 Log Ks
Figure 3. Logarithm of the enhancement calculated from the E o values of the two observed redox couples at 0.5 equiv of cation vs the logarithm of the neutral ligand binding constant for several binding enhancement values. All of the points were obtained from simulated voitammograms. EXPERIMENT
.. .. .. ... . . . . .
Po:en:;al
25
. ..
.
2023
.
Shift
30
35
a0
45
J
50
or Ccilo-
Flgure 5. Potential shift of the only observed redox couple vs the
equivalents of cation present for neutral ligands with low binding constants. The potential shift marked as “calculated potential shift” corresponds to the value obtained from eq 1 by using a value of KsEIK, = 10 000.
ously believed. Clearly, measurements on systems having intermediate binding constants should be made with considerable caution. SIMULATION Simulation of t h e Electrochemical Behavior of Systems w i t h Low Neutral Binding. Although our extensive studies of reducible macrocycles have been directed to strong cation binding systems, reports of reducible systems having lower cation binding affinities have appeared (6, 9, 14-17). Our observations regarding compound 2, which has an intermediate binding constant, made us curious about those systems having weak cation affiiities in the neutral state. The results of simulations based on hypothetical low-binding (Ks = 0.1-5) compounds are shown in Figure 5 . F’ The most striking feature of these simulations is that a single wave is observed in all cases. The potential shifts calculated as the cation concentration increases gradually taper off but continue to increase even when 50 equiv of cation is present. The potential shift calculated on the top, dotted line is essentially a limiting value that can be reached by using eq 1 only when the true binding constants are known. Experimental studies have been done with no more than 30 equiv of cation in cases having low cation affinities. Consequently, enhancement values have been substantially underestimated
4
n 4
4 0.0
-1.0
-1.32
(6).
0.0
-1.0
-1.32
Figure 4. Experimental and simulated cyclic voltammograms for 2((2-nitrophenoxy)methyl)-15-crown-5 in the presence of varying amounts of NaCIO,: (A-E) experimental voltammograms, (F-J) slmulated vdtammograms; (A, F) 0.0 equiv, (B, 0 ) 0.25 equiv, (C, H) 0.50 equlv, (D, I) 0.75 equiv, and (E, J) 1.0 equiv of NaCiO,; scan rate, 100 mV s-’.
and two Eo values cannot be measured. A real example of a compound exhibiting intermediate binding behavior is provided by 2-((2-nitrophenoxy)methyl)-15-crown-5,2. The voltammetric behavior of 2, along with the corresponding simulations, is shown in Figure 4. The binding constant for the reaction 2 + Na+ = complex is 320 (8). The previously reported value &E/& is 750, implying a &E value of 240000 (1). The simulations shown in Figure 4 accurately reproduce the 169-mV peak separations. They were obtained by using an enhancement factor of 3200, which implies a KSEvalue of 1020 000 rather than the previously reported value of 240000. In other words, the actual binding enhancement for this system is 5-fold better than we previ-
Another way to state this problem is that eq 1 cannot be applied to ligands with very small Ks values. Equation 1no longer applies for cases with small Ks values, and huge amounts of cation must be added to observe the electrochemistry of the complex. Indeed, these cases are better treated by an EC scheme in which the electron transfer step is followed by a reversible complexation equilibrium of the electrogenerated species with some other component of the solution. Classical electrochemical studies have shown that this complexation constant (KSEin our terminology) can be calculated by using an equation of the following type (18):
Eoapp = Eof+ RT/nF In KSE+ RT/nF In [M+]
(2)
which applies for cation concentrations at least 10-fold in excess of the concentration of the electroactive species. A large number of simulations have been conducted to test the applicability of eq 2 to electrochemically reducible, weakly binding ligands. We found the simulation data to be consistent with eq 2. Equation 2 must be used for systems having low neutral binding if reliable results are desired. CONCLUSIONS When electrochemical switching in macrocycles is considered, it is important to recognize that differences in cation binding affinities dramatically affect the cyclic voltammetry. When the neutral ligand binding constant is large (Ks > lo4),
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Anal. Chem. 1988, 60,2024-2027
the binding enhancement between the on and off states can be calculated from the E” values of the two observed voltammetric waves using eq 1. In this case, substoichiometric amounts of metal cations should result in two well-resolved redox couples corresponding to the free ligand and the metal complex. This response is indicative of incremental electrochemical switching. When the binding constant of the neutral ligand is low (Ks < l), can be calculated by using voltammetric data for several cation concentrations and eq 2. Only one redox couple will be observed a t all cation concentrations and the redox potential will shift anodically as the cation concentration increases. There appears to be no straightforward method to deal with cases in which 1 < Ks < lo4. In this region, the voltammetric behavior is intermediate and neither eq 1 nor 2 fully applies. Fitting the experimental cyclic voltammograms to simulated results could be a valid methodology to treat those cases and determine the binding enhancements. Thus far, among all of the crown ether systems examined, only the lariat ethers show clear, two-wave behavior that can be interpreted as the direct observation for both the bound and the unbound systems. Registry No. 1, 88548-59-8; I-, 102586-74-3; 1 Na’, 10804348-7; 1 Na, 115603-75-3; 2, 87453-20-1; 2-, 107996-01-0; 2 Na+, 115603-74-2; 2 Na, 87453-19-8; Na, 7440-23-5; C , 7440-44-0.
LITERATURE CITED (1) Kaifer, A.; Echegoyen, L.; Gustowski, D.; Goli, D.; Gokel, G. J . Am. Chem. SOC. 1983, 105, 7168.
Gustowski, D. A.; Echegoyen, L.; Goli, 0.M.; Kaifer, A,; Schultz, R. A,; Gokel, G. W. J . Am. Chem. SOC. 1984, 106, 1633. Morgan, C. R.; Gustowski, D. A.; Cleary, T. P.; Echegoyen, L.; Gokel, G. W. J . Org. Chem. 1984, 4 9 , 5008. Gustowski, D. A.; Gaeo, V. J.; Kaifer, A.; Echegoyen. L.; Godt, R . E.; Gokel, G. W. J. Chem. Soc.. Chem. Commun. 1984, 923. Delgado, M.; Echegoyen, L.; Gatto, V. J.; Gustowski, D. A.; Gokel, G. W. J . Am. Chem. SOC. 1986, 108, 4135. Maruyama, K.; Sohmiya, H.; Tsukube, H. Tetrahedron Lett. 1985, 26, 3583. Saji, T. Chem. Leff. 198S2275-276. Kaifer, A.; Gustowski, D. A.; Echegoyen, L.; Gatto, V. J.; Schultz, R. A.: Cleary, T. P.; Morgan, C. R.; Goli, D. M.; Rios, A. M.; Gokel, G. W. J . Am. Chem. SOC. 1985, 107, 1958. Wolf, R. E.; Cooper, S. R. J . Am. Chem. SOC. I964. 106, 4646. Feldberg, S.W. In Electroana&tical Chemistry; Bard, A. J., Ed.; Marcel Dekker: New York, 1969; Vol. 3. Feldberg, S. W. Computers in Chemlstty and Instrumentation; Mattson, J. s., Mark, H. B., Jr., MacDonald, H. C., Jr.. Eds.; Marcel Dekker: New York, 1972; Vol. 2, Chapter 7. Evans, D. H.; Xie, N. J . Electroanal. Chem. Interfacial Electrochem. 1982, 136, 139. Gustowski. D. A.; Gatto, V. J.; Mallen, J.; Echegoyen, L.; Gokel, G. W. J . Org. Chem. 1987, 52, 5172-5176. Nagaoka, T.; Okazaki, S.;Fujinaga, T. Bull. Chem. SOC.Jpn. 1982, 5 5 , 1967. Nagaoka, T.; Okazaki, S.; Fujinaga, T. J. Electroanal. Chem. 1982, 133, 89. Kalinowski, A . K.; TenderendaGuminska J . Electroanal. Chem. 1974, 55, 277. Peover. M. E.; Davies, J. D. J . Electroanal. Chem. 1983, 6 , 46. Galus, 2 . Fundamentals of ElectrochemicalAnalysis ; Ellis Horwood: London, 1976; Chapter 14.
RECEIVED for review November 24,1987. Accepted May 23, 1988.
Voltammetric and Liquid Chromatographic Identification of Organic Products of Microwave-Assisted Wet Ashing of Biological Samples Kenneth W. P r a t t , * H. M. Kingston, William A. MacCrehan, a n d William F. Koch
Center for Analytical Chemistry, National Bureau of Standards, Gaithersburg, Maryland 20899
Residual organic species in nitric acid digests of freeze-dried bovine liver (NBS SRM 1577a) have been Identifled by use of voltammetry, liquid chromatography, spectrophotometry, and classical chemical tests. Data from these techniques show that malor products of microwave-assisted dissolution by nitric acld Include 0-, m-, and pnitrobenroic adds (NBA). I n addition to these compounds, other organic species present in these digests irreversibly complex copper, but not zinc, and result in low values for copper by polarography. The NBAs and these other organlc specles are all ellmlnated by refluxlng the nltrlc acld dlgest In perchlorlc acid at atmospheric pressure. Poiarographlc results obtained for copper following treatment wlth perchloric acld agree with the certifled value. The use of voltammetry In the evaluatlon of wet ashing procedures is dlscussed.
Two important factors in the evaluation of sample dissolution procedures are the time required and,the completeness of decomposition of the original sample matrix. For biological samples, microwave-assisted dissolutions in sealed pressure
vessels achieve dissolution in less than 10 min with nitric acid. Microwave dissolution of human urine in HNOB( I ) was shown to result in a 105-foldreduction in the concentration of amino acids. However, this experimental result does not indicate that the original organic sample matrix was totally converted to COz,HzO, and N2 The authors noted that the nitric acid digests contain “incomplete digestion products” along with the inorganic species of interest. Although organic decomposition products do not interfere with many instrumental techniques for trace elemental analysis, voltammetry is sensitive to interference from chelating and electroactive organic components coexisting in samples during analysis. These organic species may bias the results, making examination of their origin and mechanism of formation extremely important. Previous workers (2-5), using thermal nitric acid dissolutions of biological material a t elevated temperature and pressure, have noted that the decomposition is not complete and produces “interfering organic compounds” (2), “undefined artifacts” (3),or “organic nitro compounds” (4) that result in unwanted signals and/or errors in trace-level voltammetric determinations. Samples with high protein content are more difficult to decompose completely than other biological sam-
This article not subject to US. Copyright. Published 1988 by the American Chemical Society
