Anal. Chem. 1999, 71, 5493-5500
Investigation of Alkali Metal Cation Selectivities of Lariat Ethers by Electrospray Ionization Mass Spectrometry Esther C. Kempen and Jennifer S. Brodbelt*
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, Texas 78712 Richard A. Bartsch, Youngchan Jang, and Jong Seung Kim
Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061
The alkali metal ion selectivities of several dibenzo-16crown-5 lariat ethers are investigated by electrospray ionization mass spectrometry (ESIMS). Specifically, the mass spectral peak intensities of lariat ether/alkali metal cation complexes obtained by electrospray ionization of solutions containing each lariat ether with lithium, sodium, and potassium salts are compared. The relative intensities of peaks for the lariat ether/alkali metal cation complexes indicate the metal-ion selectivities of the lariat ethers. A series of dibenzo-16-crown-5 lariat ethers containing methoxy, carboxylic acid, ester, or amide pendant groups is studied in this fashion. A majority of these lariat ethers studied are found to be selective for Na+ vs either Li+ or K+ in methanolic solution. The selectivities obtained by the electrospray mass spectrometric method are compared with reported selectivities obtained by potentiometric methods with solvent polymeric membrane electrodes. The advent of electrospray ionization (ESI) has opened new doors in the study of noncovalent complexes by mass spectrometry.1 While several studies have identified the presence of noncovalent complexes in the gas phase, more recent investigations have begun to use electrospray ionization mass spectrometry (ESIMS) for the measurement of binding affinities and selectivities. In one recent study, ESIMS was used to measure directly the relative alkali metal cation affinities of 18-crown-6 and 2.2.2cryptand by observing the peak intensities of the relevant complexes in the mass spectra.2 A similar strategy was employed for two pyridyl-containing supramolecular complexes ionized by * Corresponding author: (phone) 512-471-0028; (fax) 512-471-8696; (e-mail)
[email protected]. (1) Hopfgartner, G.; Piguet, C.; Henion, J. D.; Williams, A. F. Helv. Chim. Acta 1993, 76, 1759. Hu, P.; Ye, Q. Z.; Loo, J. A. Anal. Chem. 1994, 66, 41904194. Loo, J. A.; Holsworth, D. D.; Root-Bernstein, R. S. Biol. Mass Spectrom. 1994, 23, 6-12. Guevremont, R.; Siu, K. W. M.; Le Blanc, J. C. Y.; Berman, S. S. J. Am. Soc. Mass Spectrom. 1992, 3, 216-224. Orgozalek Loo, R. R.; Smith, R. D. J. Am. Soc. Mass Spectrom. 1994, 5, 207-220. Cheng, Z. L.; Siu, K. W. M.; Guevremont, R.; Berman, S. S. J. Am. Soc. Mass Spectrom. 1992, 3, 281-288. Lim, H. K.; Hsieh, Y. L.; Ganem, B.; Henion, J. J. Mass Spectrom. 1995, 30, 708-714. (2) Leize, E.; Jaffrezic, A.; Van Dorsselaer, A. J. Mass Spectrom. 1996, 31, 537544. 10.1021/ac990236p CCC: $18.00 Published on Web 11/05/1999
© 1999 American Chemical Society
electrospray to create doubly and triply charged ions. In these experiments, the relative proportions of these multiply charged ions in the mass spectra correlated well with predictions derived from UV spectrophotometric titration data.3 Ramanathan and Prokai used ESIMS to investigate the selective encapsulation of amino acids by cyclodextrins. Their experiments showed that the affinities of β- and γ-cyclodextrins for protonated amino acids are larger than that of R-cyclodextrin. The calculated binding energies for these complexes were within the error of the computational (MM/MD) method used to study these systems initially, and the ESIMS method offered a more promising means to estimate the stabilities of the complexes.4 Studies involving crown ethers have permitted detailed comparison of metal complexation by ESIMS vs that by conventional methods. Correlation between the predicted concentrations calculated using stability constants for complexation of Na+ and K+ by 18-crown-6 in methanol determined potentiometrically and by ESIMS peak intensities was observed by Gokel and co-workers, who also studied the complexation of two- and three-ring macrocycles with alkali-metal ions by ESIMS.5 A more in-depth investigation of the complexation of 12-crown-4, 15-crown-5, and 18crown-6 with various alkali metals and ammonium ions was performed recently in our laboratories. This study showed that ESIMS peak ratios for different complexes in multicomponent solutions correlate well with the distribution of complexes predicted using reported stability constants, when the complexes have similar solvation energies.6 This previous study validated the ESIMS method for measurement of binding selectivities of host ligands. In the present report, ESIMS is used to determine alkali metal ion selectivities for more elaborate hosts, a series of lariat ethers. Lariat ethers are crown ether compounds with one or more side arms with potential metal-ion ligating sites attached to the macrocyclic ring. There are two types of sidearms incorporated in the present group of lariat ethers. The first type includes Lewis (3) Leize, E.; Van Dorsselaer, A.; Kra¨mer, R.; Lehn, J. M. J. Chem. Soc., Chem. Commun. 1993, 990. (4) Ramanathan, R.; Prokai, L. J. Am. Soc. Mass Spectrom. 1995, 6, 866-871. (5) Wang, K.; Gokel, G. W. J. Org. Chem. 1996, 61, 4693-4697. (6) Blair, S.; Kempen, E. C.; Brodbelt, J. S. J. Am. Soc. Mass Spectrom. 1998, 9, 1049-1059.
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basic substituents that enhance binding to a guest cation by acting as a binding site outside the ring. The second type of side arms includes alkyl substituents which enhance selective complexation by enforcing a more optimal binding conformation of the ring. In many cases, both types of side arms are incorporated in the molecule to enhance the selectivities for certain ions. Alkali-metal complexation of dibenzo-18-crown-6 lariat ether compounds have been studied previously by FABMS7 and ESIMS.8,9 Gokel and coworkers used FABMS to measure the intensities of protonated vs sodium-cationized lariat ethers and noted a general correlation between the binding constants of the lariat ether in methanol and the ratio of the Na+ adducts vs protonated lariat ethers in the mass spectra.7 Liu and co-workers investigated the selectivities of sym-(hydroxy)dibenzo-16-crown-5 and sym-(benzyloxy)dibenzo16-crown-5 toward lithium, sodium, and potassium chloride salts in methanol solutions. Both of these lariat ethers were found to be selective for Li+ over Na+ and K+, in contrast to the greater selectivities for Na+ reported in aqueous solution.11 These authors then determined the stability constants of seven dibenzo-16crown-5 lariat ether complexes with Li+, Na+, and K+ in methanol. Their method involved comparison of the intensity of the lariat ether complex of interest with the intensity of a dibenzo-18-crown-6 complex as an internal standard. In these systems, the lariat ethers were observed to favor complexation with Li+ over Na+ and K+.9 The strengths of the binding interactions were directly proportional to the intensities of the signals observed. For the present study, the lariat ethers are derivatives of dibenzo-16-crown-5 (Figure 1). Gas-phase ion-molecule reactions for this set of compounds were investigated previously in our laboratories as a strategy for identifying the participation of side arms in cation binding by the lariat ethers.10 However, the most in-depth studies of these compounds have involved their incorporation into the solvent polymeric membranes of ion-selective electrodes. With these electrodes, potentiometric selectivities of the lariat ethers for Na+ relative to K+ or Li+ were determined by the fixed-interference method.11 In the present study, alkali-metal cation selectivities exhibited by these solvent polymeric membrane electrodes are compared with those determined by electrospray ionization mass spectrometry. The ESIMS method is shown to be an efficient and versatile method for evaluating the metal-ion selectivities of lariat ethers in solution. EXPERIMENTAL SECTION All electrospray experiments were performed on a Finnigan ion-trap mass spectrometer operated in the mass selective instability mode with modified electronics to allow axial modulation. The (7) Takahashi, T.; Uchiyama, A.; Yamada, K.; Lynn, B. C.; Gokel, G. W. Tetrahedron Lett. 1992, 33, 3825-3828. (8) Young, D. S.; Hung, H. Y.; Liu, L. K. Rapid Commun. Mass Spectrom. 1997, 11, 769-773. (9) Young, D. S.; Hung, H. Y.; Liu, L. K. J. Mass Spectrom. 1997, 32, 432-437. (10) Liou, C. C.; Isbell, J.; Wu, H. F.; Brodbelt, J. S.; Bartsch, R. A.; Lee, J. C.; Hallman, J. L. J. Mass Spectrom. 1995, 30, 572-580. (11) (a) Ohki, A.; Lu, J. P.; Bartsch, R. A. Anal. Chem. 1994, 66, 651-654. (b) Ohki, A.; Lu, J. P.; Huang, X. Bartsch, R. A. Anal. Chem. 1994, 66, 43324336. (12) Van Berkel, G. J.; Glish, G. L.; McLuckey, S. A. Anal. Chem. 1990, 62, 1284-1289. (13) Smetana, A. J.; Popov, A. J. J. Chem. Thermodyn. 1979, 11, 1145-1149. (14) Izatt, R. M.; Pawlak, K.; Bradshaw, J. S.; Bruening, R. L. Chem. Rev. 1991, 91, 1721-2085. Log K values from this reference were also used to calculate the ∆ logK values in Table 4.
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Figure 1. Dibenzo-16-crown-5 lariat ethers.
electrospray interface was based on a design developed at Oak Ridge National Laboratory.12 A Harvard syringe pump system was set to deliver the solution at 1.5-3 µL/min. The lariat ether solutions contained a 1:1:1:1 ratio of Li+, Na+, K+, and the lariat ether of interest (1.5 × 10-4 M in each) in chloroform-methanol (1:19). Very large excesses of salts vs host were not used because high ionic strengths have been shown to decrease formation constants in solution.13 The presence of chloroform in the solvent was necessary to solubilize the lariat ethers. Representative lariat ethers were sprayed with only one metal ion or a pair of ions per solution to ensure that no signal suppression occurred for reasons other than binding. Needle voltages for the lariat ether solutions were 3-3.5 kV. Extraction of alkali metals from aqueous solution by the lariat ethers was performed by stirring 2.0 mL of 0.050 M lariat ether solution with 2.0 mL of a solution 0.25 M in each alkali-metal chloride (LiCl, NaCl, and KCl) in deionized water for 30 min. The organic layer was removed and diluted to 10 mL with chloroform. The resulting solution was again diluted 100 times with chloroform, and the resultant solution was sprayed at a flow of 5 µL/ min at 3.75 kV. Calculations to estimate the expected selectivities for different stability constants were performed using Mathcad Plus 6.0 by Mathsoft Applications. Molecular mechanics conformational searches were performed using MMFF (Merck) force fields. These calculations were followed by ab initio Hartree-Fock STO-3G calculations that were performed on the three lowest energy conformations yielded from the conformational search. RESULTS AND DISCUSSION Overview of Structures of Lariat Ether Complexes: Computational Results. To more fully evaluate the effect of conformation on the binding of alkali-metal ions with the dibenzo-16crown-5 derivatives studied, MMFF (Merck) molecular mechanics (15) Burgess, J. Metal Ions in Solution; Wiley: New York, 1978; p 186.
Figure 3. Lowest energy conformation of (dibenzo-16-crown-5 + Li)+. Letters label the angles between the nearest oxygen atoms and their adjoining carbons. Figure 2. Lowest energy conformations of dibenzo-16-crown-5 complexes with sodium and potassium ions, nesting vs perching. (a) Nesting complex (dibenzo-16 crown-5 + Na)+. (b) Perching complex (dibenzo-16-crown-5 + K)+.
conformational searches followed by Hartree-Fock STO-3G singlepoint ab initio calculations were performed on complexes of 1, 2, 3, 5, 7, and 11 with Li+ and Na+. Calculations for (dibenzo-16crown-5 + K)+ were also performed. The lowest energy conformations for the Li+ and Na+ complexes of the lariat ethers indicate that the metal ion interacts with all of the dipoles associated with the oxygen atoms in the macrocyclic ring and both the ether oxygen and the carbonyl oxygen atoms of the lariat functionality. Computational results confirm that only Li+ and Na+ are small enough to form inclusion complexes. The calculated structures show that the potassium cation “perches” above the binding cavity, thus presenting a significantly larger surface that would be much more susceptible to the influence of exterior solvent molecules. Therefore, “nesting” complexes are produced for both Li+ and Na+, whereas less stable “perching” complexes are formed between the lariat ether and K+ (see Figure 2). The Li+ nesting complex with dibenzo-16-crown-5 has two bond angles in the rings (see A and C in Figure 3) which are distorted (from acid > ester, specifically the distances between the carbonyl oxygen and ring oxygens 5 and 6 (see Figure 5). The distance between atoms 2 and 6 increases from 3.084 Å for the ester to 3.814 Å for the acid and 3.776 Å for the amide. This trend is likely due both to steric interaction of the ester functionality with the aromatic ring and to the degree of overlap between the dipole of the carbonyl and the dipoles of ring oxygens 5 and 6. The electron density of the dipole of the carbonyl oxygen decreases with the basicity of the functionality: amide > acid > ester. This decrease of electron density in the carbonyl oxygen dipole decreases the degree of electrostatic repulsion between oxygens 2 and 5 and between 2 and 6. Although these distances do not exactly follow the trend in the electron densities, the lariat containing the ester functionality clearly has a significantly smaller cavity size compared with those of the lariats containing either the acid or amide functionalities. Although the lowest energy structures of the complexes of 7, 5, and 11 with Na+ are not discussed here for the sake of brevity, results for these complexes reflect similar trends as those described for the Li+ complexes. Previous Work. Bartsch and co-workers previously determined the selectivities of lariat ethers 1-7 and two N,N-diethyl sym-(R)dibenzo-16-crown-5-oxyacetamides by incorporating each lariat ether into a PVC membrane.11a In that work, the potentiometric selectivities for Na+ relative to K+ or Li+ for the ion-selective Analytical Chemistry, Vol. 71, No. 24, December 15, 1999
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Figure 5. Lowest energy structures of (lariat ether 7 + Li)+ and (lariat ether 5 + Li)+. Table 1. Potentiometric Selectivities of Lariat Ethers lariat ether
R1
R2
log KNa,Kpot
log KNa,Lipot
1 2 3 4 5 6 7
H H C3H7 H C3H7 H C3H7 H C3H7
H OCH3 OCH3 OCH2CO2H OCH2CO2H OCH2CO2Et OCH2CO2Et OCH2CONEt2 OCH2CONEt2
+0.42 +0.07 ( 0.03 -0.34 ( 0.03 -0.65 ( 0.03 -1.74 ( 0.03 -0.45 ( 0.04 -1.49 ( 0.02 -0.79 ( 0.03 -1.98 ( 0.02
-2.48 -3.08 ( 0.07 -2.99 ( 0.02 -3.46 ( 0.01 -3.52 ( 0.05 -3.87 ( 0.04 -3.73 ( 0.03 -3.02 ( 0.06 -2.84 ( 0.01
a
From ref 11(a).
electrode prepared from each membrane were determined in aqueous solution using the fixed interference method.11 These selectivities are listed in Table 1 as log KNa,K or log KNa,Li values in which a positive value indicates a preference for the second metal, whereas a negative value shows a preference for Na+. Most of the solvent polymeric membrane electrodes (SPMEs) showed greater response to Na+ than K+. Compounds with OCH2CO2H, OCH2CO2Et, and OCH2CON(Et)2 side arms gave the most negative values for log KNa,Kpot. The Na+/K+ selectivity increased as the functionality of the side arm was varied: ester < carboxylic acid < amide. This trend parallels the oxygen basicity of the carbonyl group in the side arm. The presence of a geminal propyl group side arm in the lariat ether significantly enhanced the Na+/ K+ selectivity, presumably because the propyl group reinforced an optimal binding conformation for the macrocycle. 5496
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All of the dibenzo-16-crown-5 derivatives studied showed high Na+/Li+ selectivities. For the lariat ether carboxylic acid derivatives, the selectivity increased as a function of the sidearm unit, amide < carboxylic acid < ester, an opposite ordering from the Na+/K+ selectivities. However, the presence of a geminal propyl side arm in the lariat ether had little influence on the Na+/Li+ selectivity. Validation of ESIMS Method. The alkali metal selectivities of the lariat ethers were assessed by the ESIMS method described in detail and validated previously.6 To ensure that this method was indeed feasible for compounds such as the lariat ethers studied here, dibenzo-18-crown-6 was used as a model compound to investigate the validity of the approximation that the peak intensities of alkali-metal complexes reflect the equilibrium distribution in solution for these types of compounds. Literature values for the binding constants of Na+ and K+ with dibenzo-18crown-6 in methanolic solution are available,14 and dibenzo-18crown-6 bears a strong resemblance to the lariat ethers studied here. Figures 6A and 6B show the ESI mass spectra obtained for solutions of dibenzo-18-crown-6 with KCl or NaCl (each component at 1.5 × 10-4 M), respectively). The theoretical concentration of the (dibenzo-18-crown-6 + K+) complex at equilibrium is 1.2 × 10-4 M, on the basis of the reported stability constant of log K ) 5.0.14 The integrated peak area for the (dibenzo-18-crown-6 + K+) complex is 487 units (Figure 6A). The theoretical concentration of the (dibenzo-18-crown-6 + Na+) complex at equilibrium is 7.8 × 10-5 M, on the basis of the reported stability constant of log K ) 4.18.14 The integrated peak area for the (dibenzo-18-crown-6 +
Figure 7. ESIMS spectrum of lariat ether 2 with LiOH, NaOH, KOH in chloroform-methanol (1:19) solution.
Figure 6. ESIMS Spectra of (A) dibenzo-18-crown-6 with KCl, (B) dibenzo-18-crown-6 with NaCl, and (C) dibenzo-18-crown-6 with KCl and NaCl in methanol.
Na+) complex is 358 units (Figure 6B). The intensities of each of these complexes scale with the calculated equilibrium concentrations, revealing that ESI mass spectral intensities reflect the solution concentrations and that the spray efficiencies for these two complexes are virtually identical. The latter point is especially important because it means that a rigorous procedure to correct for unequal ESI efficiencies of the Na+ vs K+ complexes is unnecessary. This latter result led us to neglect any correction procedure for the mass-spectral intensities of the alkali-metal complexes of the structurally similar lariat ethers. Figure 6C shows the mass spectrum of a 1:1:1 mixture of dibenzo-18-crown-6 with sodium chloride and potassium chloride in methanol (all components at 1.5 × 10-4 M). The theoretical ratio of the [dibenzo-18crown-6 + K]+/[dibenzo-18-crown-6 + Na]+ concentrations at equilibrium is 2.3, on the basis of solution of the two simultaneous equilibrium equations for complexation of Na+ and K+ (and using the reported stability constants from ref 14). The average ratio of peak intensities observed from the ESI mass spectrum for this solution was 3.0 for (dibenzo-18-crown-6 + K+)/(dibenzo-18crown-6 + Na+), which is in reasonable agreement with the theoretical ratio and is within our expected experimental error. This series of experiments verified that the ESIMS procedure was successful for estimation of the binding selectivity of dibenzo-18crown-6 and confirmed that extensive correction procedures to account for variations in spray efficiencies were unnecessary for these complexes. All experiments using lariat ethers were performed in a manner consistent with the last dibenzo-18-crown-6 experiment. Present Work. A chloroform-methanol (1:19) solution was found to be suitable for the first phase of the investigation. This mixed solvent provided solubilization of the lariat ether while maintaining a polar environment. Initial experiments showed that lariat ether/metal-ion complexes could be observed with minimal
manipulation of the spray conditions. To evaluate selectivities, a solution containing one lariat ether and from one to three alkalimetal salts was sprayed, and the intensities of the resulting peaks for the various lariat ether/alkali-metal ion complexes were integrated. Comparisons of the spectra obtained for solutions containing only one, then two or three different alkali metals provided evidence that severe suppression or discrimination effects were not operative. Thus, solutions containing all three alkali-metal ions and one lariat ether could be analyzed directly to estimate the cation selectivities. A representative ESI mass spectrum is shown in Figure 7 for lariat ether 2. The entire set of results is summarized in Table 2. The results in Table 2, although measured on the basis of intensities of gas-phase ions, actually reflect the equilibrium distribution of the complexes in the chloroform-methanol (1:19) solution and thus should not be viewed as gas-phase selectivities. As described in the next paragraphs, three factors contribute to the observed alkali metal ion selectivities of the lariat ethers: the overall cavity sizes of the lariat ethers as influenced by the side arms and their interactions with the phenyl groups, solvent effects that influence formation of perching vs nesting complexes, and the basicities of the side arms which affect the abilities of each lariat ether to extract metal ions from the solution. The interplay of these three factors also promotes the differences in selectivities observed for the SPME vs ESIMS experiments. Lariat ethers 1-3 show the lowest overall selectivity. All three types of alkali metal complexes are observed in the ESI mass spectra, unlike the results for most of the other lariat ethers. Lariat ether 1 shows a preference for Na+ over K+, whereas lariat ethers 2 and 3 exhibit nearly identical behaviors with selectivity for K+ over Na+. Complexation of Li+ is unfavorable for all three lariat ethers 1-3. Interestingly, Liu and co-workers found that a series of sym-dibenzo-16-crown-5 ethers showed selectivity for Li+ over Na+ and K+ in methanol by ESIMS,8,9 in direct contrast to the selectivity trends found for the set of structurally similar lariat ethers in the present work. The discrepancy in the results likely stems from the different procedures used to estimate the selectivities and different extents of discrimination of ions transported through the ESI interface. Since the lariat ethers used in the present study are different from the ones employed in the Liu study, a more detailed comparison is not possible. However, since our results for alkali-metal complexes with dibenzo-18-crown-6 and other hosts correlate very well with theoretical results calculated using literature binding constants derived by other more accepted methods,14,15 we are confident that our results reflect equilibrium distributions of these complexes in solution. Moreover, we can offer no logical reason the lariat ethers should show a dramatic preference for Li+ over Na+ in methanol, as reported by Liu. For Analytical Chemistry, Vol. 71, No. 24, December 15, 1999
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Table 2. Alkali-Metal Selectivities of Lariat Ethers Measured by Electrospray in Chloroform-Methanol (1:19) Solutionsa
a
lariat ether (LE)
R1
R2
% [LE + Li]+
% [LE + Na]+
% [LE + K]+
Na+/K+
1 2 3 4 5 6 7 8 9 10 11
H H C3H7 H C3H7 H C3H7 H C3H7 H C3H7
H OMe OMe OCH2COOH OCH2COOH OCH2COOEt OCH2COOEt OCH2CONMe2 OCH2CONMe2 OCH2CONH2 OCH2CONH2
7 4 5 0 0 60 77 0 0 0 0
54 40 37 79 87 40 22 60 84 73 80
39 56 58 22 13 0 1 40 16 26 20
1.4 0.7 0.6 3.6 6.7 ∞ 22 1.5 5.3 2.8 4.0
The standard deviation is (7% of the listed number.
example, dibenzo-18-crown-6 binds K+ most strongly in methanol and water, as demonstrated from several previous studies using conventional methods, and it never shows a preference for Li+. One possible explanation for Liu’s result is that their experiments may actually reflect the gas-phase selectivities of the lariat ethers, in which case the Li+ ion would be most strongly bound because it is the most charge dense cation. Comparison of the selectivities of 1-3 obtained for the ESIMS experiments relative to the selectivities reported in the SPME experiments shows some differences. The changes in the ESIMS vs SPME results are due to solvent effects that change not only the absolute solvation energies of the metals but also the relative differences in solvation energies of the metals in water vs methanol. Also important is the ability of the lariat ether side arm to efficiently extract the alkali-metal ions from the aqueous phase into the organic phase in the SPME experiments. For example, SPME containing 1 showed very modest selectivity for K+ vs Na+,11a but the ESIMS results show the opposite preference. We speculate that lack of a polar side arm prevents compound 1 from efficiently extracting the more highly solvated Na+ from aqueous solution in the SPME system. This extraction process is not an active component of binding in the ESIMS system because both the metal ions and lariat ethers are surrounded by methanol, a weaker solvating agent than water for the metal ions. Thus, the selectivity of compound 1 for Na+ over K+ in the ESIMS experiments presumably reflects the optimal fit of the cavity size rather than desolvation effects. In the ESIMS experiments, lariat ethers 2 and 3 have equivalent cation selectivities (within experimental error), following the preference K+ > Na+ . Li+. These results differ from the SPME results in which lariat 2 showed nearly equal selectivity for K+ and Na+ over Li+ and in which lariat 3 showed the preference Na+ > K+ > Li+. The computational results summarized earlier indicate that the addition of a methoxy group increases the size of the binding pocket of the lariat ethers, so a selectivity for the larger K+ over Na+ for 2 and 3 is not surprising in certain solvent environments, such as methanol. In the SPME experiments, the methoxy group plays a large role in assisting the extraction of Na+ from the aqueous solution and in stabilizing the smaller Na+ ion within the cavity. The nesting-type complexes are clearly the preferred ones in the PVC membrane due to absence of other stabilizing solvent interactions. Only the smaller Na+ can engage in these more favorable nesting-type complexes, 5498
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thus explaining the selectivity of the lariat ethers 2 and 3 (relative to 1) for Na+ in the SPME experiments. In methanol, the outer shell of K+ can remain solvated by methanol molecules when bound to the lariat ether in a perching mode, and thus lariat ethers 2 and 3 prefer K+ in the ESIMS experiments, as predicted on the basis of the larger binding pocket. For compounds 4-11 in the ESIMS study, complexation of Na+ is favored over that of K+, just like the SPME results. The potentiometric Na+/K+ selectivities for the pendent groups of ionophores follow the trend of Lewis basicity, decreasing in the order dialkylamide > carboxylic acid > ester.11a On the other hand, the order of decreasing Na+/K+ selectivity occurs in the order ester > carboxylic acid > amide > dialkylamide for the ESIMS results. We speculate that this opposite order of relative selectivity again stems from the difference in solvent environments that changes the dominant factors that influence selectivity. For potentiometric selectivities, the lariat ether must extract and desolvate the metal ion from an aqueous environment, and thus, the Lewis basicity of the pendant group plays a dominant role in this process. In the methanol environment of the ESIMS experiments, the trend in relative selectivity better reflects basicities of the lariats, rather than desolvation effects, with the amide and acid having the larger cavities that are more adaptable for encapsulation of either Na+ or K+ and the ester having the smallest cavity that is best suited for Na+ over K+. One other striking contrast between the previous SPME results and the present ESIMS results involves the unusual Li+ selectivity for the two esters, 6 and 7, observed in Table 2. Only in the ESIMS experiments do these two lariat ethers show a strong preference for complexation of Li+. The ab initio calculations summarized earlier indicate that the higher electron density of the carbonyl oxygen promotes greater electrostatic replusion with two of the ring oxygen atoms, causing expansion of the overall cavity size. The less basic carbonyl oxygens (i.e., ester < acid < amide) have lower electron density, and therefore, the degree of electrostatic replusion and corresponding cavity size increases from the ester to the acid and the amide. The lariat ethers 6 and 7 have significantly smaller calculated cavity sizes (Figure 5), and thus demonstrate the ability to favorably bind Li+. In the SPME experiments, Li+ has the greatest solvation energy and causes the highest energy penalty during extraction from the aqueous environment, thereby suppressing Li+ selectivity by any of the lariat ethers.
Table 3. Comparison of ∆KK,Na Values Obtained by Solvent-Extraction UV Techniques vs Ion-Selective-Electrode Techniques host
∆KK,Na solvent extractiona
∆KK,Na ISEb
18-Crown-6 benzo-18-crown-6 dibenzo-18-crown-6
>4.89 1.55 2.35
1.79 0.52 0.82
a Experiments were performed by use of host molecules in CDCl 3 to extract cations from aqueous solution (picrate anion was used in all b cases). Experiments were performed in methanol by monitoring the amount of free cation in solution during titration with host molecules by use of an ion-selective electrode (chloride anion was used in all cases).
The presence of a propyl group in lariat ethers 5, 9, and 11 enhances their Na+/K+ selectivities as determined by ESIMS compared with those of compounds 4, 8, and 10, respectively, which do not have an alkyl group geminal to the functional side arm. This trend is consistent with the SPME results in which incorporation of a geminal propyl group enhanced the Na+/K+ selectivities for lariat ether carboxylic acids, esters, and dialkyl amides. In the results obtained by ESIMS for the lariat ether esters 6 and 7, the percentage of the K+ complex is too small for an accurate assessment of the effect of a geminal propyl group on the Na+/K+ selectivities. It is relevant to compare not only the order of selectivities for the lariat ethers as measured by the SPME method in aqueous solution vs the ESIMS method in chloroform-methanol (1:19), as described above but also the relative range of selectivities. As shown in Table 1, the potentiometric selectivity, KNa,Kpot, varies from 0.3 (slightly greater selectivity for K+) to ∼100 (highly selective for Na+). In contrast, the Na+/K+ ratios given in Table 2 for the ESIMS results in methanolic solution have an average value of 6. The SPME selectivities are generally much greater than the ESIMS selectivities, which emphasizes another important aspect of the solvent environments. When extracting the metal ions from an aqueous solution into an organic membrane, it appears that complete encapsulation of the metal ion is a much more critical factor, thus favoring Na+ complexation in which stable nesting structures can be formed and the metal ion is fully “solvated” within the cavity. In the chloroform-methanol solutions, complexation of Na+ or K+ is less selective because methanol may solvate the nonencapsulated portion of the larger K+ ion that protrudes from the cavity in a perching mode. This solvation effect decreases the importance of complete encapsulation on the stabilization of metal ions and thus reduces the selectivity toward smaller ions vs larger ones. This general trend of the change in range of selectivities with respect to the solvent environment is consistent with solution data obtained by other methods. The difference in literature binding constants of K+ and Na+ (∆logKK,Na) with hosts 18-crown-6, benzo-18-crown-6, and dibenzo-18-crown-6 obtained by both the solvent-extraction UV method (from water into CDCl3) and the ion-selective-electrode (in methanol) method are compared in Table 3.14 The differences in the log K values involving complexation of the two alkali-metal cations when measured by the two-phase extraction method are significantly greater in all cases than the differences in the log K values measured by ion-selective electrodes in a single homogeneous solvent. This result supports the assertion that the solvent
systems in question can indeed cause significant changes in observed selectivities. Another interesting observation involves the reactivity of the lariat ether carboxylic acids 4 and 5 toward the alkali-metal cations studied. Two small peaks (
