4176
J. Phys. Chem. 1984,88, 4176-4180
be obtained by making the parametrization
+
c = -0.4 0.25yrl =0 ( X > 1.6)
(X5 1.6) (42)
We can translate the approximation into “real” coordinates giving
5. Summary Approximate analytic solutions have been obtained for the survival probability for charged pairs in high-permittivity solvents. In the case of water a particularly simple form is obtained in dimensionless coordinates with an absorbing boundary at the origin:
”* y2 erfc
4D‘t
erf
(
coth 11 /XI - 1 (4,.)1/2
)
(44)
This can be converted into a solution for reaction at any boundary X via eq 15 to give
where
S*(R,ro) = coth (rC/2ro)- coth ( r c / 2 R )
4 = -0.49, =0
+
0.5R ( R 5 0.81rcl) ( R > 0.81rcl)
The function defined in this way is compared with numerical solutions in Figure 7 for different reaction distances. The approximation, which effectively contains only one parameter, is in excellent agreement with the numerical solutions for methanol but requires far less computational effort. This solution covers the whole region of high-permittivity solvents from methanol onward, For the case of water, under most conditions the additional drift term in eq 43 is insignificant or zero and under such conditions the approximation reduces to that of eq 37, which we already know to be a good approximation for water.
which is an excellent approximation for water. In solvents such as methanol this formula requires modification which is performed in section 4.4 by incorporating a nonlinear drift on the correct distance scale to obtain eq 40. This is deconvoluted to account for arbitrary reaction distances by analogy and this procedure leads to eq 43, which is applicable to all solvents with relative permittivity greater than that of methanol (32.6), such as hydrazine (52.9), M e 2 S 0 (46.6), formic acid ( 5 8 . 5 ) , acetamide (59 at 8 3 “C), D M F (36.1),and nitrobenzene (34.8). At higher relative permittivities the approximation reduces to eq 45, which is valid for water (78.5),H202(84.2),HF (84),H C N ( 1 1 5 ) , and formamide (109). In a subsequent paper we will present approximations for low-permittivity solvents, such as a1kanes .
Partitioning Behavior and Prototroplc Interactions of Aminopyridine Isomers in Aerosol OT Inverted Micellar Media Joyce Noroski and L. J. Cline Love* Seton Hall University, Department of Chemistry, South Orange, New Jersey 07079 (Received: November 15, 1983; In Final Form: February 7 , 1984)
The association of the aminopyridines with AOT inverse micelles in cyclohexane involves partitioning equilibria greatly influenced by apparent pH. There is no evidence for precritical micelle concentration solute-surfactant monqmer association. Distribution ratios into the bulk cyclohexane of the micellar solution were found to be smaller than those for a conyentional cyclohexane-water phase extraction of the solutes. The smaller values of distribution ratios are attributed to the lower, pH of the micellar water pool interfacial region as compared to ordinary bulk water. The aminopyridines appear to be protonated upon solubilization into the micellar assembly (presumably into the core region), even at very low water content (approximately 0.5%).
Introduction Inverted micelles*aggregate in apolar solvents where the aliphatic tails of the surfactant monomers extend into the bulk solvent, and the polar head groups and counterions reside in an aqueous core where thby are hydrated by water The properties of aerosol OT (AOT) (sodium bis(2-ethylhexy1)sulfosuccinate) inverted micelles have been investigated by a variety of techniques such as light ~cattering,~ fluorescence probes: fluorescence p~larization,~ NMR, and electron capturee6 These
studies indicate that the water core’s properties change as a function of water content. At low,water concentration, the water molecules are filling the hydration sphere of the sodium counterion so that solubilized probes encounter a more viscous, less polar environment than ordinary bulk ~ a t e r . At ~ , higher ~ water concentration there are more free water molecules available so that the microenvironment is more polar and less viscous and resembles ordinary bulk water in its properties. Rate enhancements for hydrolysis reactions7,*and pK, increases for solubilized acidsgJO
(1) Eicke, H. F. Top. Curr. Chem. 1980,87, 86-144. (2) Wong, M.; Thomas, J. K.; Nowak, T. J . Am. Chem. SOC.1977, 99, 4730-5. (3) Day, R.A.; Robinson, B. H.; Clarke, J. H. R.;Doherty, J. V. J. Chem. SOC.1979, 75, 132-4. (4) Wong, M.; Thomas, J. K.; Gratzel, M. J. Am. Chem. SOC.1976, 98, 2391-7.
(5) Keh, E.; Valeur, B. J. Colloid Interface Sci. 1981, 79,465-77. (6) Calvo-Perez, V.; Beddard, G. S.; Fendler, J. H. J. Phys. Chem. 1981, 85, 2316-9. (7) El Seoud, 0. A.; daSilva, M. J. J. Chem. SOC., Perkin Trans. 2 1980, 127-31. (8) El Seoud, 0. A.; daSilva, M. J.; Barbur, L. P. J. Chem. SOC..Perkin Trans. 2 1978, 331-5.
0022-3654/84/2088-4176$01 S O / O
0 1984 American Chemical Society
The Journal of Physical Chemistry, Vol. 88, No. 18, 1984 4177
Partitioning Behavior and Prototropic Interactions
TABLE I: Absorbance Wavelength Maxima (Amx) and Molar Absorptivities (6) of an Aminopyridine Series in AOT Micellar Solution, Cyclohexane, Ethanol, and Aqueous Acid Solution" T-T* wavelength maxima and molar absorptivities cyclohexane ethanolb 0.1 M HCl*
AOT L
4-aminopyridine 3-aminopyridine 2-aminopyridine 2-(dimethy1amino)pyridine 4-(dimethy1amino)pyridine
X
262 325
304 3 17 279
c
L n ,
17230 3800 6060 6000 23300
233
292 288 310 25OC
c
7500* 3420* 4250* 31206 1300OC
HzOb
kmm
c
~m,,
t
L 9 r
t
247 302 296 313 d
1600
263
3250 4400 3780
317
17420 3620
262 290
11600 2800 4400 4270
300
6380
296
319 279
6000 18500
315 d
Wavelength b0.5 nm; concentration of solute = 6 X 10-5-1.5 X M; [AOT] = 0.10 M, with an R value of 0.1. Wavelengths in nanometers and molar absorptivities in L/(mol cm). *Values from ref 14 and 17. CValuesfrom: Cumper, C. W. N.; Singleton, A. J . Chem. SOC.B 1968, 649-51. dNot determined. indicate that the water core is dramatically different from bulk water. The similarity of the water core to water clusters found in bioaggregates and the noted increased catalytic efficiency of reactions occurring in the AOT system7,*warrant further investigation into the nature of model drug compound-micelle interactions. The series of aminopyridine isomers possess interesting photophysical properties which can be perturbed by microenvironmental, polarity, and prototropic effects, and are useful probes for examining the nature of bulk apolar solvent-AOT-water core interactions. The transitions which occur upon absorption of radiant energy are a sensitive indicator of the microenvironment, and the series are capable of protonation equilibria to form different absorbing species. They are useful model compounds for several licit and illicit drugs, such as the anthelmintic/antimalarial drug atabrine and the hallucinogenic compound lysergic acid diethylamide, and their interaction with the micellar aggregate can provide insight into drug-bioaggregate interactions. This paper describes the type of association occurring between the aminopyridine solutes and AOT inverted micelles. Such types of nitrogen heterocyclic bases have not been studied in AOT micelles to date. The results indicate that the association involves a partitioning equilibrium of the probe base between the organic bulk solvent and the core water pool, and this equilibrium may be shifted by the steric configuration of the probe. In addition, protonation of the solutes occurs which is independent of the initial pH of the added water, reflecting greatly increased apparent pK,'s of the probes. These effects are not seen at pre-cmc levels, suggesting that solute-monomer binding is not occurring in this system.
Experimental Section Reagents and Procedures. Aerosol O T was obtained from Fisher Scientific Co. (Springfield, N J ) and was purified in the following manner. The surfactant was dissolved in spectroscopic-grade benzene (Fisher Scientific) and shaken with small amounts of distilled deionized water to extract any water-soluble inorganic impurities. After removal of the benzene solvent by evaporation in a vacuum oven held at 50 O C and 30-lb pressure, the AOT was redissolved in spectrograde methanol (Fisher Scientific) and passed through a glass fiber filter paper to remove insoluble materials. The AOT-methanol solution was placed in a vacuum oven at 50 "C for 3 days to minimize its water content. Karl Fischer titrations of AOT samples consistently gave an R value of 0.1, where R is defined as the ratio of water molar concentration to surfactant molar concentration. Stock solutions of AOT-cyclohexane were prepared by weighing out the appropriate amount of surfactant in a container which was immediately closed and then dissolving the AOT in spectroscopic-grade cyclohexane in a nitrogen-purged drybox. All sample preparations were performed thereafter within the drybox because of the hygroscopic nature of AOT. The aminopyridines were obtained from Aldrich Chemical Co., Milwaukee, WI. They were recrystallized twice from either (9) Menger, F. M.; Saito, G. J . Am. Chem. SOC.1978, 100, 4376-9. (10) Smith, R. E.; Luisi, P. L. Helu. Chim. Acta 1980, 63, 2302.
acetone or methanol and oven dried. Stock solutions were prepared by weighing out the desired quantities on a Mettler microbalance (Hightstown, N J ) and dissolving them in cyclohexane. Concentrations were confirmed by absorption spectrophotometry using molar absorptivities from the literature (Table I). Instrumentation. The absorption measurements were carried out in a thermostated cell in a Beckman Acta I11 UV/vis spectrophotometer (temperature = 25.0 C f 1.0 "C). Reference solutions contained the surfactant and cyclohexane solvent at the appropriate concentrations.
Results and Discussion Spectral Features of Aminopyridines. The absorption spectral characteristics of the aminopyridine series have been thoroughly investigated by Testa and ~ ~ - w o r k e r s The ~ ~ ,a-a* ~ ~ -transitions ~~ of the 2- and 3-aminopyridines and of 2-(dimethy1amino)pyridine are the lowest energy transitions observable in their absorption spectra and are sensitive to polarity (red shifts with increasing solvent polarity) and hydrogen bonding (blue shifts with increasing H-bonding ability of the solvent). CNDO studies predict closelying n-a* and a-a* states for 2-aminopyridine such that the larger molar absorptivity of the nvr* transition causes it to overlap with the n-a* transition spectrum, making it indiscernible.l* The 4-(dimethy1amino)pyridine and 4-aminopyridine species exhibit low-energy shoulders on their major spectral peaks that disappear in polar and hydrogen-bonding solvents. These have been attributed to the n-a* t r a n ~ i t i 0 n . l ~ Of particle importance in this study are the protonation equilibria that these species can undergo, and the resultant changes which occur in their absorption spectra. Upon protonation of the pyridinic nitrogen, the a-a* low-energy absorption bands are red shifted and show a general increase in their molar absorptivities (Table I). For the 4-aminopyridine and 4-(dimethylamino)pyridine monocations, the postulated n-r* shoulders are replaced by high-intensity absorption bands. These have large molar absorptivities (17 420 and 18 500 L(mo1 cm), respectively) and are indicative of a charge-transfer contribution, probably overlapping the a-?r* transitions. Form of Solubilized Probe. Addition of AOT surfactant to cyclohexane-aminopyridine solutions results in a gradual loss of the vibrational fine structure present when the solute is dissolved (11) Weisstuch, A.; Testa, A. C. J . Phys. Chem. 1981, 72, 1982-7. (12) Magid, L. J.; Kon-no, K.; Martin, C. A. J . Phys. Chem. 1981, 85,
1434-8. (13) El Seoud, 0. A.; Chinelatto, A. M.; Shimizu, M. R. J . Colloid I n terfacial Sci. 1982, 88, 420-7. (14) Schulman, S. G.; Capomacchia, A. C.; Rietta, M. S. Anal. Chim. Acfa 1971, 56, 91-6. (15) Albert, A. In "Physical Methods in Heterocyclic Chemistry"; Katritzky, A. R., Ed.; Academic Press: New York, 1963; Vol. I. (16) Daisy, J. M.; Sonnessa, A. J. J . Phys. Chem. 1972, 76, 1895-901. (17) Weisstuch, A.; Testa, A. C. J . Phys. Chem. 1970, 74, 2299-303. (18) Testa, A. C. Wild, U. P. J . Phys. Chem. 1981, 85, 2637-9. (19) Babiak, S.; Testa, A. C. J . Phys. Chem. 1976, 80, 1882-5. (20) Sekine, T.; Hasegawa, Y. In "Solvent Extraction Chemistry"; Marcel Dekker: New York, 1977; pp 12-65. (21) Tse, Hing-Cheung; tamres, M. J . Phys. Chem. 1977, 81, 1367-75.
4178 The Journal of Physical Chemistry, Vol. 88, No. 18, 1984
Noroski and Love 0.00
Ei
IE-0.30
P3 I
-4.80
-3.20
-1.60
LOG CAOT3
Figure 3. log-log plot of the absorbance of 4-(dimethy1amino)pyridine at 279 nm vs. AOT surfactant concentration.
Figure 1. Increase in absorbance,red shifting, and loss of fine structure
of 2-aminopyridine's longest wavelength band upon solubilization into the AOT inverted micellar water core. [2-aminopyridine]= 1.1 X lo4 M, [AOT] = 0, 0.0169,0.0508,and 0.0847 M in order of increasing absorbance and red shifting of the spectra; R = 0.1,where R is equal to the water/surfactant molar ratio.
280 WAVELENGTH
340
.
.
400
(NM)
Figure 2. Absorption spectra of 3-aminopyridineat varying surfactant concentrations illustrating increasing red shifting of the entire spectrum and increasing absorbance at 325 nm with increasing surfactant; [3aminopyridine] = 5.5 X M;R = 0.1;[AOT] = 0,0.00847,0.0170, and 0.0254 M.
in organic, noninteracting solvents, and the appearance of redshifted absorption bands. Isosbestic points over various concentration ranges of the surfactant are indicative of equilibria occurring in the solution. These effects are illustrated in Figures 1 and 2. An equilibrium interaction between the AOT and aminopyridine species dissolved in cyclohexane indicates that two forms of the solute are present. Solvent studies (Table I) indicate that the new red-shift absorption bands, which grow in proportionately with increasing AOT concentration, are characteristic of the monocation of each aminopyridine isomer. The wavelength maxima and molar absorptivities of the AOT-solubilized forms of the aminopyridines coincide with the transitions observed in acidified aqueous solution. Apparently, solubilization by the surfactant involves incorporation of these solutes into the water core where conversion from the free base to the protonated species occurs. Ordinary hydrogen bonding, as occurs in ethanol or aqueous solutions, does not produce the same spectral characteristics that are seen for most of the probes dissolved in AOT solution. The pyridinic nitrogens on the aminopyridines have been found to be the most reactive sites for bonding with protons and other
e l e ~ t r o p h i l e s . ~ ~Their - ' ~ * ' pK, ~ values are listed in Table I11 (which will be discussed later), with the 4-(dimethy1amino)pyridinebeing the most basic. The other nitrogen moiety, the amino group, exhibits negative pK, values and can only be protonated under extremely acidic condition^.^^*^^*'^ The spectra indicate that the species solubilized within the AOT micellar water core are exclusively the singly protonated pyridinic nitrogen forms in an aqueous environment. An alternate mechanism of reaction other than direct protonation of the pyridinic nitrogen involves solutemonomer association which would be evident a t solution concentrations less than the critical micelle concentration (cmc). Previous investigators have shown that phenols hydrogen bond to AOT monomers and that this association occurs prior to the cmc.I2 In these studies, the binding constants for the phenol-AOT complexes were determined to be nonvariant both above and below the cmc, indicating extensive monomer participation. The possibility of this type of association for the AOT-aminopyridines was investigated by varying the surfactant concentration above and below the cmc and monitoring the 279-nm absorption wavelength maximum of the solubilized, protonated 4-(dimethy1amino)pyridine. At concentrations below the cmc a gradual increase in the absorbance value was observed. A sharp break in the absorption trend occurs at 5.5 X M AOT at which point the absorbance increases dramatically with further increases in AOT Concentration. This is shown in Figure 3. This point, taken as an approximation of the AOT cmc, is in good aggreement with values ranging from 4 to 9 X lo4 M obtained spectrophotometrically.12 Similar results were obtained by using solubilized 4-aminopyridine. The cause of the gradual increase in the absorption prior to the cmc cannot be attributed solely to hydrogen bonding of the solute with AOT pre-cmc aggregates since the experiments cannot distinguish between microenvironmental polarity changes due to the presence of small aggregates of dimers, trimers, etc., hydrogen bonding involving the small amount of water present, or hydrogen bonding with the pre-cmc aggregates. However, the possibility of appreciable pre-cmc aminopyridine-monomer binding is refuted not only by the fact that there is no site on the monomer for binding of a nucleophilic agent such as 4-(dimethylamino)pyridine, but also by the discontinuity of the AOT concentration-absorbance graph (Figure 3). Further evidence for the absence of appreciable monomer binding is the failure to obtain nonvariant binding constants above and below the cmc by using calculations assuming this type of interaction. Acidity Effects. The effect of pH on the absorbance of 2aminopyridine provides further insight into the nature of the equilibrium occurring with AOT. Maximum solubilization of 2-aminopyridine within the inverted micelle can be assumed to occur when the wavelength maximum reaches 304 nm, the wavelength maximum of the protonated form. This corresponds to the point where the absorbance increases and wavelength shifts as a function of increasing AOT concentration level off, indicating almost complete solubilization of the solute. The 2-aminopyridine species (8.5 X M) was selected as a sensitive monitor of the
Partitioning Behavior and Prototropic Interactions TABLE 11: Effect of Concentration of Water on the Absorption Spectrum of 2-Aminopyridine Solubilized in AOT Micellar Solution" Rb A_.,: nm Ad Rb A_..,c nm Ad 0.1 293 0.312 10.0 294 0.409 2.0 293 0.332 20.0 294 0.421 4.0 294 0.366 4Concentration of solute = 8.5 X M; [AOT] = 0.014 M, pH 7.0. b R is defined as the ratio of [H,O]/[AOT]. cWavelength maxima. dAbsorbance.
effects of pH on the equilibrium because both its wavelength maximum and absorbance change gradually as the amount of solubilized, protonated form increases. The AOT was maintained at a low concentration (0.04 M ) so that there would be an appreciable amount of the nonsolubilized 2-aminopyridine present. The wavelength maximum under these conditions is at a somewhat shorter wavelength than that occurring at maximum solubilization and would red shift if the pH of added water is important in the protonation step. The pH of the water incorporated into the AOT aggregate, at a constant water level of R = [H,O]/[AOT] = 0.5, has no effect on the spectrum shape and wavelength maximum (293 nm and A = 0.322 f 0.001) at pH values of 4.5, 7.0, and 9.1. At acidic pH values (1.5), there is a 3-nm red shift in the absorbance wavelength maxima, but no change in absorbance intensity. The lack of conversion of the 2-aminopyridine to the free-base form at the higher pH values can be attributed to the lower pH or higher apparent pK, that has been found characteristic of solutes solubilized within inverted micelle water The slight red shift observed for the pH 1.5 water core may be due to complete conversion of the water-solubilized free base into its protonated form, or to alteration of the water core properties and its subsequent effect on the solute's partitioning equilibria. Water Content Effects. The effect of water content on the solubilization equilibria is illustrated by the spectral data in Table 11. As the water content is increased, with constant surfactant concentration, there is a very slight increase in the absorbance wavelength maximum and a large increase in the value of the absorbance. Experimentally, the molar absorptivities remained constant with variation in water content. This was found by solubilizing small amounts of the probe into high concentrations of surfactant solutions. By assuming total solubilization and protonation of the aminopyridine species and using the total concentration of solute added, we calculated the extinction coefficients and found them to be nonvariant at different water levels. Therefore, the changes in absorbance with varying water content strongly suggest an increase in the concentration of solubilized species. This is opposite to what was found for the effect of added water on the binding constants of phenols, where competition by water for binding sites decreased the phenolsurfactant association constants.12 Apparently, a greater effective volume of water solubilizes more of the solute, which is analogous to the partitioning of more solubilizate into a phase of larger volume. Calculation of distribution ratios in this case would require a volume correction for the increasing size of the water core, and is described later. Site of Solubilization. Previous experimentation shows two possible sites for solubilization of probes within the water core, one at the interfacial region and the second within the bulk water away from the head groups of the monomers. Solubilization of p-nitrophenol into the interfacial region has been demonstrated by Menger et al., where the probe experiences at 4.5 pKa unit increase.19 The presence of a pH gradient at the interfacial region has been postulated by El Seoud and has been attributed to the ion exchange of sodium counterions by hydrogen ions.13 In these studies, two types of probe molecules were employed, one solubilized in the interfacial region and a second solubilized in the bulk water. Calculation of the pKa of the more hydrophilic acid residing in the midst of the water core required no compensation for the occurrence of ion exchange and was essentially the same as for calculations using ordinary water. The calculation of pK,'s of the less hydrophilic interface-solubilized acids required taking
The Journal of Physical Chemistry, Vol. 88, No. 18, 1984 4179 into consideration the possibility of ion exchange and the resulting lower effective pH in that region of the water core. The corrected pKis of the less hydrophilic acids were closer in value to those found in ordinary water. It is apparent from the identification of the transitions in the absorption spectra that the aminopyridines are protonated and that their microenvironment is aqueous. This protonation requires an acidic pH and indicates that they are primarily solubilized within the interfacial region of the water core. The apparent pH of their locale is lower, as shown by the lack of conversion of 2-aminopyridine to its free-base form when water of basic pH is added. Addition of pH 7 water increases the aggregation number, which enlarges the water core volume. Thus, more probe is solubilized into the water core, as shown by the increase in the absorbance values and the wavelength shifts listed in Table 11, and is indicative of a shift in equilibrium to the protonated form of the 2-aminopyridine. Equilibria of Aminopyridines. The following represent the different possible equilibria which may be occurring for the aminopyridines in the AOT medium: Apcyclohexone
3
Apinterfoce
_Is, 7
APwoter
center
t
t
H'
H+
APH'interface
Kq,
APHLote, centei
where A P is the aminopyridine free base, APH+ is the protonated form of aminopyridine, K, is the acidity constant of the acid form, and K1-K4 are the indicated equilibrium constants. Addition of surfactant to form more micelles results in dramatic spectral changes and emergence of isosbestic points in the spectra. Addition of water presumably increases the water core bulk volume over that of the interfacial region volume, yet no isosbestic points are observed nor is there appreciable change in the absorption spectra profiles with increase in the water content. The predominant spectral features, wavelength maxima and molar absorptivities, of the solubilized forms of the aminopyridines are those of the protonated species. Experimentally, the molar absorptivities remain equal to those of the protonated form at all values of water content studied. There is no spectral evidence for the presence of the aminopyridine free base in an aqueous environment. On the basis of these observations, it must be concluded that the predominant equilibria occurring are the partitioning of the aminopyridines between the cyclohexane organic bulk phase and the acidlike interfacial region, with protonation being virtually complete for species at the interface (large K1 and K2). The equilibrium constant, K3, is negligible and K2 is large such that the amount of the protonated form determined spectroscopically is approximately equal to the amount of the aminopyridine species solubilized in the water core. Distribution Ratios. Determination of the distribution ratios (Kd) for the five aminopyridine species requires assuming (i) complete protonation of the solutes upon solubilization within the water pool interfacial area and (ii) that the water content of the surfactant solution, as measured by the Karl Fisher method, composes the entire volume of the inverted micellar cores. These assumptions are necessary because of the lack of specific information about the water core at the R values studied, the unknown dimensions of the interfacial region, and the unknown intrinsic pH of the water pool. The value for the density of the water in the core (approximately 1 g/mL) calculated by previous investigators was used in the calculations.22 The distribution ratios calculated by using this approach provide information on the order of solubilities of the solutes and on the effect of micellar organization on the solubilization equilibria. (22) Mathews, M. B.; Hirschhorn, E. J . Colloid Sci. 1953, 8, 86-96.
4180 The Journal of Physical Chemistry, Vol. 88, No. 18, 1984
Noroski and Love
TABLE III: pK. Values, Dipole Moments, and Distribution Ratios for Conventional Bulk Phase Separation for the Aminoovridine Series" PK,
compd 4-aminopyridine 3-aminopyridine 2-aminopyridine
monob
9.2 6.0 6.9
2-(dimethy1amino)pyridine 4-(dimethy1amino)pyridine
Kd
did -6.3 -1.5 -7.6
5.7
9.7d
PC
4.26 3.12 2.06 1.92 4.33
pH 6.0 1.3 x 10-3 f 3 x 10-4 3.0 x 10-3 3 x 10-4 1.9 x io-* 1 x 10-3 3.5 f 0.3 0.1 f 0.03
*
pH 1.2 (H2S04) 1.6 x 10-4 4 x 10-5 9.4 X f6 X 8.4 x 10-3 5 x 10-4 2.0 x 10-2 1 x 10-3 1.3 x 1 0 4 f 2 x 10-5
* *
'Solute concentration = 6 X 10-5-1.8 X Wavelengths used for calculation of solubilized form are as follows: 4-AP = 262 nm, 3-AP = 325 nm, 2-AP = 320 nm, 2-N,N-AP = 340, 4-N,N-AP = 279 nm. The distribution ratios, Kd, are defined as the ratio [aminopyridinein organic phase]/[aminopyridine in aqueous phase]. bFrom ref 15, p 73. tunits of debyes, benzene solvent, from: Cumper, C. W. N., Singleton,A. J. Chem. SOC.B 1967, 1096. dFrom "Dissociation Constants of Organic Bases in Aqueous Solution"; IUPAC, Butterworth: London, 1965. TABLE I V Distribution Ratios for the AOT Microscopic Separation for the Aminopyridine Series'
compd 4-aminopyridine 3-aminopyridine 2-aminopyridine 2-(dimethylamino)pyridine 4-dimetthy lamino)-
pyridine
distribution ratio R = 0.1 R = 12 2.7 X IO" f 1.6 x 10-5 f 4 x 10-1 1 x 10-5 5.2 x 10-5 2.9 x 10-4 4 x 10-5 2 x 10" 1.5 x 10-4 f 1.7 x 10-3 -+ 9 x 10-5 1 x 10-4 2.3 x 10-4 3.0 x 10-3 6X 9 x 10-5 1.7 x 10-5 f 7.0 x 10-4 2 x 10" 2 x 10-4
*
*
* *
"[AOT] = 0.003-0.01 M; wavelengths used for calculation and definition of distribution ratio given in Table 111. The series of aminopyridines were studied spectroscopically at varying surfactant concentrations with a constant R value of 0.1. No further increases in the absorbance at the wavelength maxima of the protonated species were observed at concentrations above a specific surfactant concentration. Assuming complete solubilization at this maximum surfactant concentration, the molar absorptivities were calculated by using the portion of the spectrum where no significant overlap with any free-base absorption is possible. Using the moles of protonated species derived from these molar absorptivities, we approximately corrected the micellesolubilized aminopyridine concentration to its interfacial waterphase concentration by dividing by the volume of water in the total solution. The values for the distribution ratios obtained in this manner are given in Tables I11 and IV along with distribution ratios obtained for a cyclohexane-water phase separation. Among the factors that govern bulk phase separations are the energy of dissolution and the energy of solute-solvent interactions.*O The aminopyridines interact strongly with a water phase through protonation and hydrogen bonding, and these exothermic processes account for greater affinity of the aminopyridines for an aqueous phase. Substituting methyl groups for hydrogens on the amino group removes the hydrogen-bonding capability of this group, and these molecules have less affinity for the water phase. Intramolecular hydrogen bonding in the 2-aminopyridine also affects its order of partitioning. Partitioning in a micellar medium is influenced by additional factors, namely, acidity and steric hindrance during diffusion through the surfactant monomers. Table I11 lists the distribution ratios found for the aminopyridine species in water (pH 6.0)/ cyclohexane, aqueous acid (pH 1.2)/cyclohexane, and Table IV lists the distribution ratios for AOT water core separations. Increasing the acidity of the water phase in the bulk separation increases the distribution of aminopyridine into the aqueous layer. The generally small values of the micellar distribution constants relative to those found in ordinary bulk water-organic separations reflect the lower pH present within the water core interfacial region. The small apparent increase in affinity for the organic
bulk phase at higher micelle water content may be due to the error involved in correcting the concentration in the water pool for volume changes since the interfacial region is much smaller than the water bulk phase, particularly at high water content. A change in the physical properties (polarity, viscosity) of the core at R = 0.1 is also likely because the physical significance of the interacial region at this R value is unclear. For example, Eicke has suggested that the water molecules and sulfonate head groups are arranged in trimeric units bound tightly by bridging hydrogen bonds at low R values.' Also, the counterions have been found to dissociate more at higher water content and there is an increase in p ~ l a r i t y . ~ . ~ This may have an effect on the affinity of the aminopyridine nucleophiles for the aqueous core. The difference in Kd between 4-(dimethy1amino)pyridine and 4-aminopyridine in the micellar medium suggests possible steric hindrance to the approach of bulkier solutes to the water core. However, the Kd for the species was found to be concentration dependent in the ordinary bulk separation. The distribution ratio becomes larger with an increase in total probe concentration giving evidence for dimerization occurring in the cyclohexane phase. The constants were calculated at a low probe concentration for both M) in order to the micellar and bulk separation (1.5 X minimize this effect. The distribution ratios vary proportionally overall for the micellar and acidified water-organic bulk separation. Steric effects for the ortho- and meta-substituted species are difficult to ascertain on the basis of these data. Generally, the affinity for the organic phase in both the bulk and micellar separations increases going from para to meta to ortho substituents of comparable size and is probably due to a combination of steric and pH effects.
Conclusions The association of the aminopyridine isomers with AOT inverted micelles is analogous to a microscopic phase separation. The magnitude of the calculated distribution ratios and the presence of only the protonated form solubilized within the aqueous inverted micelle core are evidence for a water phase that is strictly acidic. Steric factors may play a role in the distribution of these solutes between the organic bulk and water core phases, but it is not clearly defined on the basis of the distribution ratio values obtained. Acknowledgment. We acknowledge Anthony J. Sonnessa (deceased), who provided the initial experiments and inspiration for this research. This work was supported in part by the National Science Foundation grant CHE-8216878 and the Environment Protection Agency. Although the research described in this article has been funded by the U.S. Environmental Protection Agency under assistance agreement R809474 to L.J.C.L., it has not been subjected to the Agency's required peer and administrative review and, therefore, does not necessarily reflect the view of the Agency and no official endorsement should be inferred. Registry No. AOT, 577-11-7; cyclohexane, 110-82-7; 4-aminopyridine, 504-24-5; 3-aminopyridine,462-08-8; 2-aminopyridine,50429-0; 2-(dimethylamino)pyridine, 5683-33-0; 4-(dimethylamino)pyridine, 1122-58-3.
