a42
Langmuir 1991, 7, 842-847
Fundamentals of the Zwitterionic Hydrophilic Group Robert G . Laughlin Miami Valley Laboratories, The Procter & Gamble Company, Cincinnati, Ohio 45239 Received June 21,1990 Zwitterionic functional groups possess the greatest polarity found within the nonionic class of hydrophilic groups. Their nomenclature, common misconceptions as to their classification and properties, and their ion exchange and acid-base reactions are discussed. The hydrophilicity of zwitterionic compounds is strongly influenced by the structure and basicity of the anionic substituent group, and to a lesser degree by the length of the ion bridge that binds together these oppositely charged substituent groups. Methylene groups within the ion bridge contribute to the lipophilicity of the molecules, but to a lesser degree than do methylene groups within the long chain. Molecular Structure and Polarity Practically all organic molecules are amphiphilic, in that they possess both polar and nonpolar structural features, but those which are also surfactants display highly distinctive aqueous physical behavior.lI2 Soluble surfactants readily form micellar aggregates in solution; whether soluble or not, surfactants react physically with water to form lyotropic liquid crystal phases. Most polar functional groups are not hydrophilic groups; those that are may be distinguished from those that are not by using phase criteria.’ Hydrophilic groups may be classified, on a structural basis, into two classes and five subclasses:’ I. Ionic class A. Anionic subclass B. Cationic subclass 11. Nonionic class A. Zwitterionic subclass B. Semipolar subclass C. Single bond subclass Ionic surfactants are true salts; they are compounds that consist of an electrically neutral set of two or more formally charged molecules (ions). In anionic surfactant salts (e.g. sodium dodecyl sulfate) the anionic dodecyl sulfate molecule is amphiphilic and strongly surface active, while the cationic sodium ion molecule is hydrophilic and weakly surface active. In cationic surfactant salts (e.g. dodecyltrimethylammonium chloride) the cationic molecule is amphiphilic, while the anion is hydrophilic. Both molecules of a salt influence all of its properties, although for soluble salts in a medium that promotes dissociation, the effect of one ion on another vanishes at the limit of infinite dilution. Zwitterionic surfactants are nonionic compounds; they consist of a single molecule that is electrically neutral. They are not salts, and do not interact with ions to form salts. Zwitterionic compounds do however differ importantly from other nonionic compounds in both their structure and their proper tie^.^ Structurally, they are distinguished by the fact that they possess formally charged substituent groups. These are separated by intervening atoms and are typically not electronically conjugated with each other. Historically the amino acids were the first zwitterionic molecules to be seriously investigated, and the ACS (1) Laughlin, R. G. Advances in Liquid Crystals; Brown, G. H., Ed.; Academic Press: New York, 1978; pp 41-148. (2)Ekwall, P. Advances in Liquid Crystals; Brown, G. H., Ed.; Academic Press: New York, 1975; pp 1-142. (3) Laughlin, R. G. J. SOC.Cosmet. Chem. 1981,32, 371-392.
Monograph edited by Cohn and Edsall(1943) provides a superb accounting of these investigation^.^ In this treatise the German word “zwitterion” was acknowledged, but the term “dipolar ion” was instead adopted for these structures. The term “dipolar ion” implies that zwitterions are ions, but if the earlier Arrhenius definition of “ion” is retained, then zwitterions are not ions. Possibly because of the stature of the people involved and the superb scientific quality of this treatise, the perception that zwitterions are indeed ions has persisted to this day.5~6Occasionally the term “zwitterionic” is used to describe the dipolar form of groups such as aliphatic amine or phosphine oxides. It is preferable, however, to restrict “zwitterion” to molecules which have substituent groups that bear formal charges. The term “semipolar” aptly describes functional groups within which significant charge separation between directly bonded atoms exists.’ In semipolar groups the filled orbitals on one atom and the unfilled orbitals on the other are inductively distorted by the charge separation, and may also be conjugated. Both interactions reduce the polarity of semipolar groups below that of the pure dipolar form. Polarity. The polarity of dipolar functional groups is conveniently expressed by using reduced dipole moments, PI1
cc1 = ~ / ( 4 . 8 0 4
is the bond moment (in debye units), which is obtained by using vector analysis of experimentally determined molecular moments in simple compounds. d is the measured distance between centers of electrical charge (the bond length in semipolar structures, the distance between charged centers in zwitterions). The constant 4.80 is dictated by the value of the electrostatic unit of charge. pr is useful in comparing bond moment data for different structures, because it normalizes these data with respect to variations in d. pr thus provides a measure of the magnitude of the measured excess charge within a dipole, at a distance of separation corresponding to the distance between nuclear centers within the dipole. The reduced bond moments of common dipolar functional groups are depicted in Figure 1. Among semipolar groups pr varies from ‘ 1 3 to 2/3; groups that are both operative and nonoperative as hydrophilic groups are p
(4) Edsall,J. T. In Proteins, Amino Acids, and Peptides; C o b , E. J., Edsall, J. T.,Eds.; American Chemical Soceity MonographSeries, Hafner Publishing Co.: New York, 1943. (5) Dictionary of Scientific and Technical Term; Parker, S.P., Ed.; McGraw-Hill Book Company: New York, 19M. (6) Becher, P. Dictionary of Colloid and Surface Science; Marcel Dekker, Inc.: New York, 1990.
0743-7463/91/2407-0842~02.50/0 0 1991 American Chemical Society
Langmuir, Vol. 7, No. 5, 1991 843
Fundamentals of the Zwitterionic Hydrophilic Group 1.0
E
g
f
1
::j
-All
Table I. Zwitterionic Nomenclature
Zwitterionics
~~
.7
:q .2
~~
(CH&N+CH&02-
(trimethyla"onio)acetate (betaine) ammonioacetate (glycine) 2-(trimethy1a"onio)ethane1-sulfonate 2-(trimethy1a"onio)ethyl methyl phosphate 2-(trimethylphosphonio)1-propyl sulfate
H&J+CH2COi (CH~)SN+CH~CH~SO~(CH&N+CHZCH~OP(O)~QCH~ (CH&P*CHCHzq-
I
CH3 .
- c-CI - c-0 - C-N
w
.1
Figure 1. Reduced dipole momenta (pJ for various dipolar structures.' pr = p/(4.80d). From left to right the columns represent zwitterionic compounds, semipolar bonds, doubly and triply bonded groups involving 2pr orbitals, and single bond functional groups.
found in this categ0ry.l Dipolar functional groups that are doubly or triply bonded and involve 2p7r orbitals are listed separately. While similar in polarity to semipolar groups, these are, as a class, not operative as hydrophilic groups (excepting the borderline case of amides). The reduced dipole moments of singly bonded groups are all less than l/3.l The polarity of these groups hinges principally on atomic dipoles and on electronegativity differences between bonded atoms (N-H, 0-H, and (2-0). Because zwitterionic groups possess formally charged substituents, their reduced dipole moments (Figure 1)are all unity.l14 Their polarity, using this criterion, is higher than that of any other nonionic functional group. Reduced dipole moments do not allow one zwitterionic molecule to be distinguished from another (see later). The likely numerical values of the dipole moments of zwitterions are enormous, because their formal charges may be separated by distances that are large in comparison to bond lengths within semipolar groups.' The intramolecular distances between poles within zwitterionic molecules are, however, small compared to the separations that may exist between ions in salt solutions. For example, the distance of separation of ions in 1mM salt solutions is of the order of 200 A. It was early recognized that, because of their enormous polarity, the crystal phases of zwitterionic compounds display high melting points relative to other nonionic compounds of similar structure. Meaningful melting points usually cannot be determined, because the melting process is accompanied by chemical decomposition and the melting phase reaction X L is irreversible.4
-
Nomenclature Straightforward nomenclature for zwitterionic compounds has been adopted by the IUPAC.' This nomenclature is based on the selection of a parent ion molecule that includes one of the charged groups. The IUPAC system allows either ion to serve as the parent, but it is easier to select the anion. Cationic substituents on the parent molecule are systematically named by replacing the "ium" suffix for cationic ion molecules with "io". The balance of the nomenclature is conventional, as illustrated in Table I. This nomencls'ure is useful both to name a specific molecule and to describe a class of molecules (e.g. "ammoniocarboxylates"). Further substitution may exist on the cationic substituent, or elsewhere. In glycine, no further substitution (7) IUPAC. Nomenclature of Organic Chemistry; Butterworth: London, 1965;Rule C-87.
exists. The zwitterionic form of glycine is in facile equilibrium with the tautomeric, weakly polar, aminoacetic acid molecule (H~NCHZCO~H). The distribution between tautomeric forms is determined by the degree of similarity of the acid-base properties of the substituent groups. In glycine the zwitterionic form predominates, but both the ammoniocarboxylateand the aminocarboxylic acid forms exist, e.g., in the case of p-aminobenzoic acid.' When zwitterionic molecules react with acids or bases to form anionic or cationic molecules by the loss or gain of a proton, new compounds result which are salts and are named accordingly.
Chemical Reactivity Ion Exchange. Ionic bonds exist between the ion molecules in a salt. Ionic bonds are distinguished by their nondirectionality;covalent bonds, by contrast, are strongly directional.8 The strength of an ionic bond is determined by the distance between ions, but not by direction. Ionic bonds do not display characterisvc vibrational frequencies.4 Whether or not ionic bonding exists in a particular compound is a purely structural question; it is not an issue to be decided on the basis of physical properties. Properties may be drastically altered, without altering structure, by varying the substituent groups. Betaine and glycine, for example, are highly crystalline, high melting, and very soluble in water. Phosphatidylcholineand -ethanolamine lipids are waxlike, insoluble in water, and soluble in organic solvents. All these molecules are nevertheless zwitterionic. Since Arrheniuso it has been recognized that solutions of salts may be highly conductive and characteristically undergo "ion exchange" or "ion metathesis" reactions. Provided 1)that asalt is soluble, 2) that the solvent permits dissociation, and 3) that the mobility of the dissociated ions is high, then the conductivity of salt solutions is significantly increased above that of the solvent. Further, if two different salts are placed in such a medium, then "ion exchange" reactions may occur. Ion exchange is a chemical reaction in which the partner ions of two salts switch, producingtwo new salts. Ion exchange is grossly obvious only when accompanied by phase separation Ag+,NO;
-
+ Na+,Cl-
Ag+,Cl- + Na+,NO;
The equilibrium and kinetic aspects of ion exchange reactions, as well as the extent of dissociation and magnitude of the conductivity of salt solutions, depend on the specific salts involved and the medium. Because the ionic substituents within zwitterionic molecules are covalently linked, these compounds should neither enhance the conductivity of their solutions nor (8)Pauling, L. The Nature of the Chemical Bond; Comell University Press: Ithaca, NY,1960. (9) Arrhenius, S. J. Am. Chem. Soc. 1912,34,353.
W Langmuir, Vol. 7, No. 5, 1991
Laughlin
undergo ion exchange reactions. The should, however, increase the capacitance of their solutions. All these expectations are borne out by experimental data-with one qualification.' If a zwitterionic molecule is acidic, basic, or amphoteric (that is, both acidic and basic), then proton transfer reactions must be taken into account. Conductivity. The conductivities of solutions of pure quaternary ammoniopropanesulfonates,which are neutral in an acid-base sense, are indistinguishable from that of water.1° That such zwitterionic compounds exist escaped the attention of Cohn and Edsall, who regarded all zwitterionic compounds as being amph~teric.~ The inability of zwitterionic compounds to undergo ion exchange or to enhance conductivity is evident from observations made during numerous syntheses of ammoniohexanoatesurfactants.ll Potassium bromide is formed as a byproduct of this synthesis
-
R(Me),N+(CH,),CO,Et,Br- + K+,OHR(Me),N+(CH,),CO; + K+,Br- + EtOH Potassium bromide may be selectively removed from concentrated (ca. 0.5 M) ammoniohexanoate solutions by using mixed bed ion exchange resins
--
resin+,OH-+ Br- resin+,Br- + OHresin-,H+ + K+ resin-,K+ + H+ H+ + OH- H20 Neither resin reacts by ion exchange with ammoniohexanoates. The removal of potassium bromide may be followed by using conductivity. As potassium bromide is removed, the conductivity falls, until it is slightly higher than that of the solvent. The residual conductivity is due to hydrolysis of these weakly basic surfactants. The product of hydrolysis is a quaternary ammonium hydroxide salt R(Me),N+(CH,),CO;
+ H20
R(Me),N+(CH,),CO,H,OHBecause cation exchange occurs faster than anion, the pH must be carefully monitored and kept high during this process. If the solution is allowed to become acidic, extensive loss of protonated surfactant into the cation exchange resin results. Acid-Base Chemistry. Four carbon Substituents exist on nitrogen in quaternary ammonium ions. While "positive" in an electrical sense, they are "neutral" in an acidbase sense. Ammonium ions bearing at least one proton, on the other hand, are weakly acidic. All anions are basic, but the protonation of some compounds occurs at hydrogen ion activities that are not measurable by using the glass electrode. Carboxylate anions (as in the above example) and phosphate dianions are protonated in dilute aqueous acid solutions. Alkanesulfonate or alkyl sulfate anions are protonated only in media such as concentrated sulfuric acid. Acidity functions such as Ho,rather than pH, must be utilized to quantitatively describe the protonation chemistryof these compounds.12 Azwitterionic compound that bears both an acidic group (e.g. +NH) and a basic group (e.g. 4 0 2 3 is amphoteric&. An example is glycine. A zwitterionic compound that bears an acidic positive substituent and a nonbasic negative sub(10) Laughlin, R. G. Unreported work. (11) McGrady, J.; Law+, R. G. Syntheeia 1984, 5426-428. (12) Rochester, C. H. Acrdrty Functrons; Academic Prese: New York, 1970.
Table 11. pK. Data for Ammonioalkanoic Acid Salts in Water at 26 O C * * n
H3Nt(CH2)lCOzH HsNt(CH2)2C02H H3Nt(CH2)3C02H H3Nt(CH2)4C02H HaNt(CH2)3C02H H3Nt(CH2)&02H
CHsCOzH CH3(CH2)4C02H
pK. 2.351 3.551 4.031 4.20 4.373 4.502
ARK. 2.411 1.211 0.731 0.562 0.389 0.260
AGO
AHo
-7.5 -12.6 -17.2 -19.9 -21.1 -22.2
0.98 1.08 0.39 -0.22 -0.32 -0.47
4.762 4.872
(0)
-21.9
-0.02
-0.110
stituent is acidic but not amphoteric; an example is taurine, H3N+CH2CH2S03-. A zwitterionic compound that bears a neutral positive substituent but a basic negative substituent is basic but not amphoteric; an example is betaine, (CH3)3N+CH&02-. Finally, if the charged substituents are neither acidic nor basic, then the molecule itself is neither acidic, basic, nor amphoteric. An example is a quaternary ammoniosulfonate,(CH3)&+(CH2)nSO3-). These generalizations apply only to dilute aqueous media. A surprising amount of confusion on these matters exists in the literature. Attenuation of Acidity and Basicity in Zwitterions. While anionic and cationic substituents within zwitterionic molecules react as acids or bases in a manner qualitatively similar to that of related ion molecules, their acidity or basicity is typically attenuated in comparison with that of the dissociated ions. This attenuation occurs because each ion is tethered to the other by the covalent linkage, or "ion bridge". Aqueous titration data within the homologues of ammoniocarboxylatesHsN+(CH2)nC02-provide a means of quantitatively assessing the influence of the positive field of the ammonio substituent on the basicity of the carboxylate The stronger this field, the less attractive the -COz-group is to a proton, the weaker its basicity, the stronger the acidity of its conjugate acid, and the lower the PKa of this acid. Shown in Table I1 are PK, values (and derived standard state thermodynamic data) for the dissociation of ammonioalkanoic acids chlorides having values of n = 1 to 6 and for acetic and hexanoic acid. These data reveal two important features of electrostatic interactions within zwitterionic groups. First, the number of methylenes separating the positive and negative substituents influences the pK, of the carboxylic acid group and does so in a monotonic fashion. There is no evidence whatsoever that an unusually favorable interaction exists at a particular value of n. These data imply further that the time-averaged distance between the charged groups also increases monotonically with n. Second,the magnitude of the influence of the ammonio substituent on the carboxylate anion is large for n = 1, much smaller for n = 2, and still smaller for n 1 3. It has been noted that these pKadata are remarkably linear with l/n; for the above compounds PK, = -2.55(1/n) - 4.874." The constant in this equation corresponds to the PK, at very large values of n. The agreement between the value of this constant and the pK,of hexanoic acid is remarkably good. When more than three methylenes separate substituent groups, the pK, differs from that of acetic acid by 0.6 unit or less. Since the PKa of acetic acid is hardly affected by homologation (as in hexanoic acid), the (13) Handbook of Biochemiatry and Molecular Biology; F a " , G. D., Ed.; CRC Press: Cleveland, OH, 1976. (14) Ween, J. G., Scheuing, D. R., Axe, F. U., and Kao, J. L. F., Book of Abstracts; 199th National Meeting of the American Chemical Society, Boston, MA, April 22-27,1990;American Chemical Society: Washington, DC, 1990; COLL 107.
Fundamentals of the Zwitterionic Hydrophilic Group
Within a micelle which contains predominantly zwitterionic molecules, this complex is a weaker acid than unassociated -C02H molecules.20 As the fraction of cationic molecules increases, the electrical field effects of the positive ions override this acid-weakeningeffect and the pKa falls.
4.00 1
4'50 4.20 m
-
A A
A
~
~
A
3.904
Y
A
3.60 3.30 m 3.00 a 2.70 Q
E
A A AA
+%A
,100
Langmuir, Vol. 7, No. 5, 1991 845
,300 ,500 ,700 Fraction Titrated
,900
Figure 2. Apparent pK. vs fraction of 6-(docosyldimethylammonio)hexanoatatitrated with hydrochloricacidat 25 "Cin water. The solutions are supercooled (Krafft boundary ca. 32 "C),but precipitation is not evident until the fraction titrated exceeds 0.8.
observed variability is not due to differences in the length of the ion bridge itself. That no intramolecular ion-pair-like interactions exist at a preferred ring size for zwitterionic compounds in water is entirely reasonable. The basis for the existence of energetically preferred ring sizes, e.g. in cyclic organic compounds, is the inherent directionality of covalent bonds. A ring closed by a (nondirectional) ionic bond should display no optimal ring size, as is observed. Strong electrostatic interactions-both intra- and intermolecular-may be expected in low dielectric solvents. pKa measurements are possible only for zwitterionic compounds containing the carboxylate group, but probably similar field effects exist in ammonio phosphates, sulfonates, and sulfates as well. Influence of Association on Acid-Base Chemistry. The strong fields about zwitterionic functional groups have intermolecular as well as intramolecular effects, as is evident from the titration behavior of associated systems. In general, the acid-base chemistry of micellar surfactants is complex and, like that of weak polyelectrolytes,16 cannot be described by using a single value for the pKa. In such cases the apparent PKa varies significantly with the fraction titrated. This phenomenon has been described for amine oxidel6 and amm~nioamidate'~ surfactants. Below its critical micelle concentration (cmc), the titration curve of (tetradecyldimethy1a"onio)hexanoate is accurately described by using a PKa of 4.30.18 Data on the apparent pK, of the C22 (docosyldimethy1a"onio)hexanoate as a function of the fraction titrated with hydrochloric acid are shown in Figure 2. Because of its long lipophilic group, solutions of this surfactant are micellar throughout the titration. The apparent PKa rises slightly when small amounts of the protonated form exist and then decreases as the fraction of cationic molecules increases. The initial rise likely reflects the formation of a strong complex between the carboxylate of the ammoniohexanoate molecule and the carboxylic acid group of a neighboring ammoniohexanoic acid cation N+-CO>H-02C-N+ Similar association exists within acid-soap crystals.lg
Hydrophilicity Polarity, as scaled using pr,does not adequately describe the interactions of functional groups with water. The term "hydrophilicity" has been used instead to describe this interaction.' Hydrophilicity and lipophilicity, together, determine most aspects of surfactant aqueous physical science. The 'HLB" (hydrophilic-lipophilic balance) concept reflects the pervasive importance of these two parameters.21 Lipophilicity can be scaled within families of homologues by using lipophilic group size or volume.22 Hydrophilicity cannot presently be so easily scaled, except in the case of polyfunctional Surfactants such as poly(oxyethylene) compounds. Within these surfactants variations in the number of oxyethylene groups result in "extensive" variations in hydrophilicity, due to the differing number of similarly hydrophilic functional groups. However "intensive" differences in hydrophilicity also exist, as between carboxylates and sulfates, or amine oxides and phosphine oxide^.^ The dimensions of hydrophilicity suggested from the comprehensiveanalysis of the aqueous phase behavior of amphiphilic compounds are as follows:' 1. The Thermodynamic Dimension. The free energy of hydration of hydrophilic groups must be strong enough thermodynamically to overcome similar interactions within liquid water. 2. The Multiplicity Dimension. Multiple hydrogenbonding interactions to a solvated terminal atom (usually oxygen, occasionally nitrogen) must exist. 3. The Geometric Dimension. The geometry of hydrogen bonding of these hydrated atoms must resemble that of water molecules within liquid water. The hydration must be three-dimensional, roughly tetrahedral, and may not be linear or planar, as in nitrile or carbonyl groups. These correlations taken together suggest that hydrophilicity involves the strong solvation of specific atoms in a manner that is compatible with the phase structure of liquid water. It follows that the anionic molecules of ionic surfactant salts, and the anionic substituents of zwitterionic surfactants, are probably the principal sites of solvation. The hydrophilicity of zwitterionic compounds does depend principally on the anionic substituent group, but it is also influenced by the length of the ion bridge (tether). Of the two, the intrinsic hydrophilicity of the anionic group appears to be the more important factor. Anionic Substituent Structural Effects. It is useful in assessing relative hydrophilicity to employ the correlation between hydrophilicity and basicity, in addition to phase information.' The most common anionic functional groups are carboxylate, phosphate, sulfonate, and sulfate. What is their relative basicity?
(19)Ekwall, P.Kolloid-Z. 1937,80,177-200. (20)Titrations in Nonaqueow Media; Cohen, D., Millar, I. T.,English Translators; Illife Boob (D. Van Noetrand Co., Inc.): London, 1967;pp (15)Anderson, C. F.; Morawetz, H. In Encyclopedia of Chemical 101-108. Technology; John Wiley & Sone: New York, 1982;Vol. 18,pp 520-530. (21)Becher, P.;Griffin, W. C. Detergents and EmuLsifierslNorth (16)Tokiwa, F.; Ohki, K. Bull. Chem. SOC.Jpn. 1968,41,1447-1451. (17)Corkill,J.M.;Gemmell,K.W.;Goodman,J.F.;Walker,T.,Trans. American Ed.; MC Publishing Co.: Glen Rock, NJ, 1974. Faraday SOC.1970,66,1817-1824. (22)Tanford, C. The Hydrophobic Effect: Formation of Micelles and Biological Membranes; John Wiley & Sone: New York, 1973. (18)Fu, Y. C.; Laughlin, R. G.Chem. Phya. Lipids 1980,26,121-139.
Laughlin
846 Langmuir, Vol. 7, No. 5, 1991
Table I11 CO2H PK. Go, kcal Go, kJ
+4.8 6.5 21.2
> (RO)2POzH > -SOsH +1 1.4 5.9
-9 -12 -50
> -OSOsH -12 -16.3 -68.1
Table IV increasing hydrophilicity Critical Temperature lower consolute boundary increases upper consolute boundary decreases Size of Miscibility Gap lower consolute boundary decreases upper consolute boundary decreases
increasing lipophilic group size decreases increases increases increases
As mentioned earlier, the basicities of carboxylate anions may be determined with high accuracy by direct titration. The basicities of dialkylphosphate monoanions have been determined similarly. The basicities of alkanesulfonate and alkyl sulfate anions cannot be similarly determined, but approximate values may be inferred from their behavior in strong acid by using the HOacidity function. Approximate values for the pK, values of a series of acids BH are listed in Table 111, along with the standard state free energies for proton On the basis of these data the relative intrinsic hydrophilicities of zwitterionic molecules (for a particular value of n) should fall in the order R(Me)2N+(CH2)nC02-> R(Me)2N+(CH2)n-10P(0)iOMe > R(Me)2N+(CH2),S03> R(Me)2N+(CH2),10S03-. This predicted order is fully consistent with data on the upper consolute boundary phenomenon found within this class of surfactants. (No data on single chain ammoniophosphates exist, but the upper consolute boundary has been observed in short chain lecithin-water systems.u) Data on this miscibility gap (for compounds having the same ion bridge length) are a useful measure of hydrophilicity. For both the lower consolute ("cloud point") boundary of weakly hydrophilic nonionic surfactants and the upper consolute boundary of zwitterionic surfactants, the values of the critical temperature and the area of the miscibility gap are correlated with hydrophilicity as indicated in Table IV. It would therefore be expected that ammoniosulfates should display the highest, ammoniosulfonates somewhat lower, and ammoniocarboxylates the lowest critical temperatures. In agreement with these expectations the upper consolute boundary is indeed observed in ammonio sulfates-even in the case of an octyl homologue.26 For dodecyldimethylammonio homologues the upper critical temperature of the ammonio sulfate is far above 100 "C, while that of the ammoniosulfonate lies at 0 "C. (The phosphoniosulfonate is slightly higher, at 9 OC.25) The upper consolute boundary phenomenon apparently does not exist in ammoniocarboxylates.25 Not only is it not observed for dodecyl homologues; it does not exist even in the c30 (triacontyldimethy1ammonio)hexanoatewater system. Since the area of this miscibility gap increases with increasing chain length where the phenomenon exists, the absence of this phenomenon in a Cs0 ammoniocarboxylate is astonishing. (23) Kabachnik, M. I.; Maetrukova, T. A.; Shipov, A. E.; Melentyevn, T . A. Tetrahedron 1960,9,10. (24) Tauek, R. J. M.; Oudehoorn, C.; Overbeek, J. Th. C. Biophys. Chem. 1974,2, 53-63. (25) Nilaeon,PA.,Lindman, B.;Laughlin, R. G.J. phy8. Chem. 1984, 88,6357-6362.
Ion Bridge Effects. The dependence of phase behavior on ion bridge length ( n )is complex. No good phase data exist for n = 1 or 2 within ammonio sulfates or ammoniosulfonates, because such compounds are either chemically unstable or the boundary is inaccessible (due to interference by an unrelated boundary such as the Krafft boundary). The upper critical temperature of the (dodecyldimethy1ammonio)propanesulfonate-water system (0 "C) is significantly lower than that of the corresponding ammoniobutanesulfonate (90 "C).26 A similar, but smaller, difference exists between the upper critical temperatures of (decyldimethy1a"onio)ethyl sulfate (77 "C) and (decyldimethy1ammonio)propylsulfate (90 "C).% The values of n are 3 and 4,respectively, in these structures. These perturbations of phase behavior that result from lengthening the ion bridge are significant but small relative to those that result from changing the structure of the anionic group. Both basicity and Rfdatal suggest that differences in the hydrophilicity of zwitterionics having either n = 3 or n = 4 are not large. Perhaps, these data reflect the hydrophobic effect of the methylene groups within these aliphatic ion bridges. The insertion of methylene groups into the ion bridge does affect the cmc's of zwitterionics, which show a maximum value a t n = 3.27 The upper consolute boundary is influenced in peculiar ways by varying the structure of proximate substituent groups on the cationic substituent. The homologation of proximate groups in zwitterionic surfactants shrinks the upper consolute boundary miscibility gap,% but the homologation of proximate substituents, e.g. in phosphine oxides, enlarges the lower consolute boundary miscibility gap.' In phosphine oxides the effect of homologation within a proximate substituent is not as large as the effect of homologation within the chain, but the direction is the same. This particular structural variation thus has an opposite effect on liquid-liquid miscibility in zwitterionic surfactants than it does in semipolar surfactants. Micellar association within coexisting phases bordering this boundary is normal in the (nonyldimethy1ammonio)propyl sulfate-water system.25 A model purporting to describe this phenomenon has been proposed.28 There is much yet to be learned about how and why these structural variations affect the phase behavior of zwitterionic surfactants. Conformational Structure. The conformational structure of zwitterionic groups is an important subject, but detailed analysis is beyond the scope of this article. The relative energies of different conformations must be determined principally by the balance between the electrostatic energy of interaction between charged substituents and the internal energy of the ion bridge. For saturated aliphatic ion bridge structures the all-trans conformation must have the lowest internal energy,W but in this conformation the distance between charged substituents (and the electrostatic energy term) will have the largest possible values. This unfavorable electrostatic energy may be reduced by bringing the charged groups closer together, but to do so, bonds within the ion bridge must be rotated from trans to gauche. These rotational processes are not energetically "free"; gauche bounds are higher energy structures than are trans. (26) Faulkner, P. G.;Ward, A. J. I.; Oeborne, D. W. Langmuir 1989, 5,924-926. (27) Chevalier, Y.;Germanaud, L.; Le Perchec, P. Colloid Polym. Sci. 1988,266,441-448. (28) Blankschtein, D.;Thuraton,C. M.; Benedek,C. B. J. Chem.Phy8. 1986,85, 7268-7288. (29) Eliel, E. L. Stereochemistry of Carbon Compounds; McGrawHill Book Co., Inc.: New York, 1962.
Fundamentals of the Zwitterionic Hydrophilic Group
Estimating the electrical energy term is complicated by uncertainty as to the effective value of the dielectric constant to use at molecular distances.‘ By use of cyclohexane data, the ion bridge conformational energies of zwitterionic compounds through n = 4 were estimated some years ago to be similar in magnitude to electrostatic energies, assuming a value of 20 for the effective dielectric constant. This result is qualitatively consistent with the above information, provided the magnitude of the hydrophobic effect of varying the ion bridge length is taken into account. It is worth noting that conformational structure depends on phase str~cture.~’Conformational structure within
Langmuir, Vol. 7, No. 5, 1991 847
crystal phases, in particular, will differ from that within liquid and liquid crystal phases. Information on the conformational structure of zwitterionic groups in both crystalline (so-called “gel”) and liquid crystalline phases of polar lipids exists.g0 Acknowledgment. The potentiometric titrations of 6-(docosyldimethyla”onio)hexanoate were performed by Y.-C. Fu. (30) Hauser, H.; Paecher, I.; Penrson,R. H.; Sundell, S.,Biochim. Biophys. Acta 1981,650,21-51.
