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Langmuir 1999, 15, 174-184
Molecular Recognition-Induced Function and Competitive Replacement by Hydrogen-Bonding Interactions: Amphiphilic Barbituric Acid Derivatives, 2,4,6-Triaminopyrimidine, and Related Structures at the Air-Water Interface Thomas M. Bohanon,† Pier-Lorenzo Caruso,‡ Steffen Denzinger,† Ralf Fink,† Dietmar Mo¨bius,‡ Wolfgang Paulus,† Jon A. Preece,† Helmut Ringsdorf,*,† and Dieter Schollmeyer† Institut fu¨ r Organische Chemie, Johannes-Gutenberg Universita¨ t Mainz, J.J. Becherweg 18-20, 55099 Mainz, Germany, and Max-Planck Institut fu¨ r Biophysikalische Chemie, Am Fassberg 9, 37077 Go¨ ttingen, Germany Received March 27, 1998. In Final Form: October 1, 1998 The phenomenon of molecular recognition inducing further function is common in nature. However, there are few synthetic systems which achieve this cascade type mechanism, and those are generally carried out in noncompetitive solvents. Here a synthetic system is described that partakes in recognition events at an aqueous interface, which subsequently induces a reaction. This system involves amphiphiles forming monolayers at the air-water interface where the headgroups are barbituric acid derivatives. It is subsequently seen when 2,4,6-triaminopyrimidine (TAP) is present in the subphase that the barbituric acid headgroup is cleaved by the hydrolysis of a CdC double bond which links the headgroup to the hydrophobic tail (retro-Knoevenagel reaction). This cleavage depends on four factors which are (i) the self-organization of the amphiphiles, (ii) the insertion of TAP into the monolayer by the formation of six hydrogen bonds to two adjacent barbituric acid groups (This insertion is discussed in terms of a linear (coplanar) and a zigzag type (crinkled) geometry.), (iii) the polarization of the CdC double bond due to the hydrogen-bonding interactions, and (iv) the formation of a hydrophobic cleft, upon insertion, and the trapping of water molecules therein. These studies involve the use of surface pressure-area isotherms, UV/vis and FTIR reflection spectroscopy at the air-water interface and of 1H NMR spectroscopy in homogeneous organic solution. Finally, the X-ray crystal structure of a barbituric acid TAP salt is reported in which ionic and hydrogen-bonding interactions are shown to hold the dimer pair together in the solid state. Competition experiments in the monolayer point toward barbituric acid and TAP existing as ionic/ hydrogen-bonded dimers in solution which can move their equilibria such that TAP molecules are delivered to the monolayer as neutral molecules.
Introduction Function Based on Organization. The biological world is replete with examples of molecular recognition resulting in self-assembled supramolecular structures where both the architecture and the function are often controlled by noncovalent bonding interactions,1 such as hydrogen bonding, π-π stacking, and hydrophobic as well as ionic interactions. The cell membrane is one of the most sophisticated examples of such a natural supramolecular system, perfectly showing that its function is based on its organization. Numerous attempts have been made to mimic such natural recognition processes using synthetic supramolecular systems2 and thereby trying to bridge the gap between biology, chemistry, and physics.3 Here we discuss such a synthetic example which employs hydrogen-bonding interactions to induce a chemical reaction at a Langmuir monolayer. The molecular recognition resulting from the hydrogen bond4 is extremely important in natural systems. The outstanding example is the base pairing5 of DNA, resulting † ‡
Johannes-Gutenberg Universita¨t Mainz. Max-Planck Institute fu¨r Biophysikalische Chemie.
(1) (a) Stryer, L. Biochemistry; W. H. Freeman: New York, 1988. (b) Cramer, F., Ed. Erkennen als geistiger und molekularer Prozeβ; Verlag Chemie: Weinheim, 1991. (c) Singer, S. J.; Nicolson, G. L. Science 1972, 175, 720-731. (d) Bretscher, M. S. Sci. Am. 1985, 252, 100-108. (e) Snyder. S. H. Sci. Am. 1985, 252, 132-141.
in the self-assembled double helix, which facilitates the self-replication of cells.6 Thus, much research on synthetic supramolecular systems has been centered upon the study of the hydrogen bond. However, the majority of studies (2) (a) Lehn, J.-M. Angew. Chem. 1988, 100, 91-116; Angew. Chem., Int. Ed. Engl. 1988, 27, 89-112. (b) Ringsdorf, H.; Schlarb, B.; Venzmer, J. Angew. Chem. 1988, 100, 117-162; Angew. Chem., Int. Ed. Engl. 1988, 27, 113-158. (c) Lehn, J.-M. Supramolecular Chemistry: Concepts and Perspectives; VCH: Weinheim, 1995 and references therein. (d) Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto, C. T.; Chin, D. N.; Mammen, M.; Gordon, D. M. Acc. Chem. Res. 1995, 28, 37-44. (e) Lehn, J.-M. Angew. Chem. 1990, 102, 1347-1362; Angew. Chem., Int. Ed. Engl. 1990, 29, 1304-1309. (f) Vo¨gtle, F. Supramolcular Chemistry; John Wiley & Sons: Chichester, 1996. (g) Sutherland, I., Ed. HostGuest molecular interactions: From chemistry to biology; John Wiley & Sons: Chichester, 1991. For some recent examples of such systems, see: (h) Lawrence, D. S.; Jiang, T.; Levitt, M. Chem. Rev. 1995, 95, 2229-2260. (i) Percec, V.; Heck, J.; Johansson, G.; Tomazos, D.; Kawasumi, M. J. Macromol. Sci., Pure Appl. Chem. 1994, 31, 10311070. (j) Wintner, E. A.; Conn, M. M.; Rebek, J. Acc. Chem. Res. 1994, 27, 198-203. (k) Lasic, D. D.; Needham, D. Chem. Rev. 1995, 95, 26012628. (l) Kurihira, K.; Ohto, K.; Honda, Y.; Kunitake, T. J. Am. Chem. Soc. 1994, 116, 6. (3) (a) Ahlers, M.; Mu¨ller, W.; Reichert, A.; Ringsdorf, H.; Venzmer, J. Angew. Chem. 1990, 102, 1310-1327; Angew. Chem., Int. Ed. Engl. 1990, 29, 1272-1289. (b) Mu¨ller, W.; Ringsdorf, H.; Rump, E.; Wildburg, G.; Zahng, X.; Angermaier, L.; Knoll, W.; Liley, M.; Spinke, J. Nature 1993, 262, 1706-1708. (4) (a) Schuster, P., Ed. Hydrogen bond; Springer: Berlin, 1984. (b) Jeffrey, G. A.; Saenger, W. Hydrogen Bonding in Biological Structure; Springer: Berlin, 1991. (c) Scheiner, S. Acc. Chem. Res. 1994, 27, 402408. (5) Watson, J. D.; Crick, F. H. C. Nature 1953, 171, 737-738.
10.1021/la980348w CCC: $18.00 © 1999 American Chemical Society Published on Web 12/09/1998
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Langmuir, Vol. 15, No. 1, 1999 175
Figure 1. Chemical structures of the amphiphiles 1-5 and the various substrates which were used to interact with the monolayers.
have been carried out in noncompetitive organic solvents.7 In contrast the biological world is one in which molecular recognition events occur in an aqueous environment, generally at an interface such as a cell membrane, where the interplay between molecular recognition and selforganization leads to highly sophisticated functioning supramolecular systems. Several attempts have been described to use biomembrane models which incorporate hydrogen bond donor and acceptor moieties, which recognize various substrates present in an aqueous subphase.8 Mimicking biomembrane processes using models such as monolayers,3,9 supported bilayers,10 liposomes,11 or micropipet aspiration technique bilayers12 may lead to an increased understanding of cell membrane functions and processes. (6) Albert, B.; Bray, D.; Lewis, J.; Raff, M.; Watson, J. D. Molecular Biology of the Cell; Garland publishers: New York, 1983; pp 4-8. (7) For examples, see: (a) Fan, E.; Geib, S. J.; Stoner, T. C.; Hopkins, M. D.; Hamilton, A. D. J. Chem. Soc., Chem. Commun. 1995, 12511252. (b) Hanessian, S.; Simard, M.; Roelens, S. J. Am. Chem. Soc. 1995, 117, 7630-7645. (c) Mascal, M.; Fallon, P. S.; Batsanov, A. S.; Heywood, B. R.; Champ, S.; Colclough, M. J. Chem. Soc., Chem. Commun. 1995, 805-806. (d) Paleos, C. M.; Tsiourvas, D. Angew. Chem. 1995, 107, 1839-1855. (e) MacDonald, J. C.; Whitesides, G. M. Chem. Rev. 1994, 94, 2383-2420. (f) Simard, M.; Su, D.; Wuest, J. D. J. Am. Chem. Soc. 1991, 113, 4696-4698. (g) Kimizuka, N.; Fujikawa, S.; Kuwahara, H.; Kunitake, T.; Marsh, A.; Lehn, J.-M. J. Chem. Soc., Chem. Commun. 1995, 2103-2104. (8) For some examples, see: (a) Ahlers, M.; Ringsdorf, H.; Rosemeyer, H.; Seela, F. Colloid Polym. Sci. 1990, 268, 132-142. (b) Krauch, T.; Zaitsey, S. Y.; Zubov, V. P. Colloids Surf. 1991, 57, 383-391. (c) Kurihara, K.; Ohto, K.; Honda, Y.; Kunitake, T. J. Am. Chem. Soc. 1991, 113, 5077-5079. (d) Mertesdorf, C.; Plesnivy, T.; Ringsdorf, H. Langmuir 1992, 8, 2531-2537. (e) Ahuja, R.; Caruso, P. L.; Mo¨bius, D.; Philp, D.; Preece, J. A.; Ringsdorf, H.; Stoddart, J. F.; Wildburg, G. Langmuir 1993, 9, 1534-1544. (f) van Esch, J. H.; Nolte, R. J. M.; Ringsdorf, H.; Wildburg, G. Langmuir 1994, 10, 1955-1961. (g) Kimizuka, N.; Kawasaki, T.; Kunitake, T. J. Am. Chem. Soc. 1993, 115, 4387-4388. (h) Koyano, H.; Yoshihara, K.; Ariga, K.; Kunitake, K.; Oishi, Y.; Kawano, O.; Kuramori, M.; Suehiro, K. J. Chem. Soc., Chem. Commun. 1996, 1769-1771.
However, in nature, the initial recognition process is generally followed by a cascade of interactions and reactions which achieves a desired function, for example, the immune cascade13 or enzymatic function.14 Additionally, natural systems not only depend on the molecular recognition event between the substrates to illicit the desired response, but in most cases one or both of the substrates are in addition self-organized into a superstructure which facilitates the correct geometrical arrangement for the molecular recognition and the following reaction to occur selectively and efficiently. Thus, organization leads to function. One well-documented example of self-organization being a prerequisite for molecular recognition and the consecutive reaction to occur is the cleavage of phospholipids in a Langmuir film by the phospholipase A2 present in the aqueous subphase.3,15 It is shown that the enzyme cleaves the lipids much more efficiently in self-organized solid analogous domains of the phospholipid than in the liquid analogous phase. We have recently described16 a self-organized synthetic chemical system in the form of a Langmuir film comprised of amphiphile 1 (see Figure 1), prepared by a Knoevenagel (9) (a) Adam, N. K. The Physics and Chemistry of Surfaces; Dover: New York, 1968. (b) Davies, J. T.; Rideal, E. K. Interfacial Phenomena, 2nd ed.; Academic Press: New York, 1963. (c) Knobler, C. M. Adv. Chem. Phys. 1990, 77, 397-449. (d) Ulman, A. An introduction to ultrathin organic films; Academic Press: Boston, 1991. (10) (a) Tamm, L. K.; McConnel, H. M. Biophys. J. 1985, 47, 105. (b) Sackmann, E. Science 1996, 271, 43. (c) Beyer, D.; Elender, G.; Knoll, W.; Ku¨hner, M.; Maus, S.; Ringsdorf, H.; Sackmann, E. Angew. Chem. 1996, 108, 1791-1794; Angew. Chem., Int. Ed. Engl., in press. (11) (a) Jones, M. N.; Chapman, D. Micelles, Monolayers, and Biomembranes; Wiley-Liss: New York, 1995. (b) Ostro, M. J., Ed. Liposomes: From Biophysics to Therapeutics; Dekker: New York, 1987. (12) Evans, E. A.; Kwok, R. Biochemisty 1982, 21, 4874-4879. (13) (a) Ichwaka, Y.; Halcomb, R. L.; Wong, C.-H. Chem. Br. 1994, 117-121. (b) Beun, G. D. M.; van de Velde, C. J. H.; Fleuren, G. J. Immunol. Today 1994, 15, 11-15. (14) Stryer, L. Biochemistry; W. H. Freeman: New York, 1988.
176 Langmuir, Vol. 15, No. 1, 1999 Scheme 1. Initially Proposed Model for the Interaction and Reaction of a Monolayer Formed from the Amphiphile 1 on a TAP Subphase16
reaction of barbituric acid and 4-(N,N-dihexadecylamino)benzaldehyde. When 2,4,6-triaminopyrimidine (TAP, 10-4 M) is present in the aqueous subphase, hydrolytic cleavage of the CdC double bond of the chromophore is observed (Scheme 1). To fully elaborate on and probe further this proposed interaction and reaction model of self-organization, recognition, polarization, formation of a hydrophobic cleft, and subsequent bond cleavage, various amphiphiles based on 1 were designed. First, to change the number and the strength of hydrogen-bonding interactions in the system, N-alkylated amphiphilic barbituric acid derivatives 2-4 were synthesized. In these compounds the nitrogenbearing hydrogen atoms were replaced by alkyl substituents of increasing size. Second, to elucidate the role of polarizing the CdC double bond by the hydrogen-bonding interactions with the conjugated oxygen atom of the carbonyl group belonging to the barbituric acid amphiphile 1, various specifically interacting substrates replaced TAP in the aqueous subphase (substrates which have the correct geometrical arrangement of hydrogen bond donors (15) (a) Grainger, D. W.; Reichert, A.; Ringsdorf, H.; Salesse, C. FEBS Lett. 1989, 252, 73-82. (b) Grainger, D. W.; Ahlers, M.; Meller, P.; Balnkenburg, R.; Reichert, A.; Ringsdorf, H.; Salesse, C.; Herron, J. N.; Lim, K. Controlling Binding of Proteins with Model Biomembrane Systems Through Specific Recognition. In Biomembrane Strucutre & FunctionsThe State of the Art; Gaber, B. P., Easwaran, K. R. K., ,Eds.; Adenine Press: New York, 1993. (c) Okahata, Y.; Ebara, Y. J. Chem. Soc., Chem. Commun. 1992, 116-117. (16) Ahuja, R.; Caruso, P. L.; Mo¨bius, D.; Paulus, W.; Ringsdorf, H.; Wildburg, G. Angew. Chem. 1993, 105, 1082-1084; Angew. Chem., Int. Ed. Engl. 1993, 32, 1033-1035.
Bohanon et al. Scheme 2. Synthesis of Amphiphiles 1-5
and acceptors to hydrogen bond to two amphiphiles; Scheme 1). These specifically interacting substrates were chosen in order to (i) vary the strength of the hydrogenbonding interactions with the oxygen atom of the conjugated carbonyl group (Mel, 6), (ii) vary the number of hydrogen bonds (7), and (iii) have substrates which could specifically interact with the monolayer but could not hydrogen bond with the oxygen atom of the conjugated carbonyl group (8 and 9) and thus could not polarize the CdC double bond. Furthermore, an inorganic base (NaOH) and two organic bases (10 and 11) were used as substrates to observe the effect of the basicity of the subphase on the hydrolysis. Third, to sterically block the hydrophobic cleft, two methyl groups were introduced to the chromophore of 1 to afford 5. Finally, the specificity and selectivity of the recognition process were examined by competitive replacement experiments. In these experiments the barbituric acid amphiphile 1 was either (i) cospread with urea (8) or barbituric acid (9) (specifically interacting) or (ii) spread onto an aqueous subphase containing acetamide 12 or polyacrylamide 13 (nonspecifically acting), followed by injection of an aqueous TAP solution into the subphases below the monolayers. The times of hydrolysis of the monolayers were then compared to those for monolayers of 1 on a TAP subphase alone. Results and Discussion Synthesis. The synthetic route leading to the barbituric acid amphiphiles 1-5 is outlined in Scheme 2. For the synthesis of amphiphiles 1-4, aniline 14 is reacted with 2 equiv of 1-bromohexadecane, affording N,Ndihexadecylaniline (15). Treatment of 15 with DMF and POCl3 in a Vielsmeyer reaction yields 4-(N,N-dihexadecylamino)benzaldehyde (16). Both steps can be carried out in moderate to good yields. The synthesis of amphiphile 5 initially starts with 3,5-dimethylaniline (17), which yields N,N-dihexadecyl-3,5-dimethylaniline (18)
Competitive Replacement by Hydrogen-Bonding Interactions
and, subsequently, 4-(N,N-dihexadecylamino)-2,6-dimethylbenzaldehyde (19). The benzaldehydes 16 and 19 are then reacted with barbituric acid (8), N,N′-dimethylbarbituric acid (20), N,N’-diethylbarbituric acid (21), or N,N′-diisopropylbarbituric acid (22) to yield the amphiphiles 1-5. These Knoevenagel reactions were carried out in CHCl3, with pyridine as base. Barbituric acid (8) and N,N’-dimethylbarbituric acid (20) are commercially available. N,N’-Diethylbarbituric acid (21) can be obtained by the method described by Sembritzky.19 Malonic acid is reacted with N,N’-diethylurea (23) and POCl3. After hydrolysis, the barbituric acid crystallizes. The N,N’diisopropylbarbituric acid (22) can be obtained by a similar route. N,N’-Diisopropylurea (24) (obtained by treatment of the commercially available N,N’-diisopropylcarbodiimide (25) with dilute acetic acid) is reacted with malonic acid and POCl3 followed by hydrolysis, resulting in N,N’diisopropylbarbituric acid (22). Langmuir Film Formation of the Amphiphiles. The monolayer-forming ability of the amphiphilic barbituric acid amphiphiles 1-5 was established by the surface pressure-area (p-A) isotherms at various temperatures. The collapse pressures of the monolayers formed from amphiphiles 1-4 decrease with increasing size of the N-alkyl substituent on the barbituric acid group. A monolayer of the unsubstituted amphiphile 1 collapses at 52 mN m-1, the dimethyl-substituted derivative 2 at 43 mN m-1, the ethyl-substituted amphiphile 3 at 18 mN m-1, and the diisopropyl-substituted derivative 4 at 7 mN m-1. This behavior can be explained by the increasing hydrophobicity and size of the headgroup. The monolayer formed from amphiphile 5, in which the two methyl substituents are introduced at the ortho positions of the aromatic ring of the chromophore, collapses at a pressure of 18 mN m-1 with an area per molecule of 0.80 nm2. All monolayers with the exception of 1 show a definite fluid analogous phase at 20 °C. Insertion Process: N-Alkyl Substitution of the Barbituric Acid Headgroup. It has already been reported16 that on a 10-4 M TAP subphase the insertion of TAP into the monolayer of 1 is followed by cleavage of the CdC double bond in 1. The mechanism of the insertion of TAP into the monolayer of 1 has already been discussed (Scheme 1). By substitution of the N-H hydrogen atoms of the barbituric acid headgroup of 1 with methyl-, ethyl-, and isopropyl substituents, we may perturb or even prevent the recognition process between the barbituric acid headgroups and TAP derivatives. These N-alkyl substituents not only prevent two of the six possible hydrogen bonds between the barbituric acid and complementatry systems but also sterically do not allow the other hydrogen bonds to form in a favorable coplanar geometrical arrangement. Therefore, the introduction of these bulkier substituents should help to further characterize both the recognition processes and the mechanism of the hydrolysis observed for amphiphile 1 in monolayers. In a manner similar to that for the monolayer of the unsubstituted amphiphile 1 on a TAP-containing aqueous subphase (10-4 M, pH ) 6.5), in the fluid analogous phase, the monolayers formed from the bulkier N-substituted amphiphiles 2, 3 and 4 undergo both molecular recognition (17) Compare: (a) Lehn, J.-M.; Mascal, M.; Decian, A.; Fischer, J. J. Chem. Soc., Chem. Commun. 1990, 479-481. (b) Zerkowsky, J. A.; Seto, C. T.; Wierda, D. A.; Whitesides, G. M. J. Am. Chem. Soc. 1990, 112, 9025-9026. (c) Zerkowsky, J. A.; MacDonald, J. C.; Whitesides, G. M. Chem. Mater. 1994, 6, 1250-1257. (18) Fersht, A. Enzyme Structure and Mechanism; Freeman: New York, 1985; pp 299-302. (19) Sembritzky, K. Ber. 1897, 21, 1810-1819.
Langmuir, Vol. 15, No. 1, 1999 177
Figure 2. Time-dependent UV/vis spectra of the monolayer (T ) 20 °C; surface pressure p ) 5 mN m-1) formed from the N,N′diethyl-substituted barbituric acid amphiphile (3) on an aqueous TAP subphase (10-4 M).
at the air-water interface with TAP, followed by the hydrolysis reaction, but over progressively longer periods of time. This recognition and hydrolysis can be followed by observing the time-dependent UV/vis reflection spectra of the monolayer formed at the air-water interface20 of the amphiphiles 1-4, when spread on a 10-4 M aqueous TAP subphase. As a typical example, Figure 2 shows the time-dependent UV/vis reflection spectra of the monolayer formed from the diethyl-substituted amphiphile 3 on a TAP subphase at five different time intervals. Points to note are (i) the presence of and the disappearance of the absorption band at λ ) 440 nm, which we attribute to an aggregation of the amphiphiles in the monolayer16 before the recognition process occurs, and (ii) the disappearance of the absorption band associated with 3 (λmax ) 463 nm) together with the comensurate appearance of the absorption band associated with the amphiphilic aldehyde 16 (λmax ) 375 nm). Additionally, the isosbestic point associated with the hydrolysis process should be noted, illustrating the specific nature of this event. Presumably, and as discussed before,16 the aggregation is a result of the π-π interactions21 between the aromatic moieties. However, with time the aggregation band disappears on an aqueous TAP subphase parallel to the hydrolysis (see Figure 3). This behavior can be attributed to the insertion of the TAP molecules into the monolayer, which breaks up the aggregation of the amphiphiles in the monolayersa point which will be returned to later. Second, consider the comensurate disappearance and appearance of the λmax ) 463 and 375 nm bands, respectively, together with the formation of the isosbestic point. This behavior we attribute to the hydrolytic cleavage of the CdC double bond of the amphiphile 3, releasing N,N-diethylbarbituric acid into the aqueous subphase and forming the aldehyde 16 (λmax ) 375 nm). Each of the amphiphiles 1-4 shows this behavior. (20) (a) Mo¨bius, D.; Orrit, M.; Gru¨niger, H. R.; Meyer, H. Thin Solid Films 1985, 132, 41-53. (b) Gru¨niger, H.; Mo¨bius, D.; Meyer, H. J. Chem. Phys. 1983, 79, 3701. (21) Hunter, C. A.; Sanders, J. K. M. J. Am. Chem. Soc. 1990, 112, 5525-5534.
178 Langmuir, Vol. 15, No. 1, 1999
Figure 3. (a) Representation of the nonlinear (crinkled) insertion of TAP into the N,N′-substituted barbituric acid amphiphile monolayers. (b) Schematic representation of the disturbance of the aggregation behavior of the chromophore upon insertion of the TAP into the monolayers. (c) Isochors of monolayers of amphiphile 3 on an aqueous and a TAPcontaining subphase at 20 °C. The monolayer is compressed to p ) 8 mN m-1, and then the area is kept constant.
The only difference is the increased time of insertion and hydrolysis as the N,N’-alkyl substituents become bulkier. The time of hydrolysis data are shown in Table 1. It can be seen that the hydrolysis times range from 15 min for 1 to >360 min for 4. However, it is known that the hydrolysis of such CdC double bonds is classically achieved by base catalysis, and indeed TAP is a basic substrate (pKb ) 7.20). Therefore, to check the sensitivity of the CdC double bond to the basicity of the subphase, monolayers of 1 were prepared on 10-4 M aqueous subphases of NaOH (pKb ) -15.00), dimethylamine (pKb ) 3.29) (10), and trimethylamine (pKb ) 4.26) (11). It is evident from Table 1 that these much stronger bases cleave the monolayer much more slowly, relative to TAP. Thus, it can be concluded that the hydrolytic cleavage of the CdC double bond in the monolayer is not greatly influenced by the basicity of the subphase. However, it should be noted that the two weaker organic bases (relative to NaOH) do hydrolyze the monolayer of 1 in a shorter time than NaOH. This anomaly in the behavior of the
Bohanon et al.
inorganic and organic bases can be rationalized, by viewing the organic bases (10 and 11) as more hydrophobic than the hydroxide ion. Thus, the concentration of the organic bases will be greater at the hydrophobic monolayer-covered interface of the subphase; that is, there is a greater effective molarity of hydrophobic organic bases at the interface, relative to that of the hydrophilic inorganic hydroxide ion base. Furthermore, it has to be pointed out that even in the case of the diisopropyl derivative 4 the hydrolysis time (360 min) on a TAP subphase is still much shorter than the hydrolysis time of the unsubstituted compound 1 when on a 10-4 M sodium hydroxide subphase (pH ) 10), when the hydrolysis is still far from complete after 720 min. These hydrolysis times clearly indicate that the cleavage is not just a base-catalyzed reaction but that molecular recognition plays a crucial role in initiating the cleavage of the CdC double bond. A further important point is the fact that no molecular recognition is observed between the N-substituted amphiphiles 2-4 and n-octyl-TAP in CDCl3 or CD3SOCD3 solution, as revealed by 1H NMR spectroscopic studies. Thus, the self-organization of the barbituric acid headgroups, in the monolayers at the air-water interface, makes it energetically and entropically more favorable for the TAP molecules to insert via hydrogen-bonding interactions into the films. Again, tertiary superstructure leads to the function. The insertion mechanism into the monolayer will be discussed later (Figure 3). To further probe the hydrogen bonding interactions in the monolayer formed between 1-4 and TAP molecules, reflection Fourier transform infrared spectroscopy (reflection-FTIR) at the air-water interface was utilized.22,23 It should be noted that (i) the carbonyl bands of 4 at 1587 and 1598 cm-1 found in the monolayer of 4 on an aqueous subphase are shifted when it is on the TAP-containing subphase23 and (ii) the aromatic CdN vibration28 at 1592 cm-1 of TAP in an aqueous solution is shifted when it is inserted into a monolayer of 4. These data strongly suggest that there is some interaction between the amphiphile 4 and TAP. However, manipulation of CPK models of the barbituric acid headgroup of the N,N′diisopropylbarbituric acid amphiphile 4 and TAP shows that it is impossible to have a linear, coplanar strandlike geometric arrangement, as illustrated in Scheme 1, due to the large steric demands of the bulky isopropyl group.16,17 However, by having a nonlinear (crinkled) geometry, which may approach a perpendicular arrangement of the rings of the headgroup of 4 and the TAP molecules (Figure 3a), hydrogen bonding would be permitted despite the bulky isopropyl groups. This type of (22) (a) Dluhy, R. A.; Cornell, D. G. Monolayer Structure at GasLiquid and Gas-Solid Interfaces. Infrared Spectroscopy in Colloid and Interface Science; ACS Symposium Series; American Chemical Society: In Washington, DC, 1991; pp 192-224. (b) Gericke, A.; Hu¨hnerfuss, H. Langmuir 1994, 10, 3782-3786. (c) Gericke, A.; Hu¨hnerfuss, H. Langmuir 1995, 11, 225-230. (d) Gericke, A.; Hu¨hnerfuss, H. Chem. Phys. Lipids 1994, 74, 205-210. (23) Bohanon, T. M.; Denzinger, S.; Fink, R.; Ringsdorf, H.; Weck, M. Angew. Chem. 1995, 107, 102-104; Angew. Chem., Int. Ed. Engl. 1995, 34, 48-50. (24) Zerkowsky, J. A.; Whitesides, J. M. J. Am. Chem. Soc. 1994, 116, 4298-4304. (25) Schellenberger, A. Enzymkatalyse; Springer: Berlin, 1986; p 156. (26) A literature value for the pKb of 6 was not found, though it is known that it can form both a sodium salt and a hydrochloride salt. See: Traube, W. Ber., 1900, 33, 1371-1383. (27) Lyde, D. A., Ed. CRC Handbook of Chemistry and Physics, 72nd ed.; CRC Press: Boca Raton, FL, 1991; p VIII-33. (28) Pretsch, E.; Seibl, J.; Simon, W.; Clerc, T. Strukturaufkla¨ rung organischer Verbindungen, 3rd ed.; Springer: Berlin, 1990, p I45.
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Langmuir, Vol. 15, No. 1, 1999 179
Table 1. Times of Hydrolysis of Monolayers of Amphiphiles 1-5 on Various Subphases
monolayer
substrate in subphasea
1 2 3 4 5 1 1 1 1 1 1 1 1
TAP TAP TAP TAP TAP Mel 6 7 8 9 NaOH 10 11
pKb of substrate in water 7.20 7.20 7.20 7.20 7.20 9.00 11.55 -15.00 3.29 4.26
pHb
no. of hydrogen bondsc
polarization of the double bondd
hydrophobic clefte
surface pressuref (mN m-1)
area/molf (nm2)
time for hydrolysis (min)
6.5 6.5 6.5 6.5 6.5 6.0 6.0 5.8 5.5 4.8 10 8.7 7.9
6 4 4 4 6 6 4 6 4 4 0 0 0
+ + + + + + + + -
+ + + + + + + + + -
5 5 5 5 9 5 5 5 5 5 5 5 5
0.58 0.82 0.82 0.99 1.00 0.58 0.58 0.58 0.58 0.58 0.58 0.58 0.58
15a 120 160 >360 .540 240 185 840 ∞ ∞ .720 300
