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Langmuir 1997, 13, 6354-6356
Reactivity in Monolayers versus Bulk Media: Intra- and Intermolecular Aminolysis of Esters Victor Chechik and Charles J. M. Stirling* Centre for Molecular Materials and Department of Chemistry, The University of Sheffield, Sheffield S3 7HF, U.K. Received April 2, 1997. In Final Form: August 18, 1997X Monolayers possessing reactive amino and p-nitrophenyl ester functional groups at the same or different levels with respect to the monolayer interface have been self-assembled on a gold surface. Intramolecular reactions in these monolayers are at least 1000 times slower than the same processes in the bulk medium. Control experiments with external reagents showed that the monolayer p-nitrophenyl ester group reacts readily with amines from solution, whereas nucleophilicity of the monolayer amino functionality is significantly suppressed. This unusually low reactivity of the amino group was tentatively assigned to its interaction with the gold surface.
Introduction For more than a decade, the self-assembly of thiols as monolayers on gold has been studied in relation to the nature and properties of the layers produced.1 The chemical behavior of the functional groups in such monolayers has been tested with various external reagents.2 It was found that the degree of order and the immediate environment of a functionality in a monolayer can strongly affect its reactivity.3 The consequences of the enforced structure and the degree of flexibility in such systems are important questions which bear upon the effect of order in intramolecular interactions, and we now report our findings on systems designed to throw light on these general questions. We chose the model system shown in Figure 1, which was designed to produce a series of structures in which the intramolecularly reacting groups were set either at the same or at different levels in the monolayer. The functional groups respectively located at each terminus of the arms of the Y-structure were (p-nitrophenoxy)carbonyl and amino. The displacement of the former by reaction with the latter could easily be monitored by grazing angle FT-IR spectroscopy, and the amino group could readily be generated in situ by deprotonation of the corresponding ammonium salt. We have designed reactive substrates 1-3 (Chart 1) as adsorbates for monolayer preparation. Deprotonation of the monolayers with non-nucleophilic base (2,2,6,6-tetramethylpiperidine, pKa 11.07) established the experimental system. For comparison of the intramolecular reaction within the monolayer with that of the substrate in bulk solution, substrate 7 has been synthesized (Scheme 1).4
Figure 1. Schematic illustration of a bifunctional monolayer with two reactive functional groups (X and Z) incorporated therein. Chart 1
Experimental Section Preparation of Monolayers. Gold substrates were prepared by thermal evaporation of 5 nm of Cr followed by 100 nm of Au X Abstract published in Advance ACS Abstracts, November 1, 1997.
(1) (a) Ulman, A. An Introduction to Ultrathin Organic Films: From Langmuir-Blodgett to Self-Assembly; Academic Press: New York, 1991. (b) Bain, C. D.; Troughton, E. B.; Tao, Y.-T.; Evall, J.; Whitesides, G. M.; Nuzzo, R. G. J. Am. Chem. Soc. 1989, 111, 321-335. (c) Ulman, A. Chem. Rev. 1996, 96, 1533-1554. (d) Bain, C. D.; Whitesides, G. M. Angew. Chem., Int. Ed. Engl. 1989, 28, 506-512. (2) (a) Balachander, N.; Sukenik, C. N. Langmuir 1990, 6, 16211627. (b) Lee, Y. W.; Reed-Mundell, J.; Zull, J. E.; Sukenik, C. N. Langmuir 1993, 9, 3009-3014. (c) Wasserman, S. R.; Tao, Y.-T.; Whitesides, G. M. Langmuir 1989, 5, 1074-1087. (3) (a) Liu, M.; Nakahara, H.; Shibasaki, Y.; Fukuda, K. Chem. Lett. 1993, 967-970. (b) Ahmad, J.; Astin, K. B. Langmuir 1990, 6, 17971799. (c) Fryxell, G. E.; Rieke, P. C.; Wood, L. L.; Engelhard, M. H.; Williford, R. E.; Graff, G. L.; Campbell, A. A.; Wiacek, R. J.; Lee, L.; Halverson, A. Langmuir 1996, 12, 5064-5075.
S0743-7463(97)00343-0 CCC: $14.00
onto silicon wafers which were precleaned by heating in piranha solution (7:3 mixture of concentrated sulfuric acid and 30% hydrogen peroxide) at 90 °C for 1 h. Caution! Piranha solution reacts violently with almost any organic materials and should be handled with utmost care! Gold substrates used in SPR experiments were prepared by evaporation of 3 nm of Cr and 50 nm of Au onto precleaned glass microscope slides. Prior to deposition of monolayers, the gold substrates were treated with piranha solution or concentrated HNO3 for 10 min, washed exhaustively with water and ethanol, and dried. Monolayers were prepared by dipping the precleaned substrates into 1 mM solutions of disulfides for 16 h at room temperature. We used tetrahydrofuran and dichloromethane for deposition of (4) Disulfides 1-3 cannot be used for unambiguous control experiments in bulk medium because of the possibility of an attack by an amino group from one “half” of the disulfide at the p-nitrophenyl group from another “half”.
© 1997 American Chemical Society
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Langmuir, Vol. 13, No. 24, 1997 6355 Scheme 1
Figure 2. Typical rate plot for the reaction of monolayer 1 with n-butylamine. I is the integral intensity of the 1532 cm-1 ν(NO2) peak.
monolayers 1-3 and 4-6, respectively. The substrates were then rinsed with dichloromethane/tetrahydrofuran and ethanol and dried. Instrumentation. IR spectra of monolayers were determined with a Perkin-Elmer 1725 X instrument fitted with an MCT detector and a grazing angle accessory (Spectra-Tech Inc., angle of incidence 80˚). Freshly cleaned (concentrated HNO3, 10 min) bare gold slides were used as background. The sample compartment of the spectrometer was purged with nitrogen to prevent interference from water vapor. SPR data were acquired using an instrument built in these laboratories, giving a resonance angle resolution of 0.006°. The values of thickness were calculated from the shift of resonance angle using the standard Fresnel equation.5 The refractive index of the monolayer films was assumed to be 1.45.6 Contact angles were recorded with a CCD camera attached to a Power Macintosh computer. Water drops (1 µL) were generated with a micrometer syringe (Agla). Electronic images of sessile, advancing, and receding drops were stored in the computer and analyzed using ClarisDraw software. At least three drops were analyzed for each slide. Kinetic Measurements. Slides were immersed in thermostated amine solutions in ethyl acetate (1% w/w) at 22.0 ( 0.5 °C. At intervals, slides were withdrawn, washed with ethanol, dried, and analyzed by IR spectroscopy. A pseudo first-order equation was used to calculate the rate constants. The integral intensities of the ester and both nitro peaks were shown to produce the same values of reaction rates within experimental error. We believe that the use of the first order approximation is appropriate, as it is widely used to describe physical surface events, such as adsorption or desorption of monolayers.7 All kinetic data reported are the average of at least 2 runs. A typical example of the kinetic plot is shown in Figure 2. For kinetic runs in bulk media the conversion of 7 to 8 was monitored by the appearance of p-nitrophenol at 310 nm. The same conditions as for monolayer kinetics were used (1% w/w solution of 2,2,6,6-tetramethylpiperidine in ethyl acetate, 22 °C). The reaction was found to be zeroth order with respect to the concentration of 2,2,6,6-tetramethylpiperidine and first order with respect to the concentration of the substrate in the concentration range used (10-5 to 10-4 M). Materials. Synthesis of reactive substrates 1-3 was achieved by routine peptide synthesis procedures. Boc-cystinylaminocaproic acid p-nitrophenyl ester8 was deprotected with trifluoroacetic acid and coupled with the corresponding Boc-amino acids using the mixed anhydride method9 to give compounds 4-6. Deprotection of these materials afforded disulfides 1-3. Sulfide 7 was synthesized similarly from S-benzyl-N-Boc-L-cysteine. The (5) Hansen, W. N. J. Opt. Soc. Am. 1968, 58, 380-390. (6) Peterlinz, K. A.; Georgiadis, R. Langmuir 1996, 12, 4731-4740. (7) DeBono, R. F.; Loucks, G. D.; Manna, D. D.; Krull, U. J. Can. J. Chem. 1996, 74, 677-688. (8) Chechik, V.; Stirling, C. J. M. Langmuir, in press.
optical purity of the reaction products was not investigated. All Boc-protected compounds were purified by flash chromatography and fully characterized by IR, 1H NMR spectroscopy, and elemental analysis. Compound 8 was isolated from the reaction mixture and characterized by IR and 1H NMR spectroscopy. p-Nitrophenyl perfluorooctanoate was synthesized from perfluorooctanoyl chloride (Aldrich) and p-nitrophenol in the presence of triethylamine. Full details of the synthesis of the above compounds are included in the Supporting Information to this paper.
Results and Discussion Compounds 1-3 were deposited as monolayers on a gold surface. The SPR measured thickness was 25, 25, and 31 Å for monolayers 1-3, respectively. This is slightly greater than the estimated length of the fully stretched molecules 1-3 (22, 22, and 27 Å, respectively). We believe that the discrepancy could be explained by the underestimation of the value of the refractive index of the film (see Experimental Section).6 Good correspondence between theoretical and experimental values of thickness suggests that the gold surface is fully covered with monolayers. The location of the ν(CH2) stretching peaks at 2934 and 2859 cm-1 in the FT-IR spectra suggests that the monolayers are disordered, and the high sessile water contact angles (67°), independent of structure, support this conclusion.10 The high intensities of the νa(NO2), νs(NO2), and ν(CdO) peaks at 1532, 1350, and 1767 cm-1, respectively, allowed reactions of the monolayers to be followed by FT-IR spectroscopy. To further test the coverage of the monolayers, we exposed monolayer 1 to a 1 mM solution of octadecanethiol in ethanol. If the original monolayer 1 is incomplete, we would expect octadecanethiol to fill in the voids in it (octadecanethiol does not displace compound 1, as monolayers containing amide groups are known to be resistant to replacement11). However, after 12 h of exposure the FT-IR spectrum was identical with that of the original monolayer, and there was hardly any increase in the intensity in the CH3 and CH2 regions. This is in agreement with the proposed complete coverage. When monolayers of substrates 1-3 were immersed in a 1 w/w % ethyl acetate solution of 2,2,6,6-tetramethylpiperidine to effect deprotonation of the ammonium (9) Meienhofer, J. In The Peptides: Analysis, Synthesis, Biology; Gross, E., Meienhofer, J., Eds.; Academic Press: New York, 1979; Vol. 1, pp 263-314. (10) (a) Yu, H. Z.; Zhao, J. W.; Wang, Y. Q.; Cheng, J. Z.; Gai, S. M.; Liu, Z. F. Gaodeng Xuexiao Huaxue Xuebao 1995, 16 (N 11 Supplements), 138-143. (b) Sprik, M.; Delamarche, E.; Michel, B.; Ro¨thlisberger, U.; Klein, M. L.; Wolf, H.; Ringsdorf, H. Langmuir 1994, 10, 4116-4130. (c) Kurth, D. G.; Bein, T. Langmuir 1993, 9, 2965-2973. (11) Tamchang, S. W.; Biebuyck, H. A.; Whitesides, G. M.; Jeon, N.; Nuzzo, R. G. Langmuir 1995, 11, 4371-4382.
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groups, no decrease in the intensities of the NO2 stretching frequencies, presaging departure of the p-nitrophenoxy group, was observed after 12 h. After longer periods of immersion, the infrared spectra of the monolayers showed a slow general loss of intensity, which can be attributed to desorption of the monolayer material from the gold surface or to reaction with traces of adventitious water in the solvent. Similar monolayer substrates but lacking an amino group (4-6) were found to lose infrared intensity at a comparable rate. We estimate a maximum rate constant (if any at all) for the intramolecular processes in monolayers 1-3 at 1 × 10-6 s-1. For comparison, the conversion of 7 to 8 under the same conditions in bulk medium had a rate constant of 1.4 × 10-3 s-1 or ca. 1000 times larger than those of any intramolecular process in the monolayers. The failure of all of the substrates 1-3 to react by intramolecular acyl transfer is clearly contrary to the expectation that enforced juxtaposition of the functional groups would promote interaction. At least one potentially favorable disposition of the functionalities can surely be envisaged. Even if the monolayers are completely disordered, their intramolecular reactivity should not be lower than that of the substrates in bulk medium. In seeking to understand this phenomenon further, we tested each of the two functional groups (amino and p-nitrophenoxycarbonyl) separately in reactions between monolayers and external reagents. Each of the monolayers 1-3 was immersed in a 1 w/w % solution of n-butylamine in ethyl acetate. Rapid disappearance of nitro peaks in the FT-IR spectra was observed, and clearly the monolayer ester functional group is more accessible to an external amino nucleophile than one in the monolayer itself. In each reaction of the three monolayers 1-3, the second-order rate constant was ca. 0.3 dm3 mol-1 s-1, comparable with the values of 0.1-0.2 dm3 mol-1 s-1 obtained earlier with related compounds in monolayers.8 Monolayers 1-3 react with n-butylamine even faster than the model p-nitrophenyl ester of Boc5-aminohexanoic acid in bulk medium.8 Clearly, there is no inhibition of the reactivity of the monolayer ester function. The reactivity of the monolayer amino functions was probed by treatment of the monolayers with p-nitrophenyl esters of stearic12 and perfluorooctanoic acids in the presence of 2,2,6,6-tetramethylpiperidine to ensure deprotonation. Reactions were monitored by following any increase of the infrared intensities of the ν(CH2) or ν(CF2) bands at 2930 and 1250 cm-1, respectively, on incorporation of the acyl moieties of the ester. In blank experiments with monolayers of substrates 4-6 containing amino groups protected as controls, no reaction was observed on the time scale used. Surprisingly, for monolayers of substrate 1, no reaction with p-nitrophenyl stearate was seen during 3 days, either, and even a simple model aminoterminated monolayer of 2-aminoethanethiol showed only slow incorporation of stearate. The rate constant for this reaction was ca. 3.5 × 10-3 dm3 mol-1 s-1, only about 1% of that for the aforementioned reaction with amine in solution and p-nitrophenyl ester in the monolayers 1-3. (12) Kreisky, S. Acta Chem. Scand. 1957, 11, 913-914.
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Figure 3. IR spectra of the monolayer of 3 (a) after deposition, (b) after exposure to a 1% solution of p-nitrophenyl perfluorooctanoate for 5 min, and (c) after treatment sequentially with p-nitrophenyl perfluorooctanoate and n-butylamine.
When the much more electrophilic p-nitrophenyl perfluorooctanoate is used,13 reaction is rapid with all three monolayers 1-3 demonstrating the availability of the amino group in the monolayer. The reaction sequence is illustrated in Figure 3, showing the incorporation of the fluoroacyl group into the monolayer via an external perfluoroester and the subsequent removal of the pnitrophenoxy group by an external amine. The failure to observe intramolecular as opposed to intermolecular reactions in the monolayers 1-3 clearly points to suppression of the nucleophilicity of the amino group. The reasons for such a marked effect are not yet clear. Close packing and the high steric demands of selfassembled monolayers can hardly account for the phenomenon when the same type of reaction with an external nucleophile occurs readily. Quite probably the amino groups in the monolayer interact directly or indirectly with the gold surface,14 which would limit but not prevent their interaction with electrophiles. The fact that the contact angles for monolayers 1-3 are all the same in spite of the amino group being on a long chain in 3 suggests that the hydrophilic amino group is close to the gold surface, hidden away from the monolayer-solution interface. Further experiments are under way to test this hypothesis. Supporting Information Available: Details of the synthesis of compounds 1-8 and p-nitrophenyl perfluorooctanoate (3 pages). Ordering information is given on any current masthead page. LA970343J (13) p-Nitrophenyl trifluoroacetate is 106 times more reactive toward n-butylamine than the corresponding acetate (Singh, T. D.; Taft, R. W. J. Am. Chem. Soc. 1975, 97, 3867-3869. Su, C.-W.; Watson, J. W. J. Am. Chem. Soc. 1974, 96, 1854-1857). (14) (a) Leff, D. V.; Brandt, L.; Heath, J. R. Langmuir 1996, 12, 47234730. (b) Xu, C. J.; Sun, L.; Kepley, L. J.; Crooks, R. M.; Ricco, A. J. Anal. Chem. 1993, 65, 2102-2107. (c) Wang, J.; Zhu, T.; Tang, M.; Cai, S. M.; Liu, Z. F. Jpn. J. Appl. Phys. Part 2 1996, 35, L1381-L1384.
