Crystallization of Amino Acids on Self-Assembled ... - ACS Publications

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Crystallization of Amino Acids on Self-Assembled Monolayers of Rigid Thiols on Gold Alfred Y. Lee,†,‡ Abraham Ulman,†,§ and Allan S. Myerson*,‡ Department of Chemical and Environmental Engineering, Illinois Institute of Technology, Chicago, Illinois 60616, and Department of Chemical Engineering, Chemistry and Material Science, and the NSF MRSEC for Polymers at Engineered Interfaces, Polytechnic University, Brooklyn, New York 11201 Received March 6, 2002. In Final Form: May 3, 2002 Self-assembled monolayers (SAMs) of rigid biphenyl thiols are employed as heterogeneous nucleants for the crystallization of L-alanine and DL-valine. Powder X-ray diffraction and interfacial angle measurements reveal that the L-alanine crystallographic planes corresponding to nucleation are {200}, {020}, and {011} on SAMs of 4′-hydroxy-(4-mercaptobiphenyl), 4′-methyl-(4-mercaptobiphenyl), and 4-(4mercaptophenyl)pyridine on gold (111) surfaces, respectively. In the case of DL-valine, monolayer surfaces that act as hydrogen bond acceptors (e.g., 4′-hydroxy-(4-mercaptobiphenyl) and 4-(4-mercaptophenyl)pyridine) induce the racemic crystal to nucleate from the {020} plane whereas the nucleating plane for the 4′-methyl-(4-mercaptobiphenyl) surface is the fast-growing {100} face. The observation of crystal nucleation and orientation can be attributed to the strong interfacial interactions, in particular, hydrogen bonding, between the surface functionalities of the monolayer film and the individual molecules of the crystallizing phase. Molecular modeling studies are also undertaken to examine the molecular recognition process across the interface between the surfactant monolayer and the crystallographic planes. Similar to binding studies of solvents and impurities on crystal habit surfaces, binding energies between SAMs and particular amino acid crystal faces are calculated and the results are in good agreement with the observed nucleation planes of the amino acids. In addition to L-alanine and DL-valine, the interaction of SAMs and mixed SAMs of rigid thiols on the morphology of R-glycine is examined (Kang, J. F.; Zaccaro, J.; Ulman, A.; Myerson, A. Langmuir 2000, 16, 3791), and similarly the calculations are in good agreement. These results suggest that binding energy calculations can be a valid method to screen self-assembled monolayers as potential templates for nucleation and growth of organic and inorganic crystals.

I. Introduction Crystallization from solution is a two-step process: nucleation, the birth of a crystal, and crystal growth, the growth of the crystal to larger sizes.2 In this process, prenucleation aggregates (or clusters) are formed by individual molecules, which become stable nuclei, upon reaching a critical size, and further grow into macroscopic crystals. Homogeneous nucleation is very rare and requires high supersaturation to surmount the activation barrier, ∆Gcrit. However, for a fixed supersaturation the activation barrier can be lowered by decreasing the surface energy of the aggregate, for instance, by introducing a foreign surface or substance.3 This foreign surface (or substance) includes “tailor-made” additives,4 impurities,5 organic single crystals,6 Langmuir monolayers7 floating * To whom correspondence should be addressed. Phone: 312 567 7010. Fax: 312 567 7018. E-mail: [email protected]. † Polytechnic University. ‡ Illinois Institute of Technology. § NSF MRSEC for Polymers at Engineered Interfaces. (1) Kang, J. F.; Zaccaro, J.; Ulman, A.; Myerson, A. Langmuir 2000, 16, 3791. (2) (a) Myerson, A. S. Handbook of Industrial Crystallization, 2nd ed.; Butterworth-Heinemann: Boston, 2002. (b) Myerson, A. S. Molecular Modeling Applications in Crystallization; Cambridge University Press: New York, 1999. (c) Mullin, J. W. Crystallization, 4th ed.; Butterworth-Heinemann: Boston, 2001. (3) Turnbull, D. J. Chem. Phys. 1949, 18, 198. (b) Fletcher, N. H. J. Chem. Phys. 1963, 38, 237. (4) Weissbuch, I.; Lahav, M.; Leiserowitz, L. In Molecular Modeling Applications in Crystallization; Myerson, A. S., Ed.; Cambridge University Press: New York, 1999; p 166. (5) Meenan, P. A.; Anderson, S. R.; Klug, D. L. In Handbook of Industrial Crystallization, 2nd ed.; Myerson, A. S., Ed.; Butterworth Heinemann: Boston, 2002; p 67. (6) Carter, P. W.; Ward, M. D. J. Am. Chem. Soc. 1993, 115, 11521.

at the air-water interface, and self-assembled monolayers (SAMs) immersed in solution.1 Tailor-made additives or auxiliaries are designer impurities that have one part which resembles the crystallizing species and another part that is chemically or structurally different from the solute molecule.4,8 These additives disrupt the bonding sequence in the crystals, thereby lowering the growth rate of the affected faces as evident in the case of L-alanine where hydrophobic amino acids such as L-leucine and L-valine inhibited the development of specific crystal faces, while in the presence of hydrophilic amino acids the crystal morphology did not change.9 In addition to being habit modifiers, these molecular additives can also control polymorphism, where the impurities inhibit the growth of one polymorph and, in turn, promote the growth of the other polymorph.10 Nucleation promoters such as organic single crystals and self-assembled monolayers have also been used to control polymorph selectivity, based on geometric matching between the molecular clusters and the ledges of the crystal substrates11 and interfacial hydrogen bonding between the monolayer film and solute clusters,12 respec(7) (a) Rapaport, H.; Kuzmenko, I.; Berfeld, M.; Kjaer, K.; Als-Nielsen, J.; Popovitz-Biro, R.; Weissbuch, I.; Lahav, M.; Leiserowitz, L. J. Phys. Chem. B 2000, 104, 1399. (b) Frostman, L. M.; Ward, M. D. Langmuir 1997, 13, 330. (8) (a) Berkovitch-Yellin, Z.; Ariel, S.; Leiserowitz, L. J. Am. Chem. Soc. 1985, 105, 765. (b) Addadi, L.; Weinstein, S.; Gate, E.; Weissbuch, I.; Lahav, M. J. Am. Chem. Soc. 1982, 104, 4610. (9) Li, L.; Lechuga-Ballesteros, D.; Szkudlarek, B. A.; RodriguezHornedo, N. J. Colloid Interface Sci. 1994, 168, 8. (10) (a) Weissbuch, I.; Lahav, M.; Leiserowitz, L. Adv. Mater. 1994, 6, 952. (b) Davey, R. J.; Blagden, N.; Potts, G. D.; Docherty, R. J. Am. Chem. Soc. 1997, 119, 1767.

10.1021/la025704w CCC: $22.00 © 2002 American Chemical Society Published on Web 06/22/2002

Crystallization of Amino Acids on Thiol SAMs

tively. Similar to Langmuir monolayers, self-assembled monolayers can be used as an interface across which stereochemical matching13 and hydrogen bonding14 interaction can transfer order and symmetry from the monolayer surface to a growing crystal. However, SAMs and mixed SAMs15 lack the mobility of molecules at an air-water interface and hence the possibility to adjust lateral positions to match a face of a nucleating crystal. This is clearly evident in the case of the SAMs of rigid biphenyl thiols, where even conformational adjustment is not possible. Recently, SAMs of 4-mercaptobiphenyl have been shown to be more superior to those of alkanethiolates and are stable model surfaces.16 Furthermore, the ability to engineer surface functionalities at the molecular level makes SAMs of rigid thiols very attractive as templates for heterogeneous nucleation. Organosilane monolayer films have been used to promote nucleation and growth of calcium oxalate monohydrate crystals17 and have been employed in “biomimetic” synthesis as observed in the oriented growth of CaCO318 and iron hydroxide crystals.19 Functionalized SAMs of alkanethiols have also been shown to control the oriented growth of CaCO3.20 This was also evident in the heterogeneous nucleation and growth of malonic acid crystals21 on alkanethiolate SAMs on gold where the monolayer composition strongly influenced the orientation of the malonic acid crystals. Additionally, functionalized alkanethiolate SAMs have enhanced the growth of protein crystals.22 More recently, SAMs and mixed SAMs of rigid thiols served as templates.1 It was observed that glycine nucleated in the R-form independent of the hydroxyl and pyridine surface concentration and the morphology of the glycine crystal was very sensitive to the OH and pyridine site densities. Self-assembled monolayers on solid surfaces offer many advantages for enhanced crystal nucleation. In this work, SAMs of rigid thiols on gold are employed to investigate the effects of interfacial molecular recognition on nucleation and growth of L-alanine and DL-valine crystals. In addition, molecular modeling techniques are employed to examine the affinity between monolayer surfaces and particular amino acid crystal faces and to gain a better understanding of the molecular recognition events occurring. The modeling techniques employed are similar to studies of solvent and additive interactions on crystal (11) (a) Bonafede, S. J.; Ward, M. D. J. Am. Chem. Soc. 1995, 117, 7853. (b) Mitchell, C. A.; Yu, L.; Ward, M. D. J. Am. Chem. Soc. 2001, 123, 10830. (12) Carter, P. W.; Ward, M. D. J. Am. Chem. Soc. 1994, 116, 769. (13) (a) Landau, E. M.; Levanon, M.; Leiserowitz, L.; Lahav, M.; Sagiv, J. Nature 1985, 318, 353. (b) Weissbuch, I.; Berfeld, M.; Bouwman, W.; Kjaer, K.; Als, J.; Lahav, M.; Leiserowitz, L. J. Am. Chem. Soc. 1997, 119, 933. (14) Weissbuch, I.; Popvitz, R.; Lahav, M.; Leiserowitz, L. Acta Crystallogr. 1995, B51, 115. (15) For a review on SAMs of thiols on gold see: (a) Ulman, A. An Introduction to Ultrathin Organic Films: From Langmuir-Blodgett to Self-Assembly; Academic Press: Boston, 1991. (b) Ulman, A. Chem. Rev. 1996, 96, 1533. (16) (a) Kang, J. F.; Ulman, A.; Liao, S.; Jordan, R. J. Am. Chem. Soc. 1998, 120, 9662. (b) Kang, J. F.; Jordan, R.; Ulman, A. Langmuir 1998, 14, 3983. (17) Campbell, A. A.; Fryxell, G. E.; Graff, G. L.; Rieke, P. C.; Tarasevich, B. J. Scanning Microsc. 1993, 7 (1), 423. (18) Archibald, D. D.; Qadri, S. B.; Gaber, B. P. Langmuir 1996, 12, 538. (19) Tarasevich, B. J.; Rieke, P. C.; Liu, J. Chem. Mater. 1996, 8, 292. (20) Aizenberg, J.; Black, A. J.; Whitesides, G. M. J. Am. Chem. Soc. 1999, 121, 4500. (21) Frostman, L. M.; Bader, M. M.; Ward, M. D. Langmuir 1994, 10, 576. (22) Ji, D.; Arnold, C. M.; Graupe, M.; Beadle, E.; Dunn, R. V.; Phan, M. N.; Villazana, R. J.; Benson, R.; Colorado, R., Jr.; Lee, T. R.; Friedman, J. M. J. Cryst. Growth 2000, 218, 390.

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Figure 1. Rigid 4′-substituted 4-mercaptobiphenyls.

habit23 but have never been applied to organic monolayer films as templates for nucleation. II. Experimental Section Materials. Anhydrous ethanol was obtained from Pharmco (Brookfield, CT). L-Alanine (CH3CH(NH2)CO2H), and DL-valine ((CH3)2CHCH(NH2)CO2H) were purchased from Aldrich and used without further purification. Distilled water purified with a Milli-Q water system (Millipore) was used. Details of the synthesis of the 4′-substituted 4-mercaptobiphenyl (see Figure 1) are described elsewhere.24 Gold Substrate and Monolayer Preparation. Glass slides were cleaned in ethanol in an ultrasonic bath at 40 °C for 10 min. The slides were next treated in a plasma chamber at an argon pressure of 0.1 Torr for 30 min. Afterward, they were mounted in the vacuum evaporator (Key High Vacuum) on a substrate holder, approximately 15 cm above the gold cluster. The slides were baked overnight in a vacuum (10-7 Torr) at 300 °C. Gold (purity > 99.99%) was evaporated at a rate of 3-5 Å/s until the film thickness reached 1000 Å; the evaporation rate and film thickness were monitored with a quartz crystal microbalance (TM100 model from Maxtek Inc.). The gold substrates were annealed in a vacuum at 300 °C for 18 h. After cooling to room temperature, the chamber was filled with high-purity nitrogen and the gold slides were either placed into the adsorbing solution right after the ellipsometric measurement was performed or stored in a vacuum desiccator for later use.25 Atomic force microscopy (AFM) studies24 revealed terraces of Au(111) with typical crystalline sizes of 0.5-1 µm2. Monolayers were formed by overnight (∼18 h) immersion of clean substrates in 10 µm ethanol solutions of the thiols. The substrates were removed from the solution, rinsed with copious amounts of absolute ethanol to remove unbound thiols, and blown dry with a jet of nitrogen. Contact angle measurements, IR spectroscopy, and ellipsometry showed that after 1 h, 90% or more of the SAMs are formed.26 Thus, to ensure equilibrium SAMs, the gold substrates were left overnight in the dipping solution. Crystal Growth. Nucleation and growth experiments were carried out in Quartex jars (1 oz.) at 25 °C. Supersaturated solutions (25%) of L-alanine and DL-valine were obtained by dissolving 4.58 g and 1.95 g in 22.0 g of Millipore water, respectively. The solutions were heated to 65 °C for 90 min in an ultrasonic bath to obtain complete dissolution. The solutions were cooled to room temperature for 90 min before the SAMs were carefully introduced and aligned vertically to the wall. Macrocrystals of L-alanine and DL-valine nucleated at the surfaces (23) (a) Docherty, R.; Meenan, P. In Molecular Modeling Applications in Crystallization; Myerson, A. S., Ed.; Cambridge University Press: New York, 1999; p 106. (b) Myerson, A. S.; Jang, S. M. J. Cryst. Growth 1995, 156, 459. (c) Walker, E. M.; Roberts, K. J.; Maginn, S. J. Langmuir 1998, 14, 5620. (d) Evans, J.; Lee, A. Y.; Myerson, A. S. In Crystallization and Solidification Properties of Lipids; Widlak, N., Hartel, R. W., Narine, S., Eds.; AOCS Press: Champaign, IL, 2001; p 17. (24) Kang, J. F.; Ulman, A.; Liao, S.; Jordan, R.; Yang, G.; Liu, G. Langmuir 2001, 17, 95. (25) (a) Jordan, R.; Ulman, A. J. Am. Chem. Soc. 1998, 120, 243. (b) Jordan, R.; Ulman, A.; Kang, J. F.; Rafailovich, M.; Sokolov, J. J. Am. Chem. Soc. 1999, 121, 1016. (26) Ulman, A. Acc. Chem. Res. 2001, 34, 855.

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III.2. Lattice Energy Calculation. The lattice energy Elat, also known as the cohesive or crystal binding energy, is calculated by summing all the atom-atom interactions between a central molecule and all the surrounding molecules in the crystal. If the central molecule and the n surrounding molecules each have n′ atoms, then n

Elat )

n′

n′

∑ ∑ ∑Vkij

(1)

k)1 i)1 j)1

where Vkij is the interaction between atom i in the central molecule and atom j in the kth surrounding molecules. Comparison to the “experimental” lattice energy, Vexp, allows us to assess the accuracy of the intermolecular interactions between the molecules by the defined potential function. Figure 2. Overall scheme showing the computational methodology adopted when calculating the binding energy between the crystallographic plane and the monolayer surface. and near the edge of the substrates. Only crystals having visible SAM area around them were considered, and the rest were discarded. The chosen crystals attached to the substrates were removed from the solution and stored in a vacuum desiccator for later analysis. Due to the strong adhesion of the crystal face to the SAM surface, gold marks were often observed on the crystal face that nucleated on the SAM surface. Characterization. A Rudolph Research AutoEL ellipsometer was used to measure the thickness of the monolayer surface. The He-Ne laser (632.8 nm) light fell at 70° on the sample and reflected into the analyzer. Data were taken over five to seven spots on each sample. The measured thickness of the SAMs of biphenyl thiols ranged from 12 to 14 Å, assuming a refractive index of 1.462 for all films. Powder X-ray diffraction patterns of crystalline L-alanine and DL-valine were obtained with a Rigaku Miniflex diffractometer with Cu KR radiation (λ ) 1.5418 Å). All samples were manually ground into fine powder and packed in glass slides for analysis. Data were collected from 5° to 50° with a step size of 0.1°. Crystal habits of L-alanine and DL-valine were indexed by measuring the interfacial angles using a two-circle optical goniometer. All possible measured interfacial angles were compared with the theoretical values derived from the unit cell parameters of L-alanine and DL-valine crystals.27,28

III. Modeling Section III.1. General. All of the binding energy calculations, including molecular mechanics and dynamics simulations, are carried out with the program Cerius2. The overall methodology and procedures are summarized in Figure 2. The crystal structures of each amino acid are obtained from the Cambridge Crystallographic Database (ref codes GLYCIN17, LALNIN12, and VALIDL for R-glycine, Lalanine, and DL-valine, respectively). To accurately predict the crystal morphology, molecular mechanics simulations using a suitable potential function (or force field) are performed. In this work, molecular simulations are carried out using the DREIDING 2.21 force field.29 The van der Waals forces are approximated with the Lennard-Jones 12-6 expression, and hydrogen bonding energy is modeled using a Lennard-Jones-like 12-10 expression. The Ewald summation technique is employed for the summation of long-range van der Waals and electrostatic interactions under the periodic boundary conditions, and the charge distribution within the molecule is calculated using the Gasteiger method.30 (27) Simpson, H. J.; Marsh, R. E. Acta Crystallogr. 1966, 20, 550. (28) Mallikarjunan, M.; Rao, S. T. Acta Crystallogr. 1969, B25, 296. (29) Mayo, S. L.; Olafson, B. D.; Goddard, W. A., III J. Phys. Chem. 1990, 94, 8897.

Vexp ) -∆Hsub - 2RT

(2)

where the term 2RT represents a compensation factor for the difference between the vibrational contribution to the crystal enthalpy and gas-phase enthalpy31 and ∆Hsub is the experimental sublimation energy. III.3. Morphological Predictions. The morphology of each amino acid crystal is predicted using the attachment energy (AE)32 calculation and the Bravais-FriedelDonnay-Harker (BFDH) law.33 The habit or shape of the crystal depends on the growth rate of the faces present. Faces that are slow growing have the greatest morphological importance, and conversely, faces that are fast growing have the least morphological importance and are the smallest faces on the grown crystal. The simplest morphological simulation is the BFDH law which assumes that the linear growth rate of a given crystal face is inversely proportional to the corresponding interplanar distance after taking into account the extinction conditions of the crystal space group. The attachment energy of a crystal face is the difference between the crystal energy and the slice energy. Hartman and Bennema32 found that the relative growth rate of a face is directly proportional to the attachment energy and as a result, the more negative the attachment energy (or more energy released) for a particular face, the less prominent that face is on the crystal. Conversely, faces with the lowest attachment energies are the slowest growing faces and thus have the greatest morphological importance. III.4. Molecular Modeling of SAMs of 4-Mercaptobiphenyls on a Au(111) Surface. Molecular dynamics (MD) simulations are useful techniques in gaining insights on the structural and dynamical properties of selfassembled monolayers. In contrast to molecular mechanics, molecular dynamics computes the forces and moves the atom in response to forces, while molecular mechanics computes the forces on the atoms and changes their position to minimize the interaction energy. Recently, MD simulations have been used to investigate the packing order and orientation of rigid 4-mercaptobiphenyl thiol monolayers on gold surfaces. Results show that hydrogenterminated biphenylmercaptan packs in the herringbone conformation34 and suggest average tilt angles of 8°. (30) Gasteiger, J.; Marsili, M. Tetrahedron 1980, 36, 3219. (31) Williams, D. E. J. Phys. Chem. 1966, 45, 3370. (32) (a) Hartman, P.; Bennema, P. J. Cryst. Growth 1980, 49, 145. (33) (a) Bravais, A. Etudes Crystallographiques; Gauthier-Villars: Paris, 1866. (b) Friedel, M. G. Bulletin de la Societe Francaise de Mineralogie 1907, 30, 326. (c) Donnay, J. D.; Harker, D. Am. Mineral. 1937, 22, 446.


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The binding energy (φBE) of each crystallographic surface with the monolayer surface is

φBE ) φIE - (φM + φS)

Figure 3. Snapshots of (a) 4′-methyl-4-mercaptobiphenyl, (b) 4′-hydroxy-4-mercaptobiphenyl, (c) 4-(4-mercaptophenyl)pyridine, and (d) mixed SAMs of 4′-methyl-4-mercaptobiphenyl and 4′-hydroxy-4-mercaptobiphenyl (top view).

Based on this work, molecular mechanics simulations are performed for hydroxy- and methyl-terminated 4-mercaptobiphenyl along with 4-(4-mercaptophenyl)pyridine for binding studies with different crystallographic planes. In the periodic model, each unit cell contains four biphenyl molecules and the geometric parameters are a ) 10.02 Å, b ) 42.25 Å, c ) 10.11 Å and R ) 138.3°, β ) 119.9°, γ ) 95.7°. The length in the y-direction is set to ∼42 Å to ensure two-dimensional periodicity. Also, the gold atoms are arranged in a hexagonal lattice along the XY plane with a nearest neighbor atom of 2.88 Å, and the biphenyl occupied a (x3 × x3)R30° Au(111) lattice. To simulate different 4′-substituted 4-mercaptobiphenyls, minimization was carried out by fixing the biphenyl moiety and varying the substituents at the 4′-position. As a result, the simulated models yielded uniform ordered SAMs of 4′-substituted 4-mercaptobiphenyls and 4-(4-mercaptophenyl)pyridine with identical packing structure and dynamics to those of a hydrogen-terminated monolayer of biphenylmercaptan (Figure 3). However, this is not true experimentally since adsorption of different 4′-substituted 4-mercaptobiphenyls on gold surfaces results in different monolayer structures and thus one of the main assumptions made in this work. III.5. Binding of Crystal Habit Faces to SAMs of 4-Mercaptobiphenyls on a Au(111) Surface. Based on BFDH and attachment energy morphology prediction, crystal habit faces with the highest morphological importance are chosen for binding studies. The crystal surfaces of interest are cleaved and extended to a 3 × 3 unit cell and partially fixed, allowing flexibility in the tail atoms of the amino acid molecules and a more accurate representation of the effects of SAMs of rigid thiols on the crystallographic plane in the calculation of binding energies. The crystal surface is then docked onto a 3 × 1 × 3 partially fixed nonperiodic monolayer surface, and the conjugate gradient energy minimization technique is performed. Next, the crystal surface is moved to another site on the monolayer surface and the minimization calculations are again performed. This process was repeated 15-20 times to obtain the global minimum. For each monolayer surface, numerous calculations are carried out with different crystallographic planes of each amino acid. (34) Ulman, A.; Kang, J. F.; Shnidman, Y.; Liao, S.; Jordan, R.; Choi, G. Y.; Zaccaro, J.; Myerson, A. S.; Rafailovich, M.; Sokolov, J.; Flesicher, C. Rev. Mol. Biotech. 2000, 74, 175.

(3)

where φIE is the minimum interaction energy of the monolayer and crystal surfaces, φM is the minimum energy of the monolayer surface in the absence of the crystal face but in the same conformation as it adopts on the surface, and φS is the minimum energy of the crystal surface with no monolayer surface present and in the same molecular conformation in which it docks on the surface. Negative values of binding energies indicate preferential binding of the crystallographic surfaces with SAMs of 4-mercaptobiphenyl. In cases where the binding energy is positive, there is a less likely chance that the particular crystal face will interact and nucleate on the monolayer surface. Thus, using this approach it is possible to screen self-assembled monolayers as possible templates for nucleation and growth of crystals. IV. Results and Discussion IV.1. Crystallization of Amino Acids on SAMs on Gold. L-Alanine crystallizes from water in the orthorhombic space group P21212 (a ) 6.025 Å, b ) 12.324 Å, and c ) 5.783 Å),27 and the morphology of the crystals is bipyramidal, dominated by the {020}, {120}, {110}, and {011} growth forms,35 as shown in Figure 4. The crystal grown in aqueous solution is indexed by comparing the interfacial angles measured by optical goniometry and theoretical values based on the unit cell of L-alanine. Powder X-ray diffraction patterns (Figure 5) and interfacial angle measurements reveal that L-alanine crystals nucleating on SAM surfaces crystallize in the orthorhombic space group with similar unit cell dimensions. However, functionalized SAMs induce the formation of L-alanine crystals in different crystallographic directions. L-Alanine crystals display the normal bipyramidal habit but are randomly oriented with the different surfaces. In methyl-terminated SAMs, L-alanine selectively nucleated on the {020} plane on the surface (Figure 6), whereas in 100% OH SAM surfaces, L-alanine nucleated on an unobserved {200} side face. The crystal exhibits a similar morphology as observed in aqueous solution with an appearance of a {200} face adjacent to the {110} planes (Figure 6). In both cases, the area of each crystal face is substantially larger than those of the other faces on the crystal. The SAM surfaces almost act as an additive or impurity molecule specifically interacting with the crystal face and consequently reducing the relative growth rate and modifying the habit. Crystallization of L-alanine on 4-(4-mercaptophenyl)pyridine surfaces resulted in the {011} face as the plane corresponding to nucleation (Figure 6). The preferential interaction of the monolayer with the {011} face can be attributed to hydrogen bonding at the crystal-monolayer interface. Unlike the other two surfaces where they can serve as both hydrogen bond donors and acceptors (4′-hydroxy-4-mercaptobiphenyl) or solely as H-bond donors (4′-methyl-4-mercaptobiphenyl), the pyridine electron pair at the surface only serve as hydrogen bond acceptors. The binding of the pyridine surface and the {011} plane can be explained by the amino and methyl groups protruding out perpendicular to the plane (Figure 7) and forming N- H‚‚‚N and C-H‚‚‚N hydrogen bonds with the SAM surface, respectively. In contrast, the 100% (35) Lehmann, M. S.; Koetzle, T. F.; Hamilton, W. C. J. Am. Chem. Soc. 1972. 101, 2657.

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Figure 4. Crystallographic image (a) and morphology (b) of L-alanine crystal grown from aqueous solution.

Figure 5. X-ray diffractograms of L-alanine nucleated on functionalized SAMs, compared with L-alanine crystallized from aqueous solution (bottom). Indices of the crystallographic planes corresponding to the diffraction intensities of major peaks are indicated at the top.

CH3 and 100% OH SAM surfaces do not interact as strongly with the hydrogen bond donating plane. In a similar manner, the appearance of an unobserved {200} face of L-alanine grown in aqueous solution on [Au]-SC6H4-C6H4-OH can be attributed to hydrogen bonds forming between the two surfaces. The {200} surface contains alternating methyl (CH3) and carboxylic groups (COO-) that form N-H‚‚‚O and O‚‚‚H-O with the hydroxide group of the monolayer film (Figure 7), ideal for binding with surfaces that can serve as both hydrogen bond donors and acceptors. As a result, the preferential interaction leads to the stabilization and appearance of the {200} face. The oriented nucleation of L-alanine crystals on functionalized SAMs arises due to the different molecular structures of each crystal face. Similar to the adsorption of additive onto a crystal face, the interaction (or binding) with the monolayer surface depends on the functional group that each crystal face possesses. As a result of preferential interactions with specific crystal faces, interfacial molecular recognition directs nucleation and subsequently influences the crystal growth.

In addition to L-alanine, SAMs of rigid thiols are employed to investigate the possibility of inhibiting the racemic crystal and inducing the formation of one of its enantiomers. The powder X-ray diffraction pattern (Figure 8) reveals that DL-valine nucleates in the monoclinic form independent of the hydroxyl, methyl, or pyridine surface concentration and that there was no trace of conglomerates. DL-Valine crystallizes in the monoclinic space group P21/c with a unit cell of dimensions a ) 5.21 Å, b ) 22.10 Å, c ) 5.41 Å, and β ) 109.2°.28 Although the structural literature reports three separate space group assignments, Leiserowitz and co-workers36 have shown that two of the three space groups (P21 and P1) are highly improbable for racemic crystals. Interfacial angle measurements and powder X-ray diffraction undertaken in this work agreed much better with the theoretical values and simulated pattern based on the unit cell of the monoclinic space group (36) Wolf, S. G.; Berkovitch-Yellin, Z.; Lahav, M.; Leiserowitz, L. Mol. Cryst. Liq. Cryst. 1990, 186, 3.


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Figure 6. Crystallographic image and morphology of L-alanine crystals nucleated on (a,b) SAMs of 4′-methyl-4-mercaptobiphenyl, (c,d) SAMs of 4′-hydroxy-4-mercaptobiphenyl, and (e,f) SAMs of 4-(4-mercaptophenyl)pyridine.

Figure 7. Molecular structure of the {011} and {200} planes of L-alanine.

confirming the notion that the space group of DL-valine is indeed P21/c. In aqueous solution, DL-valine crystallizes as hexagonal platelets dominated by a slow-growing {020} flat face with {100}, {002}, and {202 h } side faces. Similar to L-alanine, the morphologies of DL-valine crystals are very sensitive to the surface concentration. On monolayer surfaces that serve as H-bond acceptors, DL-valine crystals nucleated from the flat {020} plane (Figure 9), whereas in methylterminated SAMs, the fast-growing {100} face is the nucleating plane and the hexagonal platelet crystal is

almost oriented perpendicular to the SAM surface, tilting uniformly in one direction, suggesting that in addition to the functional group of the SAM the geometry of the SAM also affects the orientation of the crystal. The specific interactions between the {020} plane and the [Au]-SC6H4-C6H4-OH and [Au]-S-C6H4-C5H4N surfaces occur because of the strong interfacial hydrogen bonding interactions. On the molecular level, the {020} plane has a very rough surface topography with methyl groups protruding diagonally out of the plane, allowing possible hydrogen bonding opportunities (Figure 10). In the

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Figure 8. X-ray diffractograms of DL-valine nucleated on functionalized SAMs, compared with DL-valine crystallized from aqueous solution (bottom). Indices of the crystallographic planes corresponding to the diffraction intensities of major peaks are indicated at the top.

Figure 9. Crystallographic image and morphology of DL-valine crystals grown on (a,b) SAMs of 4-(4-mercaptophenyl)pyridine, (c,d) SAMs of 4′-hydroxy-4-mercaptobiphenyl, and (e,f) SAMs of 4′-methyl-4-mercaptobiphenyl.

hydroxy-terminated SAMs, C-H‚‚‚O hydrogen bonds are formed, whereas on the pyridine surface, the slow-growing crystal face is linked by C-H‚‚‚N hydrogen bonds. Clearly, during crystal growth, differences in the surface chemistry of the SAMs lead to different interfacial interactions and thus oriented crystallization of amino acids. Specifically, hydrogen bonding is responsible for the epitaxial crystallization of L-alanine and DL-valine on the monolayer substrates. The employment of SAMs of biphenyl rigid thiols as supramolecular templates obviously controls and promotes the nucleation of amino acids and provides an alternative route to crystal engineering. IV.2. Molecular Modeling of Amino Acids on SAMs on Gold. R-Glycine. R-Glycine crystallizes in the monoclinic space group P21/n in a unit cell of dimensions a )

5.084 Å, b ) 11.820 Å, c ) 5.458 Å, and β ) 119.95°.37 The calculated lattice energy, obtained by the summation of intermolecular interactions from the central molecule using the DREIDING 2.21 force field, is -58.2 kcal/mol. In the summation, convergence occurred at an interaction distance of 30 Å. Compared to the experimental value,38 Vexp ) -67.0 kcal/mol, the calculated cohesive energy may seem high, but the energy is consistent with that of Lin et al.39 (Elat ) -59.0 kcal/mol) and Boek et al.40 (Elat ) (37) Kvick, A.; Canning, W. M.; Koetzle, T. F.; Williams, G. J. Acta Crystallogr. 1980, B36, 115. (38) Raabe, G. Z. Naturforsch., A 2000, 55, 609. (39) Lin, C. H.; Gabas, N.; Canselier, J. P.; Pepe, G. J. Cryst. Growth 1998, 191, 791. (40) Boek, E. S.; Feil, D.; Briels, W. J.; Bennema, P. J. Cryst. Growth 1991, 114, 389.


Figure 10. Molecular structure of the {020} plane of DL-valine.

-53.1 kcal/mol). Consequently, the DREIDING 2.21 force field is suitable for the modeling of the growth morphology and binding energy calculations. Figure 11 shows the predicted crystal morphologies. The slow-growing {020} face dominates both the BFDH and AE crystals; however, there is a distinct difference as can be seen in the absence of the {101 h } and {111 h } faces and the reduction in the areas of the {011} and {110} faces in the AE crystal. Also, both crystals agree very well with those of Lin et al.39 and Boek et al.40 Based on the predicted morphologies, the morphologically important faces investigated for binding studies are {020}, {011}, and {110}. Additionally, the crystallographic planes corresponding to the nucleation surface for the different SAM surfaces are examined (Table 1). The binding studies, using minimization techniques, were carried out for different R-glycine habit surface planes and monolayer surfaces. Figure 12 shows an example of a typical binding energy calculation where the crystallographic plane {101} is cleaved from the unit cell and extended and then docked onto the 4′-methyl-(4-mercaptobiphenyl) surface. The optimum binding site of a crystal habit plane was taken to be the position where the binding

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is at its minimum. Generally, the surface binding energy is negative which indicates that there is an affinity between the two surfaces. The more negative the binding energy, the more likely that a particular crystallographic plane is the nucleation surface on the self-assembled monolayer. In cases where the binding energy is positive, the crystal face is less likely to interact and bind with the monolayer surface. Table 2 lists the minimum binding energies for several crystallographic surfaces docked on SAMs of rigid thiols. The optimum minimum binding energy position for two of the particular crystal faces that selectively interact with the monolayer surface can be seen in Figure 13. For each of these interactions, the binding energies are negative suggesting that the crystal face might bind to the monolayer surface. The binding forces between the two surfaces basically consist of electrostatic interaction, hydrogen bonding, and van der Waals forces. However, many of the R-glycine crystal faces did not interact with the SAM surfaces. For instance, nearly all of the slowgrowing faces that dominated the attachment energy and BFDH morphology resulted in positive binding energies suggesting that only certain crystallographic planes selectively bind to the biphenyl monolayer. One lone exception is the {011} R-glycine crystal face, which strongly binds to the 4′-hydroxy-(4-mercaptobiphenyl) monolayer and is consistent with the experimental result. The strong interaction can be attributed to the surface chemistry of the smooth {011} face which contains alternating amino (NH3+) and carboxylic groups (COO-) that form hydrogen bonds with the hydroxide groups of the monolayer film (Figure 13a). In contrast, binding energies for the observed crystallographic planes that nucleated on SAMs of rigid 4-(4-mercaptophenyl)pyridine, 4′-hydroxy-(4-mercaptobiphenyl), and their mixed SAMs with 4′-methyl-(4mercaptobiphenyl) on gold are negative showing further evidence for preferential surface binding with the monolayer.

Figure 11. Theoretical habits of amino acids according to the BFDH method and the attachment energy method. Table 1. Crystallization of r-Glycine on Self-Assembled Monolayers of Rigid Thiols on Gold SAM

crystallographic surface nucleated on the SAM

CH3-C6H4-C6H4-SH OH-C6H4-C6H4-SH C5H4N-C6H4-SH CH3-C6H4-C6H4-SH (50%)/OH-C6H4-C6H4-SH (50%) CH3-C6H4-C6H4-SH (25%)/C5H4N-C6H4-SH (75%) CH3-C6H4-C6H4-SH (75%)/C5H4N-C6H4-SH (25%)

{h0l}, probably {101} {011} {1105} {h0l}, probably {101} {121} {010}

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Figure 12. Typical example of a binding energy calculation showing the two surfaces being extended and the docking of the {101} R-glycine face onto the 4′-methyl-4-mercaptobiphenyl surface. Table 2. Summary of Calculated Binding Energies (kcal/mol) of Major Crystal Faces of r-Glycine on SAMs of Rigid Thiols monolayer

crystallograp hic surfaces {110} {020} {011}

CH3-C6H4-C6H4-SH

6.13

12.1

19.3

OH-C6H4-C6H4-SH

5.59

10.1

-13.1

C5H4N-C6H4-SH

9.14

-17.5

-1.27

CH3-C6H4-C6H4-SH (50%)/OH-C6H4-C6H 4-SH (50%)

3.23

34.5

4.51

CH3-C6H4-C6H4-SH (25%)/C5H4N-C6H4-S H (75%)

24.1

-2.16

CH3-C6H4-C6H4-SH (75%)/C5H4N-C6H4-S H (25%)

31.1

16.7

Energy calculations (Figure 14) are also performed for low-index {h0l} faces on SAMs and mixed monolayers of 4′-methyl-(4-mercaptobiphenyl) and 4′-hydroxy-(4-mercaptobiphenyl) to determine which of the likely low-index faces might interact with the monolayer. For the 100% CH3 surface, the crystallographic plane that would most likely induce nucleation is found to be the {101} plane, consistent with the experimental work. However, for the 50% CH3 surface the minimum binding energy occurred at the {103} plane suggesting that the mixed monolayer has a greater affinity to nucleate from the {103} plane than from the observed {101} crystal plane. Binding energies ranged from -21.1 to 11.6 kcal/mol for the 100% CH3 surface and from -4.18 to 12.45 kcal/mol for the mixed monolayer surface. In both cases, the binding energies are negative for the {101} and {103} planes along with the {102} and {302} planes for methyl-terminated SAMs. Although the minimization calculation is performed 1520 times, it is possible that the global minimum was never

-8.12 7.05

observed crystal plane nucleated on the SAM {h0l}, probably {101} -21.1 {011} -13.1 {1105} -2.68 {h0l}, probably {101} -3.45 {121} -11.4 {010} -8.34

found for the {101} plane in the case of the mixed monolayer surface. Also, the higher binding energy might be a result of the alternating methyl- and hydroxyterminated SAMs’ packing arrangement. In this simulation, it was assumed that the mixed monolayer packed in an alternating manner; however, this is not true since mixed SAMs can pack in any different arrangement such as two segregated regions with equal percentages of methyl- and hydroxy-terminated SAMs, and as a result, binding energies vary due to the geometry of the mixed SAMs (Figure 15). Consequently, further work is still needed in modeling of crystal faces with mixed monolayer surfaces. L-Alanine. The theoretical morphologies predicted from the BFDH and the attachment energy method of L-alanine are shown in Figure 11 using the DREIDING 2.21 force field, and the calculated lattice energy is -58.8 kcal/mol compared to the experimental crystal energy of -65.5 kcal/ mol.41 Although the calculated lattice energy is low, the


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Figure 13. Optimum binding energy position of (a) the {011} R-glycine face on 4′-hydroxy-4-mercaptobiphenyl and (b) the {020} R-glycine face on 4-(4-mercaptophenyl)pyridine.

Figure 14. Binding energies of low-index {h0l} faces of R-glycine embedded into SAMs of rigid thiols.

predicted AE habit resembles that of a typical L-alanine crystal grown in aqueous solution as shown in Figure 4. The only difference is the appearance of the {120} growth form which the AE morphology does not account for due to the approximations used in the prediction. The attachment energy method neglects the effects of solvent during crystallization from solution and assumes growth by sublimation in a vacuum. In the BFDH method, the predicted habit takes into account only the crystal lattice geometry and as a result, the habit agrees very poorly with the experimental crystal morphology. Based on the L-alanine crystal grown in aqueous solution and the predicted habits, the {020}, {120}, {110}, {101}, (41) Kwon, O. Y.; Kim, S. Y.; No, K. T.; Kang, Y. K.; Jhon, M. S.; Scheraga, H. A. J. Phys. Chem. 1996, 100, 17670.

and {011} faces are chosen for binding energy studies along with the {200} face, which is the nucleation plane for hydroxy-terminated SAMs. Each crystal face is docked onto the functionalized SAMs, and the binding energies are calculated to determine which crystal face is most likely to be the nucleation plane and bind (or interact) with the monolayer surface. The binding energies are summarized in Table 3, and the calculations show good recognition between the two surfaces. However, positive binding energies did result for cases such as the {110} face docked on the pyridine surface, indicating that the {110} face does not favorably interact with the monolayer surface probably due to the absence of the hydrogen bonding. The optimum binding energies for the crystal faces that preferentially interact with biphenyl monolayers

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Figure 15. Schematic diagram of the different packing arrangements of mixed SAMs of 4′-hydroxy-4-mercaptobiphenyl and 4′-hydroxy-4-mercaptobiphenyl on Au(111): (a) alternating mixed SAMs and (b) segregated mixed SAMs. Table 3. Binding Energies (kcal/mol) of Morphologically Important Faces of L-Alanine on SAMs of Rigid Thiols crystallogra phic surfaces monolayer

{020}

{120}

{110}

{101}

{011}

{200}

OH-C6H4-C 6H4-SH CH3-C6H4-C 6H4-SH C5H4N-C6H4-SH

-16.1 -32.3 -6.25

-23.6 -10.4 -15.3

7.34 -18.1 26.2

-15.4 -36.2 -2.17

-11.5 1.96 -22.8

-42.1 -13.3 -4.97

are shown in Figure 16. Similar to R-glycine, the binding forces consist of van der Waals forces, electrostatic interactions, and hydrogen bonding. In particular, hydrogen bonding plays a major role in the molecular recognition events occurring at the interface. The appearance and stabilization of the {200} face can be directly related to the alternating methyl (CH3) and carboxylic groups (COO-) on the outer layer of the surface, forming hydrogen bonds with the hydroxide groups of the organic monolayer (Figure 16) in a manner similar to that of the {011} R-glycine crystal face with the hydroxy-terminated monolayer. The minimum binding energy for each SAM surface agrees very well with the experimental results with the exception of methyl-terminated SAMs where the {101} face seems more likely to bind than the {020} face. Since the binding energies are very close, it is possible that the global minimum was not found and that only the local minimum was determined or it might just be the surface chemistry of the {101} face where there are more hydrogen bonding opportunities compared to those on the {020} face. Nonetheless, binding energies of L-alanine on functionalized SAMs of rigid thiols are very useful in examining the crystal-monolayer interface at the molecular level and allowing us to assess the affinity of various crystallographic planes with a particular monolayer surface. DL-Valine. DL-Valine crystallizes in the monoclinic space group P21/c. Similar to R-glycine, the unit cell consists of a network of hydrogen bonds. The theoretical habits of DL-valine are predicted using the DREIDING 2.21 force field and shown in Figure 11. Although the experimental lattice energy is -70.2 kcal/mol and the calculated crystal energy is -58.2 kcal/mol,41 the attachment energy model predicts a platelike crystal dominated by a slow-growing flat {020} face connected by {011} and {100} side faces, consistent with DL-valine crystals grown from aqueous solution with {100}, {002}, and {202 h } side faces. The appearance of these new faces and the disappearance of the {011} face can be attributed to the neglect of solvent used in the prediction method. The presence of solvents can strongly inhibit certain faces or promote the appearance of faces that usually do not appear. Crystal faces that appeared in the attachment energy prediction and from crystals grown in aqueous solution

Table 4. Binding Energies (kcal/mol) of Morphologically Important Faces of DL-Valine on SAMs of Rigid Thiols crystallograp hic surfaces monolayer

{020}

{011}

{100}

{002} {20-2}

OH-C6H4-C 6H4-SH -32.1 -14.2 -13.9 -11.6 -18.7 CH3-C6H4-C 6H4-SH -14.2 -9.61 -17.3 -12.9 -3.18 C5H4N-C6H4-SH -39.5 -9.94 -9.70 -13.8 -15.2

are chosen for binding studies. The crystallographic planes {020}, {011}, {002}, {100}, and {202 h } are docked onto the SAM surfaces, and energy minimization calculations are performed to calculate the binding energies. Table 4 summarizes the binding energies for various crystallographic planes, and Figure 17 shows several of the optimum binding energy positions of the specific crystal faces embedded into the functionalized SAMs. The minimum binding energy for hydoxy and pyridine surfaces occurred at the observed {020} nucleation plane, while the minimum binding energy for methyl-terminated SAMs is the {100} face, consistent with the experimental result, indicating that the functionalized biphenyl monolayer induces the face-selective crystallization of DL-valine. Similar to R-glycine and L-alanine, hydrogen bonding between monolayer surfaces and crystal faces is the main reason for the specific interaction and face-selective nucleation. On pyridine- and hydroxy-terminated surfaces that serve as H-bond acceptors, DL-valine nucleated from the {020} plane. This is evident in Figure 17 in which methyl groups from the crystallographic plane are protruding diagonally out of the plane and forming C-H‚‚‚N hydrogen bonds with the pyridine surface and C-H‚‚‚O hydrogen bonds with the hydroxy surface. Clearly, the {020} face has a great affinity for surfaces that serve as H-bond acceptors, and this is reflected in the binding energies. Hydrogen bonding at the crystal-monolayer interface is the main reason for the specific interaction between the two surfaces. It is evident in all three cases of amino acids on SAMs of rigid biphenyl thiols. Binding energy calculations account for this, along with other forces such as electrostatic interactions and van der Waals forces, and reflect very well the ability of a crystal face of an amino acid to preferentially bind with a specific monolayer surface, thus providing a valid method to screen SAMs as


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Figure 16. Optimum binding energy position of (a) the {011} L-alanine face on 4-(4-mercaptophenyl)pyridine, (b) the {101} L-alanine face on 4′-methyl-4-mercaptobiphenyl, and (c) the {200} L-alanine face on 4′-hydroxy-4-mercaptobiphenyl.

potential nucleants for the nucleation and growth of organic crystals. Despite the good agreement with the experimental results, further work is still needed. The assumption that 4′-substituted 4-mercaptobiphenyl packs in the same manner as the hydrogen-terminated monolayer of biphenylmercaptan is not valid since the adsorption of different 4′-substituted 4-mercaptobiphenyls on gold surfaces results in different monolayer structures. The orientation of the platelet DL-valine crystal on methyl surfaces suggests that in addition to the terminal group of the SAMs, the geometry of the SAMs affects the crystal orientation and cannot be ignored in the modeling of the

monolayer surface. Further development of the docking methodology is also needed than the laborious approach of manual docking to obtain the global minimum adopted in this work. Together with improved force fields, molecular modeling enables us to rationally design supramolecular templates with different motifs capable of promoting nucleation and controlling crystal growth and, in turn, engineer crystals. V. Conclusions SAMs of rigid 4′-substituted 4-mercaptobiphenyls are employed as templates for the heterogeneous nucleation

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Figure 17. Optimum binding energy position of (a) the {100} DL-valine face on 4′-methyl-4-mercaptobiphenyl, (b) the {020} DL-valine face on 4′-hydroxy-4-mercaptobiphenyl, and (c) the {020} DL-valine face on 4-(4-mercaptophenyl)pyridine.

and growth of amino acid crystals. Specifically, L-alanine and DL-valine nucleate on hydroxy- and methyl-terminated SAM covered substrates and monolayer films of 4-(4mercaptophenyl)pyridine. Different crystal morphologies of the same crystal structure are observed at the solidsolution interface, suggesting that the monolayer composition has a significant influence on the crystal nucleation and orientation. The observation of different crystallographic planes as nucleation surfaces for various surface concentrations can be attributed to the strong interfacial interaction, in particular, hydrogen bonding, between the amino acid molecules and the monolayers during nucleation. To gain a better understanding of the effects of functionalized SAMs on the crystallization of amino acids, molecular modeling studies are undertaken to probe the monolayer surfaces’ affinity for particular amino acid crystal faces by calculating the binding energies

between the two surfaces, similar to solvent and impurity interactions on crystal habit surfaces. The binding energy results were in good agreement with the observed nucleated crystallographic planes and provided some insight into how crystal surfaces interact with the monolayer films and which faces will preferentially nucleate. Furthermore, the surface calculations demonstrate that binding energies can be an effective screening tool for self-assembled monolayers as nano-templates for heterogeneous nucleation and growth of organic crystals and inorganic crystals. Acknowledgment. This work was supported by the National Science Foundation MRSEC for Polymers at Engineered Interfaces. A.Y.L. thanks Polytechnic University for the Donald F. Othmer Fellowship. LA025704W

Crystallization of Amino Acids on Self-Assembled ... - ACS Publications

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