CRYSTAL GROWTH & DESIGN 2006 VOL. 6, NO. 3 625-628
Communications Self-Poisoning at {011} Faces of r-Resorcinol Crystals May Explain Its Unidirectional Growth in the Vapor Phase: A Molecular Modeling Study Isabelle Weissbuch,* Leslie Leiserowitz,* and Meir Lahav* Department of Materials and Interfaces, The Weizmann Institute of Science, 76100-RehoVot, Israel ReceiVed August 18, 2005; ReVised Manuscript ReceiVed December 12, 2005
ABSTRACT: In a recent paper, Srinivasan and Sherwood reported that R-resorcinol crystals grow unidirectionally at the {01h1h} faces in the vapor phase and suggested that this phenomenon of unidirectional growth is intrinsic to polar crystals. Here, we present a molecular modeling study suggesting a plausible “self-poisoning” mechanism that may explain the unidirectional growth of R-resorcinol in the vapor phase, a process that does not exclude the inhibition of crystal growth by solvent. Introduction The “riddle” of the unidirectional crystal growth of R-resorcinol in aqueous solutions, as first reported by Wells,1 continues to attract interest with regard to the role played by solvent in shaping the morphology of polar crystals. Previous stereochemical studies2 using “tailor-made” additives and growth kinetics3 as well as molecular dynamics simulations4,5 have demonstrated that strong solvent interactions at the slow-growing {011} (i.e., (011) and (01h1)) faces compared to the hemihedral fast-growing {01h1h} (i.e., (011h) and (01h1h)) faces can explain the solvent effect. In a recent paper, Srinivasan and Sherwood6 reported that R-resorcinol crystals grow unidirectionally at the {01h1h} faces also in the vapor phase and suggested that this phenomenon of unidirectional growth is intrinsic to polar crystals, although there may well be a solvent effect superimposed on this intrinsic difference. Here, we present a molecular modeling study suggesting a plausible “self-poisoning” mechanism that may explain the unidirectional growth of R-resorcinol in the vapor phase, a process that does not exclude the inhibiting role played by solvent on crystal growth. Proposed Mechanism for the Unidirectional Growth of r-Resorcinol in the Vapor Phase. The packing arrangement of the polar crystal of R-resorcinol and the hemihedral faces, “hydroxyl-rich” and “phenyl-rich”, at the two ends of the polar c-axis of the crystal are shown in Figure 1. The experimental rates of growth at the hemihedral faces at the two opposite ends of the crystal in the vapor phase have been found to be unequal, with a preferential growth along the -c polar direction at the hydroxyl-rich {01h1h} faces, and the anisotropy of growth increased with an increase of the degree of supersaturation.6 A possible mechanism to explain this anisotropy involves docking of misoriented resorcinol molecules at the slow growing (011) and (01h1) faces resulting in a “self-poisoning” of these faces. In the proposed mechanism, the misfitted molecules act in a mode akin to orcinol and phloroglucinol, which are stereospecific “tailormade” inhibitors2 affecting growth at the hemihedral {011] faces * To whom correspondence should be addressed. E-mail: meir.lahav@ weizmann.ac.il (M.L.);
[email protected] (I.W.);
[email protected] (L.L.).
Figure 1. Packing arrangement of R-resorcinol crystal viewed along the a-axis. The {011} faces where the phenyl groups are exposed and {01h1h} faces where the OH groups are exposed are shown as yellow lines. A family of {011} planes is shown as red lines, for clarity.
of R-resorcinol.2 To support such a mechanism, we performed layer, attachment, and binding energy calculations of misoriented host molecules relative to that of normal host molecules at various sites on the (011) and (01h1h) surfaces and of the phenols pyrogallol, orcinol, and phloroglucinol.
Computational Procedure for Estimating the Relative Binding and Attachment Energies. All computations were performed
10.1021/cg050424a CCC: $33.50 © 2006 American Chemical Society Published on Web 02/11/2006
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Figure 2. Docking resorcinol molecules in misorientations I and II in the two crystallographically different sites 1 (a) and 2 (b) at the (011) face viewed edge-on along the -b + c. For clarity, the misoriented molecules are drawn as “cylinder” and the other molecules as “stick”. Note that in the sites 1 and 2 the molecules in each pair are related to each other by n glide symmetry, whereas molecules in sites 1 and 2, related by a glide in the bulk, are crystallographically independent at the (011) surface. Table 1. Difference in Layer, Attachment, and Binding Energies (∆El, ∆Eatt, and ∆Eb) of Resorcinol Molecules Docked In Various Misorientations Compared With a Host Molecule at the (011) and (01h1h) Faces misorientation I
misorientation II
misorientation III
face (hkl)
El
Eatt
site
∆El
∆Eatt
∆Eb
∆El
∆Eatt
∆Eb
(011)
-31.9 -38.9 -35.5 -35.3
-44.0 -42.4 -44.0 -42.4
1 2 1 2
-3.9 6.9
46.5 94.0
42.6 100.9
-8.1 4.2
48.9 69.9
40.8 74.1
(01h1h)
using Cerius2 software (Accelrys Inc., San Diego, CA).7 The crystal structure of R-resorcinol was constructed using the 3D builder and the lattice energy was minimized by the Minimizer with molecules constrained as rigid bodies and comprising atomic charges calculated using the charge-equilibration method. The R-resorcinol crystal was cleaved parallel to the (011) plane with a depth of two unit cells using the 3D surface builder. From the cleaved uV unit cell, a crystal slice was constructed as a nonperiodic superstructure of 3 × 3 unit cells comprising 72 molecules. The energy expression was setup using Dreiding 2.21 force field including van der Waals, electrostatic, and hydrogen bond contributions. The layer energy (El), defined as the energy released when a new layer is formed, was calculated as the sum of intermolecular interactions between one resorcinol host molecule as a rigid body placed in the center in each of the two symmetry related crystallographic sites on either (011) or (01h1h) surfaces and its neighbors inside the crystal slice. The attachment energy Eatt, defined as the energy released when a new layer is attached to the crystal, was calculated as the sum of the intermolecular interactions between one host molecule as a rigid body placed in each of the two symmetry related crystallographic sites on either (011) or (01h1h) surfaces in the crystal slice of 72 molecules and an oncoming outside layer of 36 molecules. The layer energy measures the stability of the layer and the attachment energy has been related to the growth rate perpendicular to the layer.8 Resorcinol molecules assuming different orientations were inserted in each crystallographic site at (011) and (01h1h) surfaces and their orientation was optimized by minimizing the energy under similar constraints, as a rigid body and the other 71 molecules with fixed atoms. Orcinol, phloroglucinol, and pyrogallol as “tailormade” auxiliary molecules were treated in a similar manner. The binding energies at each of the surface sites for a host molecule were calculated as Eb ) El + Eatt for a resorcinol molecule docked in various orientations and as E′b ) E′1 + E′att for a “tailor-
∆El
∆Eatt
∆Eb
14.6 9.2
22.8 41.9
37.4 51.1
made” auxiliary. From the calculated differences in ∆El, ∆Eatt, and ∆Eb for the (011) and (01h1h) faces of either misoriented resorcinol or various auxiliary molecules as compared to a host resorcinol molecule, the stereoselective interactions occurring at the growing crystal surfaces could be evaluated. Results The rationale behind the choice of molecular misorientation at the (011) face is that the molecule, on docking, need not form all the original contacts, yet does not incur repulsive ones, but must expose, at the surface, an atomic group that will act as a growth perturber to an oncoming resorcinol layer. Thus, an OH group, that normally forms intralayer hydrogen bonds, is interchanged with a C-H group that is normally exposed at the crystal surface. Applying these constraints, only one OH group participating in intralayer hydrogen bonds may be replaced by a CH group. With such a procedure, only two misorientations are possible, labeled I and II, for a resorcinol molecule to dock into any of the two crystallographic sites 1 and 2 at the (011) surface as shown in Figure 2. The results of the layer ∆E1, attachment ∆Eatt, and binding ∆Eb energy calculations of misoriented molecules relative to that of normal host molecules at various crystallographic sites on the (011) and (01h1h) surfaces are shown in Table 1. Although the misorientations I and II lead to a loss of a OH‚‚‚O hydrogen bond, energy minimization yielded favorable docking energies for both orientations. The resorcinol molecules in misorientations I and II can easily dock in site 1 with a gain in energy of 3.9 and 8.1 kcal/mol, respectively (see Table 1 and Figure 2a). These values result from a gain in electrostatic and van der Waals contributions during the energy minimization process. A possible reason for this anomalous behavior that the misoriented molecule can fit better into the surface layer than the properly oriented ones is the lack of a packing constraint in the emerging
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Figure 3. Docking a resorcinol molecule in misorientation III in the two crystallographically different sites at the (01h1h) face.
Figure 4. (a-c) Docking orcinol and pyrogallol auxiliaries molecules in various crystallographic sites at the (011) and (01h1h) faces. Table 2. Difference in Layer, Attachment, and Binding Energies of a “Tailor-Made” Inhibitor Molecule Compared with a Host Molecule (∆El, ∆Eatt, and ∆Eb) at the (011) and (01h1h) Face orcinol face (hkl)
El
Eatt
(011)
-31.9 -38.9 -35.5 -35.3
-44.0 -42.4 -44.0 -42.4
(01h1h)
phloroglucinol
pyrogallol
site
∆El
∆Eatt
∆Eb
∆El
∆Eatt
∆Eb
∆El
∆Eatt
∆Eb
1 2 1 2
-6.2 1.4
1.1 × 1.3 × 105
1.1 × 1.3 × 105
-5.5 1.6
141 340
136 340
-9.7 1.3 -5.5 -1.0
1.7 2.5 32.2 3.2
-8.0 3.8 26.7 2.2
103
direction normal to the layer. Therefore, we conclude that the misoriented molecules I and II, particularly the latter, can dock at the (011) face in site 1 almost as efficiently as the properly oriented molecules. By contrast, the resorcinol molecules can hardly dock in site 2 in both misorientations I and II (Table 1, Figure 2b). It is not possible to apply the above-mentioned rationale for docking misoriented molecules at the (01h1h) face. Indeed, as one could intuitively rationalize, a molecule in misorientation III cannot dock at the (01h1h) face, as shown in Figure 3, since the penalty in energy would be high (14.6 and 9.2 kcal/mol in Table 1). The molecules docked on the (011) face in site 1 in misorientations I and II lead to prohibitive attachment energies (Eatt) of an oncoming layer compared with a host molecule (∆Eatt ) 46.5 and
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48.9 kcal/mol in Table 1). This penalty when a new layer is attached to the crystal would imply an inhibition of crystal growth in the direction normal to the (011) face. By contrast, a resorcinol molecule cannot dock in any misorientation on the (01h1h) face resulting in a unidirectional growth along the polar c-direction in the vapor phase. Effect of “Tailor-Made” Auxiliaries on the Growth of r-Resorcinol Crystal. To substantiate the self-poisoning model, given that the misoriented resorcinol molecules would behave in a manner similar to “tailor-made” inhibitors, computer modeling was performed for docking orcinol, phloroglucinol, and pyrogallol molecules which inhibit growth of R-resorcinol.2 The results are shown in Table 2 and Figure 4. Orcinol and phloroglucinol can easily dock replacing a host molecule on the (011) face with their
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added (CH3 or OH) group emerging therefrom, as shown in Figure 4a for orcinol. Such adsorption would impede further addition of oncoming layers since the difference in attachment energy implies a high energetic cost (see Table 2). Pyrogallol can affect the (01h1h) face in a similar manner, being easily adsorbed in the two sites at the (01h1h) face, as shown in Figure 4b, resulting in the calculated gain in layer energy (-5.5 and -1.0 kcal/mol, respectively) but impeding further growth in this direction due to the energetic cost (32.2 and 3.2 kcal/mol, respectively) in attachment energy at least in one site, as shown in Table 2. On the other hand, pyrogallol can easily bind also at the (011) face in site 1 (-9.7 kcal/mol) as shown in Figure 4c and Table 2 but slightly impede normal growth in a direction perpendicular to it due to the energetic cost (1.7 kcal/mol) in attachment energy. Although this result does not take into account the solvent effect, it appears to be in disagreement with the experimental observation that, for R-resorcinol grown from aqueous solutions in the presence of a mixture of orcinol and pyrogallol, HPLC analysis of material taken from the two opposite ends of the polar axis showed the presence of occluded pyrogallol at the (01h1h) end of the crystal, whereas only of orcinol at the (011) end of the crystal.2 To explain this experimental result, we propose that a hydrated pyrogallol molecule would be repelled from being docked in the corrugated (011) face, which normally grows very slowly, since this face is more hydrated than the opposite relatively smooth (01h1h) face by C-H‚‚‚O(water) and resorcinol O-H‚‚‚O(water) binding, according to various computational studies.2,4
space group symmetry of the corresponding crystal sectors from orthorhombic Pna21 to monoclinic Pn since the a glide relating sites 1 and 2 in the bulk is absent at the {01h1h} face (see caption to Figure 2). A similar reduction in crystal symmetry should occur at the opposite {011} end, assuming the site selective occlusion of the misoriented resorcinol molecules. Related reduction in the symmetry in crystals grown with “tailor-made” auxiliaries have been previously reported in the mixed crystals asparagine monohydrate/ aspartic acid and E-cinamamide/β-thienyl-E-acrylamide.9-11 The operation of the self-poisoning mechanism has been noticed in several laboratories in accounting for the crystallization of lactose12 and the precipitation of the γ-polymorph of glycine grown in basic or acidic aqueous conditions.13 A related mechanism has been proposed in the computational studies on the crystal growth of urea in aqueous solutions.14 Self-poisoning at crystal surfaces is also present during growth of disordered crystals where the various sectors should display different degrees of disorder depending upon the binding and attachment energies of misoriented molecules.15,16 Finally, the proposed self-poisoning mechanism in the vapor phase may occur during the R-resorcinol growth in solution but which should not negate the possibility of a simultaneous solventinduced inhibition.
Discussion and Conclusion
(1) Wells, A. F. Discuss. Faraday Soc. 1949, 5, 197. (2) Wireko, F. C.; Shimon, J. W.; Frolow, F.; Berkovitch-Yellin, Z.; Lahav, M.; Leiserowitz, L. J. Phys. Chem. 1987, 91, 472. (3) Davey, R. J.; Milisavljevic, B. C.; Bourne, J. R. J. Phys. Chem. 1988, 92, 2032. (4) Hussain, M.; Anwar, J. J. Am. Chem. Soc. 1999, 121, 8583. (5) Khoshkoo, S.; Anwar, J. J. Chem. Soc., Faraday Trans. 1996, 92, 1023. (6) Srinivasan, K.; Sherwood, J. N.; Cryst. Growth Des. 2005, 5, 1359. (7) Cerius2 software, Accelrys, San Diego, CA. (8) Hartman, P.; Perdok, W. G. Acta Crystallogr. 1955, 8, 49. (9) Weisinger-Lewin, Y.; Frolow, F.; McMullan, R. K.; Koetzle, T. F.; Lahav, M.; Leiserowitz, L. J. Am. Chem. Soc. 1989, 111, 1035. (10) Vaida, M.; Shimon, S. J. W.; Weisinger-Lewin, Y.; Frolow, F.; Lahav, M.; Leiserowitz, L.; McMullan R. K. Science 1988, 241, 1475. (11) Vaida, M.; Shimon, L. J. W.; van Mil, J.; Ernst-Cabrera, K.; Addadi, L.; Leiserowitz, L.; Lahav, M. J. Am. Chem. Soc. 1989, 111, 1029. (12) Visser, R. A.; Bennema, P. Neth. Milk Dairy J. 1983, 37, 109. (13) Towler, C. S.; Davey, R. J.; Lancaster, R. W.; Price, C. J. J. Am. Chem. Soc. 2004, 126, 13347. (14) Liu, X. Y.; Boek, E. S.; Briels, W. J.; Bennema, P. Nature 1995 374, 342. (15) Lahav, M.; Leiserowitz, L. Cryst. Growth Des. 2006, 6, 619. (16) Gervais, C.; Wust, T.; Hulliger, J. J. Phys. Chem. B 2005, 109, 12582 and references therein.
Acknowledgment. We thank the U.S.-Israel Binational Science Foundation for financial support.
References Computer modeling involving docking and attachment energy calculations demonstrate that resorcinol molecules can easily dock in one crystallographic site at the {011} faces with a faulty orientation so exposing an OH perturber group toward these crystal surfaces and thus act as “tailor-made” inhibitors. For this reason, similar computations were performed also for the “tailor-made” inhibitors pyrogallol, orcinol, and phloroglucinol, which inhibit growth of {01h1h} or {011} faces depending upon the additive, when R-resorcinol is grown in aqueous solutions.2 Experimental evidence in favor of the “self-poisoning” mechanism for R-resorcinol crystals grown in water may be obtained by low-temperature X-ray and neutron diffraction studies of sectors of crystals grown in the presence of pyrogallol. This additive when in high concentration in the crystallizing solution (∼20% w/w) drastically reduces the growth rate of the fast-growing {01h1h} faces, allowing the crystal to develop substantially at the opposite slowgrowing {011} end2 that should incorporate an amount of occluded misoriented resorcinol molecules sufficient for detection, provided the proposed self-poisoning mechanism is manifest. The pyrogallol additive, having been found occluded through the {01h1h} faces, would occupy a subset of crystallographic sites on occlusion so that the growth process should be accompanied by a reduction in
CG050424A
