Segregation into Chiral Enantiomeric Conformations of an Achiral

Article pubs.acs.org/crystal

Segregation into Chiral Enantiomeric Conformations of an Achiral Molecule by Concomitant Polymorphism Basanta Kumar Rajbongshi,† Nisanth N. Nair,† M. Nethaji,‡ and Gurunath Ramanathan*,† †

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur-208016, India Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore-560012, India

‡

S Supporting Information *

ABSTRACT: An analogue of the green fluorescent protein (GFP) luminophore crystallizes from a methanol solution impregnated with dichloromethane, into a pair of chiral crystals. Thermal analysis, fluorescence emission studies, and crystal packing analysis show that the two crystals are different materials. The two polymorphs arise from the rotation of a monosubstituted benzene ring about a C−N bond which results in the formation of two strong bifurcated C−H···O intermolecular bonds to oxygen O(6). The color difference has been ascribed to a difference in the packing of the two crystal forms. Theoretical studies supported by low temperature NMR show low kinetic energy barriers (∼10 kJ mol−1) separating the asymmetric units of the two crystal structures, suggesting that the driving force for the polymorphism could be the result of packing of two different asymmetric units.

1. INTRODUCTION Polymorphism is the existence of a material in more than one solid crystalline form.1,2 Polymorphic materials are of crucial importance to medicinal chemists because quite often these materials exhibit different dissolution rates in the body which therefore affect the bioavailability of the drug.3 Intramolecular torsions about single bonds with low kinetic barriers (0.5−3 kcal/mol) often produce conformational structures which are stabilized by favorable short contacts resulting in the formation of conformational polymorphs.4 The appearance of concomitant polymorphs in solution is due to an interplay of kinetic and thermodynamic factors, with the kinetic factor playing the dominant role.5 The role of these factors on product distribution depends heavily on the conditions of crystallization, like for example, the level of saturation of the solution, temperature of crystallization, and rates of evaporation. Slow evaporation or cooling yields the thermodynamically most stable polymorph as the major product, whereas fast evaporation or cooling yields a kinetically trapped polymorph. Normally crystallization to a kinetically trapped polymorph is rare due to the prevalence of flux toward the thermodynamically stable state. A system of concomitant polymorphs will be converting slowly toward the thermodynamically stable state at an exponential rate depending on the free energy barriers separating them. Pasteur reported spontaneous segregation of chiral compounds by crystallization in 1848 for racemic tartaric acid.6 Pairs of resolvable racemates have recently been called “kryptoracemates”.7 Flack has suggested the use of the term sohnke space groups to address crystallographic space groups wherein only proper symmetry operations are allowed into which these kryptoracemates can crystallize.8 Here, we © 2012 American Chemical Society

demonstrate that the chiral conformations of an achiral molecule spontaneously segregate into a pair of chiral crystals in sohnke space groups P4 1 and P43 by concomitant polymorphism. The phenomenon occurs spontaneously and the two crystal forms differ in their color and physical properties. The molecule that we report here, (4Z)-4-(4methoxybenzylidene)-1-phenyl-2-(4-phenyl-buta-(1E)-(3E)-dienyl)-1,4-dihydro-5H-imidazolin-5-one (MPDI), is an analogue of the green fluorescent protein (GFP) luminophore (Figure 1). The GFP luminophore is formed via a post-translational internal cyclization of the Ser65-Tyr66-Gly67 tripeptide followed by α,β − dehydrogenation of the tyrosine9 in the protein.10 In a continuing work on organic solar cells based on imidazolin-5ones, this molecule was synthesized to study solar cell efficiency.11 Using a combination of experimental and theoretical studies, we scrutinize the properties of the two crystal forms and explain the genesis of polymorphism in this compound.

2. EXPERIMENTAL SECTION The imidazolin-5-one under study was synthesized in four steps (Scheme S1, Supporting Information) starting from glycine. Reactions in the first three steps were done following reported procedures.12−16 The final product was obtained by a solvent free Lewis acid catalyzed melt reaction of the imidazolin-5-one (obtained in step III) with transcinnamaldehyde. Crystallization of a column purified product in methanol impregnated with dichloromethane followed by slow evaporation in air at 20 °C produced orange (form A) and red Received: October 3, 2011 Revised: February 25, 2012 Published: March 5, 2012 1823

dx.doi.org/10.1021/cg201313g | Cryst. Growth Des. 2012, 12, 1823−1829

Crystal Growth & Design

Article

Figure 1. (a) Molecular structure of (4Z)-4-(4-Methoxybenzylidene)-1-phenyl-2-(4-phenyl-buta-(1E)-(3E)-dienyl)-1,4-dihydro-5H-imidazolin-5one (MPDI). Inset shows the structure of the GFP luminophore. (b) Orange (form A) and red (form B) crystals of the synthesized imidazolin-5-one obtained from methanol solution impregnated with dichloromethane. Some red crystals were removed from this picture to get a better picture. (form B) needle like crystals (Figure 1). The orange crystal was seen to appear first followed by the appearance of a large amount of red crystals. The red crystals were observed to be harder, thicker, and longer than the orange crystals. The number of red crystals was also more than the orange form in each crystallization attempt. The compound was characterized completely by high field 1H NMR, 13C NMR, IR and mass spectra (Figures S1−S4, Supporting Information). Existence of two concomitant polymorphs, orange and red needles (Figure 1), was confirmed by single-crystal X-ray diffraction studies and differential scanning calorimetry (DSC) of the two crystals. Single-crystal X-ray diffraction data were collected at 293 K on a Bruker AXS SMART APEX CCD diffractometer equipped with a molybdenum sealed tube (λ = 0.71073 Å) and highly oriented graphite monochromator. The data integration and reduction were processed with SAINT+.17 An empirical absorption correction was applied to the collected reflection data with SADABS.18 The structures were solved using WinGX version 1.70.01 package. Direct method using SHELX 9718 was used for solving the structures. The structures were further refined using full matrix least-squares on F2 (SHELX 97).19 All the non-hydrogen atoms were refined anisotropically. The hydrogen atoms were refined isotropically and treated as riding atoms by using SHELXL default parameters. A DSC experiment was performed in a Perkin-Elmer Pyris Diamond differential scanning calorimeter, with αalumina as the reference, under nitrogen atmosphere at a flow rate of 20 mL/min. The temperature was increased at the rate of 10 °C from 50 to 200 °C. Solid state fluorescence spectra were recorded on a Spex Fluorolog-3 spectrofluorimeter. Temperature-dependent 1H NMR were measured at −20 °C, −10 °C, 0 °C, +15 °C, +30 °C, and +50 °C in JEOL 500 MHz NMR spectrometer and the data were analyzed in Delta (version 4.3.6) software.

the static calculations, except that we have used a finite boundary condition20 with a cubic box of 22 Å.

4. RESULTS AND DISCUSSION 4.1. Single-Crystal X-ray Crystal Structure. The X-ray single-crystal structure data obtained for the two forms of crystals, form A and form B, are tabulated in Table 1. Form A Table 1. Crystallographic Data for the Two Crystals, Form A and Form B of MPDI single crystal formula formula weight temperature/K crystal system space group a/Å b/Å c/Å α/° β/° γ/° V/Å3 Z Dc/g cm−3 μ/mm−1 F(000) crystal size/mm θ/range/° reflections collected independent reflections data/restraints/ parameters goodness-of-fit on F2 final R indices [I > 2σ (I)]

3. THEORETICAL METHODS AND MODELS Total energy calculations for two crystal structures were performed using the Kohn−Sham density functional theory (DFT) in its plane wave pseudopotential formulation20 as implemented in the CPMD code.21 The PBE22 exchangecorrelation functional was chosen, and the core electrons were taken into account using the ultrasoft pseudopotentials23 with a plane wave cutoff of 25 Ry. Periodic calculations were performed using a 1 × 1 × 3 supercell at the gamma point, which was adequate for a convergence of total energy per unit cell to less than 1 kJ/mol with respect to the supercell size. In vacuo molecular dynamics simulations of one of the asymmetric units were performed by Car−Parrinello molecular dynamics20 simulation techniques with 4 au as the time step and an orbital mass of 500 au. The whole system was equilibrated to 300 K by Nosé-Hoover chain thermostats.20 Molecular dynamics calculations were performed using same technical details as used for

form A

form B

C27H22N2O2 406.47 293(2) tetragonal P43 19.967(3) 19.967(3) 5.440(10) 90.00 90.00 90.00 2169.1(6) 4 1.245 0.079 856 0.27 × 0.17 × 0.12 2.04−28.31 14283 5168 5168/1/281

C27H22N2O2 406.47 293(2) tetragonal P41 19.971(17) 19.971(17) 5.437(6) 90.00 90.00 90.00 2168.7(4) 4 1.245 0.079 856 0.31 × 0.18 × 0.12 2.28−28.33 14181 5199 5199/1/281

0.914 R1 = 0.065, wR2 = 0.1903

1.100 R1 = 0.058, wR2 = 0.1537

and form B crystallize with enantiomeric space groups P43 and P41 respectively in tetragonal unit cells. The asymmetric unit in both crystals contains one molecule of MDPI. As clearly shown in Figure 2, the molecule crystallizes in form A and form B as mirror images. The hydrogen bond parameters observed in the crystal structures of the two forms are shown in Table 2. The packing diagrams (Figure 2) of the two crystals show that in form A, four molecules pack in the unit cell to form a pyramidal cavity. 1824



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Figure 2. Mirror images of the packing of molecules in form B and form A crystals of MPDI. One molecule from each polymorph has been highlighted to show their mirror image symmetry. The blue box represents the unit cell in the two forms.

Table 2. Hydrogen Bonding Parameters of the Hydrogen Bonds Observed in the Crystal Structures of Form A and Form B single crystal

D−H···A

D−H (Å)

d(H···A) (Å)

d(D···A) (Å)

∠D−H···A (°)

symmetry codes

Form A

C(15)−H(15)···O(6) C(31)−H(31B)···π C(17)−H(17)···π C(19)−H(19)···O(6) C(31)−H(31B)···π C(17)−H(17)···π

0.93(32) 0.96(37) 0.93(30) 0.93(27) 0.96(4) 0.93(28)

2.35(25) 2.75(3) 2.70(3) 2.35(20) 2.74(2) 2.70(2)

3.251(40) 3.447(39) 3.579(31) 3.254(34) 3.438(32) 3.575(29)

163.19(20) 130.47(22) 157.32(19) 163.06(17) 129.71(18) 157.13(17)

x, y, −1 + z x, y, z −x, 1 − y, −2.5 + z x, y, −1 + z 1 − x, −y, −0.5 + z 1 − y, x, −1.75 + z

Form B

Figure 3. (a) Tetragonal pyramid in form A, viewed along the (0 0 1) axis. The pyramid is formed at the center of the unit cell and the herringbone (C−H···π) interactions are present at the corner of the unit cell. (b) Tetragonal pyramid in form B, viewed along the (0 0 1) axis. The pyramid is formed at the corner of the unit cell and the herringbone interactions are present at the center of the unit cell. The herringbone interactions are shown as dotted green lines (C(17)−H(17)···π). In both panels the views are down the c axis.

to note that the unit cell is shifted by (a + b)/2, where a and b are unit cell dimensions in form B. The base of the pyramid is approximately a square with edge length 15.72 Å and height 11.58 Å. In form B, four molecules pack about the unit cell to form a groove where the monosubstituted benzene rings (C14−C19) attached to the imidazolin-5-one ring form the seat at the

This cavity looks like a tetragonal pyramid that lies along the crystallographic (0 0 1) axis. The 4-methoxybenzylidene imidazolin-5-one (polar head) part is oriented along the base of the pyramid, while the phenyl butadienyl (apolar tail) part is oriented to form the tip of the pyramid (Figure 3). The monosubstituted benzene rings (C14−C19) attached to the imidazolin-5-one rings are oriented toward the corners of the unit cell at the base of the tetragonal pyramid. It is interesting 1825



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center of the unit cell (Figure 2); the numbering scheme is as shown in Figure 1. There is virtually no difference in hydrogen bonded interactions in the two forms of crystals. In both form A and form B, the herringbone interactions (C−H···π) and C−H···O interactions play the pivotal role in formation of the supramolecular pyramids (Figure 3). In both forms, the molecules form a growing pyramid and if one considers their surfaces inside, one gets a groove that is held by three T-shaped herringbone motifs arising out of C−H···π intermolecular interactions (see Figure S5, Supporting Information for details). A close inspection into the crystal structures show marginal differences in the intermolecular C···C contacts as shown in Table 3 (Also see Supporting Information, Table S1). A

experimental evidence on these polymorphic forms using thermal gravimetric analysis. The results of the differential scanning calorimetry are illustrated in Figure 4. The polymorph

Table 3. Intermolecular C···C Contacts in Form A and Form B intermolecular contact

form A (d/ Å)

form B (d/ Å)

differences (Δd [form A form B]/Å)

C(10)···C(12) C(10)···C(13) C(15)···C(18) C(15)···C(31) C(16)···C(19) C(16)···C(31) C(18)···C(31)a C(18)....C(31)b C(19)···C(31) C(31)···C(16)

3.5888(58) 3.8956(54) 3.9648(47) 3.9156(54) 3.7586(50) 3.7181(55) 3.5010(59) 3.8057(59) 3.7058(58) 3.7181(49)

3.5742(48) 3.8835(46) 3.7514(42) 3.6977(46) 3.9592(39) 3.4917(50) 3.7097(48) 3.7097(41) 3.9057(47) 3.8031(50)

0.015 0.012 0.213 0.218 −0.201 0.226 −0.209 0.096 −0.200 −0.085

Figure 4. Differential scanning calorimetric (DSC) plots. Polymorph A melts at 5 °C before polymorph B. For both the polymorphs, DSC was done at identical heating rates.

form A melts at 172 °C while form B melts at 177 °C. The heat change during the phase change in case of form A is very small, being 9.2 mJ and the latent heat of fusion is 3.06 J g−1. For form B these values are respectively 349.91 mJ and 49.56 J g−1. Clearly the higher melting point of form B is the result of slightly denser packing in form B than in form A. 4.3. Solid State Fluorescence Spectra. We also wanted to probe the color differences in the two polymorphic forms in the solid state. Hence, solid state fluorescence spectra of the two polymorphs were recorded and the same are depicted in Figure 5. Both polymorphs were excited at 455 nm. The

Symmetry element y, −x + 1, +z − 3/4. bSymmetry element y, −x + 1, +z + 1/4.

a

majority of the intermolecular contacts are marginally shorter in form B than the corresponding intermolecular contacts in form A. However, there are significant differences too. For example, C(15)···C(18), C(15)···C(31), C(16)···C(31), and C(18)···C(31) intermolecular contacts are shorter in form B by 0.21 Å, 0.22 Å, 0.23 Å and 0.10 Å respectively. Conversely the intermolecular contacts C(16)···C(19), C(18)···C(31), and C(19)···C(31) are longer in form B by 0.20, 0.21, and 0.20 Å respectively than in form A. From Table 3 it is clear that the distance C(18)···C(31) remains the same in form B for both the symmetry elements, while they are different in form A indicating that form B is more densely packed than form A. Involvement of two symmetry related hydrogen atoms, H(15) in form A and H(19) in form B, in formation of a C− H···O type hydrogen bond indicates rotation of the C(14)− C(19) benzene ring. Overlay of the asymmetric units (Figure 6a) of the two forms of crystals shows differences in the dihedral angles of the imidazolin-5-one ring with the C(14)− C(19) ring and with the monosubstituted benzene ring (C(24)−C(29)) of the phenylbutadienyl part. In form A, the C(2)−N(1)−C(14)−C(19) dihedral angle is −116° with 64° deviation from planarity of the C(14)−C(19) benzene ring with the imidazolin-5-one ring, while in form B, it is −67°. The angle made by C(14)−C(19) benzene rings in the two forms of the overlaid structure is 49°. Thus from above description of the X-ray structures it is clear that form A and form B are different polymorphs that differ in their intermolecular interactions and packing. 4.2. Thermal Analysis. In view of the results of crystal structure analyses presented above, we decided to obtain more

Figure 5. Solid state fluorescence spectra of concomitant polymorphs. In polymorph A, the first shoulder is at 599 nm and in polymorph B it is red-shifted at 613 nm.

emission spectra look almost similar except for a few minor differences. For both the polymorphs, the highest intensity emission band was observed around 665 nm which is the lowest energy emission band. Prior to this lowest energy emission band there are two distinct shoulders. The position of the first shoulder is different for both crystal forms. In form A it was around 599 nm while in form B the same lay around 613 1826



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Figure 6. (a) Overlay of the asymmetric units of asymA (form A) and asymB (form B) obtained from X-ray diffraction. (b) Minimum energy structure of asymmetric unit A (asymA) (yellow) is mapped to that of B (asymB) (black) to demonstrate the differences in their conformations. (c) Various conformations (silver color) of asymA sampled at 300 K during 10 ps of molecular dynamics simulations in vacuo displayed together with asymB, showing that the conformational space of asymB is sampled within the time scale of the simulation.

nm. The second shoulder was found around 638 nm in each case. Moreover in form A, the two shoulders are prominent while in form B they are feeble. The emission spectra were found to remain almost identical when the samples were excited at different wavelengths. These results strengthen the observation that the both crystal forms indeed have different optical properties. 4.4. Theoretical Calculations. In order to understand the mechanism of the polymorphism and also to further support the experimental observations, we have carried out detailed theoretical calculations. To corroborate the stability of form B over form A, we calculated the potential energy difference of form A and B by using periodic DFT taking their X-ray structures. These calculations show that form B is about 59 kJ/ mol (per unit cell) more stable than form A. This implies that form B is thermodynamically more stable than form A in their crystal structures. This supports the experimental observation that form B is formed in excess during the crystallization. The energy difference of forms A and B stipulated here is only based on the potential energy estimates and is a qualitative estimate of thermodynamic stability of form B over A. Further, the optical band gap was measured from the energy differences between the highest occupied and the lowest unoccupied bands (at the Gamma point). Form A and B are having band gap very close to each other: 1.52 and 1.50 eV, respectively. This is in qualitative agreement with the observed color difference between A and B. No difference can be noticed in the localization of highest occupied and lowest unoccupied orbitals of both form A and form B (see Supporting Information Figure S6). Thus the color changes can be ascribed entirely to the minor differences in the packing in their crystal structures. The asymmetric units of form A (asymA) and B (asymB) differ mainly by the rotation of the C(14)−C(19) phenyl rings and puckering of the imidazoline-5-one rings (Figure 6a, b). Short gas phase molecular dynamics simulations (for 10 ps time scale) at 300 K from asymA sampled the conformational space of asymB as well, showing that at room temperature the effective free energy barrier for converting from asymA to asymB is about 1 kBT ≈ 2.5 kJ/mol at 300 K (Figure 6c). By static calculations, we have found that asymB is thermodynamically more stable than asymA by 8 kJ mol−1. This implies that the barrier on going from asymB → asymA is only about 10.5 kJ mol−1 (Figure 7). These results clearly account for the

Figure 7. Energy profile diagram for the two polymorphs - asymA and asymB. ΔF# (asymA → asymB) is ∼2.5 kJmol−1, ΔF# (asymB → asymA) is 10.5 kJ mol−1.

observation of form B, as the major product. The extremely low kinetic barriers of the two polymorphs imply that conformational space of asymA and asymB are accessible at room temperature from one to the other, although asymB is more stable, and thus more sampled. The enantiomeric conformations of MPDI have extremely low kinetic barriers in solution, but during the process of nucleation, there is a step up of the barriers for which MPDI spontaneously segregates into two enantiomeric conformational concomitant polymorphs, form A and form B. These conformations are diastereomeric with respect to the planar achiral conformation. 4.5. Temperature-Dependent 1H NMR. In view of the results from the calculations above, it became important to see if the two conformations could be detected in the NMR time scale as the intervening conformations are diastereomers and hence likely to have different chemical shifts. We also explored if these can be determined by low temperature NMR (Figure 8). These spectra offer a limited evidence of the existence of these conformations in solution supporting the theoretical results (Figures 6 and 7). 1H NMR spectra of MPDI in CDCl3 were recorded at six different temperatures and are shown in Figure 8. At low temperatures from −20 to 0 °C, all the protons are properly resolved. More importantly the monosubstituted 1827



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Figure 8. 1H NMR (CDCl3, 500 MHz) of MPDI at six different temperatures. The signal corresponding to the methoxy group is not shown.

kinetic barriers. However, during nucleation, MPDI segregates into two enantiomeric conformational concomitant polymorphs due to step up of the activation energy barriers. Form B is thermodynamically more stable than form A, which accounts for form B, the major product. Although one conformation of the imidazolin-5-one is thermodynamically more stable than the other, the kinetic barrier at low temperatures “traps” some amount of molecules to a thermodynamically less stable isomer, thus segregating them into two different crystal forms that are chiral. The difference in melting points of the two polymorphs is small, but the difference in the latent heat of fusion is substantial. They show different colors and deviations in the positions of the first shoulder in the solid-state fluorescence spectra. The difference in thermal properties and solid-state fluorescence spectra suggests forms A and B are concomitant polymorphs. Crystal structure studies along with temperature-dependent 1H NMR studies and theoretical calculations suggest that concomitant polymorphism arises from segregation of two rotamers which rotate about the N(1)−C(14) bond. Since barriers of rotation are small enough, the concomitant polymorphs may be suggested as conformational polymorphs.24

benzene ring (C(14)−C(19)) attached to the imidazolin-5-one ring resolves into two multiplets equivalent to two protons (multiplet a) and three protons (multiplet b) at −20 to 0 °C. The distinct appearance of all the protons into appropriate signals is better understood from the integration of the signals of the spectrum at −20 °C (Figure S7, Supporting Information). At higher temperatures from +15 °C, the multiplets (a, b) begin to coalesce and at +50 °C, a single multiplet (ab) equivalent to five protons is observed. Moreover, other signals indicated by arrow also seem to change, of course to an insignificant extent. This observation clearly supports fast rotational dynamics of the C(14)−C(19) benzene ring about the N(1)−C(14) single bond and agrees with the theoretical results of molecular dynamics simulations performed on both conformations.

5. CONCLUSIONS We have reported two polymorphic crystals of MPDI each colored differently. While the molecule is achiral, the crystals are enantiomorphic and the two crystal forms were then analyzed using several methods. Analysis of the structures reveals that the presence of C−H···O interactions and herringbone interactions (C−H···π) plays a pivotal role in formation of the supramolecular pyramids. The difference in the hydrogen-bonded interactions is very subtle to explain the color difference. However, in form B molecules pack slightly more tightly than in form A, which is probably the reason for enhancement of color from orange in form A to red in form B. Both the polymorphs show supramolecular pyramidal structures. The orientations of the molecules in packing diagrams of form A and in form B are exactly opposite. In form A, herringbone interactions are present at the corners of the unit cells and in form B, these are present at the centers of the unit cells. In both forms, the herringbone (C(17)−H(17)···π) interactions are present at the junction of adjacent pyramids. In solution, the enantiomeric conformations of MPDI have low

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ASSOCIATED CONTENT

S Supporting Information *

Experimental details of synthesis, characterization of the products, molecular packing in the supramolecular pyramids, crystallographic information files. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] Notes

The authors declare no competing financial interest. 1828



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ACKNOWLEDGMENTS We would like to dedicate this work to Prof. P. Balaram on his 63rd birthday. B.K.R. thanks the Council of Scientific and Industrial Research (CSIR) for senior research fellowship (SRF). G.R. thanks the department of science and technology (DST), Government of India for financial assistance. We also thank anonymous reviewers whose comments have enhanced the quality of this manuscript.

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REFERENCES

(1) Brittain, H. G. Polymorphism in Pharmaceutical Solids; Marcel Dekker: New York, 1999. (2) Bernstein, J. Polymorphism in Molecular Crystals; Oxford University Press: New York, 2002. (3) Lee, A. Y.; Myerson, A. S. MRS Bull. 2006, 31, 881−886. (4) (a) Nangia, A. Acc. Chem. Res. 2008, 41, 595−604. (b) Reddy, L. S.; Chandran, S. K.; George, S.; Babu, N. J.; Nangia, A. Cryst. Growth Des. 2007, 7, 2675−2690. (c) Kumar, V. S. S.; Addlagatta, A.; Nangia, A.; Robinson, W. T.; Broder, C. K.; Mondal, R.; Evans, I. R.; Howard, J. A. K.; Allen, F. H. Angew. Chem., Int. Ed. 2002, 41, 3848−3851. (5) Bernstein, J.; Davey, R. J.; Henck, J.-O. Angew. Chem., Int. Ed. Engl. 1999, 38, 3440−3461. (6) Pasteur, L. Ann. Chim. Phys. 1848, 24, 442−459. (7) Fabian, L.; Brock, C. P. Acta Crystallogr. 2010, B66, 94−103. (8) Flack, H. D. Helv. Chim. Acta 2003, 86, 905−921. (9) Tsien, R. Y. Annu. Rev. Biochem. 1998, 67, 509−544. (10) Bell, A. F.; He, X.; Wachter, R. M.; Tonge, P. J. Biochemistry 2000, 39, 4423−4431. (11) Jain, V.; Rajbongshi, B. K.; Mallajosyula, A. T.; Bhattacharjya, G.; Iyer, S. S. K.; Ramanathan, G. Sol. Energy Mater. Sol. Cells 2008, 92, 1043−1046. (12) Vogel, A. I. In Vogel’s Textbook of Practical Organic Chemistry; Furniss, B. S.; Hannaford, A. J.; Smith, P. W. G.; Tatchell, A. R. Eds.; ELBS Longman Singapore Publishers Pvt. Ltd.: Singapore, 1996. (13) Hoshina, H.; Tsuru, H.; Kubo, K.; Igarashi, T.; Sakurai, T. Heterocycles 2000, 53, 2261−2274. (14) Bhattacharjya, G.; Agasti, S. S.; Ramanathan, G. ARKIVOC 2006, 10, 152−161. (15) Badr, M. Z.; El-Sherief, H. A. H.; Tadros, M. E. Bull. Chem. Soc. Jpn. 1982, 55, 2267−2270. (16) Rajbongshi, B. K.; Ramanathan, G. J. Chem. Sci. 2009, 121, 973− 982. (17) SAINT+, version 6.02 [M], Bruker AXS, Inc.: Madison, WI, 1999. (18) Sheldrick, G. M. SADABS: Empirical Absorption Correction Program; University of Göttingen: Göttingen, Germany, 1997. (19) Sheldrick, G. M. SHELXS97 and SHELXL97, Programs for Crystal Structure Analysis (Release 97-2); University of Göttingen: Germany, 1997. (20) Marx, D.; Hutter, J. Ab initio Molecular Dynamics: Basic Theory and Advanced Methods; Cambridge University Press: Cambridge, 2009. (21) CPMD, Copyright IBM Corp 1990−2009, Copyright MPI fuer Festkoerperforschung Stuttgart 1997−2001; see also http://www. cpmd.org. (22) Perdew, J. P.; Burke, K.; Ernzerhof, M. Phys. Rev. Lett. 1996, 77, 3865−3868. (23) Vanderbilt, D. Phys. Rev. B 1990, 41, 7892−7895. (24) (a) Munshi, P.; Venugopala, K. N.; Jayashree, B. S.; Row, T. N. G. Cryst. Growth Des. 2004, 4, 1105. (b) Roy, S.; Banerjee, R.; Nangia, A.; Kruger, G. J. Chem. Eur. J. 2006, 12, 3777−3788.

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Segregation into Chiral Enantiomeric Conformations of an Achiral

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