CRYSTAL GROWTH & DESIGN
Structural Aspects of a Dendrimer Precursor Determined Directly from Powder X-ray Diffraction Data Pan,†
Cheung,†
2004 VOL. 4, NO. 3 451-455
Harris,*,†
Zhigang Eugene Y. Kenneth D. M. Edwin C. Constable,‡ and Catherine E. Housecroft‡
School of Chemistry, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom, and Department of Chemistry, University of Basel, Spitalstrasse 51, 4056 Basel, Switzerland Received August 23, 2003
ABSTRACT: The structure of 3,5-dimethoxybenzyl alcohol has been determined directly from powder X-ray diffraction data using the genetic algorithm technique for structure solution followed by Rietveld refinement. This material is the precursor to a family of dendrimer materials, and structural features exhibited by 3,5-dimethoxybenzyl alcohol in the solid state may be important in the rationalization of higher generation dendrimer materials within this family. Introduction
Scheme 1
The design and preparation of organic molecules that self-assemble into supramolecular architectures by means of noncovalent interactions has become a major focus of research. One class of molecules that are of interest within this field are dendrimers, which are large, highly branched molecules composed of a core moiety and radiating chains that have well-defined size, shape, and surface properties. Dendrimers are synthesized in a carefully controlled generation-like manner, either employing the divergent approach,1 in which the dendrimer is grown outward from the core to the periphery, or by the convergent approach,2 in which the growth direction is from the periphery to the core. The highly branched architecture leads to voids within the dendrimer molecule, with the core and the surface exhibiting distinct microenvironments. These unique characteristics lead to a range of applications of dendrimeric systems, such as their use as micelles,3 as sequestering agents in biotechnological applications (e.g., for DNA binding and as capsules for drug delivery),4 as building blocks for a range of applications in materials science,5 and (in the form of metallodendrimer complexes) as materials with potential light-harvesting properties.6 Important issues also devolve upon the surface properties of dendrimers.7 At all stages of the growth process, dendrimers are monodisperse, and their structural homogeneity and regularity are conducive to the development of structureproperty relationships, employing techniques such as solid-state NMR spectroscopy and X-ray diffraction. Solid-state NMR is particularly useful for studying molecular motion in the solid state, and thus has considerable potential for characterizing the dynamics of dendrimer branches, and single-crystal X-ray diffraction is the technique of choice for determination of the time-averaged structural properties. For successive dendrimer generations, however, it becomes increas* To whom correspondence
[email protected]. † University of Birmingham. ‡ University of Basel.
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ingly difficult to grow single crystals of suitable size and quality for investigation by single crystal X-ray diffraction. In such cases, structure determination using powder X-ray diffraction data may be the only viable route for structural characterization. Nevertheless, recent advances8 in the techniques available for carrying out complete structure determination of molecular solids directly from powder diffraction data provide new opportunities for obtaining structural understanding in such cases. In this paper, we report the structural elucidation of a dendrimer precursor material, 3,5dimethoxybenzyl alcohol (denoted 1; Scheme 1), which has exploited these new opportunities for carrying out crystal structure determination directly from powder X-ray diffraction data. As shown in Schemes 2 and 3, synthetic strategies have been developed for preparing dendrimers based on 1 as the building unit. Thus, functionalization of 1 to give the reactive bromomethyl compound 2 followed by coupling with 3,5-dihydroxybenzyl alcohol yields the second generation species 3. A similar strategy may be used to synthesize higher generation dendrimers (e.g., 4) starting from compound 3 (Scheme 3). Details of the synthesis and characterization of the higher generation dendrimers will be published in a separate paper. Background To Structure Determination from Powder Diffraction Data Among recent developments in techniques for solving crystal structures directly from powder diffraction data, the “direct-space” strategy8,9 is particularly suitable in the case of molecular materials. In this strategy, trial
10.1021/cg0300329 CCC: $27.50 © 2004 American Chemical Society Published on Web 03/19/2004
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Scheme 3
crystal structures are generated in direct space, with the quality of each trial structure assessed by direct comparison between the powder diffraction pattern calculated for the trial structure and the experimental powder diffraction pattern (in our work, this comparison is made using the weighted powder profile R-factor, Rwp, which implicitly takes peak overlap into consideration). In the present paper, direct-space structure solution has been carried out using our genetic algorithm (GA) technique10 to locate the trial structure corresponding to the global minimum in Rwp. In this method, a population of trial structures is allowed to evolve subject to rules and operations (mating, mutation, and natural selection) analogous to those that govern evolution in biological systems. Each structure in the population is specified by its “genetic code”, which represents, for each molecule in the asymmetric unit, the position {x, y, z} and orientation {θ, φ, ψ} of the molecule in the unit cell, and the molecular conformation (defined by variable torsion angles {τ1, τ2, ..., τn}). The quality (“fitness”) of each structure in the population is assessed from its value of Rwp. New structures are generated by the mating and mutation operations. In the natural selection procedure, only the structures of highest fitness (i.e., lowest Rwp) are allowed to pass from one generation to the next generation. In the GA structure solution calculation, the population is allowed to evolve for a specified number of generations or until convergence is reached. After the population has been allowed to evolve for a sufficiently large number of generations, the evolutionary process is such that the best structure in the population (i.e., with lowest Rwp) should be close to the correct crystal structure. Details of the GA technique for structure solution, as implemented in the current work, are given elsewhere.10 The best structure solution
obtained in the GA structure solution calculation is used as the starting structural model for Rietveld refinement.11 Experimental and Computational Details Synthesis of 1 was carried out using the method summarized in Scheme 1. High quality powder X-ray diffraction data for a sample of 1 were recorded at ambient temperature in transmission mode on a Siemens D5000 diffractometer [CuKR1 radiation (Ge-monochromated); linear position-sensitive detector covering 8° in 2θ; 2θ range 5°-70°; step size 0.0194°]. Prior to recording the powder diffraction pattern, the powder sample was tested (using a method described elsewhere12) to ensure that it was free of the effects of preferred orientation. The powder X-ray diffraction data were indexed using the programs DICVOL13 and TREOR,14 leading to the following unit cell with orthorhombic metric symmetry: a ) 13.37 Å, b ) 12.79 Å, c ) 5.07 Å (V ) 867 Å3). On the basis of systematic absences, the space group was assigned as P212121. A good quality Le Bail fit15 (Rp ) 0.020; Rwp ) 0.034) was obtained for this unit cell and space group, serving both to confirm the correctness of the unit cell and to establish suitable profile parameters for use in the structure solution calculation. Density considerations suggest that there is one molecule in the asymmetric unit, consistent with results from highresolution solid-state 13C NMR studies on this material. The crystal structure of 1 was solved directly from the powder X-ray diffraction data using our GA technique implemented in the program EAGER.16 In the structure solution calculation, each trial structure was defined by a total of nine structural variables: {x, y, z, θ, φ, ψ, τ1, τ2, τ3}. The three variable torsion angles are defined in Figure 1. The population comprised 100 structures, and in each generation 50 mating operations and 20 mutation operations were carried out. The best structure (Rwp ) 0.15) obtained in the GA structure solution calculation was used as the starting structural model for Rietveld refinement. Rietveld refinement was carried out using the GSAS program.17 Standard restraints were applied to bond lengths and
Structural Aspects of a Dendrimer Precursor
Crystal Growth & Design, Vol. 4, No. 3, 2004 453 Table 1. Fractional Atomic Coordinates in the Final Refined Crystal Structure of 1a
Figure 1. The structural fragment used in the genetic algorithm structure solution calculation for 1, comprising all non-hydrogen atoms of the molecule. The three variable torsion angles are indicated by arrows.
C1 C2 C3 C4 C5 C6 C7 O8 O9 C10 O11 C12 H2 H4 H6 H7A H7B H10A H8 H10B H10C H12A H12B H12C
x
y
z
0.4485(7) 0.4271(9) 0.5743(7) 0.760(1) 0.7946(6) 0.640(1) 0.2838(7) 0.330(1) 0.9701(9) 1.140(1) 0.5263(9) 0.324(2) 0.3102 0.8643 0.6632 0.1005 0.2962 1.2434 0.2227 1.2568 1.0371 0.3111 0.3499 0.1561
0.0704(3) 0.1118(3) 0.0705(3) -0.0077(4) -0.048(2) -0.0073(4) 0.1145(3) 0.2198(3) -0.1329(3) -0.1584(4) 0.1018(4) 0.1763(6) 0.1666 -0.0329 -0.0324 0.1075 0.0703 -0.0967 0.2340 -0.2130 -0.1785 0.2163 0.2169 0.1366
0.1408(3) 0.2373(3) 0.3170(2) 0.2973(2) 0.2003(2) 0.1218(2) 0.0658(4) 0.0353(4) 0.1898(2) 0.2716(4) 0.4240(3) 0.4332(3) 0.2491 0.3492 0.0571 0.0893 0.0065 0.2890 -0.0110 0.2522 0.3278 0.3740 0.4904 0.4410
a Space group P2 2 2 ; final refined lattice parameters: a ) 1 1 1 5.0722(2) Å, b ) 12.7862(5) Å, c ) 13.3605(4) Å.
Figure 2. Experimental (+ marks), calculated (solid line), and difference (lower line) powder X-ray diffraction profiles for the crystal structure of 1. Tick marks indicate reflection positions. The calculated powder diffraction profile is for the final refined crystal structure. bond angles in the initial cycles of refinement and were gradually relaxed as the refinement progressed. Isotropic displacement parameters were refined for all non-hydrogen atoms (with a common value refined for the atoms of the phenyl ring). The methoxy and hydroxyl groups were assigned on the basis of hydrogen bonding considerations and on consideration of the results from refinement of the isotropic displacement parameters. Toward the end of the refinement, hydrogen atoms were introduced into the structure at calculated positions (C-H ) 0.98 Å), with the isotropic displacement parameter of each hydrogen atom constrained to be 1.2 times the value for the atom to which it is bonded. The hydrogen atom of the hydroxyl group was located from a difference Fourier map. The final Rietveld refinement (see Figure 2 and Table 1) gave Rp ) 0.024 and Rwp ) 0.035 for 3349 data points (λ ) 1.54056 Å, resolution ) 1.35 Å). The refined unit cell parameters were a ) 5.0722(2) Å, b ) 12.7862(5) Å, c ) 13.3605(4) Å.
Discussion In the molecular conformation of 1 in the crystal structure, all non-hydrogen atoms are coplanar, with the exception of the oxygen atom of the hydroxyl group (Figure 3). The torsion angle around the C-C bond that links the -CH2OH group to the aromatic ring is ca. 67°. In contrast, the carbon atoms of both methoxy (-OCH3) groups are coplanar with the aromatic ring, as commonly observed, for example, in derivatives of anisole.18 The conformation of 1 in the crystal structure is consistent with the observation that the oxygen atom of CH2OH groups tends to deviate further from the adjoining aromatic plane than the carbon atom of methoxy groups19 (unless substituents ortho to methoxy groups prohibit coplanarity with the aromatic ring20). The relative orientations of the O-C bonds of the two
Figure 3. The molecular conformation of 1 in the crystal structure.
methoxy groups are nonparallel, in contrast to the crystal structure of 1,3,5-trimethoxybenzene, for which one pair of methoxy groups adopts a parallel orientation.21 Clearly, the hydroxyl group of 1 has the possibility to participate in O-H‚‚‚O hydrogen bonds as a hydrogen bond donor (to a neighboring methoxy or hydroxyl group) and/or as a hydrogen bond acceptor (from a neighboring hydroxyl group), and indeed infinite onedimensional hydrogen bonded chains of the type O-H‚‚‚O-H‚‚‚O-H, involving O-H‚‚‚O interactions (H‚‚‚O, 2.15 Å; O‚‚‚O, 2.82 Å; O-H‚‚‚O, 139.2°) between hydroxyl groups, are formed parallel to the a-axis (Figure 4a). As shown in Figure 4b, the molecules involved in a hydrogen-bonded chain of this type form stacks parallel to the a-axis, and adjacent molecules along a given chain alternate between two neighboring stacks. The two stacks of molecules that give rise to one
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ing molecules within a given stack are parallel to each other (Figure 4b), the distance (5.07 Å) between the centroids of the rings and the orientations of the planes of the rings relative to the centroid-centroid vector are such that there are no significant π‚‚‚π interactions. Along the c-axis (see Figure 4c), short C-H‚‚‚O contacts (H‚‚‚O, 2.54 Å; C‚‚‚O, 3.37 Å; C-H‚‚‚O, 148.7°) may be identified, involving a C-H bond on the aromatic ring of one molecule and the oxygen atom of one of the methoxy groups of a neighboring molecule. These C-H‚‚‚O interactions give rise to zigzag chains of molecules running parallel to the c-axis (in Figure 4a, these chains run into the page). As evident from Figure 4c, these C-H‚‚‚O hydrogen-bonded chains are orthogonal to the O-H‚‚‚O hydrogen-bonded tapes discussed above, and each molecule lies at the intersection of a chain and a tape. It is interesting to compare the crystal structure of 1 with that of benzene-1,3,5-trimethanol,22 which can be considered to be derived from 1 by replacing the two methoxy groups in 1 by CH2OH groups. In the crystal structure of benzene-1,3,5-trimethanol, each of the three hydroxyl groups acts as both a hydrogen bond donor and a hydrogen bond acceptor, resulting in a complex threedimensional network of O-H‚‚‚O hydrogen bonds, in contrast to the one-dimensional chains of O-H‚‚‚O hydrogen bonds observed for 1. Concluding Remarks As discussed above, compound 1 is the precursor for a family of dendrimeric materials, and its structural characterization establishes a basis for comparison with higher generation dendrimers. The presence of the same functional groups in the higher generation dendrimers offers commonality in the possible interactions that may arise in their crystal structures, and the structural investigations reported here reveal aspects of hydrogen bonding and crystal packing that may well be found in higher generation dendrimers. Furthermore, from a practical point of view, higher generation dendrimers formed from 1 may be expected to be of poorer crystallinity, such that structure determination of these materials may be possible only by exploiting the powder X-ray diffraction techniques employed in the present work.
Figure 4. (a) Crystal structure of 1 viewed along the c-axis (the dotted lines indicate O-H‚‚‚O interactions, which form chains running in the horizontal direction). (b) View in the same direction as panel a showing only the molecules from two stacks that form an individual O-H‚‚‚O hydrogen-bonded tape. (c) Crystal structure of 1 viewed along the a-axis (dotted lines indicate C-H‚‚‚O contacts, which form zigzag chains running along the vertical direction; the O-H‚‚‚O hydrogen bonded chains, which are also indicated by dotted lines, run essentially into the plane of the page). In panels a-c, hydrogen atoms not involved in hydrogen bonding are omitted for clarity.
of these chains may be described as a hydrogen-bonded “tape” that runs along the a-axis, and as seen in Figure 4c, the approximate plane of one of these tapes is either (011) or (011). Although the aromatic rings of neighbor-
Acknowledgment. We are grateful to EPSRC (general support to K.D.M.H. and postdoctoral research fellowship to E.Y.C.) and Bruker-AXS and the University of Birmingham (studentship to Z.P.) for financial support. Dr. S. J. Kitchin is thanked for help with solidstate NMR spectroscopy. References (1) (a) Tomalia, D. A.; Naylor, A. M.; Goddard, W. A., III. Angew. Chem. Int. Ed. Engl. 1990, 102, 119. (b) Newkome, G. R.; Moorefield, C. N.; Baker, G. R.; Johnson, A. L.; Behara, R. K. Angew. Chem. Int. Ed. Engl. 1991, 103, 1205. (c) Issberner, J.; Bo¨hme, M.; Grimme, S.; Nieger, M.; Paulus, W.; Vo¨gtle, F. Tetrahedron: Asymmetry 1996, 7, 2223. (2) (a) Hawker, C. J.; Frechet, J. M. J. J. Chem. Soc. Chem. Commun. 1990, 1010. (b) Moore, J. S.; Xu, Z. Macromol. 1991, 24, 5893. (3) Newkome, G. R.; Yao, Z.-Q.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2003.
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