www.sciencemag.org/cgi/content/full/329/5989/299/DC1
Supporting Online Material for Single-Crystal X-ray Structure of 1,3-Ddimethylcyclobutadiene by Confinement in a Crystalline Matrix Yves-Marie Legrand, Arie van der Lee, Mihail Barboiu* *To whom correspondence should be addressed. E-mail:
[email protected]
Published 16 July 2010, Science 329, 299 (2010) DOI: 10.1126/science.1188002 This PDF file includes: Materials and Methods Scheme S1 Figs. S1 to S7 Table S1 References
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A. Synthesis All compounds were purchased from Aldrich and used without purification. Preparation of G4C. The tetra-p-sulfocalix[4]arene, C (0.020 g, 1 equiv.) and guanidinium chloride GCl (0.010 g, 4 equiv.) were dissolved in 1 mL D2O. After 24 hours, colorless single crystals were obtained at room temperature. Preparation of G4C{Me21}. The tetra-p-sulfocalix[4]arene, C (0.020 g, 1 equiv), guanidine hydrochloride GCl (0.010 g, 4 equiv.) and 4,6-dimethyl-α-pyrone (0.003 g, 1 equiv.) were dissolved in 1 mL D2O (Scheme S1). After 17 H, colorless single crystals were obtained at room temperature. High quality X-ray crystallographic data confirmed the high purity of the crystals formed.
Scheme S1. Synthetic route to obtain G4C{Me21} The average distance dX-Cg = 3.67 Å between the pyrone methyl group C8 and the four aromatic rings of the calixarene in the structure of G4C{Me21} is below the median value for CH-π interactions in proteins (3.8 Å). (S1) Additionally, the angle gamma and the distance dH-Perp are within standard values for CH-π interactions (S1), as reported in Table S1. It is therefore evident that the methyl group is not only sitting, by van der Waals contact, in the hydrophobic pocket of the calixarene, but is also held tightly in one position, through three CH-π interactions, on the same carbon C8 (Fig. S1). Moreover, it is likely that the methyl group, which is a sigma (inductive) electrondonating group, stabilizes the resonance structure being formed under UV-irradiation. Table S1. Analysis of X-H...Cg(π-Ring) Interactions (H...Cg < 3.0 Å - Gamma < 30.0°) X C(8) C(8) C(8)
H -H(103) -H(104) -H(105)
Cg(j) Cg(1) Cg(2) Cg(3)
H..Cg/Å 2,91 2,74 2,81
H-Perp/Å -2,80 2,72 2,74
Gamma/° 15,42 5,91 12,48
X-H..Cg/° 137 155 160
X..Cg/Å 3,66 3,62 3,72
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Figure S1: CH-π interactions in G4C{Me21}. The calixarene hydroxyl groups have been removed for clarity. The interactions are represented by dotted lines. The centroids of the aromatic rings are represented by small blue circles. Single crystal photolysis experiments: In situ X-ray observation was performed using a single crystal placed on the goniometer, immersed in a N2 flow to cool it down to 175 K. The crystal was then, under continuous phi-rotation, irradiated using a Bluepoint 2.1UV point source (λ=320-500 nm) to obtain G4C{Me21’} intermediate state, G4C{Me23&Me2CBDR}, and final G4C{Me2CBDS&Me2CBDR} X-ray structures. It is notable that the tetra-guanidinium-p-sulfonatocalix[4]arene G4C matrix remains unchanged upon irradiation, while the structure of confined compound of interest has been photochemically modified. The confined G4C{Me21} architecture was photochemically transformed into transient intermediate G4C{Me21’}, and then into the G4C{Me23&Me2CBDR}
architecture.
dimethylcyclobutadiene-based
Further
irradiation
yielded
G4C{Me2CBDS&Me2CBDR}
crystal
the
1,3-
confined
architectures. Steric hindrance and supramolecular interactions allow CO2 to stay in close proximity to Me2CBDS & Me2CBDR molecules and to influence their geometries.
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The metastable species can exist at the experimental temperature for at least several days without experiencing damage. An explanation for the twin structures may arise from the lack of homogeneity in the irradiation process. Although the single crystal was continuously rotated during irradiation at 175 K, two faces of the crystal were possibly less exposed to light, as was the inside of the crystal, creating zones of intensely exposed species and zones of partially exposed species. If the twinning of the structure arose from evolution of the transient species over 15 hours, it would not have been possible to record the same data twice within a 72 hours interval. Further details of crystallographic data are provided below. B. Crystallographic Data X-ray data were collected on a Gemini S four-circle diffractometer (Oxford-Diffraction) using Mo-Ka monochromatic radiation at 175 K. The structure solution was obtained using the ab-initio charge flipping method with Superflip (S2), and refined using nonlinear least-squares (S3); the electron density maps were calculated by CRYSTALS (S3), and visualized with the MCE program (S4). Figs S3 to S8 have been prepared with VESTA, a 3D visualization system for electronic and structural analysis (S5). In an X-ray diffraction experiment the intensities of Bragg reflections are measured, which are proportional to the squared modulus of the observed structure factor |Fobs|. The complex structure factor is the inverse Fourier transform of the electron density in the structure. In order to obtain the electron density, the complex structure factor – modulus plus phase – should thus be known. The phases are recovered by a mathematical process from the amplitudes, here using the charge flipping methodology (S2). The electron density map is the primary information that is obtained from an X-ray diffraction experiment. What follows is a – biased – atomic interpretation of this electron density map: the electron density maxima in the map are assigned to the different atomic species assumed to be present in the structure, and a refinement of this
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atomistic model is attempted using the tabulated scattering factors of the different atomic elements. In classical crystallography, spherical atomic scattering factors are used (also in this study), which can never be expected to model correctly all properties of the electron density map, such as bonding effects. Very high resolution experimental data – higher than obtained in this study – should be used to more properly describe other effects than is possible in the simple spherical atomistic model. Other problematic features are the presence of disorder which is often poorly described by a simple atomistic model. Deficiencies of the employed model can be uncovered by special density maps, such as the difference map, which is the inverse Fourier transform of the difference between the moduli of the observed and calculated structure factor (|Fobs| and |Fcalc|) combined with the calculated phase φcalc, or simply the observed electron density map, which is the inverse Fourier transform of the observed structure factor modulus combined with φcalc. Inspection of these maps could thus reveal more information about the structure than the interpreted atomistic model can do. In this study the observed electron density maps have been calculated and show that atomic disorder appears in the successive series of irradiations. The highest electron density levels (in red) – which are clearly present in the non-irradiated G4C{Me21} molecule - tend to disappear and the lowest levels tend to extend more or less diffusely along the bonds and below and above the initial plane of the molecules. This is characteristic of atomic disorder and is in general difficult to model with simple atomistic models. The principal characteristics, however, have been captured in a twomolecule atomistic model of which the populations have been refined. It should be interpreted from this two-molecule atomistic model that the two molecules never exist together in the same unit cell. Instead, in the hypothesis of a 50%-50% population probability for molecules A and B, respectively, 50% of the unit cells contain molecule A and the other 50% contain molecule B. A number of soft constraints were applied in order to keep bond distances and angles in reasonable chemical ranges. In the structures of G4C{Me23&Me2CBDR} and G4C{Me2CBDS&Me2CBDR} the total occupancy of sites C3 and C300, and that of C5 and C500, were kept fixed at 1.00 (and associated protons), but the individual
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occupancies were allowed to vary within the given constraint that the occupancies of C3 and C5 be identical, and those of C300 and C500 as well. In G4C{Me23&Me2CBDR} the
occupancies
refined
G4C{Me2CBDS&Me2CBDR}
to these
0.773(3)
and
occupancies
0.227(3),
were
0.627(2)
whereas and
for
0.373(2),
respectively. In addition the site occupancy factor of the H99-O74-H100 water molecule was refined for G4C{Me21’}, G4C{Me23&Me2CBDR} and G4C{Me2CBDS&Me2CBDR} whereas for G4C{Me21} it was fixed at 1.00. Not refining these site occupancy factors led to unrealistically high atomic displacement factors for these three structures. For G4C{Me26’}, G4C{Me25} it was possible to refine both the occupancy factor and the isotropic atomic displacement factor, which finally led to realistic displacement parameters in approximate agreement with the two other fully occupied water molecule sites. For G4C{Me2CBDS&Me2CBDR} it was not possible – due to strong correlations – to refine both the occupancy and the displacement parameter, so in that case the atomic displacement parameter of O74 was fixed at a value close to those found for G4C{Me21’} and G4C{Me23&Me2CBDR} and only the occupancy factor was refined. The final occupancy factors for O74 and associated protons are 0.488, 0.438, and 0.194 for
G4C{Me21’},
G4C{Me23&Me2CBDR},
and
G4C{Me2CBDS&Me2CBDR},
respectively.
Crystallographic Data for G4C: Formula=C32H46N12O17S4, T = 175 K, Mr = 999.09 gmol−1, crystal size = 0.080x0.200x0.310 mm3, triclinic, space group P−1, a = 12.3140(6), b = 13.1507(5), c = 14.3758(6) Å, α = 90.796(3)ο, β = 92.492(4)ο, γ = 93.663(3)ο, V = 2320.71(17) Å3, Z = 2, ρcalcd= 1.430 gcm−3, μ= 0.285 mm−1, θmax= 33.674, 41567 reflections measured, 16869 unique, 5645 with I>2σ(I), Rint=0.101, =0.125, refined parameters = 634, R1(I>2σ(I)) = 0.0534, wR2(I>2σ(I)) = 0.0570 R1(all data) = 0.1862, wR2(all data) = 0.0570, GOF = 1.153, Δρ(min/max)=-0.44/ 0.65 eÅ−3.
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Common
data S
for
G4C{Me21},
G4C{Me21’},
G4C{Me23&Me2CBDR}
and
R
G4C{Me2CBD &Me2CBD }: Formula = C39H58N12O21S4, T = 175 K, Mr = 1159.22 g.mol−1, crystal size = 0.100x0.120x0.220 mm3, Monoclinic, space group P121/c1 Crystallographic Data for G4C{Me21}: a = 13.6203(3), b = 13.0436(3), c = 28.5132(6) Å, α = 90ο, β = 94.708(2)ο, γ = 90ο, V = 5048.50(19) Å3, Z = 4, ρcalcd= 1.525 g.cm−3, μ= 0.280 mm−1, θmax= 32.843, 76870 reflections measured, 17346 unique, 5403 with I>2σ(I), Rint=0.055, =0.092, refined parameters = 686, R1(I>2σ(I)) = 0.0483, wR2(I>2σ(I)) = 0.0588 R1(all data) = 0.1860, wR2(all data) = 0.0588, GOF = 0.997, Δρ(min/max)=-0.77/ 0.45 eÅ−3. Crystallographic Data for G4C{Me21’}: a = 13.9567(8), b = 12.9746(9), c = 28.3358(13) Å, α = 90.0ο, β = 95.435(5)ο, γ = 90.0ο, V = 5108.1(4) Å3, Z = 4, ρcalcd= 1.525 gcm−3, μ= 0.280 mm−1, θmax= 26.749, 76870 reflections measured, 17346 unique, 4801 with I>2σ(I), Rint = 0.050, = 0.0659, refined parameters = 696, R1 (I>2σ(I)) = 0.0826°, wR2(I>2σ(I)) = 0.0913, R1(all data) = 0.1256, wR2(all data) = 0.0913, GOF = 0.9487, Δρ(min/max)=-0.69/ 1.21 eÅ −3 . Crystallographic Data for G4C{Me23&Me2CBDR}, a = 13.9864(7), b = 12.9728(5), c = 28.3173(14) Å, α = 90.0ο, β = 95.309(5)ο, γ = 90.0ο, V = 5115.9(4) Å3, Z = 4, ρcalcd= 1.525 gcm−3, μ= 0.280 mm−1, θmax= 24.505°, 76870 reflections measured, 17346 unique, 3393 with I>2σ(I), Rint = 0.050, = 0.1008, refined parameters = 689, R1(I>2σ(I)) = 0.0904, wR2(I>2σ(I)) = 0.0685, R1(all data) = 0.1643, wR2(all data) = 0.0685, GOF = 1.0208, Δρ(min/max)=-0.58/ 0.90 eÅ−3.
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Crystallographic Data for G4C{ Me2CBDR &Me2CBDR}, a = 14.0561(5), b = 12.9422(5), c = 28.3637(10) Å, α = 90ο, β = 95.620(4)ο, γ = 90ο, V = 5135.0(3) Å3, Z = 4, ρcalcd= 1.499 gcm−3, μ= 0.275 mm−1, θmax= 28.607°, 76870 reflections measured, 17346 unique, 4156 with I>2σ(I), Rint = 0.050, = 0.1171, refined parameters = 694, R1(I>2σ(I)) = 0.0809, wR2(I>2σ(I)) = 0.1392 R1(all data) = 0.1649, wR2(all data) = 0.1392, GOF = 0.8854, Δρ(min/max)=-0.63/ 0.97 eÅ−3. Comparison of the three-dimensional structures of G4C and G4C{Me21} The structures of G4C and G4C{Me21} do not have the same packing although the 4,6dimethyl-α-pyrone moiety is partially inserted in the hydrophobic calixarene internal cavity. Figure S2 and Figure S3 show (non-perspective) views along the a-, b- and caxis, respectively. They show that in both cases the structure is organized in G4C and G4C{Me21} layers perpendicular to the b*-axis in the first case, and perpendicular to the c*-axis in the second case.
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Figure S2: Parallel structure views down the a-axis for G4C (upper) and G4C{Me21} (lower). Hydrogen bonds are represented by dotted lines.
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Figure S3. Parallel structure views down the c-axis for G4C (upper) and down the baxis for G4C{Me21} (lower). Hydrogen bonds are represented by dotted lines.
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Figure S4. Top view of the two-dimensional hydrogen bond network in the structure of G4C. Hydrogen bonds are represented by dotted lines In the α-pyrone-free structure the interaction between the layers is van der Waals like, and no hydrogen bonds are found between the layers. Fig. S4 shows the twodimensional hydrogen bond network formed in G4C; sulfonate and guanidinium moieties form an interpenetrating double hexagonal network. (23) In the α-pyronecontaining structure, however, a number of hydrogen bonds are found between the G4C{Me21} moieties. The hydrogen bonds form an interconnected three-dimensional network between water molecules (a single independent one in G4C and three independent ones in G4C{Me21}), guanidium moieties, sulfonate moieties and in the case of the α-pyrone-containing structure also Me21. The main difference between G4C and G4C{Me21}, apart from the intercalated Me21 molecule, is the relative stacking of the guanidinium moieties, which is close to parallel to the overall stacking for all four independent moieties in G4C (Fig. S5-upper), but for only one in G4C{Me21}. The three other ones are close to perpendicular to the overall stacking and in addition, close to parallel to the Me21 moiety (Fig. S5-lower).
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Figure S5: Perspective structure views approximately down the a*-axis for G4C (upper) and approximately down the a*-axis for G4C{Me21} (lower). Hydrogen bonds are represented by dotted lines.
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Figure S6. Top view (upper) of the three-dimensional hydrogen bond network in the structure of G4C{Me21} between the calixarene layers. The lower figure represents the corresponding side view. Hydrogen bonds are represented by dotted lines. Calixarene moieties have been removed for clarity.
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Figure S7. X-ray crystallographic observation of dynamically rotational equilibrium between Me2CBDR and Me2CBDS within confined conditions. The structures are stabilized by H-bonds (dO---H = 2.83 A) represented in yellow, between the C-H of Me2CBDR and Me2CBDS molecules and the sulfonate groups.
Internal free volume calculations for the G4C superstructure compared to Cram’s hemicarcerand and β-cyclodextrin host molecules. The free volume calculation was performed using the rolling sphere methodology implemented in the program PLATON (S6). The calculation uses the van der Waals radii to define the space which is occupied by atoms and molecules and then employs a spherical probe of a given radius on a grid to find empty regions. The probe radius was 1.2 Å and the grid spacing for the sampling 0.2 Å. The solvent accessible void volume inside the G4C calixarene internal pocket capped by guadinium moieties calculated in this way is 46 Å3 (with van der Waals radii of 1.70, 1.20, 1.55, 1.52, and 1.80 A for C, H, N, O, S, respectively). This value needs to be compared with Cram's hemicarcerand structure (S7,S8), but unfortunately its detailed crystallographic structure was never published, and thus cannot be found in the Cambridge Structural Database (CSD). Therefore the very close sulphur analogue reported in (S9) – CSD code YOCRAJ – was used for the void calculation. The solvent was withdrawn from the cage and the
27
calculation run with the same set of conditions as for G4C, yielding 135 Å3. Similarly, the cage void volume for two adjacent beta-cyclodextrins is calculated to be 253 Å3.
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