Cyclodextrin-Templated Porphyrin Nanorings

α- and β-Cyclodextrins have been used as scaffolds for the synthesis of six- and seven-legged templates by functionalizing every primary CH2OH with a 4-pyridyl moiety. Although these templates are flexible, they are very effective for directing the synthesis of macrocyclic porphyrin oligomers consisting of six or seven porphyrin units. The transfer of chirality from the cyclodextrin templates to their nanoring hosts is evident from NMR and circular dichroism spectroscopy. Surprisingly, the mean effective molarity for binding the flexible α-cyclodextrin-based template within the six-porphyrin nanoring (74 m) is almost as high as for the previously studied rigid hexadentate template (180 m). The discovery that flexible templates are effective in this system, and the availability of a template with a prime number of binding sites, open up many possibilities for the template-directed synthesis of larger macrocycles.


G. References S45
Preparation of c-P6!T6* a) T6* (5.5 mg, 3.13 µmol) and P2 (20 mg, 12.5 µmol) were dissolved in chloroform (15 mL) and diisopropylamine (DIPA, 0.20 mL). The solution was sonicated for 2 h and cooled to room temperature. A catalyst solution was prepared by dissolving dichlorobis(triphenyl-phosphine)-palladium(II) (2.9 mg, 4.0 µmol), CuI (7.2 mg, 37 µmol) and 1,4-benzoquinone (5.4 mg, 50 µmol) in chloroform (15 mL) and DIPA (0.2 mL). The catalyst solution was added to the mixture and stirred under air at room temperature overnight. The reaction mixture was passed through a plug of alumina using chloroform as eluent. The crude mixture was separated on size exclusion column (Biobeads SX-1, 200-400 mesh) using toluene as eluent to give the product c-P6!T6* as reddish-brown solid (12 mg, 59%). b) T6* (5.5 mg, 3.13 µmol) and P1 (20 mg, 25 µmol) were dissolved in chloroform (15 mL) and diisopropylamine (DIPA, 0.20 mL). The solution was sonicated for 2 h and cooled to room temperature. A catalyst solution was prepared by dissolving dichlorobis(triphenyl-phosphine)-palladium(II) (2.9 mg, 4.0 µmol), CuI (7.2 mg, 37 µmol) and 1,4-benzoquinone (10.8 mg, 100 µmol) in chloroform (15 mL) and DIPA (0.2 mL). The catalyst solution was added to the mixture and the reaction was stirred under air at room temperature and UV-vis monitoring during the reaction process (0.5 h interval) indicated the reaction to completion at 6 h. The reaction mixture was passed through a plug of alumina using chloroform as eluent. The crude mixture was separated on size exclusion column (Biobeads SX-1, 200-400 mesh) using toluene as eluent. Two major bands were collected from the column: the first band was collected for the following c-P12!(T6*) 2 synthesis; the second band was collected, dried and precipitated using chloroform/methanol to give the product c-P6!T6* as reddish-brown solid (4.5 mg, 22%               The 1 H-NMR spectrum of c-P12!(T6*) 2 is too complicated to be assigned in detail because this complex consists of a mixture of four diastereomers: the c-P12 can exist in two enantiomeric conformations, each of which can bind two T6* units with their narrow primary rings both pointing the same way or with their rims pointing in opposite directions. However the structure of c-P12!(T6*) 2 is supported by the fact that its 1 H NMR, 1 H DOSY spectra and UV-vis spectra are similar to those of the previously reported figure-of-eight complex c-P12!(T6) 2 . S6

D. Circular Dichroism Spectroscopy
Circular dichroism spectra and the corresponding UV-Vis spectra were measured on a JASCO 815 instrument.

E. Small-Angle X-ray Scattering Analysis of c-P6!T6* and c-P7!T7*
Synchrotron radiation SAXS data were collected using standard procedures on the I22 beamline at the Diamond Light Source (UK) equipped with a photon-counting detector. The beam was focused onto the detector placed at a distance of 1.25 m from the sample cell. The covered range of momentum transfer was 0.03 < q < 1.0 Å -1 (q = 4!sin(!)/", where 2! is the scattering angle and " = 1.00 Å is the X-ray wavelength). The data were normalized to the intensity of the transmitted beam; the scattering of the solvent was subtracted using an in-house program. To check for radiation damage during the SAXS experiment, the data were collected in 300 successive 1 s frames. Samples of c-P6!T6* and c-P7!T7* were dissolved in toluene at known concentrations (~10 -4 M) and placed in a solution cell with mica windows (1 mm path length). Simulated scattering curves from molecular models were obtained by fitting to the experimental scattering data using the program CRYSOL. S7 The program GNOM S8 was used to calculate pair distribution functions (PDF) and radii of gyration (R g ) from experimental and simulated scattering data.
Titrations with porphyrin monomer P1' were carried out to compare the Lewis basicity of pyridine and ligands L1-L2. These results were not used in the calculation of effective molarities.
All titrations were performed in chloroform (passed through short basic alumina column to remove stabilizers) at 298 K. All titrations were carried out at constant porphyrin concentration by adding porphyrin to the ligand stock solution before titrations started. Titration curves were fitted to a 1:1 binding isotherm using the equation: where A is the observed absorption at a specific wavelength or difference of absorption at two wavelengths; A initial is the starting absorption at this wavelength or difference of absorption in these two wavelengths; A # is the asymptotic final absorption at this wavelength or difference of absorption in these two wavelengths; K a is the association constant between ligand and porphyrin host; [L] is the concentration of ligand; [P] 0 is the concentration of porphyrin host.
The results are detailed in Table S1 and Figures S31-S38. In the spectra, the bold black lines represent starting points and the red lines represent terminal points.

F2. Titrations of Monodentate Ligands with Nanorings c-P6 and c-P7
c-P6 was titrated with the ligands shown in Fig. S39 (quinuclidine, pyridine, 4-phenylpyridine and methyl isonicotinate) to measure their association constants. Unless stated otherwise, all the titrations were performed in chloroform (passed through short basic alumina column) at 298 K and the concentrations of porphyrin nanorings were 1.8 µM. All titrations were carried out at constant porphyrin concentration by adding porphyrin to the ligand stock solution before titrations started.

Fig. S39
Ligands used for measurements of reference association constants of c-P6.
c-P7 was titrated with the ligands shown in Fig. S40 (quinuclidine, pyridine and 4-pyridinepropanoic acid methyl ester) to measure their association constants. The spectra for titration of c-P6 with monodentate ligands are slightly nonisobestic, which can lead to uncertainly in the association constant. This problem was minimized by taking the differences between absorption at 828 nm (the right shoulder of titration terminal spectra) and absorption at 736 nm (the left shoulder of titration starting spectra) to give the largest yet reliable change in absorption. The results were found to be self-consistent and consistent with previously published data. S9 Titration curves were fitted to a 1:1 binding isotherm using the equation (S.1) similar to Section F1. However, the [P] 0 is a 6-fold multiply for the concentration of c-P6 and 7-fold multiply for the concentration of c-P7, as they have multiple porphyrin units inside each molecule.
The results are listed in the tables and figures below. In the spectra, the bold black lines represent starting points and the red lines represent terminal points.  Table S2 The association constants of c-P6 and ligands (1:1 association constants in M -1 ).

F3. Denaturation Titrations c-P6!T6
was titrated with quinuclidine only, because quinuclidine is the only commonly used ligand to displace the template from c-P6!T6. The corresponding denaturation constant is labeled as K qp6t6 . c-P6!T6* and c-P7!T7* were titrated both with quinuclidine and pyridine. The corresponding denaturation constants are labeled as K qp6t6* , K pyp6t6* , K qp7t7* and K pyp7t7* , respectively. Unless stated otherwise, all the titrations were performed in chloroform (passed through short basic alumina column) at 298 K. All titrations were carried out at constant porphyrin concentration by adding porphyrin to the ligand stock solution before titrations started.
All the data were fitted to the n-dentate breaking-up binding isotherm, equation S.2.
where A is the observed absorption at a specific wavelength or difference of absorption in two wavelengths; A initial is the starting absorption at a specific wavelength or difference of absorption in two wavelengths; A # is the terminal absorption at a specific wavelength or difference of absorption in two wavelengths; K dn is the dissociation constant between ligand and porphyrin nanoring complex; [L] is the concentration of ligand; [P] 0 is the concentration of porphyrin nanoring complex; n is the number of binding sites of nanoring complexes. For c-P6!T6 and c-P6!T6*, n = 6; for c-P7!T7*, n = 7.
The titration results are listed in the tables and figures below. In the spectra, the bold black lines represent starting points and the red lines represent terminal points.

F4. Calculation of Effective Molarities S9
The formation constants K f of nanoring-template complexes were calculated from equation S.3, where K L is the association constants of the template-free ring c-Pn with ligand L; K dn,L is the denaturation constants of the nanoring-template complex with this ligand; n is the chelation number of nanoring-template complexes. For c-P6!T6 and c-P6!T6*, n = 6; for c-P7!T7*, n = 7. The uncertainty in LogK f was calculated from equation S.4: The resulting values of log K f are listed in Table S5: The geometric average effective molarities (!") of the nanoring complexes were calculated from equation S.5, where K chem,n is the statistically corrected value of K f . As is shown in Fig. S65, for c-P6!T6 and c-P6!T6*, K ! = 768; for c-P7!T7*, K ! = 1792. K 1 is the reference single-site microscopic binding constant statistically corrected for binding to one face of a porphyrin (i.e. half of the binding constants measured in reference association titrations in Section F2). The uncertainties in the values of log!" were calculated from equation S.6: The geometric average effective molarities of the nanoring complexes are listed in Table S6: