Tuning the Circumference of Six-Porphyrin Nanorings

Most macrocycles are made from a simple repeat unit, resulting in high symmetry. Breaking this symmetry allows fine-tuning of the circumference, providing better control of the host–guest behavior and electronic structure. Here, we present the template-directed synthesis of two unsymmetrical cyclic porphyrin hexamers with both ethyne (C2) and butadiyne (C4) links, and we compare these nanorings with the symmetrical analogues with six ethyne or six butadiyne links. Inserting two extra carbon atoms into the smaller nanoring causes a spectacular change in binding behavior: the template affinity increases by a factor of 3 × 109, to a value of ca. 1038 M–1, and the mean effective molarity is ca. 830 M. In contrast, removing two carbon atoms from the largest nanoring results in almost no change in its template-affinity. The strain in these nanorings is 90–130 kJ mol–1, as estimated both from DFT calculation of homodesmotic reactions and from comparing template affinities of linear and cyclic oligomers. Breaking the symmetry has little effect on the absorption and fluorescence behavior of the nanorings: the low radiative rates that are characteristic of a circular delocalized S1 excited state are preserved in the low-symmetry macrocycles.


■ INTRODUCTION
Symmetry confers beauty and simplicity. Most large synthetic macrocycles are constructed from a repeating monomer unit, resulting in a highly symmetric structure (C n or D nh ), which expedites their synthesis and spectroscopic characterization; for example, it gives simple NMR spectra. 1 Conversely, a less symmetrical design brings structural versatility: it allows the diameter of the macrocycle to be adjusted in smaller increments in order to optimize binding to a specific guest. In π-conjugated macrocycles, if the singlet electronic excited state is delocalized over the whole ring, high symmetry makes the S 0 −S 1 transition forbidden; thus, reducing the symmetry is expected to increase the radiative rate and increase the fluorescence quantum yield. 2,3 Previously, we reported the template-directed synthesis of two 6-fold symmetric cyclic porphyrin hexamers, c-P6 [b 6 ] and c-P6[e 6 ], linked via butadiyne (C4) and ethyne (C2) bridges, using templates T6 and T6*, respectively (Figure 1). 4−6 Here, we show that low-symmetry (C 2v ) versions of these macrocycles, c-P6 [b 5 e] and c-P6[be 5 ], can be synthesized using the same T6 and T6* templates. We demonstrate that the ability to adjust the circumference, by adding or removing two carbon atoms, has a dramatic effect on the binding behavior of these nanorings. In contrast, the changes in symmetry are too subtle to have a strong effect on the radiative rates of the singlet excited states, and the photophysical behavior of the parent structures is preserved.
■ RESULTS AND DISCUSSION Molecular Modeling. Density functional theory (DFT; B3LYP, 6-31G* basis set, in vacuum) was used to calculate optimized geometries of the free nanorings and their template complexes, to estimate the level of strain, and to predict which templates would be effective for nanoring synthesis. 7 The strain in each nanoring (ΔH strain ) was estimated by calculating the free energy change for a homodesmotic reaction: 8 cyclic hexamer + linear dimer → linear octamer. The results (Table  1) show a gradual reduction in strain with ring expansion.
The complementarity of the templates was estimated from the average distances of the six zinc atoms from the centroid (R Zn ) for the template-free nanorings ( Table 1). The ideal template radius (R N,ideal ) for each nanoring was calculated by subtracting the crystallographic out-of-plane distance of the zinc atom (0.37 Å) and the Zn−N(pyridine) bond length (2.15 Å) from R Zn . 5 The calculated radii of T6 and T6* (R N ) are 10.03 and 8.30 Å, respectively, allowing us to calculate the misfit (R N − R N,ideal ) as listed in Table 1. These data lead to the surprising conclusion that, if we ignore the angular deviation from D 6h symmetry in the low-symmetry nanorings, then T6* and T6 are expected to fit the unsymmetrical rings better than the symmetrical rings for which they were originally designed. 4,6 T6 is slightly too small for c-P6 [b 6 ] and slightly too big for c-P6[b 5 e], while T6* is slightly too big for c- The smaller unsymmetrical nanoring c-P6[be 5 ]·T6* was synthesized in 25% yield by palladium-catalyzed oxidative coupling of the linear C2-linked hexamer HC 2 -l-P6[e 5 ]-C 2 H in the presence of the T6* template. This linear hexamer was prepared from a known bromoporphyrin hexamer 6 by Sonogashira coupling as shown in Scheme 1. The unsymmetrical nanoring c-P6[be 5 ] is easier to synthesize than c-P6[e 6 ] both because oxidative Glaser coupling is a more efficient reaction than Sonogashira coupling, for the final cyclization step, and because the T6* template matches the cavity of c-P6[be 5 ] better than that of c-P6[e 6 ] (Table 1).
NMR Spectroscopy. The 1 H NMR spectra of the four nanoring−template complexes are compared in Figure 3. Resonances from β-pyrrole protons nearest to an ethyne bridge are easy to identify by virtue of their high chemical shifts (ca. 10 ppm). 10 The spectra were fully assigned using 2D NMR techniques (as detailed in the SI).     Table 2 (see the SI for details). The nanorings all bind the templates much more strongly than the corresponding linear hexamers. Inserting two carbon atoms into c-P6[e 6 ] to give c-P6[be 5 ] results in a colossal increase in affinity for T6*; log K f increases from 29.0 to 38.5.
The level of chelate cooperativity 12,13 in the porphyrin hexamer template complexes was evaluated by calculating the effective molarities, EM, by comparing the stability of each complex with that of a single-site reference interaction, using eq 1 where EM is the geometric mean of the effective molarities for five intramolecular interactions, K chem is the statistically corrected formation constant of the hexamer−template complex (K chem = K f /768), and K 1 is the statistically corrected binding constant of a monovalent reference ligand for a zinc porphyrin monomer. We use 4-phenylpyridine (K 1 = 1.7 × 10 4 M −1 ) as a reference for T6 and 4-phenylethynylpyridine (K 1 = 3.2 × 10 3 M −1 ) as a reference for T6*. The values of log EM listed in Table 2 highlight the exceptionally high chelate cooperativity of the c-P6[be 5 ]·T6* complex; log EM = 2.9 ± 0.1; EM = 830 ± 190 M. This is among the highest effective molarities found for any noncovalent supramolecular complex. 13−15 The difference in formation constant between c-P6[b 6 ]·T6 and c-P6[b 5 e]·T6 is surprisingly subtle. Presumably, the weaker binding of c-P6[b 5 e] reflects its lack of D 6h symmetry because, according to our DFT calculations, its sizecomplementarity is better than that of c-P6 [b 6 ] (Table 1). We carried out a 1 H NMR experiment to check the relative affinities of c-P6 [b 6 ] and c-P6[b 5 e] for T6 in CDCl 3 . The competition equilibrium constant K C is defined as shown in Figure 5 and eq 2. The data from UV−vis−NIR denaturation titrations (  ] ratio is 1.23 ± 0.10, giving K C = 1.5 ± 0.2 (in CDCl 3 at 298 K). The strain energy in a porphyrin nanoring (ΔG strain ) can be estimated from the difference in binding energy of the template with the corresponding cyclic and linear oligomers, as expressed by eqs 3. 4,16  (Table 2) are similar to the strain enthalpies from DFT (ΔH strain , Table 1), indicating that the main cause for the weaker binding of the linear oligomers is the enthalpy cost of bending the linear oligomer into a cyclic conformation. This analysis assumes that there is no significant change in conformation, or increase in strain, when the nanoring binds the template and that the strain in the bound linear oligomer is essentially the same as the strain in the nanoring. Equation 3 does not provide a good estimate of the strain if the template and/or nanoring undergo deformation on complexation, as is the case when c-P6[e 6 ] binds T6*; here, the low value of ΔG strain reflects the poor shape complementarity between the nanoring and the template. Photophysical Behavior. The absorption and fluorescence spectra of the nanorings and their template complexes

Journal of the American Chemical Society
Article are compared in Figure 6. Fluorescence lifetimes, quantum yields, and radiative rates are listed in Table 3. 17 The spectra of c-P6 [b 6 ] and c-P6 [b 5 e] are very similar (with and without bound T6). There is a larger difference between the spectra of c-P6[e 6 ] and c-P6[be 5 ], which probably reflects the greater strain in these complexes and the severe dome-shaped distortions in c-P6[e 6 ]·T6* (Figure 2d). Data for a typical linear hexamer, THS-l-P6 [b 5 ]-THS, are also included in Table  3, for comparison. Linear conjugated porphyrin oligomers of this type generally have high radiative rates and fluorescence quantum yields. 17,18 All of the nanorings have much lower fluorescence quantum yields and radiative rates than linear oligomers, as would be expected for a forbidden S 1 −S 0 transition in a symmetrical circular π-system. 2,3,17 Comparison of the radiative rates for c-P6[e 6 ] and c-P6[be 5 ] suggests, that in this case, lowering the symmetry increases the oscillator    a All measurements were carried out in toluene (containing 1% by volume of pyridine for the template-free nanorings to suppress aggregation). Fluorescence lifetimes were measured using excitation at 810 nm and detection at 1050 nm. Fluorescence quantum yields were measured using THS-l-P6 [b 5 ]-THS as a standard. 17 Radiative rates are calculated as k rad = Φ f /τ f .

Journal of the American Chemical Society
Article strength, but in general, the reduction in symmetry seems to be too subtle to have a strong effect on the photophysical behavior.