Allosteric Guest Binding in Chiral Zirconium(IV) Double Decker Porphyrin Cages

Abstract Chiral zirconium(IV) double cage sandwich complex Zr(1)2 has been synthesized in one step from porphyrin cage H21. Zr(1)2 was obtained as a racemate, which was resolved by HPLC and the enantiomers were isolated in >99.5 % ee. Their absolute configurations were assigned on the basis of X‐ray crystallography and circular dichroism spectroscopy. Vibrational circular dichroism (VCD) experiments on the enantiomers of Zr(1)2 revealed that the chirality around the zirconium center is propagated throughout the whole cage structure. The axial conformational chirality of the double cage complex displayed a VCD fingerprint similar to the one observed previously for a related chiral cage compound with planar and point chirality. Zr(1)2 shows fluorescence, which is quenched when viologen guests bind in its cavities. The binding of viologen and dihydroxybenzene derivatives in the two cavities of Zr(1)2 occurs with negative allostery, the cooperativity factors α (=4 K2/K1) being as low as 0.0076 for the binding of N,N’‐dimethylviologen. These allosteric effects are attributed to a pinching of the second cavity as a result of guest binding in the first cavity.

polarization microscope and are uncorrected. Optical rotations were measured on an Anton Paar Polarimeter MCP100.
Cyclic voltammograms were measured in a 0.1 M solution of tetrabutyl ammonium hexafluorophosphate, with a platinum electrode, an amorphous carbon electrode and silver/silver choride 3M potassium chloride reference electrode.
Molecular models were compiled using the Spartan '14 TM chemistry software (equilibrium geometry, PM3, semi-empirical method, gas phase) Fluorescence titrations were performed by preparing a 0.1 mM stock solution of (±)-Zr(1) 2 and a 2 mM stock solution of G1 in a degassed 1:1 v:v mixture of CH 2 Cl 2 and MeCN. From these stock solutions the following solutions were prepared: three 3.0 µM solutions of (±)-Zr(1) 2 , a mixture of 0.8 mM G1 and (±)-Zr(1) 2 , and a mixture of 0.08 mM G1 and (±)-Zr(1) 2 . The latter two mixtures were added in small quantities to one of the first three solutions under constant irradiation at 399 nm with a 5 nm excitation bandwidth, while obtaining the emission spectra between the additions to provide the data presented in Tables 3 -5. This data at multiple wavelengths was fitted altogether using an online fitting tool: http://app.supramolecular.org/bindfit/ [s1,s2] to provide the binding parameters shown in Table S6 and the fits depicted in Tables S7 -S9. Circular dichroism titrations were performed in a similar way as the fluorescence titrations, but at a higher host concentration of 8 µM (Tables S10 -S12). A number was added to all data points to make them positive, because the fitting tool does not allow negative numbers. This number was subtracted for Figure S11. UV-Vis titrations were performed and analyzed analogous to the fluorescence titrations, and provided the spectra in Figure S13 and the binding parameters shown in Table S13. The concentration of (±)-Zr(1) 2 in all solutions is 2.0 µM, solutions containing G1 had concentrations of 0.08 mM, 0.8 mM and 8 mM. The measured and fitted data are depicted in Tables S14-16 and S17-19, respectively. NMR titrations were performed by the addition of a solution of the appropriate guest with the host to a solution with the host (to account for dilution). Host concentrations varied from 0.20 to 1.0 mM. Chemical shifts obtained from the titrations for various host proton signals (Tables S20 -S32) were multiplied by the concentration of the host and fitted using the online program http://limhes.net/optim/ to yield the fits depicted in Tables S20 -S32. The titration spectra overlays are presented in Figures S34 -S45.
The emission life time was determined by a time correlated single photon counting experiment (TCSPC) irradiating a 0.65 M solution of (±)-Zr(1) 2 . Excitation is done by the output of a fully automatic tunable Ti:sapphire laser (Chameleon Ultra, Coherent), The final excitation wavelength (398 nm) is made with second harmonics generation (SHG APE). The repetition rate is decreased from the fundamental 80 MHz to a lower value (8 MHz) using a pulse picker (PulseSelect, APE). Fundamental light is guided via a delay line to a fast photodiode (PD) and use as the reference pulse. The excitation beam is directed to the cuvet, where the emission is collected using an uncoated, UV Fused Silica Aspheric Lens, f=50mm (Edmunds), at the magic angle (54.7) and focused on the entrance slit of the monochromator (Newport Cornerstone 260, f=250mm, grating 300ln/mm blaze 422 or grating 300ln/m blaze 750nm). A multichannel plate photomultiplier tube (MCP-PMT, R3809U-50, Hamamatsu) is used for wavelengths below 550nm, a second multichannel plate photomultiplier tube (MCP-PMT R3809U-51, Hamamatsu) is used above 550nm. The signal from the MCP's is amplified (RF Amplifier 8347A Hewlett Packard) to have a more stable output the CFD (constant fraction desciminator) in the TCSPC electronics. The time between reference signal and output the MCP is measured using a TCSPC board Becker & Hinkle). Delay adjustments are done using an optical delay in the reference signal path and an electronic delay box (Ortec model 425). Although the excitation source produces sub-picosecond pulses, the electronics and the detector cause a broadening of the signal and are the limiting factor of the time resolution. The overall instrument response function (IRF) is around 20-25 ps (FWHM) measured from scattering from a ceramic plate at the excitation wavelength. The final histogram of the TCSPC is made using the SPCM program (Becker & Hinkle). Figure S1. Numbering of the carbon atoms in (±)-Zr(1) 2 ; the signs I-IV indicate the four quadrants in which each of the porphyrin cages is divided for the assignment of the NMR signals.
Syntheses Zr(Et 2 N) 4 [s3] : ZrCl 4 (549 mg, 2.36 mmol) and Li(Et 2 N) (760 mg, 9.61 mmol) were dissolved in argon-purged dry diethyl ether (9 mL) under an inert atmosphere. The mixture was stirred for 22 hours at 20 °C. The suspension was filtered under an inert atmosphere and the filtrate was concentrated in vacuo, redissolved in n-pentane (10 mL), and filtered again. The n-pentane was removed in vacuo to yield Zr(Et 2 N) 4 as a yellow/orange liquid, which was used in the synthesis of (±)-Zr(1) 2 without any further analysis or yield determination.

HPLC
Analytical chiral HPLC separation of (±)-Zr(1) 2 • The sample was dissolved in dichloromethane, injected on the chiral column, and detected with an UV detector at 254 nm and a circular dichroism detector at 254 nm. The flow-rate was 1 mL/min.
• First fraction: 18 mg of the first eluted enantiomer with ee > 99.5 %