Photocontrolled Release and Uptake of a Porphyrin Guest by Dithienylethene‐Tethered β‐Cyclodextrin Host Dimers

Abstract

Two photoswitchable dithienylethene‐tethered β‐cyclodextrin dimers were synthesized to function as host molecules with an externally controllable binding affinity. The cyclodextrin cavities of these dimers are linked through their secondary sides by a photochromic dithienylethene unit that is connected to the secondary rim either directly (4) or through propyl spacers (9). Irradiation with light switches these dimers between a relatively flexible (open) and a rigid (closed) form. The binding properties of the dimers depend on the configuration of the dithienylethene spacer, as is shown by microcalorimetry performed with tetrakis‐sulfonatophenyl porphyrin (TSPP) as a guest molecule. The differences in binding properties are most pronounced for the more rigid dimer 4, which binds TSPP 35 times more strongly in the open form (4 a) than in the closed form (4 b). The values found for the enthalpy of binding (ΔH°) indicate that this difference in binding is due to the loss of cooperativity between the two β‐cyclodextrin cavities in the closed form. Molecular modeling shows that 4 b is not able to bind TSPP effectively in both cyclodextrin cavities. The open and closed forms of the more flexible dimer 9 show no substantial difference in their binding of TSPP. Thermodynamic values indicative of strong binding of TSPP by two β‐cyclodextrin cavities were measured for both forms of the dimer, and molecular modeling confirms that both are flexible enough to tightly bind TSPP. The binding differences between the forms of dimer 4 allow the photocontrolled release and uptake of TSPP, which renders control of the ratio of complexed to free TSPP in solution possible.

Complexation of Charged Porphyrins by Charged and Metal‐Chelated EDTA‐Tethered β‐Cyclodextrin Dimers: A Thermodynamic Study on the Influence of Tether Charge and Flexibility on Binding Affinity

“…plexes with different binding stoichiometries, the smaller TSPP forming a 1:1 complex with 1 and the larger TBPyP being bound by two CD dimers 1. This is in accordance with previous complexation studies of CD dimers with TSPP [16,17,19] and TBPyP. [16] It is well known that TSPP, because of its small size, can only accommodate two CD cavities (i.e., one CD dimer).…”

“…Such significant differences in binding can be sufficient to achieve substantial release of guest molecules from the CD dimer upon metal chelation. [17] Calorimetry was shown to be a powerful tool for the elucidation of the complexation thermodynamics, as it allows interpretation of the influence of metal chelation and charges upon the binding properties of the EDTA-tethered CD dimers. Attribution of the separate contributions of electrostatic and hydrophobic interactions is readily achieved for interactions in which one of the two is systematically changed.…”

“…Previous studies with a photoswitchable dithienylethene-tethered CD dimer coupled through propyl linkers also gave only minor differences in binding affinity for TSPP with varying tether flexibility. [17] Influences of electrostatic interactions on binding properties as seen for CD dimer 1 and TSPP are not uncommon. Similarly, electrostatic interactions have been shown to influence the binding properties of diazocoronand-tethered CD dimers, [7] and cationic mono-and diamino-CDs are known to exhibit higher/lower affinities than native CDs towards negatively/positively charged guests.…”

Noncovalently-Bound Cyclodextrin Dimers and Related Compounds. (Review)

“…It was observed that 23a binds porphyrin 16a more strongly than 23b does. This binding difference of 23 allows the photocontrolled reversible release and uptake of porphyrin 16a in solution [46] …”

From Zeolite to Host-Guest Nanocomposite Materials

“…It is possible that porphyrins are applied as guest molecules for special purposes. For example, a supramolecular system composed of photoswitchable -cyclodextrin dimmers (host) and tetrakis-sulfonatophenyl porphyrin (guest) is a good candidate for using as photocontrollable (drug) delivery systems and might find application in, for example, photodynamic cancer therapy [92]. Besides, porphyrin nanostructures are attractive building blocks because of their electronic, optical, and catalytic properties [93][94][95].…”