Scheme 1.12 Illustrating the concept of a timer with reset capacity through a metamorphosis cycle.
Source: Slavcheva, et al. 2018. © 2018 Elsevier.
1.4.3 6,8 Rearrangements
In Scheme 1.13, the 6,8 rearrangement is shown. Two necessary requirements are needed to observe this reaction in flavylium‐derived systems: (i) a hydroxyl group in position C5 and (ii) the lack of symmetry through the binary axis identified in Scheme 1.13 by the traced line. For example, with the natural symmetrical 3‐deoxyanthocyanidins such as luteolinidin and apigeninidin, the 6,8 rearrangement is not observed. The 6,8 rearrangement in the flavylium cation was first reported (Jurd 1963) for 4’,5,7,8‐tetrahydroxyflavylium and for 6/8‐C‐glycosyl‐3‐deoxyanthocyanidins (Bjorøy et al. 2009). More recently, a complete study extended to the other species of the multistate present in moderately acidic medium was reported (Scheme 1.13), R=Br (Cruz et al. 2016, 2017).
In very acidic medium, equilibrium is established between c. 50% of each flavylium cation. The two flavylium cation isomers were separated by HPLC and lyophilized. The usual pH jumps followed by stopped flow permitted us to obtain the absorption spectra of the two neutral quinoidal base isomers and study the respective kinetic processes. At pH=3.7 (Figure 1.7), the equilibrium absorption spectrum can be fitted with the contributions of 0.45A6 + 0.45A8 + 0.1Ct.
In the case of the 6,8 rearrangements for R=CH3 or phenyl (Basílio et al. 2017) the 8 derivative is the only one observed and equilibrium in moderately acidic medium is established between A8 and Ct (c. 20%). The pH‐dependent equilibrium between flavylium cation and a mixture of quinoidal base (major species) and trans‐chalcone was previously reported for 5‐deoxyanthocyanidins (Sousa et al. 2014; Brouillard et al. 1982). At moderately acidic pH values there is some spectral evidence that the two quinoidal base isomers are in equilibrium, but the spectral variations are relatively small. In order to unveil the two isomers other strategies should be used; see below.
Scheme 1.13 General scheme of the 6,8 rearrangement. R=Br or R=CH3 or R=Phenyl.
Source: Adapted from Cruz et al. 2016. © 2016 John Wiley & Sons.
Figure 1.7 The absorption spectra of equilibrated solutions of the compound 8‐bromo,4′,5,7 trihydroxyflavylium R=Br (3.3x10‐5 M) at pH=3.7 can be fitted with a contribution of 0.45A6+0.45A8+0.1Ct.
Source: Adapted from Cruz et al. 2016. © 2016 John Wiley & Sons.
1.4.3.1 Unveiling the 6,8 Rearrangement Through Host‐Guest Complexation
A step further to the study of the 6,8 rearrangement was achieved by host‐guest complexation. It is known that while cucurbiturils complex preferentially the flavylium cation (Basílio and Pina 2014), cyclodextrins prefer the chalcones (Petrov 2013b). The sulfobutylether derivative of β‐cyclodextrin (captisol) was used due to its better solubility in water, when compared with β‐cyclodextrin. The complexation with captisol was used to unveil the 6‐phenyl isomer from the 8‐phenyl‐5,7‐dihydroxyflavylium (Basílio et al. 2017). The NMR and UV‐vis spectrophotometry indicates that the fraction of Ct increases very significantly in the presence of captisol. Irradiation of this solution at pH=5.0 leads to a photostationary state, constituted by quinoidal bases A6 and A8 (Scheme 1.14). In fact, immediate acidification of the photostationary state to pH=1.0 shows the presence of the two respective flavylium cation isomers, with the 6‐phenyl isomer reverting slowly to the more stable 8‐phenyl isomer.
The host‐guest strategy was used to form the 6‐phenyl isomer from the 8‐phenyl‐5,7‐dihydroxyflavylium profiting from the capacity of cucurbit[7]uril to complex preferentially the former (Basílio et. al 2017) as well as for 6,8‐bromo‐apigeninidin (Basílio et al. 2016).
From bottom to top in Scheme 1.15, the 1H NMR spectra of the two isomers are shown. After addition of the host only the 6‐bromo isomer is observed. Addition of adamantine, which possesses a very high association constant with this host, permits to release and isolate the 6‐bromo isomer (Scheme 1.16). The system slowly reaches equilibrium by formation of the 8‐bromo isomer.
Scheme 1.14 Qualitative energy level diagram to account for the pH jumps and the photochemistry of the 6,8 rearrangement of 8‐phenyl‐5,7‐dihydroxyflavylium in the presence of the captisol host. Traced energy levels are tentatively positioned. The arrow of the excitation energy is not in scale.
Scheme 1.15 1H NMR of 6‐bromo‐5,7‐dihydroxyflavylium and its 8‐bromo isomer in the presence of cucurbit[7]uril.
Source: Adapted from Basílio et al. 2017. © 2017 John Wiley & Sons.
Scheme 1.16 Discrimination, isolation, and 6,8 rearrangement of 6‐bromo‐5,7 dihydroxyflavylium and its 8‐bromo isomer in the presence of cucurbit[7]uril. Reproduced from Basílio et al. (2017), with permission.
Source: Adapted from Basílio et al. 2017. © 2017 John Wiley & Sons.
1.5
