Ruthenium porphyrin-ß-cyclodextrin complexes as supramolecular enzyme models for regioselective cleavage of carotenoids

Wang, Hao. Ruthenium porphyrin-ß-cyclodextrin complexes as supramolecular enzyme models for regioselective cleavage of carotenoids. 2006, Doctoral Thesis, University of Basel, Faculty of Science.


Official URL: http://edoc.unibas.ch/diss/DissB_7628

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All naturally occurring vitamin A derives from enzymatic oxidative cleavage of β,β-carotene or other carotenoids with pro-vitamin A activity. Two metabolic pathways of β,β-carotene to retinal (vitamin A aldehyde) have been proposed: the central cleavage providing 2 mol of retinal, and the excentric cleavage yielding apo-β-carotenals first, which are subsequently transformed into retinal. Each pathway is used preferentially in mammalian β,β-carotene metabolism, depending on the specific tissue.
Due to their unusual reactivity to regioselectively cleave one double bond in a conjugated polyene of very hydrophobic substrates, these enzymes present a formidable challenge to chemists interested in enzyme catalysis.
Regarding the central cleavage of carotenoids, considerable progress has been accomplished both with respect to the identification/isolation of the proteins from various tissues/species and concerning the synthesis of structural remote enzyme models which effectively mimic the enzymatic reaction.
The excentric oxidative cleavage of carotenoids is not only significant to mammals but even more important in the plant kingdom providing metabolites used as fragrances and for defensive mechanism.
The latter research area is overall less advanced than the former in particular no enzyme mimics have been available at the outset of this thesis.
Encouraged by the success of complex 46 as an enzyme mimic for central cleavage of carotenoids (scheme 46), we decided to develop related supramolecular models to mimic the reactivity and selectivity of the enzymes catalyzing the excentric cleavage of carotenoids. Within this context, three β-CD linked ruthenium porphyrin complexes have been designed and synthesized.
The first generation enzyme mimic, complex 58, designed by computer modelling, comprises a rigidly linked dimeric β-CD moiety as the substrate recognition site and a ruthenium porphyrin, attached to one of the primary faces of β-CDs, as site of reactivity.
However, the reactivity of complex 58 towards 17,17’-dinor-φ,φ-carotene 84 reveals that this supramolecular model actually mimics the central cleavage pathway (scheme 47), which is consistent with the crystal structure of β-CD dimer moiety obtained later (figure 29). Owing to the modification of β-CD via 2,3-manno-epoxide and intramolecular self-assembling by hydrogen-bonding network, the diamide linker sits between β-CDs, blocking the entrance of the substrate to the second β-CD unit.
In order to avoid “capping” of β-CD by the linker, the second complex 89 was designed and synthesized (scheme 48). The dimeric β-CD moiety is linked by a C6-flexible chain directly on C(2). It is conceived that the linker might act as a loop outside the dimeric β-CD moiety, holding β-CDs together via a hydrogen-bonding network to produce an extended cavity as the substrate binding site. The results with 89/TBHP reveals that this complex cleaves carotenoids at C(13’)-C(14’) double bond, mimicking excentric cleavage to a certain extent.
The fact that mono-β-CD complex 83 could mimic the central cleavage of carotenoids was then used to design and prepare complex 113 which contains a rigid biphenyl linker, attached to the secondary face of β-CD, to increase the distance between the β-CD unit and the ruthenium porphyrin moiety (figure 30).
The reactivity of complex 113/TBHP towards carotenoid 84 is solvent dependent. A central cleavage was observed in DMF, whereas an excentric cleavage at C(14’)-C(13’) double bond was observed in the biphasic system. NOE spectra and computational calculation suggests that complex 113 adopts a partial folded conformaion in DMF, reducing the distance between β-CD and active ruthenium center.
In conclusion the work presented here comprises the synthesis of several new monomeric and dimeric β-CD-ruthenium porphyrin complexes which in the presence of TBHP show the reactivity required to cleave conjugated double bond to aldehydes, depending on the relative orientation/distance of the substrate binding site (β-CD) to the reactive site (Ru=O). These complexes, binding carotenoids in a supramolecular fashion, cleave the symmetric polyolefins either at the central C(15)-C(15’) or slightly excentric C(13’)-C(14’) double bond. As such, these complexes mimic to a certain extent both classes of enzymes which metabolize carotenoids in nature.
Advisors:Woggon, Wolf-Dietrich
Committee Members:Constable, Edwin C. and Mayor, Marcel
Faculties and Departments:05 Faculty of Science > Departement Chemie > Former Organization Units Chemistry > Organische Chemie (Gademann)
UniBasel Contributors:Woggon, Wolf-Dietrich and Mayor, Marcel
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:7628
Thesis status:Complete
Number of Pages:137
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edoc DOI:
Last Modified:05 Apr 2018 17:32
Deposited On:13 Feb 2009 15:42

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