Synthesis of riboflavin analogues and isotopologues as probes for spectroscopic studies

Abstract: The catalytic moiety of flavins, i.e., the 7,8-dimethylisoalloxazine chromophore, is an amphoteric heterocycle comprising a lipophilic xylene moiety and a hydrophilic pyrimidine motif. The accessibility/reactivity of the flavin can be modulated by introduction of variation into the pyrimidine ring and the benzenoid domain. Reconstituted flavoproteins with artificial flavins have provided valuable information on the interaction of the flavin with its protein environment, the accessibility to flavin sites by reactive molecules, as well as the mechanistic analysis of flavoenzymes.

The preparation of riboflavin derivatives involving systematic modification of the xylene moiety was accomplished via a modified “alloxan condensation” approach, where an aspect of novelty was brought to the topic by the use of the o-fluoronitro benzene approach. The optical experiments revealed a substantial influence of the substitution pattern on the photo-physical properties of the respective riboflavin analogue. Furthermore, we accomplished the synthesis of riboflavin and demethyl riboflavin isotopologues with totally or partially deuterated methyl groups, i. e., [8α-2H]7-demethylriboflavin, [8α,8α-2H2]7-demethylriboflavin, [8α,8α,8α-2H3]7-demethylriboflavin, [7α-2H]riboflavin, [7α,7α-2H2]riboflavin, [7α,7α,7α-2H3]riboflavin, [8α,8α-2H2]riboflavin, and [8α,8α-2H2]8α-hydroxyriboflavin, for the first time.

By using different synthetic routes for purposes of introduction isotopes to different positions of 5-deazariboflavin, a series of stable-isotope labeled 5-deazariboflavin were synthesized in labeling patterns of [10-15N], [5-13C], [1,3-15N2], [2-13C], [1,3-15N2-2-13C], [4a-13C], [4,10a-13C2], [4,4a,10a-13C3], respectively, in this work. These serve as probes for the characterization of the altered photo-physical properties of the LOV2 domain of Avena sativa phototropin induced on replacing the native flavin mononucleotide (FMN) cofactor by 5-deazaFMN.

By exploiting nuclear spin hyperpolarization generated via the photo-CIDNP effect, it is possible to study the short-lived radical species generated by in-situ light excitation. In this study, the relative hyperfine couplings were determined for the 1H nuclei of the FMN neutral and anionic radicals as well as four structural analogues with different methylation patterns (7-demethylFMN, 8-demethylFMN, 7,8-didemethylFMN and 7,8-didemethyl-9-methylFMN) for the first time, aiming to explore the influence of the substituents at the isoalloxazine moiety on the electronic structure in an aqueous environment

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Universität Freiburg, Dissertation, 2021

Klassifikation und Themen

• Schlagwort: Chemische Synthese ; Herstellung ; Vitamin B2

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2021
• Urheber: Chen, Jing
• Beteiligte Personen und Organisationen: Weber, Stefan ; Albert-Ludwigs-Universität Freiburg. Institut für Physikalische Chemie ; Albert-Ludwigs-Universität Freiburg. Fakultät für Chemie und Pharmazie ; Magnetische Resonanz

Weitere Informationen

• DOI: 10.6094/UNIFR/219815
• URN: urn:nbn:de:bsz:25-freidok-2198157
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 25.03.2025, 13:49 MEZ