Tuning the Quantum Chemical Properties of Flavins via Modification at C8

Rajiv K. Kar, Sam Chasen, Maria Andrea Mroginski, Anne Frances Miller

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Flavins are central to countless enzymes but display different reactivities depending on their environments. This is understood to reflect modulation of the flavin electronic structure. To understand changes in orbital natures, energies, and correlation over the ring system, we begin by comparing seven flavin variants differing at C8, exploiting their different electronic spectra to validate quantum chemical calculations. Ground state calculations replicate a Hammett trend and reveal the significance of the flavin π-system. Comparison of higher-level theories establishes CC2 and ACD(2) as methods of choice for characterization of electronic transitions. Charge transfer character and electron correlation prove responsive to the identity of the substituent at C8. Indeed, bond length alternation analysis demonstrates extensive conjugation and delocalization from the C8 position throughout the ring system. Moreover, we succeed in replicating a particularly challenging UV/Vis spectrum by implementing hybrid QM/MM in explicit solvents. Our calculations reveal that the presence of nonbonding lone pairs correlates with the change in the UV/Vis spectrum observed when the 8-methyl is replaced by NH2, OH, or SH. Thus, our computations offer routes to understanding the spectra of flavins with different modifications. This is a first step toward understanding how the same is accomplished by different binding environments.

Original languageEnglish
Pages (from-to)12654-12669
Number of pages16
JournalJournal of Physical Chemistry B
Issue number46
StatePublished - Nov 25 2021

Bibliographical note

Funding Information:
R.K.K. and A.-F.M. thank the Einstein Foundation of Berlin for support. Aspects of the work described were supported by the National Science Foundation, Chemistry of Life Processes, CHE-1808433. M.A.M. thanks the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy, EXC 2008-390540038-UniSysCat, for funding. The authors thank Vikram Gazula of the University of Kentucky and Sebastian Kraus of the Technische Universität Berlin for providing technical support of computing facilities. R.K.K. dedicates this paper to Annapurna Kar in recognition of wisdom and guidance over the years.

Publisher Copyright:
© 2021 American Chemical Society.

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry


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