Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design
Journal article, 2015

Fluorescent base analogues (FBAs) comprise a family of increasingly important molecules for the investigation of nucleic acid structure and dynamics. We recently reported the quantum chemical calculation supported development of four microenvironment sensitive analogues of the quadracyclic adenine (qA) scaffold, the qANs, with highly promising absorptive and fluorescence properties that were very well predicted by TDDFT calculations. Herein, we report on the efficient synthesis, experimental and theoretical characterization of nine novel quadracyclic adenine derivatives. The brightest derivative, 2-CNqA, displays a 13-fold increased brightness (epsilon Phi(F) = 4500) compared with the parent compound qA and has the additional benefit of being a virtually microenvironment-insensitive fluorophore, making it a suitable candidate for nucleic acid incorporation and use in quantitative FRET and anisotropy experiments. TDDFT calculations, conducted on the nine novel qAs a posteriori, successfully describe the relative fluorescence quantum yield and brightness of all qA derivatives. This observation suggests that the TDDFT-based rational design strategy may be employed for the development of bright fluorophores built up from a common scaffold to reduce the otherwise costly and time-consuming screening process usually required to obtain useful and bright FBAs.

Fluorophore

Base Analog

Probes

Photophysical Properties

Pyrrolo-Dc

Density

Cytosine Analog

Nucleic-Acid

Nucleoside

Oligonucleotides

Author

Anders Foller Füchtbauer

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Blaise Dumat

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Moa Sandberg Wranne

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Christopher Lawson

University of Gothenburg

S. Preus

Aarhus University

Mattias Bood

University of Gothenburg

Henrik Gradén

AstraZeneca AB

Marcus Wilhelmsson

Chalmers, Chemistry and Chemical Engineering, Chemistry and Biochemistry, Physical Chemistry

Morten Grötli

University of Gothenburg

Scientific Reports

2045-2322 (ISSN)

Vol. 5 art. no. 12653- 12653

Areas of Advance

Nanoscience and Nanotechnology (2010-2017)

Life Science Engineering (2010-2018)

Subject Categories

Physical Chemistry

Biochemistry and Molecular Biology

Organic Chemistry

DOI

10.1038/srep12653

More information

Latest update

4/18/2018