Second-Generation Fluorescent Quadracyclic Adenine Analogues: Environment-Responsive Probes with Enhanced Brightness
Artikel i vetenskaplig tidskrift, 2015

Fluorescent base analogues comprise a group of increasingly important molecules for the investigation of nucleic acid structure, dynamics, and interactions with other molecules. Herein, we report on the quantum chemical calculation aided design, synthesis, and characterization of four new putative quadracyclic adenine analogues. The compounds were efficiently synthesized from a common intermediate through a two-step pathway with the Suzuki-Miyaura coupling as the key step. Two of the compounds, qAN1 and qAN4, display brightnesses (εΦF) of 1700 and 2300, respectively, in water and behave as wavelength-ratiometric pH probes under acidic conditions. The other two, qAN2 and qAN3, display lower brightnesses but exhibit polarity-sensitive dual-band emissions that could prove useful to investigate DNA structural changes induced by DNA-protein or -drug interactions. The four qANs are very promising microenvironment-sensitive fluorescent adenine analogues that display considerable brightness for such compounds. Polarity and pH probes: 2-Aminopurine has long been the standard for fluorescent base analogues. Four new fluorescent probes suitable for the replacement of adenine in nucleic acids are presented. Based on their high structural similarity to their parent compound, quadracyclic adenine, they have the potential to be excellent A analogues. Their improved photophysical properties also suggest that they could be significantly brighter than 2-aminopurine inside nucleic acid systems (see figure; ΦF: fluorescence quantum yield).

C-C coupling


Nucleic acids

Aromatic substitution

Fluorescent probes


Blaise Dumat

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Mattias Bood

Göteborgs universitet

Moa Sandberg Wranne

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Chris Lawson

Göteborgs universitet

Anders Foller Füchtbauer

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

S. Preus

Aarhus Universitet

J. Streling

Göteborgs universitet

H. Gradén

AstraZeneca R&D

E. Wellner

Aarhus Universitet

Morten Grötli

Göteborgs universitet

Marcus Wilhelmsson

Chalmers, Kemi och kemiteknik, Kemi och biokemi, Fysikalisk kemi

Chemistry - A European Journal

0947-6539 (ISSN) 1521-3765 (eISSN)

Vol. 21 10 4039-4048


Nanovetenskap och nanoteknik (SO 2010-2017, EI 2018-)

Livsvetenskaper och teknik (2010-2018)


Fysikalisk kemi


Organisk kemi



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