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Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design.

Foller Larsen A, Dumat B, Wranne MS, Lawson CP, Preus S, Bood M, Gradén H, Wilhelmsson LM, Grøtli M - Sci Rep (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Engineering/Chemistry and Biochemistry, Chalmers University of Technology, S-41296 Gothenburg, Sweden.

ABSTRACT
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 (εΦF = 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.

No MeSH data available.


Measured fluorescence quantum yields of the quadracyclic adenine family plotted against the quantum chemically calculated oscillator strength values of their respective S0 → S1 transition.For one compound (3-MeOqA), the oscillator strength of the S0 → S2 transition was used in lieu of that of the S0 → S1 transition (see text for explanation).
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f3: Measured fluorescence quantum yields of the quadracyclic adenine family plotted against the quantum chemically calculated oscillator strength values of their respective S0 → S1 transition.For one compound (3-MeOqA), the oscillator strength of the S0 → S2 transition was used in lieu of that of the S0 → S1 transition (see text for explanation).

Mentions: We envisioned that the synthetic methodology developed for the qAN-family could be applied to rapidly generate a series of novel substituted qA analogues. Three functionalities were chosen that were expected to influence the electronic properties and therefore modulate the fluorescence. Herein, we report the synthesis and photophysical characterization of nine novel quadracyclic adenine analogues (Figs 1 and 3) bearing cyano-, fluorine- or methoxy-substituents on the outer benzene ring of the qA scaffold. While the aim of this work was to develop new and brighter fluorophores, a large number of structures were screened in order to test our TDDFT-based design strategy more generally compared to our previous studies36. The dye series reported and investigated here thus draw a general picture of the ability of quantum chemical calculations to predict the relative brightness within a series of dye structures.


Development of bright fluorescent quadracyclic adenine analogues: TDDFT-calculation supported rational design.

Foller Larsen A, Dumat B, Wranne MS, Lawson CP, Preus S, Bood M, Gradén H, Wilhelmsson LM, Grøtli M - Sci Rep (2015)

Measured fluorescence quantum yields of the quadracyclic adenine family plotted against the quantum chemically calculated oscillator strength values of their respective S0 → S1 transition.For one compound (3-MeOqA), the oscillator strength of the S0 → S2 transition was used in lieu of that of the S0 → S1 transition (see text for explanation).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530663&req=5

f3: Measured fluorescence quantum yields of the quadracyclic adenine family plotted against the quantum chemically calculated oscillator strength values of their respective S0 → S1 transition.For one compound (3-MeOqA), the oscillator strength of the S0 → S2 transition was used in lieu of that of the S0 → S1 transition (see text for explanation).
Mentions: We envisioned that the synthetic methodology developed for the qAN-family could be applied to rapidly generate a series of novel substituted qA analogues. Three functionalities were chosen that were expected to influence the electronic properties and therefore modulate the fluorescence. Herein, we report the synthesis and photophysical characterization of nine novel quadracyclic adenine analogues (Figs 1 and 3) bearing cyano-, fluorine- or methoxy-substituents on the outer benzene ring of the qA scaffold. While the aim of this work was to develop new and brighter fluorophores, a large number of structures were screened in order to test our TDDFT-based design strategy more generally compared to our previous studies36. The dye series reported and investigated here thus draw a general picture of the ability of quantum chemical calculations to predict the relative brightness within a series of dye structures.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Chemical Engineering/Chemistry and Biochemistry, Chalmers University of Technology, S-41296 Gothenburg, Sweden.

ABSTRACT
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 (εΦF = 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.

No MeSH data available.