title: Rules for the design of highly fluorescent nucleoside probes: 8-(substituted cinnamyl)-adenosine analogues.
abstract: Currently, there are no tools that can help the design of useful fluorescent analogues. Hence, we synthesized a series of 8-(substituted cinnamyl)-adenosine analogues, 5-17, and established a relationship between their structure and fluorescence properties. We attempted to find a correlation between maximum emission wavelengths (λ(em)) of 5-17 or their quantum yields (φ), and Hammett constants (σ(p) and σ(m)) of the substituent on the cinnamyl moiety. A linear correlation was observed at low-medium σ values, but not at high σ values (≥0.7). Next, we explored correlation between λ(em) and φ of 5-17 and computed HOMO and LUMO energy levels of fragments of 5-17, i.e., 8-vinyl 9-Me-adenine (fluorescent molecule), 18, and substituted toluene rings (fluoresence modulators), 19-30. High φ correlated with relatively close LUMO levels of 19-30 and 18 (-0.076 to -0.003 eV). The electron density of LUMO of nitro analogues 9 and 15 is localized on the aryl ring only, which explains their low φ. Calculation of HOMO-LUMO gap of 5-17 enables accurate prediction of the λ(abs) for a planned analogue, and LUMO levels of an aryl moiety vs 8-vinyl 9-Me-adenine, allows the prediction of high or low φ. These findings lay the ground for prediction of fluorescence properties of additional analogues having a similar structure.
authors.affiliation: Department of Chemistry, Gonda-Goldschmied Medical Research Center and the Lise-Meitner-Minerva Center of Computational Quantum Chemistry, Bar-Ilan University , Ramat-Gan 52900, Israel.
authors.forename: Lital
authors.initials: L
authors.lastname: Zilbershtein-Shklanovsky
authors.forename: Michal
authors.initials: M
authors.lastname: Weitman
authors.forename: Dan Thomas
authors.initials: DT
authors.lastname: Major
authors.forename: Bilha
authors.initials: B
authors.lastname: Fischer
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D015345:Oligonucleotide Probes / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013050:Spectrometry, Fluorescence
chemical_list: D005456:Fluorescent Dyes; D015345:Oligonucleotide Probes; D000241:Adenosine