Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA
There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modifie...
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2020-04-01
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| author | Ali Heidari Arash Ghorbani-Choghamarani Maryam Hajjami Robert H. E. Hudson |
| author_facet | Ali Heidari Arash Ghorbani-Choghamarani Maryam Hajjami Robert H. E. Hudson |
| author_sort | Ali Heidari |
| collection | DOAJ |
| description | There has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4–8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (∆T<sub>m</sub> = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences. |
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| language | English |
| last_indexed | 2024-03-10T20:16:58Z |
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| series | Molecules |
| spelling | doaj.art-fca7fc78b261431c8b13ecf7ba680c912023-11-19T22:33:52ZengMDPI AGMolecules1420-30492020-04-01258199510.3390/molecules25081995Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNAAli Heidari0Arash Ghorbani-Choghamarani1Maryam Hajjami2Robert H. E. Hudson3Department of Chemistry, The University of Western Ontario, London, ON N6A 5B7, CanadaDepartment of Chemistry, Faculty of Science, Ilam University, Ilam 69315516, IranDepartment of Chemistry, Faculty of Science, Ilam University, Ilam 69315516, IranDepartment of Chemistry, The University of Western Ontario, London, ON N6A 5B7, CanadaThere has been much effort to exploit fluorescence techniques in the detection of nucleic acids. Canonical nucleic acids are essentially nonfluorescent; however, the modification of the nucleobase has proved to be a fruitful way to engender fluorescence. Much of the chemistry used to prepare modified nucleobases relies on expensive transition metal catalysts. In this work, we describe the synthesis of biaryl quinazolinone-uracil nucleobase analogs prepared by the condensation of anthranilamide derivatives and 5-formyluracil using inexpensive copper salts. A selection of modified nucleobases were prepared, and the effect of methoxy- or nitro- group substitution on the photophysical properties was examined. Both the dihydroquinazolinone and quinazolinone modified uracils have much larger molar absorptivity (~4–8×) than natural uracil and produce modest blue fluorescence. The quinazolinone-modified uracils display higher quantum yields than the corresponding dihydroquinazolinones and also show temperature and viscosity dependent emission consistent with molecular rotor behavior. Peptide nucleic acid (PNA) monomers possessing quinazolinone modified uracils were prepared and incorporated into oligomers. In the sequence context examined, the nitro-substituted, methoxy-substituted and unmodified quinazolinone inserts resulted in a stabilization (∆T<sub>m</sub> = +4.0/insert; +2.0/insert; +1.0/insert, respectively) relative to control PNA sequence upon hybridization to complementary DNA. All three derivatives responded to hybridization by the “turn-on” of fluorescence intensity by ca. 3-to-4 fold and may find use as probes for complementary DNA sequences.https://www.mdpi.com/1420-3049/25/8/1995peptide nucleic acidnucleobase-modified PNAsolid-phase synthesisdihydroquinazolinonequinazolinonequinazolinone based nucleobase |
| spellingShingle | Ali Heidari Arash Ghorbani-Choghamarani Maryam Hajjami Robert H. E. Hudson Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA Molecules peptide nucleic acid nucleobase-modified PNA solid-phase synthesis dihydroquinazolinone quinazolinone quinazolinone based nucleobase |
| title | Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA |
| title_full | Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA |
| title_fullStr | Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA |
| title_full_unstemmed | Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA |
| title_short | Fluorescent Biaryl Uracils with C5-Dihydro- and Quinazolinone Heterocyclic Appendages in PNA |
| title_sort | fluorescent biaryl uracils with c5 dihydro and quinazolinone heterocyclic appendages in pna |
| topic | peptide nucleic acid nucleobase-modified PNA solid-phase synthesis dihydroquinazolinone quinazolinone quinazolinone based nucleobase |
| url | https://www.mdpi.com/1420-3049/25/8/1995 |
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