Login Register Cart 0
Generic placeholder image

Current Chemical Biology

Editor-in-Chief

ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Seleno-Functionalization of BODIPY Fluorophores Assisted by Oxidative Nucleophilic Hydrogen Substitution

Author(s): Beatriz S. Cugnasca, Felipe Wodtke and Alcindo A. Dos Santos*

Volume 15, Issue 3, 2021

Published on: 04 May, 2021

Page: [215 - 221] Pages: 7

DOI: 10.2174/2212796815666210504084205

Price: $65

Abstract

Background: The most current reported methods of chalcogen insertion into BODIPY’s nuclei are based on nucleophilic substitution reactions of halogenated derivatives, metal-catalyzed cross-coupling reactions, or assistance by radical mechanisms. Recent reports describe Oxidative Nucleophilic Hydrogen Substitution (ONHS) reactions involving the functionalization of BODIPY nuclei by thiols, but the generalities of the strategy for other chalcogens was not yet demonstrated. Herein we report our contribution on the selenium-functionalization of BODIPY by ONHS in high yield.

Objective: Aryl-Se-functionalization of 2,6-brominated BODIPY’s nuclei by ONHS reaction.

Methods: The procedure consists of a direct reaction of 2,6-brominated BODIPYs with in situ generated PhSeH in THF, at room temperature, under a nitrogen atmosphere. The corresponding products were isolated and purified by conventional flash column chromatography. Full structure characterization was performed by 1H, 13C, 19F, and 77Se NMR and DFT calculation.

Results: Densely functionalized 2,6-dibrominated/3,5-diseleno-BODIPYs were obtained as corresponding products, leading to versatile molecular scaffolds. Their structural features were contrary to those initially expected by the original experimental applied conditions. A mechanistic investigation was performed to conclude that ONHS reaction is governing the transformation, thereby damaging the nucleophilic substitution of the halogen atoms.

Conclusion: To sum up, new densely functionalized BODIPY derivatives were synthesized by a highly selective, simple, fast, metal-free, and efficient insertion of PhSe- residues into the 3,5-positions, governed by an Oxidative Nucleophilic Hydrogen Substitution (ONHS) reaction in high yields. It was observed that the presence of halogen (Br) into the 2,6-positions of the BODIPY core is mandatory for the ONHS reaction, which is completely inert when the 2,6-hydrogenated analogues are used in the same experimental conditions.

Keywords: BODIPY, seleno-BODIPY, chalcogeno-BODIPY, selenides, oxidative nucleophilic hydrogen substitution, chalcogen.

« Previous Next »
Graphical Abstract

[1]
Boens N, Verbelen B, Ortiz MJ, Jiao L, Dehaen W. Synthesis of BODIPY dyes through postfunctionalization of the boron dipyrromethene core. Coord Chem Rev 2019; 399: 213024.
[http://dx.doi.org/10.1016/j.ccr.2019.213024]
[2]
Escobedo JO, Rusin O, Lim S, Strongin RM. NIR dyes for bioimaging applications. Curr Opin Chem Biol 2010; 14(1): 64-70.
[http://dx.doi.org/10.1016/j.cbpa.2009.10.022] [PMID: 19926332]
[3]
Hilderbrand SA, Weissleder R. Near-infrared fluorescence: application to in vivo molecular imaging. Curr Opin Chem Biol 2010; 14(1): 71-9.
[http://dx.doi.org/10.1016/j.cbpa.2009.09.029] [PMID: 19879798]
[4]
Weissleder R, Tung CH, Mahmood U, Bogdanov A Jr. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol 1999; 17(4): 375-8.
[http://dx.doi.org/10.1038/7933] [PMID: 10207887]
[5]
Becker A, Hessenius C, Licha K, et al. Receptor-targeted optical imaging of tumors with near-infrared fluorescent ligands. Nat Biotechnol 2001; 19(4): 327-31.
[http://dx.doi.org/10.1038/86707] [PMID: 11283589]
[6]
Loudet A, Burgess K. BODIPY dyes and their derivatives: syntheses and spectroscopic properties. Chem Rev 2007; 107(11): 4891-932.
[http://dx.doi.org/10.1021/cr078381n] [PMID: 17924696]
[7]
Nogueira CW, Zeni G, Rocha JBT. Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev 2004; 104(12): 6255-85.
[http://dx.doi.org/10.1021/cr0406559] [PMID: 15584701]
[8]
Manjare ST, Kim Y, Churchill DG. Selenium- and tellurium-containing fluorescent molecular probes for the detection of biologically important analytes. Acc Chem Res 2014; 47(10): 2985-98.
[http://dx.doi.org/10.1021/ar500187v] [PMID: 25248146]
[9]
Mukherjee AJ, Zade SS, Singh HB, Sunoj RB. Organoselenium chemistry: role of intramolecular interactions. Chem Rev 2010; 110(7): 4357-416.
[http://dx.doi.org/10.1021/cr900352j] [PMID: 20384363]
[10]
Fox MA, Chanon M, Eds. Photoinduced electron transfer. Amsterdam: Elsevier 1988.
[11]
Kavarnos GJ. Fundamentals of photoinduced electron transfer. Fundamentals and practical aspects. In: Mattay J, Ed. Photoinduced Electron Transfer V Topics in Current Chemistry. Springer, Berlin, Heidelberg. 1993; 168.
[http://dx.doi.org/10.1007/3-540-56746-1_7]
[12]
de Silva AP, Moody TS, Wright GD. Fluorescent PET (photoinduced electron transfer) sensors as potent analytical tools. Analyst (Lond) 2009; 134(12): 2385-93.
[http://dx.doi.org/10.1039/b912527m] [PMID: 19918605]
[13]
Escudero D. Revising intramolecular Photoinduced Electron Transfer (PET) from first-principles. Acc Chem Res 2016; 49(9): 1816-24.
[http://dx.doi.org/10.1021/acs.accounts.6b00299] [PMID: 27575871]
[14]
Shi WJ, Huang Y, Liu W, et al. BODIPY-based “OFF-ON” fluorescent probe for fast and selective detection of hypochlorite in living cells. Dyes Pigm 2019; 170: 107566.
[http://dx.doi.org/10.1016/j.dyepig.2019.107566]
[15]
Al Anshori J, Slanina T, Palao E, Klán P. The internal heavy-atom effect on 3-phenylselanyl and 3-phenyltellanyl BODIPY derivatives studied by transient absorption spectroscopy. Photochem Photobiol Sci 2016; 15(2): 250-9.
[http://dx.doi.org/10.1039/C5PP00366K] [PMID: 26790756]
[16]
Hayashi Y, Yamaguchi S, Cha WY, Kim D, Shinokubo H. Synthesis of directly connected BODIPY oligomers through Suzuki-Miyaura coupling. Org Lett 2011; 13(12): 2992-5.
[http://dx.doi.org/10.1021/ol200799u] [PMID: 21591621]
[17]
Zhao N, Xuan S, Fronczek FR, Smith KM, Vicente MGH. Stepwise polychlorination of 8-chloro-BODIPY and regioselective functionalization of 2,3,5,6,8-pentachloro-BODIPY. J Org Chem 2015; 80(16): 8377-83.
[http://dx.doi.org/10.1021/acs.joc.5b01147] [PMID: 26186141]
[18]
Lakshmi V, Ravikanth M. Brominated boron dipyrrins: synthesis, structure, spectral and electrochemical properties. Dalton Trans 2012; 41(19): 5903-11.
[http://dx.doi.org/10.1039/c2dt00019a] [PMID: 22460271]
[19]
Xu XH, Liu C, Mei Y, Song QH. BODIPY-based selenides as fluorescent probes for rapid, sensitive and mitochondria-specific detection of hypochlorous acid. J Mater Chem B 2019; 7(43): 6861-7.
[http://dx.doi.org/10.1039/C9TB01641D] [PMID: 31613291]
[20]
Fron E, Coutiño-Gonzalez E, Pandey L, et al. Synthesis and photophysical characterization of chalcogen Substituted BODIPY Dyes. New J Chem 2009; 33(7): 1490-6.
[http://dx.doi.org/10.1039/b900786e]
[21]
Gong D, Zhu X, Tian Y, et al. A phenylselenium-substituted bodipy fluorescent turn-off probe for fluorescence imaging of hydrogen sulfide in living cells. Anal Chem 2017; 89(3): 1801-7.
[http://dx.doi.org/10.1021/acs.analchem.6b04114] [PMID: 28208279]
[22]
Palao E, Slanina T, Klán P. Construction of the carbon-chalcogen (S, Se, Te) bond at the 2,6-positions of BODIPY via Stille cross- coupling reaction. Chem Commun (Camb) 2016; 52(80): 11951-4.
[http://dx.doi.org/10.1039/C6CC06923A] [PMID: 27711346]
[23]
Perrin DD, Amarego WL. Purification of laboratory chemicals. 4th ed.. UK : Butterworth-Heinemann 1997.
[24]
Sharpless KB, Young MW. Olefin synthesis. rate enhancement of the elimination of alkyl aryl selenoxides by electron- withdrawing substituents. J Org Chem 1975; 40(7): 947-9.
[http://dx.doi.org/10.1021/jo00895a030]
[25]
Madhu S, Gonnade R, Ravikanth M. Synthesis of 3,5-bis(acrylaldehyde) boron-dipyrromethene and application in detection of cysteine and homocysteine in living cells. J Org Chem 2013; 78(10): 5056-60.
[http://dx.doi.org/10.1021/jo4004597] [PMID: 23597279]
[26]
Soares-Paulino AA, Giroldo L, Pradie NA, et al. Nanomolar detection of palladium (II) through a novel seleno-rhodamine-based fluorescent and colorimetric chemosensor. Dye Pigm 2020; 179: 108355.
[http://dx.doi.org/10.1016/j.dyepig.2020.108355]
[27]
Soares-Paulino AA, Giroldo L, Celante G, Lodeiro C, Dos Santos AA. Formation of an emissive telluroxide promoted by Hg2+ in aqueous environment: A new naked-eye and ratiometric rhodamine dimer fluorescent mercury(II) probe. Dyes Pigm 2018; 159: 121-7.
[http://dx.doi.org/10.1016/j.dyepig.2018.06.005]
[28]
Gonçalves AC, Capelo JL, Lodeiro C, Santos AAD. A seleno-pyrene selective probe for Hg2+ detection in either aqueous or aprotic systems. Sens Actuators B Chem 2017; 239: 311-8.
[http://dx.doi.org/10.1016/j.snb.2016.08.014]
[29]
Pilla V, Gonçalves AC, Dos Santos AA, Lodeiro C. Lifetime and Fluorescence Quantum Yield of Two Fluorescein-Amino Acid-Based Compounds in Different Organic Solvents and Gold Colloidal Suspensions. Chemosensors (Basel) 2018; 6(3)
[http://dx.doi.org/10.3390/chemosensors6030026]
[30]
Gonçalves AC, Sato NC, Santos HM, Capelo JL, Lodeiro C, dos Santos AA. The confidence of blue: A new highly selective bio-inspired coumarin emissive probe for fluoride recognition. Dyes Pigm 2016; 135: 177-83.
[http://dx.doi.org/10.1016/j.dyepig.2016.02.032]
[31]
Gonçalves AC, Pilla V, Oliveira E, et al. The interaction of Hg(2+) and trivalent ions with two new fluorescein bio-inspired dual colorimetric/fluorimetric probes. Dalton Trans 2016; 45(23): 9513-22.
[http://dx.doi.org/10.1039/C6DT01180B] [PMID: 27193690]
[32]
Gonçalves AC, Luis Capelo J, Lodeiro C, Dos Santos AA. A selective emissive chromogenic and fluorogenic seleno-coumarin probe for Cu2+ detection in aprotic media. Photochem Photobiol Sci 2017; 16(7): 1174-81.
[http://dx.doi.org/10.1039/C7PP00036G] [PMID: 28604906]
[33]
Soares-Paulino AA, Giroldo L, Celante G, et al. Oxidation of tellurium dyes induced by mercury: More insights on the naked- eye and fluorescent Hg2+ detection. Dyes Pigments 2019; 160: 208-16.
[http://dx.doi.org/10.1016/j.dyepig.2018.07.055]
[34]
Heredia AA, Soria-Castro SM, Castro-Godoy WD, et al. Multistep synthesis of organic selenides under visible light irradiation: A continuous-flow approach. Org Process Res Dev 2020; 24(4): 540-5.
[http://dx.doi.org/10.1021/acs.oprd.9b00548]
[35]
Saba S, Rafique J, Franco MS, et al. Rose Bengal catalysed photo-induced selenylation of indoles, imidazoles and arenes: a metal free approach. Org Biomol Chem 2018; 16(6): 880-5.
[http://dx.doi.org/10.1039/C7OB03177G] [PMID: 29340417]
[36]
Weber ACH, Coelho FL, Affeldt RF, Schneider PH. Visible-light promoted stereoselective arylselanyl functionalization of alkynes. Eur J Org Chem 2018; 2018(47): 6738-42.
[http://dx.doi.org/10.1002/ejoc.201801303]
[37]
Ma F, Zhou L, Liu Q, Li C, Xie Y. Selective photocatalysis approach for introducing ArS units into BODIPYs through thiyl radicals. Org Lett 2019; 21(3): 733-6.
[http://dx.doi.org/10.1021/acs.orglett.8b03954] [PMID: 30673254]
[38]
Nogueira CW, Rocha JBT. Diphenyl diselenide a janus-faced molecule. J Braz Chem Soc 2010; 21(11): 2055-71.
[http://dx.doi.org/10.1590/S0103-50532010001100006]
[39]
Lemir ID, Castro-Godoy WD, Heredia AA, Schmidt LC, Argüello JE. Metal- and photocatalyst-free synthesis of 3-selenylindoles and asymmetric diarylselenides promoted by visible light. RSC Advances 2019; 9(39): 22685-94.
[http://dx.doi.org/10.1039/C9RA03642C]
[40]
Kumaraswamy G, Ramesh V, Gangadhar M, Vijaykumar S. Catalyst and sensitizer-free visible-light-induced C(sp2)−h chalcogenation of arenes/ heteroarenes with dichalcogenides. Asian J Org Chem 2018; 7(8): 1689-97.
[http://dx.doi.org/10.1002/ajoc.201800332]
[41]
Chen J, Chen R, Mei L, et al. Visible-light-induced difunctionalization of styrenes: An efficient and green protocol for the synthesis of β-Acyloxyselenides. Asian J Org Chem 2020; 9(2): 181-4.
[http://dx.doi.org/10.1002/ajoc.201900676]
[42]
Rathore V, Kumar S. Visible-light-induced metal and reagent-free oxidative coupling of: sp 2 C-H bonds with organo-dichalcogenides: synthesis of 3-organochalcogenyl indoles. Green Chem 2019; 21(10): 2670-6.
[http://dx.doi.org/10.1039/C9GC00007K]
[43]
Wang D, Guo X, Wu H, et al. Visible light excitation of BODIPYs enables dehydrogenative enamination at their α-positions with aliphatic amines. J Org Chem 2020; 85(13): 8360-70.
[http://dx.doi.org/10.1021/acs.joc.0c00620] [PMID: 32508102]
[44]
Leen V, Gonzalvo VZ, Deborggraeve WM, Boens N, Dehaen W. Direct functionalization of BODIPY dyes by oxidative nucleophilic hydrogen substitution at the 3- or 3,5-positions. Chem Commun (Camb) 2010; 46(27): 4908-10.
[http://dx.doi.org/10.1039/c0cc00568a] [PMID: 20532331]
[45]
Zhang M, Hao E, Zhou J, et al. Synthesis of pyrrolyldipyrrinato BF2 complexes by oxidative nucleophilic substitution of boron dipyrromethene with pyrrole. Org Biomol Chem 2012; 10(10): 2139-45.
[http://dx.doi.org/10.1039/c2ob06689k] [PMID: 22302220]
[46]
Roacho RI, Metta-Magaña A, Peña-Cabrera E, Pannell K. Unprecedented one-pot sequential thiolate substitutions under mild conditions leading to a red emissive BODIPY dye 3,5,8-tris(PhS)- BODIPY. Org Biomol Chem 2015; 13(4): 995-9.
[http://dx.doi.org/10.1039/C4OB01892C] [PMID: 25429697]
[47]
Leen V, Van der Auweraer M, Boens N, Dehaen W. Vicarious nucleophilic substitution of α-hydrogen of BODIPY and its extension to direct ethenylation. Org Lett 2011; 13(6): 1470-3.
[http://dx.doi.org/10.1021/ol200148u] [PMID: 21332155]
[48]
Duran-Sampedro G, Agarrabieta RA, Garcia-Moreno I, et al. Chlorinated BODIPYs: surprisingly efficient and highly photostable laser dyes. Eur J Org Chem 2012; (32): 6335-50.
[http://dx.doi.org/10.1002/ejoc.201200946]

Rights & Permissions Print Cite
Article Metrics
8
2
1
© 2024 Bentham Science Publishers | Privacy Policy