Near-infrared benzodiazoles as small molecule environmentally-sensitive fluorophores

Abstract

The development of fluorophores emitting in the near-infrared spectral window has gained increased attention given their suitable features for biological imaging. In this work, we have optimised a general and straightforward synthetic approach to prepare a small library of near-infrared-emitting C-bridged nitrobenzodiazoles using commercial precursors. C-bridged benzodiazoles have low molecular weight and neutral character as important features that are not common in most near-infrared dyes. We have investigated their fluorescence response in the presence of a wide array of 60 different biomolecules and identified compound 3i as a potential chemosensor to discriminate between Fe²⁺ and Fe³⁺ ions in aqueous media.

Graphical abstract

Keywords

fluorescence / probes / iron / screening / library

References

[1] Park S J, Yeo H C, Kang N Y, Kim H, Lin J, Ha H H, Vendrell M, Lee J S, Chandran Y, Lee D Y, . Mechanistic elements and critical factors of cellular reprogramming revealed by stepwise global gene expression analyses. Stem Cell Research (Amsterdam), 2014, 12(3): 730–741

[2] Carter K P, Young A M, Palmer A E. Fluorescent sensors for measuring metal ions in living systems. Chemical Reviews, 2014, 114(8): 4564–4601

[3] Jiao X Y, Li Y, Niu J Y, Xie X L, Wang X, Tang B. Small-molecule fluorescent probes for imaging and detection of reactive oxygen, nitrogen, and sulfur species in biological systems. Analitycal Chemistry, 2018, 90(1): 533–555

[4] Han J Y, Burgess K. Fluorescent indicators for intracellular pH. Chemical Reviews, 2010, 110(5): 2709–2728

[5] Dedecker P, De Schryver F C, Hofkens J. Fluorescent proteins: shine on, you crazy diamond. Journal of the American Chemical Society, 2013, 135(7): 2387–2402

[6] Gong J, Liu C, Jiao X J, He S, Zhao L C, Zeng X S. A novel near-infrared fluorescent probe with an improved Stokes shift for specific detection of Hg²⁺ in mitochondria. Organic & Biomolecular Chemistry, 2020, 18(27): 5238–5244

[7] Kwon H Y, Liu X, Choi E G, Lee J Y, Choi S Y, Kim J Y, Wang L, Park S J, Kim B, Lee Y A, . Development of a universal fluorescent probe for gram-positive bacteria. Angewandte Chemie International Edition, 2019, 58(25): 8426–8431

[8] Devaraj N K, Weissleder R. Biomedical applications of tetrazine cycloadditions. Accounts of Chemical Research, 2011, 44(9): 816–827

[9] Chen G Q, Guo Z, Zeng G M, Tang L. Fluorescent and colorimetric sensors for environmental mercury detection. Analyst (London), 2015, 140(16): 5400–5443

[10] Chan J, Dodani S C, Chang C J. Reaction-based small-molecule fluorescent probes for chemoselective bioimaging. Nature Chemistry, 2012, 4(12): 973–984

[11] Duong T Q, Kim J S. Fluoro- and chromogenic chemodosimeters for heavy metal ion detection in solution and biospecimens. Chemical Reviews, 2010, 110(10): 6280–6301

[12] Yraola F, Ventura R, Vendrell M, Colombo A, Fernandez J C, de la Figuera N, Fernandez-Forner D, Royo M, Forns P, Albericio F. A re-evaluation of the use of rink, BAL, and PAL resins and linkers. QSAR & Combinatorial Science, 2004, 23(2–3): 145–152

[13] Sainlos M, Iskenderian W S, Imperiali B. A general screening strategy for peptide-based fluorogenic ligands: probes for dynamic studies of PDZ domain-mediated interactions. Journal of the American Chemical Society, 2009, 131(19): 6680–6682

[14] Kalstrup T, Blunck R. Dynamics of internal pore opening in K(V) channels probed by a fluorescent unnatural amino acid. Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(20): 8272–8277

[15] Sachdeva A, Wang K H, Elliott T, Chin J W. Concerted, rapid, quantitative, and site-specific dual labeling of proteins. Journal of the American Chemical Society, 2014, 136(22): 7785–7788

[16] Lampkowski J S, Uthappa D M, Young D D. Site-specific incorporation of a fluorescent terphenyl unnatural amino acid. Bioorganic & Medicinal Chemistry Letters, 2015, 25(22): 5277–5280

[17] FitzGerald L I, Aurelio L, Chen M, Yuen D, Rennick J J, Graham B, Johnston A P R. A molecular sensor to quantify the localization of proteins, DNA and nanoparticles in cells. Nature Communications, 2020, 11(1): 1–13

[18] Fernandez A, Vermeren M, Humphries D, Subiros-Funosas R, Barth N, Campana L, MacKinnon A, Feng Y, Vendrell M. Chemical modulation of in vivo macrophage function with subpopulation-specific fluorescent prodrug conjugates. ACS Central Science, 2017, 3(9): 995–1005

[19] Subiros-Funosas R, Mendive-Tapia L, Sot J, Pound J D, Barth N, Varela Y, Goni F M, Paterson M, Gregory C D, Albericio F, . A Trp-BODIPY cyclic peptide for fluorescence labelling of apoptotic bodies. Chemical Communications, 2017, 53(5): 945–948

[20] Barth N D, Subiros-Funosas R, Mendive-Tapia L, Duffin R, Shields M A, Cartwright J A, Henriques S T, Sot J, Goni F M, Lavilla R, . A fluorogenic cyclic peptide for imaging and quantification of drug-induced apoptosis. Nature Communications, 2020, 11(1): 1–14

[21] Osseiran S, Austin L A, Cannon T M, Yan C, Langenau D M, Evans C L. Longitudinal monitoring of cancer cell subpopulations in monolayers, 3D spheroids, and xenografts using the photoconvertible dye DiR. Scientific Reports, 2019, 9(1): 1–10

[22] Anorma C, Hedhli J, Bearrood T E, Pino N W, Gardner S H, Inaba H, Zhang P, Li Y F, Feng D, Dibrell S E, . Surveillance of cancer stem cell plasticity using an isoform-selective fluorescent probe for aldehyde dehydrogenase 1A1. ACS Central Science, 2018, 4(8): 1045–1055

[23] Barth N D, Marwick J A, Vendrell M, Rossi A G, Dransfield I. The “Phagocytic synapse” and clearance of apoptotic cells. Frontiers in Immunology, 2017, 8: 1708–1717

[24] Yi Z, Luo Z, Barth N D, Meng X, Liu H, Bu W, All A, Vendrell M, Liu X. In vivo tumor visualization through MRI off-on switching of NaGdF4-CaCO₃ nanoconjugates. Advanced Materials, 2019, 31(37): e1901851

[25] Samanta A, Vendrell M, Yun S W, Guan Z, Xu Q H, Chang Y T. A photostable near-infrared protein labeling dye for in vivo imaging. Chemistry, an Asian Journal, 2011, 6(6): 1353–1357

[26] Chen C, Tian R, Zeng Y, Chu C C, Liu G. Activatable fluorescence probes for “turn-on” and ratiometric biosensing and bioimaging: from NIR-I to NIR-II. Bioconjugate Chemistry, 2020, 31(2): 276–292

[27] Wang P Y, Fan Y, Lu L F, Liu L, Fan L L, Zhao M Y, Xie Y, Xu C J, Zhang F. NIR-II nanoprobes in-vivo assembly to improve image-guided surgery for metastatic ovarian cancer. Nature Communications, 2018, 9(1): 1–10

[28] Vahrmeijer A L, Hutteman M, van der Vorst J R, van de Velde C J H, Frangioni J V. Image-guided cancer surgery using near-infrared fluorescence. Nature Reviews. Clinical Oncology, 2013, 10(9): 507–518

[29] Guo Z Q, Park S, Yoon J, Shin I. Recent progress in the development of near-infrared fluorescent probes for bioimaging applications. Chemical Society Reviews, 2014, 43(1): 16–29

[30] Wirth R, Gao P, Nienhaus G U, Sunbul M, Jaschke A. SiRA: a silicon rhodamine-binding aptamer for live-cell super-resolution RNA imaging. Journal of the American Chemical Society, 2019, 141(18): 7562–7571

[31] Koide Y, Urano Y, Hanaoka K, Piao W, Kusakabe M, Saito N, Terai T, Okabe T, Nagano T. Development of NIR fluorescent dyes based on Si-rhodamine for in vivo imaging. Journal of the American Chemical Society, 2012, 134(11): 5029–5031

[32] Ramos A A, Nascimento F B, de Souza T F M, Omori A T, Manieri T M, Cerchiaro G, Ribeiro A O. Photochemical and photophysical properties of phthalocyanines modified with optically active alcohols. Molecules (Basel, Switzerland), 2015, 20(8): 13575–13590

[33] Pal A K, Varghese S, Cordes D B, Slawin A M Z, Samuel I D W, Zysman-Colman E. Near-infrared fluorescence of silicon phthalocyanine carboxylate esters. Scientific Reports, 2017, 7(1): 1–14

[34] Wong R C H, Lo P C, Ng D K P. Stimuli responsive phthalocyanine-based fluorescent probes and photosensitizers. Coordination Chemistry Reviews, 2019, 379: 30–46

[35] Ilina K, MacCuaig W M, Laramie M, Jeouty J N, McNally L R, Henary M. Squaraine dyes: molecular design for different applications and remaining challenges. Bioconjugate Chemistry, 2020, 31(2): 194–213

[36] Xia G M, Wang H M. Squaraine dyes: the hierarchical synthesis and its application in optical detection. Journal of Photochemistry and Photobiology A Chemistry, 2017, 31: 84–113

[37] Mathew S, Yella A, Gao P, Humphry-Baker R, Curchod B F E, Ashari-Astani N, Tavernelli I, Rothlisberger U, Nazeeruddin M K, Gratzel M. Dye-sensitized solar cells with 13% efficiency achieved through the molecular engineering of porphyrin sensitizers. Nature Chemistry, 2014, 6(3): 242–247

[38] Mellanby R J, Scott J I, Mair I, Fernandez A, Saul L, Arlt J, Moral M, Vendrell M. Tricarbocyanine N-triazoles: the scaffold-of-choice for long-term near-infrared imaging of immune cells in vivo. Chemical Science (Cambridge), 2018, 9(36): 7261–7270

[39] Okuda K, Okabe Y, Kadonosono T, Ueno T, Youssif B G M, Kizaka-Kondoh S, Nagasawa H. 2-Nitroimidazole-tricarbocyanine conjugate as a near-infrared fluorescent probe for in vivo imaging of tumor hypoxia. Bioconjugate Chemistry, 2012, 23(3): 324–329

[40] Cosco E D, Caram J R, Bruns O T, Franke D, Day R A, Farr E P, Bawendi M G, Sletten E M. Flavylium polymethine fluorophores for near- and shortwave infrared imaging. Angewandte Chemie International Edition, 2017, 56(42): 13126–13129

[41] Benson S, Fernandez A, Barth N D, de Moliner F, Horrocks M H, Herrington C S, Abad J L, Delgado A, Kelly L, Chang Z, . SCOTfluors: small, conjugatable, orthogonal, and tunable fluorophores for in vivo imaging of cell metabolism. Angewandte Chemie International Edition, 2019, 58(21): 6911–6915

[42] Yun S W, Kang N Y, Park S J, Ha H H, Kim Y K, Lee J S, Chang Y T. Diversity oriented fluorescence library approach (DOFLA) for live cell imaging probe development. Accounts of Chemical Research, 2014, 47(4): 1277–1286

[43] Lee J S, Vendrell M, Chang Y T. Diversity-oriented optical imaging probe development. Current Opinion in Chemical Biology, 2011, 15(6): 760–767

[44] Luo X, Qian L J, Xiao Y S, Tang Y, Zhao Y, Wang X, Gu L Y, Lei Z H, Bao J M, Wu J H, . A diversity-oriented rhodamine library for wide-spectrum bactericidal agents with low inducible resistance against resistant pathogens. Nature Communications, 2019, 10(1): 1–12

[45] Burchak O N, Mugherli L, Ostuni M, Lacapere J J, Balakirev M Y. Combinatorial discovery of fluorescent pharmacophores by multicomponent reactions in droplet arrays. Journal of the American Chemical Society, 2011, 133(26): 10058–10061

[46] Kaplan J, Ward D M. The essential nature of iron usage and regulation. Current Biology, 2013, 23(15): R642–R646

[47] Dev S, Babitt J L. Overview of iron metabolism in health and disease. Hemodialysis International. International Symposium on Home Hemodialysis, 2017, 21: S6–S20

[48] Trivedi P C, Bartlett J J, Pulinilkunnil T. Lysosomal biology and function: modern view of cellular debris bin. Cells, 2020, 9(5): 1131–1166

[49] Xu H, Ren D. Lysosomal physiology. Annual Review of Physiology, 2015, 77(1): 57–80

Acknowledgments

The authors acknowledge funding from Medical Research Scotland (Sam Benson: 879-2015) and an ERC Consolidator Grant (DYNAFLUORS, Marc Vendrell: 771443). This work was also supported by National Research Foundation funded by the Ministry of Science, ICT & Future Planning, South Korea (Jun-Seok Lee: NRF- 2018M3A9H4079286, NRF-2020R1A2C2004422).

Electronic Supplementary Material

Supplementary material is available in the online version of this article at https://dx.doi.org/10.1007/s11705-021-2080-8 and is accessible for authorized users.

Open Access

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

RIGHTS & PERMISSIONS

2021 The Author(s) 2021. This article is published with open access at link.springer.com and journal.hep.com.cn