Cyanine dyes are widely used in bioimaging, sensing, optoelectronic, and medicinal applications due to their tunable photophysical properties. However, controlling their electronic structures and photophysical properties remains a challenge. Here we report a general synthetic route to pentamethine and heptamethine cyanines bearing C1' chain substituents that allow substantial control of their electronic, photophysical, and photochemical properties. By varying the terminal heterocycle and introducing various substituents at the 1'-position, we investigated the role of symmetry breaking and its impact on bond length alternation (BLA) and out-of-plane rotation (OPR). Our analysis shows that OPR, coupled with BLA, suppresses or hypsochromically shifts the first absorption band, thereby significantly altering the absorption properties of the studied dyes. This effect is particularly pronounced in structures with different heterocyclic end groups and bulky or electron deficient substituents at the 1'-position. Through quantum chemical calculations and spectroscopic analyses, we demonstrate how these modifications can be used to tune optical properties of these dyes across the visible region, paving the way for their further customization.

Department of Chemistry Faculty of Science Masaryk University 62500 Brno Czech Republic

Department of Physical Chemistry University of Chemistry and Technology Prague 16628 Prague 6 Czech Republic

RECETOX Faculty of Science Masaryk University 62500 Brno Czech Republic

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Mishra A., Behera R. K., Behera P. K., Mishra B. K., Behera G. B.. Cyanines during the 1990s: A Review. Chem. Rev. 2000;100:1973–2012. doi: 10.1021/cr990402t. PubMed DOI

Sun W., Guo S., Hu C., Fan J., Peng X.. Recent Development of Chemosensors Based on Cyanine Platforms. Chem. Rev. 2016;116:7768–7817. doi: 10.1021/acs.chemrev.6b00001. PubMed DOI

Pansare V. J., Hejazi S., Faenza W. J., Prud’homme R. K.. Review of Long-Wavelength Optical and NIR Imaging Materials: Contrast Agents, Fluorophores, and Multifunctional Nano Carriers. Chem. Mater. 2012;24:812–827. doi: 10.1021/cm2028367. PubMed DOI PMC

Shi C., Wu J. B., Pan D.. Review on Near-Infrared Heptamethine Cyanine Dyes as Theranostic Agents for Tumor Imaging, Targeting, and Photodynamic Therapy. J. Biomed. Opt. 2016;21:050901. doi: 10.1117/1.JBO.21.5.050901. PubMed DOI

Luo S., Zhang E., Su Y., Cheng T., Shi C.. A Review of NIR Dyes in Cancer Targeting and Imaging. Biomaterials. 2011;32:7127–7138. doi: 10.1016/j.biomaterials.2011.06.024. PubMed DOI

Alander J. T., Kaartinen I., Laakso A., Pätilä T., Spillmann T., Tuchin V. V., Venermo M., Välisuo P.. A Review of Indocyanine Green Fluorescent Imaging in Surgery. Int. J. Biomed. Imaging. 2012;2012:940585. doi: 10.1155/2012/940585. PubMed DOI PMC

Zhu D., Li G., Xue L., Jiang H.. Development of Ratiometric Near-Infrared Fluorescent Probes Using Analyte-Specific Cleavage of Carbamate. Org. Biomol. Chem. 2013;11:4577–4580. doi: 10.1039/c3ob40932e. PubMed DOI

Guo Z., Nam S., Park S., Yoon J.. A Highly Selective Ratiometric Near-Infrared Fluorescent Cyanine Sensor for Cysteine With Remarkable Shift and Its Application in Bioimaging. Chem. Sci. 2012;3:2760–2765. doi: 10.1039/c2sc20540h. DOI

Myochin T., Kiyose K., Hanaoka K., Kojima H., Terai T., Nagano T.. Rational Design of Ratiometric Near-Infrared Fluorescent PH Probes With Various pKa Values, Based on Aminocyanine. J. Am. Chem. Soc. 2011;133:3401–3409. doi: 10.1021/ja1063058. PubMed DOI

Gorka A. P., Nani R. R., Schnermann M. J.. Cyanine Polyene Reactivity: Scope And Biomedical Applications. Org. Biomol. Chem. 2015;13:7584–7598. doi: 10.1039/C5OB00788G. PubMed DOI PMC

Russo M., Janekova H., Meier D., Generali M., Stacko P.. Light in a Heartbeat: Bond Scission by a Single Photon above 800 nm. J. Am. Chem. Soc. 2024;146:8417–8424. doi: 10.1021/jacs.3c14197. PubMed DOI PMC

Schulte A. M., Alachouzos G., Szymański W., Feringa B. L.. Strategy for Engineering High Photolysis Efficiency of Photocleavable Protecting Groups through Cation Stabilization. J. Am. Chem. Soc. 2022;144:12421–12430. doi: 10.1021/jacs.2c04262. PubMed DOI PMC

Štacková L., Muchova E., Russo M., Slavicek P., Stacko P., Klan P.. Deciphering the Structure–Property Relations in Substituted Heptamethine Cyanines. J. Org. Chem. 2020;85:9776–9790. doi: 10.1021/acs.joc.0c01104. PubMed DOI

Tovtik R., Muchova E., Štacková L., Slavíček P., Klán P.. Spin–Vibronic Control of Intersystem Crossing in Iodine-Substituted Heptamethine Cyanines. J. Org. Chem. 2023;88:6716–6728. doi: 10.1021/acs.joc.3c00005. PubMed DOI PMC

Mustroph H.. Cyanine Dyes. Phys. Sci. Rev. 2020;5:20190145. doi: 10.1515/psr-2019-0145. DOI

Lee H., Berezin M. Y., Henary M., Strekowski L., Achilefu S.. Fluorescence Lifetime Properties of Near-Infrared Cyanine Dyes in Relation to Their Structures. J. Photochem. Photobiol., A. 2008;200:438–444. doi: 10.1016/j.jphotochem.2008.09.008. PubMed DOI PMC

Mustroph H., Towns A.. Fine Structure in Electronic Spectra of Cyanine Dyes: Are Sub-Bands Largely Determined by a Dominant Vibration or a Collection of Singly Excited Vibrations? ChemPhysChem. 2018;19:1016–1023. doi: 10.1002/cphc.201701300. PubMed DOI PMC

Zhang J., Wang W., Shao J., Chen J., Dong X.. Small Molecular Cyanine Dyes for Phototheranostics. Coord. Chem. Rev. 2024;516:215986. doi: 10.1016/j.ccr.2024.215986. DOI

Mourot B., Jacquemin D., Siri O., Pascal S.. Coupled Polymethine Dyes: Six Decades of Discoveries. Chem. Rec. 2024;24:e202400183. doi: 10.1002/tcr.202400183. PubMed DOI

P Neme N., Jansen T. L. C., Havenith R. W. A.. Cyclopentene ring effects in cyanine dyes: a handle to fine-tune photophysical properties. Phys. Chem. Chem. Phys. 2024;26:6235–6241. doi: 10.1039/D3CP05219B. PubMed DOI PMC

Feng L., Chen W., Ma X., Liu S. H., Yin J.. Near-Infrared Heptamethine Cyanines (Cy7): From Structure, Property to Application. Org. Biomol. Chem. 2020;18:9385–9397. doi: 10.1039/D0OB01962C. PubMed DOI

Guo L., Yang M., Dong B., Lewman S., Van Horn A., Jia S.. Engineering Central Substitutions in Heptamethine Dyes for Improved Fluorophore Performance. JACS Au. 2024;4:3007–3017. doi: 10.1021/jacsau.4c00343. PubMed DOI PMC

Pascal S., Haefele A., Monnereau C., Charaf-Eddin A., Jacquemin D., Le Guennic B., Andraud C., Maury O.. Expanding the Polymethine Paradigm: Evidence for the Contribution of a Bis-Dipolar Electronic Structure. J. Phys. Chem. A. 2014;118:4038–4047. doi: 10.1021/jp501358q. PubMed DOI

Autschbach J.. Why the Particle-in-a-Box Model Works Well for Cyanine Dyes but Not for Conjugated Polyenes. J. Chem. Educ. 2007;84:1840. doi: 10.1021/ed084p1840. DOI

Tolbert L. M., Zhao X.. Beyond the Cyanine Limit: Peierls Distortion and Symmetry Collapse in a Polymethine Dye. J. Am. Chem. Soc. 1997;119:3253–3258. doi: 10.1021/ja9626953. DOI

Gieseking R. L., Ravva M. K., Coropceanu V., Brédas J.-L.. Benchmarking Density Functional Theory Approaches for the Description of Symmetry Breaking in Long Polymethine Dyes. J. Phys. Chem. C. 2016;120:9975–9984. doi: 10.1021/acs.jpcc.6b02100. DOI

Xu W., Leary E., Sangtarash S., Jirasek M., González M. T., Christensen K. E., Abellan Vicente L., Agraït N., Higgins S. J., Nichols R. J.. et al. A Peierls Transition in Long Polymethine Molecular Wires: Evolution of Molecular Geometry and Single-Molecule Conductance. J. Am. Chem. Soc. 2021;143:20472–20481. doi: 10.1021/jacs.1c10747. PubMed DOI

Bouit P.-A., Aronica C., Toupet L., Le Guennic B., Andraud C., Maury O.. Continuous Symmetry Breaking Induced by Ion Pairing Effect in Heptamethine Cyanine Dyes: Beyond the Cyanine Limit. J. Am. Chem. Soc. 2010;132:4328–4335. doi: 10.1021/ja9100886. PubMed DOI

Lin H. H., Lim I., Sletten E. M.. Counterion Exchange Enhances the Brightness and Photostability of a Fluorous Cyanine Dye. Chem. - Eur. J. 2024;30:e202402514. doi: 10.1002/chem.202402514. PubMed DOI PMC

Eskandari M., Roldao J. C., Cerezo J., Milián-Medina B., Gierschner J.. Counterion-Mediated Crossing of the Cyanine Limit in Crystals and Fluid Solution: Bond Length Alternation and Spectral Broadening Unveiled by Quantum Chemistry. J. Am. Chem. Soc. 2020;142:2835–2843. doi: 10.1021/jacs.9b10686. PubMed DOI

Masunov A. E., Anderson D., Freidzon A. Y., Bagaturyants A. A.. Symmetry-Breaking in Cationic Polymethine Dyes: Part 2. Shape of Electronic Absorption Bands Explained by the Thermal Fluctuations of the Solvent Reaction Field. J. Phys. Chem. A. 2015;119:6807–6815. doi: 10.1021/acs.jpca.5b03877. PubMed DOI

Pascal, S. ; Bouit, P.-A. ; Le Guennic, B. ; Parola, S. ; Maury, O. ; Andraud, C. In Symmetry Loss of Heptamethine Cyanines: An Example of Dipole Generation by Ion-Pairing Effect, Proceedings, Organic Photonic Materials and Devices XV; SPIE, 2013.

Cao X., Tolbert R. W., McHale J. L., Edwards W. D.. Theoretical Study of Solvent Effects on the Intramolecular Charge Transfer of a Hemicyanine Dye. J. Phys. Chem. A. 1998;102:2739–2748. doi: 10.1021/jp972190e. DOI

Silva G. L., Ediz V., Yaron D., Armitage B. A.. Experimental and Computational Investigation of Unsymmetrical Cyanine Dyes: Understanding Torsionally Responsive Fluorogenic Dyes. J. Am. Chem. Soc. 2007;129:5710–5718. doi: 10.1021/ja070025z. PubMed DOI PMC

Peng X., Yang Z., Wang J., Fan J., He Y., Song F., Wang B., Sun S., Qu J., Qi J., Yan M.. Fluorescence Ratiometry and Fluorescence Lifetime Imaging: Using a Single Molecular Sensor for Dual Mode Imaging of Cellular Viscosity. J. Am. Chem. Soc. 2011;133:6626–6635. doi: 10.1021/ja1104014. PubMed DOI

Cao J., Fan J., Sun W., Guo Y., Wu H., Peng X.. The Photoprocess Effects of an Amino Group Located at Different Positions Along the Polymethine Chain in Indodicarbocyanine Dyes. RSC Adv. 2017;7:30740–30746. doi: 10.1039/C7RA04556E. DOI

Sissa C., Painelli A., Terenziani F., Trotta M., Ragni R.. About the Origin of the Large Stokes Shift in Aminoalkyl Substituted Heptamethine Cyanine Dyes. Phys. Chem. Chem. Phys. 2020;22:129–135. doi: 10.1039/C9CP05473A. PubMed DOI

Cao J., Hu C., Sun W., Xu Q., Fan J., Song F., Sun S., Peng X.. The Mechanism of Different Sensitivity of meso-Substituted and Unsubstituted Cyanine Dyes in Rotation-Restricted Environments for Biomedical Imaging Applications. RSC Adv. 2014;4:13385–13394. doi: 10.1039/c3ra46612d. DOI

Owens E. A., Bruschi N., Tawney J. G., Henary M.. A Microwave-Assisted and Environmentally Benign Approach to the Synthesis of Near-Infrared Fluorescent Pentamethine Cyanine Dyes. Dyes Pigm. 2015;113:27–37. doi: 10.1016/j.dyepig.2014.07.035. DOI

Yang X., Hou Z., Wang D., Mou Y., Guo C.. Design, Synthesis and Biological Evaluation of Novel Heptamethine Cyanine Dye-Erlotinib Conjugates as Antitumor Agents. Bioorg. Med. Chem. Lett. 2020;30:127557. doi: 10.1016/j.bmcl.2020.127557. PubMed DOI

Ernst L. A., Gupta R. K., Mujumdar R. B., Waggoner A. S.. Cyanine Dye Labeling Reagents for Sulfhydryl Groups. Cytometry. 1989;10:3–10. doi: 10.1002/cyto.990100103. PubMed DOI

Doi T., Oikawa K., Suzuki J., Yoshida M., Iki N.. Development of a Near Infrared Fluorescence Labeling Reagent: Synthesis of Indole-Functionalized Indocyanine Green Derivatives. Synlett. 2012;2012:306–310. doi: 10.1055/s-0031-1290139. DOI

Blanchard, S. C. ; Altman, R. ; Warren, J. D. ; Zhou, Z. . Dye Compositions, Methods of Preparation, Conjugates Thereof, and Methods of Use. U.S. Patent US9,631,096B2, 2013.

Han J., Engler A., Qi J., Tung C.-H.. Ultra Pseudo-Stokes Shift Near Infrared Dyes Based on Energy Transfer. Tetrahedron Lett. 2013;54:502–505. doi: 10.1016/j.tetlet.2012.11.060. PubMed DOI PMC

Lee H., Mason J. C., Achilefu S.. Heptamethine Cyanine Dyes With a Robust C–C Bond at the Central Position of the Chromophore. J. Org. Chem. 2006;71:7862–7865. doi: 10.1021/jo061284u. PubMed DOI

Štacková L., Stacko P., Klan P.. Approach to a Substituted Heptamethine Cyanine Chain by the Ring Opening of Zincke Salts. J. Am. Chem. Soc. 2019;141:7155–7162. doi: 10.1021/jacs.9b02537. PubMed DOI

Hao Z., Hu L., Wang X., Liu Y., Mo S.. Synthesis of Heptamethine Cyanines from Furfural Derivatives. Org. Lett. 2023;25:1078–1082. doi: 10.1021/acs.orglett.2c04289. PubMed DOI

Wang L., Yan M., Zhang B., Zhao J., Deng W., Lin W., Guan L.. Approach to Introducing Substituent on the Dipole Conjugate Chain: The D– π–A Methine Chain Electrophilic Substitution. Org. Lett. 2018;20:60–63. doi: 10.1021/acs.orglett.7b03345. PubMed DOI

Hamer F. M., Rathbone R. J.. Symmetrical Dicarbocyanines Having a Methyl Group as Substituent on the Chain. J. Chem. Soc. 1945:595–600. doi: 10.1039/jr9450000595. DOI

Berneth, H. ; Fäcke, T. ; Rõlle, T. ; Kostromine, S. ; Bruder, F.-K. ; Hõnel, D. . Holographic Media Containing Chain-Substituted Cyanine Dyes. U.S.Patent US9,760,060B2, 2015.

Le Guennic B., Jacquemin D.. Taking Up the Cyanine Challenge with Quantum Tools. Acc. Chem. Res. 2015;48:530–537. doi: 10.1021/ar500447q. PubMed DOI PMC

Burdett J. K., Lee S.. Peierls Distortions in Two and Three Dimensions and the Structures of AB Solids. J. Am. Chem. Soc. 1983;105:1079–1083. doi: 10.1021/ja00343a001. DOI

Zhang Q., Xu S., Lai F., Wang Y., Zhang N., Nazare M., Hu H.-Y.. Rapid Synthesis of γ-Halide/Pseudohalide-Substituted Cyanine Sensors with Programmed Generation of Singlet Oxygen. Org. Lett. 2019;21:2121–2125. doi: 10.1021/acs.orglett.9b00404. PubMed DOI

Roxburgh C. J., Sammes P. G., Abdullah A.. Steric and Substituent Effects on the Photoreversibility of Novel Indolospirobenzopyrans: Acid Deuterolysis, UV and 1H NMR Spectroscopy. Dyes Pigm. 2009;82:226–237. doi: 10.1016/j.dyepig.2009.01.006. DOI

Fischer E., Wagner P.. Ueber Rosindole. Ber. Dtsch. Chem. Ges. 1887;20:815–818. doi: 10.1002/cber.188702001185. DOI

Toutchkine A., Nguyen D.-V., Hahn K. M.. Merocyanine Dyes With Improved Photostability. Org. Lett. 2007;9:2775–2777. doi: 10.1021/ol070780h. PubMed DOI

Meguellati K., Spichty M., Ladame S.. Reversible Synthesis and Characterization of Dynamic Imino Analogues of Trimethine and Pentamethine Cyanine Dyes. Org. Lett. 2009;11:1123–1126. doi: 10.1021/ol802913b. PubMed DOI

Knübel G., Franck B.. Biomimetische Synthese eines octavinylogen Porphyrins mit aromatischem [34] Annulensystem. Angew. Chem. 1988;100:1203–1211. doi: 10.1002/ange.19881000913. DOI

Dorie J., Gouesnard J.-P., Martin M. L.. Nuclear Magnetic Resonance Investigations of Iminium Ion Intermediates. Part 9. Multinuclear Study of the Reaction Between Lewis Acids and Vinylogous Amides. J. Chem. Soc., Perkin Trans. 1981;2:912–917. doi: 10.1039/p29810000912. DOI

McConnell D. B., Condie G. C., Kumar N., Black D. S.. The Extended Vilsmeier Reaction of Dimethoxy-Activated Indoles. Arkivoc. 2021;2020:176–184. doi: 10.24820/ark.5550190.p011.399. DOI

Anthes R., Benoit S., Chen C.-K., Corbett E. A., Corbett R. M., DelMonte A. J., Gingras S., Livingston R. C., Pendri Y., Sausker J., Soumeillant M.. An Improved Synthesis of a Selective Serotonin Reuptake Inhibitor. Org. Process Res. Dev. 2008;12:178–182. doi: 10.1021/op700126w. DOI

Yan L. H., Skiredj A., Dory Y., Delpech B., Poupon E.. 5-Aminopenta-2, 4-dienals: Synthesis, Activation towards Nucleophiles, Molecular Modeling and Biosynthetic Implications in Relation to the Manzamine Alkaloids. Eur. J. Org. Chem. 2014;2014:4973–4984. doi: 10.1002/ejoc.201402331. DOI

Gamon N., Reichardt C.. Zur Konfiguration von 1, 3, 3-Trialkyl-2-methylenindolinen mit Substituenten an der Methylengruppe. Chem. Ber. 1982;115:1746–1754. doi: 10.1002/cber.19821150509. DOI

Dar N., Ankari R.. Theoretical Models, Preparation, Characterization and Applications of Cyanine J-Aggregates: A Minireview. ChemistryOpen. 2022;11:e202200103. doi: 10.1002/open.202200103. PubMed DOI PMC

Åkesson E., Sundström V., Gillbro T.. Solvent-Dependent Barrier Heights of Excited-State Photoisomerization Reactions. Chem. Phys. Lett. 1985;121:513–522. doi: 10.1016/0009-2614(85)87132-3. DOI

Yu A., Tolbert C. A., Farrow D. A., Jonas D. M.. Solvatochromism and Solvation Dynamics of Structurally Related Cyanine Dyes. J. Phys. Chem. A. 2002;106:9407–9419. doi: 10.1021/jp0205867. DOI

West W., Geddes A.. The Effects of Solvents and of Solid Substrates on the Visible Molecular Absorption Spectrum of Cyanine Dyes. J. Phys. Chem. A. 1964;68:837–847. doi: 10.1021/j100786a023. DOI

Lepkowicz R. S., Przhonska O. V., Hales J. M., Fu J., Hagan D. J., Van Stryland E. W., Bondar M. V., Slominsky Y. L., Kachkovski A. D.. Nature of the Electronic Transitions in Thiacarbocyanines With a Long Polymethine Chain. Chem. Phys. 2004;305:259–270. doi: 10.1016/j.chemphys.2004.06.063. DOI

Terenziani F., Przhonska O. V., Webster S., Padilha L. A., Slominsky Y. L., Davydenko I. G., Gerasov A. O., Kovtun Y. P., Shandura M. P., Kachkovski A. D.. et al. Essential-State Model for Polymethine Dyes: Symmetry Breaking and Optical Spectra. J. Phys. Chem. Lett. 2010;1:1800–1804. doi: 10.1021/jz100430x. DOI

Ishchenko A. A., Derevyanko N., Zubarovskii V., Tolmachev A.. Influence of Length of the Polymethine Chain on Width of Absorption Bands of Symmetric Cyanine Byes. Theor. Exp. Chem. 1985;20:415–422. doi: 10.1007/BF00516576. DOI

Pronkin P., Tatikolov A.. Isomerization and Properties of Isomers of Carbocyanine Dyes. Sci. 2019;1:19. doi: 10.3390/sci1010019. DOI

Matikonda S. S., Hammersley G., Kumari N., Grabenhorst L., Glembockyte V., Tinnefeld P., Ivanic J., Levitus M., Schnermann M. J.. Impact of Cyanine Conformational Restraint in the Near-Infrared Range. J. Org. Chem. 2020;85:5907–5915. doi: 10.1021/acs.joc.0c00236. PubMed DOI PMC

Lutsyk P., Piryatinski Y., Kachkovsky O., Verbitsky A., Rozhin A.. Unsymmetrical Relaxation Paths of the Excited States in Cyanine Dyes Detected by Time-Resolved Fluorescence: Polymethinic and Polyenic Forms. J. Phys. Chem. A. 2017;121:8236–8246. doi: 10.1021/acs.jpca.7b08680. PubMed DOI

Piryatinski Y., Verbitsky A. B., Dmytruk A., Malynovskyi M. B., Lutsyk P. M., Rozhin A. G., Kachkovsky O. D., Prostota Y., Kurdyukov V. V.. Excited state relaxation in cationic pentamethine cyanines studied by time-resolved spectroscopy. Dyes Pigm. 2021;193:109539. doi: 10.1016/j.dyepig.2021.109539. DOI

Shvo Y., Shanan-Atidi H.. Internal rotation in olefins. I. Kinetic investigation by nuclear magnetic resonance. J. Am. Chem. Soc. 1969;91:6683–6689. doi: 10.1021/ja01052a025. DOI

Henrichs P. M., Gross S.. Conformational analysis of carbocyanine dyes with variable-temperature proton Fourier transform nuclear magnetic resonance spectroscopy. J. Am. Chem. Soc. 1976;98:7169–7175. doi: 10.1021/ja00439a009. DOI

Jiao L., Song F., Cui J., Peng X.. A Near-Infrared Heptamethine Aminocyanine Dye With a Long-Lived Excited Triplet State for Photodynamic Therapy. Chem. Commun. 2018;54:9198–9201. doi: 10.1039/C8CC04582H. PubMed DOI

Redmond R. W., Gamlin J. N.. A Compilation of Singlet Oxygen Yields From Biologically Relevant Molecules. Photochem. Photobiol. 1999;70:391–475. doi: 10.1111/j.1751-1097.1999.tb08240.x. PubMed DOI

Wilkinson F., Helman W. P., Ross A. B.. Quantum Yields for the Photosensitized Formation of the Lowest Electronically Excited Singlet State of Molecular Oxygen in Solution. J. Phys. Chem. Ref. Data. 1993;22:113–262. doi: 10.1063/1.555934. DOI

Wu X., Zhu W.. Stability Enhancement of Fluorophores for Lighting up Practical Application in Bioimaging. Chem. Soc. Rev. 2015;44:4179–4184. doi: 10.1039/C4CS00152D. PubMed DOI

Byers G. W., Gross S., Henrichs P.. Direct and Sensitized Photooxidation of Cyanine Dyes. Photochem. Photobiol. 1976;23:37–43. doi: 10.1111/j.1751-1097.1976.tb06768.x. PubMed DOI

Li D. H., Gamage R. S., Oliver A. G., Patel N. L., Usama S. M., Kalen J. D., Schnermann M. J., Smith B. D.. Doubly Strapped Zwitterionic NIR-I and NIR-II Heptamethine Cyanine Dyes for Bioconjugation and Fluorescence Imaging. Angew. Chem. 2023;135:e202305062. doi: 10.1002/ange.202305062. PubMed DOI PMC

Gidi Y., Ramos-Sanchez J., Lovell T. C., Glembockyte V., Cheah I. K., Schnermann M. J., Halliwell B., Cosa G.. Superior Photoprotection of Cyanine Dyes With Thio-Imidazole Amino Acids. J. Am. Chem. Soc. 2023;145:19571–19577. doi: 10.1021/jacs.3c03058. PubMed DOI

Koripelly G., Meguellati K., Ladame S.. Dual Sensing of Hairpin and Quadruplex DNA Structures Using Multicolored Peptide Nucleic Acid Fluorescent Probes. Bioconjugate Chem. 2010;21:2103–2109. doi: 10.1021/bc100335f. PubMed DOI

Moser D., Duan Y., Wang F., Ma Y., O’Neill M. J., Cornella J.. Selective Functionalization of Aminoheterocycles by a Pyrylium Salt. Angew. Chem., Int. Ed. 2018;57:11035–11039. doi: 10.1002/anie.201806271. PubMed DOI

Sharghi H., Asemani O.. Methanesulfonic Acid/SiO2 as an Efficient Combination for the Synthesis of 2-Substituted Aromatic and Aliphatic Benzothiazoles from Carboxylic Acids. Synth. Commun. 2009;39:860–867. doi: 10.1080/00397910802431214. DOI

Cheng Y., Peng Q., Fan W., Li P.. Room-Temperature Ligand-Free Pd/C-Catalyzed C–S Bond Formation: Synthesis of 2-Substituted Benzothiazoles. J. Org. Chem. 2014;79:5812–5819. doi: 10.1021/jo5002752. PubMed DOI

Padilha N. B., Penteado F., Salomão M. C., Lopes E. F., Bettanin L., Hartwig D., Jacob R. G., Lenardão E. J.. Peroxide-Mediated Oxidative Coupling of Primary Alcohols and Disulfides: Synthesis of 2-Substituted Benzothiazoles. Tetrahedron Lett. 2019;60:1587–1591. doi: 10.1016/j.tetlet.2019.05.021. DOI

Guo Y.-Q., Chen F., Deng C.-L., Zhang X.-G.. Iodine-Promoted Ring-Opening Methylation of Benzothiazoles With Dimethyl Sulfite. Chem. Commun. 2021;57:1923–1926. doi: 10.1039/D0CC08096A. PubMed DOI

Zhang S., Fan J., Li Z., Hao N., Cao J., Wu T., Wang J., Peng X.. A Bright Red Fluorescent Cyanine Dye for Live-Cell Nucleic Acid Imaging, With High Photostability and a Large Stokes Shift. J. Mater. Chem. B. 2014;2:2688–2693. doi: 10.1039/C3TB21844A. PubMed DOI

Percival W. C., Wagner R. B., Cook N. C.. Grignard Reactions. XXI. 1 The Synthesis of Aliphatic Ketones2. J. Am. Chem. Soc. 1953;75:3731–3734. doi: 10.1021/ja01111a036. DOI

Chikashita H., Komazawa S.-i., Ishimoto N., Inoue K., Itoh K.. Nonacidic and Highly Chemoselective Protection of the Carbonyl Function. 3-Methylbenzothiazolines as a Base-and Acid-Resistant Protected Form for the Carbonyl Groups. Bull. Chem. Soc. Jpn. 1989;62:1215–1225. doi: 10.1246/bcsj.62.1215. DOI

Liang B., Cai X., Xu S., Huang J., Deng H., Ren W., Chen J., Lo T. W. B., Chen X., Zhu Z.. NaOAc-Promoted [3 + 1+2] Annulation of O-Pivaloyl Oximes, Aldehydes, and 2-Methylbenzothiazole Salts: Synthesis of 1-Azaphenothiazines. J. Org. Chem. 2024;89:13438–13449. doi: 10.1021/acs.joc.4c01590. PubMed DOI

Cyanines Substituted on the Polymethine Chain: Synthesis, Resulting Properties, and Application Use Cases