Synthesis of unsymmetrical Si-rhodamine fluorophores and application to a far-red to near-infrared fluorescence probe for hypoxia

Hanaoka, Kenjiro; Kagami, Yu; Piao, Wen; Myochin, Takuya; Numasawa, Koji; Kuriki, Yugo; Ikeno, Takayuki; Ueno, Takahiro; Komatsu, Toshimitsu; Terai, Takuya; Nagano, Tetsuo; Urano, Yasuteru

doi:10.1039/c8cc02451k

Cited by 41 publications

(32 citation statements)

References 23 publications

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“…10 was recovered in a pure form by conventional flash-column chromatography over regular silica gel (yield 61%). The next step was the formation of the unsymmetrical bis(bromoaryl) derivatives 12 and 13 through a Friedel-Crafts alkylation reaction between 6-bromo-1-methylindoline 9 (or 8bromojulolidine 10) and a benzyl-type cation generated from 4-(diallylamino)-2-bromobenzyl alcohol 11 (see ESI for its synthesis) in the presence of BF3•Et2O in DCM [64]. This reaction provided 12 and 13 in good reproducible yields (86% and 80% respectively).…”

Section: Synthesis Of Unsymmetrical Si-pyronin Dyes Bearing a Tertiary Aniline Unitmentioning

confidence: 99%

Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

Dejouy¹,

Renault²,

Valverde³

et al. 2020

Preprint

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Fluorogenic detection of reactive (bio)analytes is often achieved with "smart" probes, whose activation mechanism causes the release of aniline-based fluorophores. Indeed, the protection-deprotection of their primary amino is the simplest way to induce dramatic and valuable changes in spectral features of the fluorogenic reporter. In this context, and due to their small size and intrinsic hydrophilicity, we focused on pyronin dyes and related heteroatom analogs (i.e., formal derivatives of 3-imino-3H-xanthen-6-amine and its silicon analog) for their use as optically tunable aniline-based fluorophores. To overcome some severe limitations associated with the use of such fluorogenic scaffolds (i.e., poor aqueous stability and spectral features only in the green-yellow spectral range), the synthesis of novel unsymmetrical derivatives of (Si)-pyronins bearing a single bulky tertiary aniline (i.e., N-methylindoline and julolidine) was explored and presented in this Article. This structural alteration has been found to be beneficial to dramatically lower electrophilicity of the meso-position and to reach attractive fluorescence properties within the far-red spectral region.

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Section: Synthesis Of Unsymmetrical Si-pyronin Dyes Bearing a Tertiary Aniline Unitmentioning

confidence: 99%

Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

Dejouy¹,

Renault²,

Valverde³

et al. 2020

Preprint

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“…To this end, fluorescence imaging combined with an appropriate molecular probe has become a facile and powerful tool for the detection of biologically relevant species . Since far‐red to near‐infrared (FR‐NIR) fluorescence imaging can increase tissue penetration depth and minimize issues associated with autofluorescence of natively occurring fluorophores, much effort has been made to develop various novel long‐wavelength fluorescent probes based on established fluorophores such as cyanine, and newly developed fluorophores such as chromenylium‐cyanine dyes, heteroatom‐substituted rhodamine dyes, and others . However, most previously reported long‐wavelength fluorescent dyes still suffer from small Stokes shifts and sometimes low quantum yields, which results in self‐quenching and low signal‐to‐noise ratio .…”

Section: Introductionmentioning

confidence: 99%

Donor and Ring‐Fusing Engineering for Far‐Red to Near‐Infrared Triphenylpyrylium Fluorophores with Enhanced Fluorescence Performance for Sensing and Imaging

Wen

Zhang

Ren

et al. 2019

Chemistry A European J

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Fluorescent probes have become an indispensable tool in the detection and imaging of biological and disease‐related analytes due to their sensitivity and technical simplicity. In particular, fluorescent probes with far‐red to near‐infrared (FR‐NIR) emissions are very attractive for biomedical applications. However, many available FR‐NIR fluorophores suffer from small Stokes shifts and sometimes low quantum yields, resulting in self‐quenching and low contrast. In this work, we describe the rational design and engineering of FR‐NIR 2,4,6‐triphenylpyrylium‐based fluorophores (TPP‐Fluors) with the help of theoretical calculations. Our strategy is based on the appending of electron‐donating substituents and fusing groups onto 2,4,6‐triphenylpyrylium. In contrast to the parent TPP with short emission wavelength, weak quantum yields, and low chemical stability, the obtained novel TPP‐Fluors display some favorable properties, such as long‐wavelength emission, large Stokes shifts, moderate to high quantum yields, and chemical stability. TPP‐Fluors demonstrate their biological value as mitochondria‐specific labeling reagents due to their inherently positive nature. In addition, TPP‐Fluors can also be applied to develop ratiometric fluorescent probes, as the electron‐donating ability of the 2,6‐phenyl substituents is closely correlated with their emission wavelength. A proof‐of‐concept ratiometric probe has been developed by derivatizing the amino groups of TPP‐Fluor for the detection and imaging of nitroreductase in vitro and in hypoxic cells.

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“…Silicon rhodamines are versatile fluorescent dyes that found extensive use in super-resolution microscopy [1–8] and as probes for targeting various biomolecules [9–12] or sensors for metal ions [13–17], pH [15], voltage [18] or metabolites [19–22]. Since our group is interested in synthesizing new tumor tracers for intraoperative imaging of cancerous lesions, we were interested in silicon rhodamines due to their fluorescence properties in the biological window (650 nm to 1350 nm).…”

Section: Introductionmentioning

confidence: 99%

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

Kanagasundaram

Timmermann

Kramer

et al. 2019

Beilstein J. Org. Chem.

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Background: Silicon rhodamines are of particular interest because of their advantageous dye properties (fluorescence- and biostability, quantum efficiency, tolerance to photobleaching). Therefore, silicon rhodamines find frequent application in STED (stimulated emission depletion) microscopy, as sensor molecules for, e.g., ions and as fluorophores for the optical imaging of tumors. Different strategies were already employed for their synthesis. Because of just three known literature examples in which Suzuki–Miyaura cross couplings gave access to silicon rhodamines in poor to moderate yields, we wanted to improve these first valuable experimental results. Results: The preparation of the xanthene triflate was enhanced and several boron sources were screened to find the optimal coupling partner. After optimization of the palladium catalyst, different substituted boroxines were assessed to explore the scope of the Pd-catalyzed cross-coupling reaction. Conclusions: A number of silicon rhodamines were synthesized under the optimized conditions in up to 91% yield without the necessity of HPLC purification. Moreover, silicon rhodamines functionalized with free acid moieties are directly accessible in contrast to previously described methods.

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Synthesis of unsymmetrical Si-rhodamine fluorophores and application to a far-red to near-infrared fluorescence probe for hypoxia

Cited by 41 publications

References 23 publications

Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

Synthetic Routes to Novel Fluorogenic Pyronins and Silicon Analogs with Far-Red Spectral Properties and Enhanced Aqueous Stability

Donor and Ring‐Fusing Engineering for Far‐Red to Near‐Infrared Triphenylpyrylium Fluorophores with Enhanced Fluorescence Performance for Sensing and Imaging

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

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