Modular Synthetic Approach to Silicon-Rhodamine Homologues and Analogues via Bis-aryllanthanum Reagents

Abstract

A modular synthetic approach toward diverse analogues of the far-red fluorophore silicon-rhodamine (SiR), based on a regioselective double nucleophilic addition of aryllanthanum reagents to esters, anhydrides, and lactones, is proposed. The reaction has improved functional group tolerance and represents a unified strategy toward cell-permeant, spontaneously blinking, and photoactivatable SiR fluorescent labels. In tandem with Pd-catalyzed hydroxy- or aminocarbonylation, it serves a streamlined synthetic pathway to a series of validated live-cell-compatible fluorescent dyes.

A general, highly efficient and facile synthesis of biocompatible rhodamine dyes and probes for live-cell multicolor nanoscopy

“…Xanthones with methoxy and allyl amino substituents (K17- With the key intermediates K2-K21 in hand, we explored the scope of the developed 4carboxyrhodamine synthesis method (Scheme 1, B). Classical oxygen, carbon or silicon bridged rhodamines (2-4) were obtained in significantly fewer synthetic steps and 72-90% yields, which is 3-7 times higher compared to previously published synthetic procedures 22,23 (Scheme 1, B). In addition, the synthetic method was found to be compatible with ketones possessing amino groups fused to the aromatic ring (Figure S1, K5-K19), providing compounds 5-9 in 12-77% yields.…”

“…Unsymmetrical ketones K10-K16 showed a good solubility in THF resulting in usual high 55-71% yields for compounds 10-16. In addition, rhodamines possessing primary (22) or secondary amino (23)(24) substituents were obtained via palladium catalyzed allyl group cleavage of the compounds with allyl amino substituents 17-19. Similarly, rhodol (25) or carbofluorescein (26) were obtained from methoxy protected intermediates 20-21 after BBr3 mediated demethylation (Scheme 1, B).…”

“…The multistep synthetic path resulted in relatively low total yield of 13-21% and limited structural diversity (Figure 1). Recently, Butkevich A. N. proposed an alternative synthetic strategy relying on nucleophilic addition of bis-aryllanthanum species to 3-bromophtalic anhydride, followed by palladium catalyzed carbonylative hydroxylation resulting in a total 24-45% yield 23 (Figure 1). While this method did provide 4-carboxy rhodamines in less steps and in higher total yield, we found that many starting compounds, especially unsymmetrical dibromides, are challenging or even not possible to obtain.…”

A long-wavelength xanthene dye for photoacoustic imaging

“…The addition of lanthanum(III) salt to further activate the carbamoyl group improved the overall yield to 33% (Figure 4). 25 KeJuR shows slightly red-shifted absorbance maximum, and blue-shifted emission maximum compared to KeTMR under the same solvent conditions (Figure 5, Table S3). In aqueous solution (PBS, pH 7.2, 0.5% DMSO), KeJuR has an absorbance maximum at 861 nm (ε = 21000 M -1 cm -1 , FWHM = 2080 cm -1 ) and a broad emission at 988 nm (FWHM = 1743 cm -1 ).…”

Radiolabeled Silicon-Rhodamines as Bimodal PET/SPECT-NIR Imaging Agents

“…The new class of fluorophores are named silicon-rhodamines (SiRs) with absorption and emission properties at nearly 650 nanometers. So far, several synthesis methods are exhaustively reported for SiRs [42,[44][45][46][47][48][49][50]. Among other fluorescent dyes, SiRs exhibit biocompatible characteristics: enhanced photostability and high quantum yields, water solubility, reduced autofluorescence and the ability to be simply coupled to biological targeting vectors [41][42][43][44]46].…”