Synthesis of N,N‐Dialkylamino‐nor‐Dihydroxanthene‐Hemicyanine Fused Near‐Infrared Fluorophores and Their First Water‐Soluble and/or Bioconjugatable Analogues

Abstract

The effective synthesis of extended conjugated N,N-dialkylamino-nor-dihydroxanthene-based fluorophores is described from diversely functionalized salicylic aldehydes. The access to these original fluorescent derivatives proceeded in two steps through a one-pot construction of the unusual nor-dihydroxanthene (nor-DHX) scaffold followed by a diversification step providing a wide variety of nor-DHX-hemicyanine fused dyes emitting in the range of 730-790 nm. The versatility of our approach has enabled a further extension to the late-stage introduction of negatively/positively charged polar groups onto their terminal nitrogen heterocyclic subunit, thereby giving access to the first water-soluble and/or bioconjugatable members of this emerging class of NIR fluorophores. Our water-solubilizing method is easily implementable, and the nor-DHX-hemicyanine skeleton maintains satisfying fluorescence quantum yields (5-20 %) under physiological conditions. Finally, the bioconjugation ability of fluorescent derivatives bearing a free carboxylic acid was demonstrated through the covalent labeling of a model protein, namely, bovine serum albumin.

Activity-based NIR fluorescent probes based on the versatile hemicyanine scaffold: design strategy, biomedical applications, and outlook

“…2E, an aldehyde was first obtained as a key intermediate via a “one-pot” reaction of two commercially available raw materials, which could be used for condensation reactions with various Fischer bases to open the door for the high-throughput preparation of NIR fluorophores. 87–89…”

A Fluorescent Probe with a Double Reaction Site for Hydrazine Detection in Water Samples

“…[16,17] As a convenient detection tool, the fluorescence probe was widely used in a variety of substances. [18][19][20][21] The fluorescent probe used to detect hydrazine is mainly based on aldehyde condensation, [22,23] hydrogen bonding, [24,25] conversion of malonitrile to imine, [26] ester group deprotection, [27][28][29][30][31] nucleophilic addition cyclization. [32,33] In our previous works, there are three fluorescent probes had developed for hydrazine detection.…”

A Natural Light Visible Colorimetric Responses Fluorescent Probe for Hydrazine Detection

“…A fluorescent probe is an analytical tool, which meets this requirement. [17][18][19][20] N2H4 fluorescent probes were developed based on hydrogen bonding, 21,22 aldehyde condensation, 23,24 ester group deprotection, [23][24][25][26][27] and conversion of malonitrile to imine. 28 In our previous work, there were two fluorescent probes we had developed for hydrazine detection.…”