Developing new red-shifted optical tools is of great interest due to the increased distance light can travel through tissue and the low extinction coefficients of naturally occurring substances in the near infrared region. More recently, the near infrared (NIR) II window (1000 – 1700 nm) has emerged as an optimal region for in vivo fluorescence imaging. While the NIR-II demonstrates great promise, the toolbox of bright fluorophores for this region needs expansion. Cyanine dyes are a prime scaffold for the development of NIR-II probes, as they are known for their ability to be predictably red-shifted by increasing the length of the polymethine chain. Those with chain lengths beyond seven carbons, however, often have decreased fluorescence quantum yields (ΦF) and stability. We hypothesized that the addition of electron donating groups to a flavylium heterocycle would impart red-shifted absorbance and emission properties without diminished ΦF or photostability. Herein, we present a panel of cyanine dyes with dimethylamino flavylium heterocycles displaying bright emission in the NIR-I and NIR-II. The syntheses, photophysics, and photostability of four cyanine dyes with 1, 3, 5, and 7 methines from 7-N,N-dimethylamino-4-methyl-flavylium perchlorate are described. The 1-dimethylamino cyanine is achieved through an oxygen-dependent mechanism with loss of formaldehyde, while the remainder of the series is accessed by the introduction of the activated heterocycle to an aldehyde or bis-aldehyde equivalent. The absorption and photoluminescence spectra of the dimethylamino flavylium cyanines span from the long wavelength end of the visible to the NIR-II, with emissions from 684 – 1061 nm. Notably, the 7-dimethylamino flavylium cyanine dye is 13x brighter than IR 26 and at least 2x brighter than IR 1061, positioning it as an ideal probe for in vivo imaging.

Panel of dimethylamino flavylium cyanine dyes spanning the NIR-I and NIR-II regions

253rd National Meeting (2017)

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