Rational design of next-generation hemicyanine chromophores for multispectral optoacoustic tomography
TL;DR
This work applies a structure–property design strategy to develop next-generation hemicyanine scaffolds for deep-tissue PA imaging and introduces targeted modifications to red-shift absorption and enhance heat generation.
Abstract
Near-infrared (NIR) small-molecule dyes are promising contrast agents because NIR excitation enables deeper tissue penetration and lower background. Hemicyanine dyes offer a tunable donorπ–acceptor scaffold, but many show limited NIR absorption and inefficient nonradiative decay, reducing photoacoustic (PA) output (Gardner et al. 2021). Here, we apply a structure–property design strategy to develop next-generation hemicyanine scaffolds for deep-tissue PA imaging (Ding et al. 2023; MacCuaig et al. 2024). Starting from a xanthene-like hemicyanine platform featuring an electron-rich phenolic donor, we introduce targeted modifications to red-shift absorption and enhance heat generation (Brøndsted and Stains 2024). We investigate difluoro substitution on the cyclohexene/ polymethine bridge to tune electron distribution and stability, and O→S replacement to access thioxanthene analogs expected to further bathochromically shift absorption and suppress fluorescence (Brøndsted and Stains 2024). A modular synthesis yields a focused dye library with systematic donor/acceptor/bridge variation. Structures are confirmed by 1 H NMR, optical properties by UV–Vis and fluorescence spectroscopy, and PA performance by multispectral optoacoustic