Giant SRS signal enhancements from near-infrared cumulenes

Electronic pre-resonance stimulated Raman scattering (epr-SRS) microscopy has boosted the sensitivity of vibrational imaging, which was largely relied on xanthene-based palette. Recently, cumulenes have been reported as a new set of Raman imaging probes with distinct vibrational frequencies in the range of 1900–2050 cm⁻¹. Here, we develop near-infrared cumulenes with computational assistance, which expand the structural diversity of epr-SRS probes. With near-infrared absorption, cumulenes exhibit giant SRS signal enhancements, achieving more than 2 orders of magnitude increase over non-resonant cumulene and reaching nearly 1900 times relative intensity versus 5-ethynyl-2'-deoxyuridine (RIE = 1889), which is among the strongest reported for small molecules in the cell-silent Raman window. Furthermore, we demonstrated organelle-specific SRS imaging of near-infrared cumulene in live cells with high biocompatibility. The near-infrared cumulenes provide a new direction for developing epr-SRS imaging probes and show great potential for multiplexed SRS imaging with enhanced sensitivity.