Citation: Zhimin Wu, Syed Ali Abbas Abedi, Rongrong Huang, Lili Lin, Xiaogang Liu. Barrierless conical intersection as a photophysical design principle for photoacoustic and photothermal contrast agents[J]. Chinese Chemical Letters, ;2026, 37(12): 112315. doi: 10.1016/j.cclet.2025.112315 shu

Barrierless conical intersection as a photophysical design principle for photoacoustic and photothermal contrast agents

Zhimin Wu ^{a, b} ,
Syed Ali Abbas Abedi ^{b, c} ,
Rongrong Huang ^{b, c} ,
Lili Lin ^{a, *,} ,
Xiaogang Liu ^{c, *,}

a.
Shandong Key Laboratory of Medical Physics and Image Processing & Shandong Provincial Engineering and Technical Center of Light Manipulations, School of Physics and Electronics, Shandong Normal University, Ji’nan 250358, China
b.
Fluorescence Research Group, Singapore University of Technology and Design, Singapore 487372, Singapore
c.
School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, Singapore 637371, Singapore

linll@sdnu.edu.cn

xiaogang.liu@ntu.edu.sg

Received Date: 30 August 2025
Revised Date: 22 December 2025
Accepted Date: 22 December 2025
Available Online: 23 December 2025

Figures(4)

Photoacoustic imaging (PAI) and photothermal therapy (PTT) require contrast agents that combine strong near-infrared (NIR) absorption, high photothermal conversion efficiency, and exceptional photostability. Despite the proliferation of PAI/PTT contrast agents, most have been developed empirically, with limited mechanistic understanding guiding design. Here, we introduce the NIR–barrierless access to conical-intersection thermocycling (NIR-BLACIT) model as a guiding photophysical framework for high-performance PAI/PTT agents. In this model, strong NIR absorption couples to ultrafast, barrierless transitions to conical intersection (CI) formation and rapid nonradiative decay, minimizing excited-state lifetimes and maximizing heat release. Using combined computational and experimental analysis, we identify structural determinants of NIR-BLACIT behavior in positive examples (T-AzHCy series and QC-1) and negative controls (indocyanine green (ICG) and E-AzCy7). We demonstrate that backbone-integrated azo linkages enhance the TICT propensity, lower rotational barriers, and increase the driving energies toward CI access. Guided by this principle, we designed NN7Cy and NNBDP, two novel azo-cyanine derivatives, that achieve strong NIR absorption, high oscillator strengths, and (nearly) barrierless CI access. This strategy extends beyond azo linkages; other low-energy-gap systems, such as BAF dyes, also meet the NIR-BLACIT criteria. Our findings establish NIR-BLACIT as a predictive and generalizable design principle for next-generation optoacoustic and photothermal agents.
- Photoacoustic imaging (PAI),
- Photothermal therapy (PTT),
- Near-infrared (NIR) dyes,
- NIR-BLACIT model,
- Conical intersection (CI),
- Twisted intramolecular charge transfer (TICT),
- Azo-cyanine dyes
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