Asymmetric Xanthene with Noncovalent Conformation Locks to Attain High Fluorescence >1500 nm

Fluorescence imaging in the NIR-IIb window (1500-1700 nm) enables unparalleled tissue penetration and contrast, yet efficient organic fluorophores >1500 nm remain extremely scarce due to intrinsic trade-offs between emission wavelength and brightness in symmetric molecular designs. To date, molecular scaffolds predominantly adopt either symmetric planar or twisted frameworks, which can individually optimize the long emission wavelength (λem) or high quantum yield (ϕ) but fail to overcome this fundamental optical trade-off simultaneously. In this study, we propose a rational asymmetric design that integrates planar ACQ units with twisted AIE rotors within a single molecular scaffold, uniting the complementary advantages of long λem, a high molar extinction coefficient (ε), and elevated ϕ. We further introduce the concept of intermolecular noncovalent conformational locks (NoCLs) that can precisely tune the photophysical properties within nanoparticles. To validate this concept, we design and synthesize a systematic library of asymmetric dyes (T-X-J, T-X-BJ, J-X-BJ, and T-Si-BJ) by combining heteroatom-substituted xanthene cores (O, Si) with structurally diverse electron-donating groups (T, J, BJ), alongside symmetric analogues (T-X-T, J-X-J, BJ-X-BJ, T-Si-T, and BJ-Si-BJ) as controls. Embedding these dyes into a heteroatom-rich polymer matrix (Pttc-TTQ) establishes intermolecular noncovalent conformational locks (C-H···π and C-H···O) for enabling precise regulation of dihedral angles and significantly enhancing ϕ in nanoparticles. Notably, T-Si-BJ exhibits emission >1500 nm in CH2Cl2, representing the first asymmetric organic dye with emission maxima in the NIR-IIb window, and demonstrates the brightest (14.1 M-1 cm-1) nanoparticles with emission maxima at 1320 nm and tail signal extending into the NIR-IIb region among the reported optical trade-off fluorophores in H2O (Scheme 1). T-Si-BJ was further prepared as polymer dots (Pdots) for high-contrast, deep-tissue vascular imaging and AI-assisted resolution of hindlimb vasculature. This study provides a synthetically versatile and structurally diverse platform for NIR-IIb fluorophores, demonstrating that asymmetric donor-acceptor-donor scaffolds coupled with polymer-mediated geometry control can simultaneously optimize the emission wavelength and brightness.