Rational Design of Asymmetric Polymethines to Attain NIR(II) Bioimaging at >1100 nm

Abstract

Organic molecules having emission in the NIR(II) region are emergent and receiving enormous attention. Unfortunately, attaining accountable organic emission intensity around the NIR(II) region is hampered by the dominant internal conversion operated by the energy gap law, where the emission energy gap and the associated internal reorganization energy λ int play key roles. Up to the current stage, the majority of the reported organic NIR(II) emitters belong to those polymethines terminated by two symmetric chromophores. Such a design has proved to have a small λ int that greatly suppresses the internal conversion. However, the imposition of symmetric chromophores is stringent, limiting further development of organic NIR(II) dyes in diversity and versatility. Here, we propose a new concept where as far as the emissive state of the any asymmetric polymethines contains more or less equally transition density between two terminated chromophores, λ int can be as small as that of the symmetric polymethines. To prove the concept, we synthesize a series of new polymethines terminated by xanthen-9-yl-benzoic acid and 2,4-diphenylthiopyrylium derivatives, yielding AJBF1112 and AEBF1119 that reveal emission peak wavelength at 1112 and 1119 nm, respectively. The quantum yield is higher than all synthesized symmetric polymethines of 2,4-diphenylthiopyrylium derivatives (SC1162, 1182(SC1162, , 1185(SC1162, , and 1230) in this study. λ int were calculated to be as small as 6.2 and 7.3 kcal/mol for AJBF1112 and AEBF1119, respectively, proving the concept. AEBF1119 was further prepared as a polymer dot to demonstrate its in vitro specific cellular imaging and in vivo tumor/bone targeting in the NIR(II) region.

Doubly Strapped Zwitterionic NIR‐I and NIR‐II Heptamethine Cyanine Dyes for Bioconjugation and Fluorescence Imaging

“…NIR-II dyes have inherently low fluorescence quantum yields and the measured values in DMSO of 0.10 % for dsZW1015 and 0.11 % for unstrapped isomer 7 (Table 1) are comparable to literature NIR-II dyes in nonpolar organic solvents. [74] In water, NIR-II fluorescence quantum yields are even lower, [51][52][53] but we were pleased to find that the fluorescence quantum yield in PBS for dsZW1015-1 (0.014 %) is more than double the value for unstrapped isomer 7 (0.006 %). There are two likely reasons for the increased brightness.…”

Molecular Design of NIR-II Polymethine Fluorophores for Bioimaging and Biosensing

“…Except for phosphate group modification, elaborate semiconducting polymer dots can also target the bones, attributed to the rapid accumulation and long-term retention of polymer nanoparticles with a small diameter in bone. For example, Chan and co-workers developed a series of semiconducting polymer dots containing NIR-II asymmetric polymethine fluorophores which were applied in in vivo tumor/bone targeting imaging in the NIR-II windows (Figure B) . After injecting Pdots into the live mice with 4T1 tumors, the systemic vascular constructions in the live mouse were clearly visualized under a 1064 nm laser excitation.…”

Engineering Near-Infrared Fluorescent Probes Based on Modulation of Molecular Excited States

“…This is primarily due to the following: (i) Nonradiative transitions including internal conversion (IC) from the S 1 to S 0 are important relaxation pathways that compete with radiative decay (photon emission). Owing to the energy gap law, compared with dyes in the visible region, NIR fluorophores exhibit much faster nonradiative deactivation pathway along with reduced emission intensity (fluorescence quenching), hampering their bioimaging applications. (ii) The extremely low energy electronic transition of NIR fluorophores generally requires an extended conjugated system (such as the polymethine π-electron system).…”