Deciphering the Structure–Property Relations in Substituted Heptamethine Cyanines

Abstract

Heptamethine cyanines (Cy7) are fluorophores essential for modern bioimaging techniques and chemistry. Here, we systematically evaluated the photochemical and photophysical properties of a library of Cy7 derivatives containing diverse substituents in different positions of the heptamethine chain. A single substitution allows modulation of their absorption maxima in the range of 693–805 nm and photophysical properties, such as quantum yields of singlet-oxygen formation, decomposition, and fluorescence or affinity to singlet oxygen, within 2–3 orders of magnitude. The same substituent in different positions of the chain often exhibits distinctly contradictory effects, demonstrating that both the type and position of the substituent are pivotal for the design of Cy7-based applications. The combination of experimental results with quantum-chemical calculations provides insights into the structure–property relationship, the elucidation of which will accelerate the development of cyanines with properties tailored for specific applications, such as fluorescent probes and sensors, photouncaging, photodynamic therapy, or singlet-oxygen detection.

Cyanine‐Flavonol Hybrids for Near‐Infrared Light‐Activated Delivery of Carbon Monoxide

“…In addition, such a system exhibits high customization potential for further applications owing to the presence of several versatile structural elements. The N ‐substituents of the indolenine heterocycles can be used to tune its solubility in aqueous media or for bioconjugation of enzyme ligands and antibodies, whereas the C4′ position of the heptamethine chain can be used to tune absorption spectra or photostability, or to attach targeting residues . The phenyl substituent of the flavonol moiety is introduced at a late stage of the synthesis, which allows for the installation of additional substituents.…”

Near-infrared dyes for two-photon absorption in the short-wavelength infrared: strategies towards optical power limiting

“…dipolar) structures, including the solvent polarity, 113,114 ionpairing effects [115][116][117][118][119] or substitution of electron-donating moieties at the centre of the polymethine chain. [120][121][122] The design of polymethines is a foolproof strategy to reach NIR absorption with strong extinction coefficients, thus the chemistry and optical properties of polymethines has thrilled scientists for decades. 106,123 Polymethine structures are ubiquitous in the design of red to NIR dyes, as exemplified with the famous Indocyanine Green 31, an FDA-approved cationic heptamethine which features a strong absorption in the NIR, with molar extinction coefficient εmax ~ 194000 M -1 cm -1 (Figure 16).…”

Prevalent Bioimaging Scaffolds: Synthesis, Photophysical Properties and Applications

“…Furthermore, significant bathochromic shifts of absorption and emission maxima are observed with EWGs, whereas EDGs cause hypsochromic shifts (i. e., to shorter wavelengths) but largely preserve or even enhance fluorescence quantum yields. [80,84] Interestingly, the effects of EWGs and EDGs on fluorescence quantum yield as well as absorption and emission maxima are inverted when these substituents are placed one position further in the cyanine chain. [73,80] It should also be noticed that many cyanine derivatives exhibit very small Stokes shifts (e. g., < 25 nm).…”

“…[80,84] Interestingly, the effects of EWGs and EDGs on fluorescence quantum yield as well as absorption and emission maxima are inverted when these substituents are placed one position further in the cyanine chain. [73,80] It should also be noticed that many cyanine derivatives exhibit very small Stokes shifts (e. g., < 25 nm). This problem can successfully be overcome in cyclohexene-bridged heptamethine derivatives by introducing an aminoalkyl substituent in the R 4' -position that facilitates intramolecular charge transfer and thus leads to redshifted emission.…”

“…A) Structure‐property relationship of indocyanines in terms of water solubility, photostability, and possible positions for further functionalization. B) Selected examples show influence of chain length on photophysical properties in methanol; [66,69b,71b,80] ϵ unit: M −1 cm −1 . C) Selected example for the use of cyanines as bioimaging fluorophores.…”