Photophysical Tuning of Shortwave Infrared Flavylium Heptamethine Dyes via Substituent Placement

Abstract

Optical imaging in the shortwave infrared region (SWIR, 1000-2000 nm) provides high-resolution images in complex systems. Here we explore substituent placement on dimethylamino flavylium polymethine dyes, a class of SWIR fluorophores. We find that the position of the substituent significantly affects the λ_max and fluorescence quantum yield. Quantum-mechanical calculations suggest that steric clashes control the extent of π-conjugation. These insights provide design principles for the development of fluorophores for enhanced SWIR imaging.

Figure 1.

Systematic exploration of structural modifications of Flav7 (1). Previous work on derivatives at the seven-position, includeing methoxy and diphenylamine with a shift in λ_max. Current work on exploring dimethylamino substitutions at different positions (five-, six-, and eight- on the heterocycle (3–5).

Figure 2.

Normalized (A) absorbance and (B) emission of the flavylium polymethines discussed. (C) Photophysical data of unsubstituted (IR-27, 2) and dimethylamino substituted heptamethines (1, 3–5). All samples were taken in dichloromethane. ^aData was previously reported. ^bPhotophysical data was taken with crude sample.

Figure 3.

(A) Represented by Flav7; torsion angles are defined by α (V₁ to V_2, red to blue) and β (V₃ to V_2, green to blue) using the normal of the plane of the polymethine (V₁), flavylium (V₂) and substituent (V₃). (B) Table of α and β angles for Flav7 dyes. (C,D) Heterocycle structures of (C) 5-Flav7 and (D) 8-Flav7 at the S₀ state, optimized with M06–2X/6–31+G(d,p). The polymethine chain is omitted for clarity. The dihedral angles at the substituted positions of the flavylium heterocycles are highlighted in green to show the rotation of the NMe₂ group in 5-Flav7 and 8-Flav7.

Figure 4.

(A) HOMOs and LUMOs of Flav7 (1) and (5,6 and 8)-Flav7 (3–5) at M06–2X/6–31+G(d,p) level of theory. Polymethine chains were omitted for clarity. Explicit frontier molecular orbital information can be found in the SI. (B) Table of calculated λ_max,calc,abs (nm) determined by theoretical HOMO-LUMO gap (eV). Δ is the difference between experimental and calculated λ_max,abs.

Figure 5.

(A) Structures of azetidine-substituted flavylium heptamethines (12, 13). (B) Structure of 6- and 7-aminocoumarins (10, 11). (C) Φ_F of flavylium heptamethine and coumarin dyes in dichloromethane and decanol, respectively. ^aPreviously reported by our group. ^bPreviously reported. (D) Fold change of Φ_F between six- and seven-substituted flavylium heptamethine or coumarin fluorophore.

Scheme 1.

Synthetic scheme for dimethylamino flavylium heptamethines 3–5 with substituents at the five-, six-, and eight- positions. (a) RuPhos Pd G3 (0.10 eq), RuPhos (0.10 eq), Cs₂Co_3, HNMe₂, toluene, 110 °C, 24 h. for 6a and 6b. (b) SPhos Pd G3 (0.10 eq), SPhos (0.10 eq) Cs₂Co_3, HNMe₂, toluene, 110 °C, 24 h. for 6c. (c) MeMgBr (1.4M), THF, r.t. d) 2,6-di-tert-butyl-4methyl-pyridine, n-butanol/toluene or acetic anhydride, 100 °C, 15 min. Refer to SI for further experimental details.