Visibly emissive and responsive extended 6-aza-uridines

Abstract

A family of extended 5-modified-6-aza-uridines was obtained via Suzuki coupling reactions with a common brominated precursor. Extending the conjugated-6-aza-uridines with substituted aryl rings increases the push-pull interactions yielding enhanced bathochromic shifts and solvatochromism compared to the parent nucleosides. For example, the methoxy substituted derivative 1d displays λmax abs around 375 nm, with visible emission maxima at 486 nm (Φ = 0.74) and 525 nm (Φ = 0.02) in dioxane and water, respectively.

Figure 1

Evolution of the design elements leading to visibly emitting nucleosides.

Scheme 1. Syntheses of Nucleosides 1a–f

See Supporting Information for synthetic procedures and analytical data.

Figure 2

(a, b) X-ray crystal structures of 4 and 1d, respectively; (c) overlay of X-ray the crystal structure of 1c (orange) with uridine (blue); overlaying the ribose rings shows minimal impact on the sugar pucker (rmsd = 0.04 Å); (d) schematic top view illustrating the relative conformation of the nucleobases in uridine (blue) and 1c (orange).

Figure 3

Molar absorptivity (dotted line) and emission (solid line) spectra for 1a (purple), 1b (blue), 1c (green), 1d (dark green), 1e (orange), and 1f (red) in dioxane (a) and water (b). Emission was recorded after excitation at λ_abs max for each derivative (Table 1). Calculated Stokes shift in kcal/mol for spectra taken in dioxane are correlated with Hammett σ_para (c) and Hammett σ⁺_para (d).

Figure 4

(a,b) Assessing the effect of solvent polarity on absorption (dotted line) and emission (solid line), in dioxane (bold black line), methanol (bold red line), and their mixtures (black lines) for 1c (6.7 × 10^–6 M) and 1d (2.0 × 10^–6 M); respectively. (c, d) Correlating Stokes shift vs E_T(30) values obtained from dioxane–methanol mixtures for 1c (90%:10% → 10%:90%; slope: 0.36 and R² = 0.95) and 1d (90%:10% → 40%:60%; slope: 0.35 and R² = 0.98). Experimental errors are smaller than the data symbols; see SI for enlarged correlations (Figures S8.1 and S8.2).