Benz[c,d]indolium-containing Monomethine Cyanine Dyes: Synthesis and Photophysical Properties

Abstract

Asymmetric monomethine cyanines have been extensively used as probes for nucleic acids among other biological systems. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and benz[e]indole adjoining benz[c,d]indol-1-ium, which was found to directly influence their optical and energy profiles. In this study the optical properties vs. structural changes were investigated using nuclear magnetic resonance and computational approaches. The twisted conformation unique to monomethine cyanines was exploited in DNA binding studies where the newly designed sensor displayed an increase in fluorescence when bound in the DNA grooves compared to the unbound form.

Keywords: DFT calculations; DNA grooves; cyanine dye; optical properties; synthesis; unsymmetrical.

Figure 1

Commercially available asymmetric monomethine cyanine dyes.

Scheme 1

Synthesis of Monomethine Dyes.

Figure 2

Absorbance (solid lines) and emission (dashed lines) in methanol/glycerol 9/1 spectra at 20 μM.

Figure 3

Frontier molecular orbitals of 6a constrained in planar (left) and twisted (right) configurations.

Figure 4

HOMO and LUMO orbital analysis of differing heterocycles in the monomethine system; energies (black), HOMO-LUMO gaps (blue).

Figure 5

Experimental and Calculated λ_max values.

Figure 6

¹H-NMR shift of meso-proton in DMSO-d₆ at 25 °C, Calculated EMP on the right.

Figure 7

Dye 6b with fixed torsion angles and planar geometry suggested to bind to the major (left) and minor (right) grooves of dsDNA by computational studies.

Figure 8

Emission spectra of dye 6b (10 μM) in Tris-HCl buffer with and without ct-DNA (excitation wavelength 520 nm).