Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

Abstract

The acid-catalyzed reaction of benzo[e(g)] derivatives of 2,3,3-trimethylindolenines with o-chloranil leads to new 2-(benzo[e(g)]indolin-2-yl)-5,6,7-trichloro-1,3-tropolones and 2-(benzo[e(g)]indolin-2-yl)-4,5,6,7-tetrachloro-1,3-tropolones. Based on the results of PBE0/6-311+G(d,p) calculations, the structural and energetic characteristics of the tautomeric forms of the obtained 1,3-tropolones were determined. The structure of 2-(3,3-dimethyl-3H-benzo[g]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone was determined by X-ray diffraction analysis. The compounds obtained are capable of switching emission at 420-440 nm and 476-530 nm upon successive exposure to CN^- and Hg²⁺ ions in an acetonitrile solution. 2-(1,1-Dimethyl-1H-benzo[e]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone exhibited high in vitro cytotoxic activity against A431 skin cancer and H1299 lung cancer cell lines.

Keywords: 1,3-tropolones; X-ray diffraction; cytotoxic activity; fluorescence; o-chloranil; quantum chemical DFT calculations.

Scheme 1

Synthesis of 2-hetaryl-substituted 1,3-tropolones 1.

Scheme 2

Synthesis of 1,3-tropolones 7a,b and 8a,b. Reagents and conditions: method A: dioxane, reflux; method B: AcOH, 40–50 °C.

Figure 1

Structural characteristics of (NH) and (OH) tautomeric forms of compounds 7 and 8 in the gas phase according to PBE0/6-311+G(d,p) calculations. Bond lengths are given in Ångstrom.

Figure 2

Scheme of HMBC correlations of compound 7a in DMSO-d₆.

Figure 3

Molecular structure of 2-(3,3-dimethyl-3H-benzo[g]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone (7b).

Figure 4

Result of matching structures of 7b (solid lines) and 2-(3,3-dimethylindolin-2-yl)-5,6,7-trichloro-1,3-tropolone (dashed lines) at the positions of N(1), C(2), and C(9) atoms.

Figure 5

Absorption and emission spectra of compound 8b in acetonitrile before (1,1’) (c 2.5 × 10⁻⁵ mol L^–1) and after the addition of CN⁻ (2,2’) and F⁻ (3,3’) ions (c 5.0 × 10⁻⁵ mol L⁻¹).

Scheme 3

Possible binding mode of 7 and 8 with CN⁻ and F⁻.

Figure 6

Dose–response curves for H1299 and A431 cells treated with compound 7a for 24 h. *Significant difference compared to control samples, p < 0.05.