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Figure 1.

Compounds under investigation.

A) Schematic representation of AI-III-52 (left) and MJ-238 (right) IQN derivatives for which the X-ray structures of the Top1-DNA-drug complex are available (PDB-ID 1TL8 and 1SC7 for AI-III-52 and MJ-238 respectively). The compounds have the same relative orientation observed in the X-ray structure B) Chemical structure of the investigated indenoisoquinolines.

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Figure 1 Expand

Figure 2.

NSC314622 in aprotic solvents.

UV/Vis absorption spectra of the indenoisoquinoline NSC314622 in CCl4 (dot-dashed line) and in DMSO (full line). The wavelength of the peaks are annotated. The inset represents a close-up view of the absorption in the 300–400 nm interval.

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Figure 2 Expand

Figure 3.

Derivative compounds in aprotic solvents.

UV/Vis absorption spectra of indenoisoquinoline derivatives NSC725776 (top) and NSC724998 (bottom) recorded in CCl4 (dot-dashed lines) and in DMSO (full lines).

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Figure 3 Expand

Figure 4.

TD-DFT vs. UV-Vis for NSC314622.

Comparison of UV/Vis absorption spectra of the indenoisoquinoline NSC314622 in CCl4 (red line) and in DMSO (black line) with TD-DFT calculated transitions. The inset represents a close-up view of the absorption in the 300–400 nm interval. The TD-DFT transitions (dashed vertical lines), calculated in CCl4 and DMSO using C-PCM, are reported as red and black circles respectively and the wavelength of the transitions are annotated. The OS are all rescaled by a factor of 0.25 in order to permit a direct visual comparison with experimental spectra.

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Figure 4 Expand

Figure 5.

TD-DFT vs. UV-Vis for derivative compounds.

Comparison UV/Vis absorption spectra of indenoisoquinoline derivatives NSC725776 (top) and NSC724998 (bottom) in CCl4 (red lines) and in DMSO (black lines) with TD-DFT calculated transitions. The TD-DFT transitions (dashed vertical lines), calculated in CCl4 and DMSO using C-PCM, are reported as red and black circles respectively and the wavelength of the transitions are annotated. The OS are all rescaled by a factor of 0.25 in order to permit a direct visual comparison with experimental spectra.

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Figure 5 Expand

Table 1.

NSC314622 in aprotic solvents.

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Table 1 Expand

Table 2.

NSC725776 in aprotic solvents.

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Table 2 Expand

Table 3.

NSC724998 in aprotic solvents.

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Figure 6.

Localization of MOs involved in TD-DFT transitions.

A–B) Isodensity surface, enclosing values between −0.05 to +0.05 (red negative values, blue positive values), of the difference of NSC314622 MOs involved in transition at 290 nm (T1) and at 270 nm (T2) (see text for details). C–D) Isodensity surface of the change of T1 and T2 when passing from CCl4 to DMSO. The values of T1 and T2 change range from −0.19 to +0.05. In the Figure are reported the surfaces enclosing the region where the values is between −0.01 and +0.01, in red negative values and blue positive values.

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Figure 6 Expand

Figure 7.

UV-Vis in water.

Absorption spectra of NSC314622 (full line), NSC725775 (dashed line) and NSC724998 (dashed dotted line) (10–5 M) recorded in PBS at pH 7.2.

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Table 4.

NSC314622 in Water (1).

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Table 4 Expand

Figure 8.

IQN in equilibrium with its zwitterionic forms.

A) polarization of the lactam group B) polarization of the carbonyl group of the indeno moiety.

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Table 5.

NSC314622 in Water (2).

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Table 5 Expand