Table 1.
Binding affinities (log Ks); thermal denaturation effects and proposed binding modes of chosen phenanthridine and phenanthridinium derivatives with natural and synthetic polynucleotides: ds-DNA and ds-RNA.
| Ligand | pH | log Ksa(∆Tmb) / Binding modec | |||||
| ctDNA | dA–dT | dAdT–dAdT | rA–rU | dG–dC | rG–rC | ||
| 1 | 7.5 | 5.6d ,(–) / IC | – | – | – | – | |
| 4 | 5 | –, (20.6) / MG | 7.4, (29.5) / MG | –, (25.0) / MG | 7.4, (35.4e/–1.8) / IC | 6.6, (–) / IC | – |
| 7 | –, (5.6) / MG | 6.5, (9.8) / MG | –, (10.3) / MG | 5.7, (5.0) / NSA | 5.8, (–) / IC | ||
|
5 R = (CH2)4 |
6.2 | – | 5.2, (–f/45.3) / IC + ESI | – | 5.7, (–f/21.5) / IC + ESI | – | 6.5,(–) / IC + ESI |
|
5 R = (CH2)6 |
6.2 | – | 5.7, (–f/42.5) / IC, NSA | – | 8.0, (–f/20.7) / IC, NSA | – | 6.3,(–) / IC, NSA |
|
6 R = (CH2)6 |
6.2 | – | –g, (25.6) / GB | – | 5.3, (3.9) / GB | – | 6.5,(–) / GB |
| 7 | 6.2 | – | 6.0, (–) / GB, ESI | – | –g ,(–) / GB, ESI | – | 5.7,(–) / GB, ESI |
| 8 | 5 | 5.8, (25.8) / IC, ESI | –, (11.1) / IC, ESI | – | 5.1, (9.5) / IC, ESI | – | 5.8,(–) / IC, ESI |
| 7 | 6.6, (5.7) / IC | –, (12.1) / IC | – | 6.2, (5.2) / IC | – | 5.2, (–) / IC | |
|
9 (n = 2) |
5 | 5.5, (2f/22.6) / MG | 5.8 (3.3f/27.7) / MG | – | 5.2 (0e/1.1) / NSA | – | 6.6h, (–) / NSA |
|
9 (n = 6) |
5 | 6.3, (2.9) / MG | 5.7, (3.4) / MG | – | 5.2 (0e/0.9) / NSA | – | 6.8h, (–) / NSA |
|
9 (n = 9) |
5 | 6.0, (7.7) / IC | 6.1, (3.8) / IC | – | 6.0, (10.6e/–2.0) / IC | – | 5.0, (–) / IC |
|
10 R = Gly |
5 | 5.,5 (8.1) / IC | – | – | – | – | – |
| 7 | 4.7, (–) / IC | – | – | – | – | – | |
|
11 R = Gly |
5 | 6.9, (16.5) / IC | – | – | – | – | – |
| 7 | 6.0, (–) / IC | – | – | – | – | – | |
|
14 (bis-uracil analogue) |
5 | – | 4.6, (18.0) / PIC, HB | 5.1 / PIC | 5.0, (2e/12.4) / PIC | – | – |
|
14 (bis-adenine analogue) |
5 | – | 5.0, (6.0) / MG | 5.3, (1.1) / MG | 5.1, (1.5e/0.3) / GB | – | – |
| 16 | 5.5 | – | –, (7.7i) / IC, MB | 6, (7.4i ) / IC, MB | 9.3, (34.3 i) / IC, MB | – | – |
| 19 | 5 | 6.4, (19.6) / TIC | 5.4, (10f/20) / TIC, MB | 6.1 / TIC | 6.5, (35.6) / TIC | 6.1, (–) / TIC | 6.8, (–) / TIC |
| 7 | –, (19.4) / TIC | 5.6, (11.3f/21.6) / TIC, MB | 5.9 / TIC | 6.5, (25.5) / TIC | 6.9j, (–) / TIC | 6.1, (–) / TIC | |
| 20 | 6.5 | – | – | – | 5.9, (19.0k) / IC | – | 5.5,(–) / IC |
aBinding constants calculated from titration data by processing according to the Scatchard equation. br = [compound]/[polynucleotide] = 0.2 if not stated otherwise. cIC = intercalation; MG = minor groove; NSA = non-specific agglomeration; GB = undefined groove binding; BIC = bis-intercalation; ESI = electrostatic interaction; HB = hydrogen bonding; PIC = partial intercalation; MB = mixed binding mode; TIC = threading intercalation. dBinding constants calculated from ethidium bromide displacement experiments [52]. eBiphasic thermal denaturation transitions at pH 5 due to different RNA forms [62]. fBiphasic thermal denaturation transitions due to bMB, values for both transitions given when possible. gNot possible to calculate due to systematic deviation of experimental data from best-fitted Scatchard isotherm. hCumulative binding constants for mixed binding mode. ir = [compound]/[polynucleotide] = 0.1. jPolynucleotide is poly(dG–dC)2. kr = [compound]/[polynucleotide] = 0.5.