4-Aza-9(10H)-acridone

Abstract

The crystal packing of the title compound, CI2H8N20, is dominated by hydrogen bonding and 7r-Tr-type interactions along the short axial direction. Each molecule is hydrogen bonded to two adjacent molecules which are part of the same stacked column. The N--H...N hydrogen bonds have an N...N distance of 2.95 A,. CommentThe title compound, (I), has been employed as a reagent in the synthesis of potential DNA intercalative drugs (Denny, Atwell & Cain, 1977). During the attempted crystallization of one such intercalator, small yellow crystals formed which were subsequently shown by Xray crystallography to be those of the title compound.2.14,~ between atoms 09 and H3 (-x, ½+y, 3-z), which results in a deviation for H3 of 0.21 (8)1( from the calculated six-membered ring plane.The replacement of atom C4 in the parent acridone (II) with N4 in the present structure provides an extra potential hydrogen bond. The N--H..-O hydrogen bond of compound (II) is replaced with an N--H...N bond involving N4 in (I). The hydrogen-bond pattern of (II) connects adjacent stacks of molecules extending through the crystal in a direction perpendicular to the 7r-Tr stacking direction. In compound (I), the stacking is also in the short axial direction, but the hydrogen bonding only links two stacked piles of molecules. Each molecule is hydrogen bonded to two adjacent molecules taking part in 7r-Tr stacking interactions such that the chain of hydrogen-bonded molecules extends The majority of the bond lengths in compound (I) (between non-H atoms) are within 3cr of those of the parent 9(10H)-acridone compound, (II) (Potts & Jones, c 1995), and most of the bond angles at the C atoms in the title compound fall in the range 118-120 ° . The angles falling outside this range are those involving atoms C9 and N10, and most of the angles that are part of the 4-aza ring. The bonds to atom N4 in (I) are significantly shorter than those to C4 in (II) and the internal ring angle at N4 is significantly smaller than that at C4. The two outer tings of the 4-aza three-ring system are individually planar, with no ring atoms dev!ating from their calculated planes by more than 0.01 A. The central ring adopts a slight boat-type conformation with atoms C9 and N10 each deviating from the calculated ring plane by 0.036 (4)

Hydration Changes in the Association of Hoechst 33258 with DNA

“…75,76 For Hoechst and Hoechst analogs bound with A/T rich sequences, water is associated with the polar terminal groups -phenol and piperazine. 73,77,78,79 For example, when the phenol has an hydroxyl at the meta position (see Fig. 1 for the p-OH derivative), this OH associates with a network of approximately 30 waters that continues into the major groove.…”

“…1 for the p-OH derivative), this OH associates with a network of approximately 30 waters that continues into the major groove. 79 The higher affinity of meta-OH derivatives of Hoechst suggests that this hydration network provides an enthalpic anchor for the ligand. 74 Femtosecond resolved fluorescence studies indicate the presence of weakly bound waters in the Hoechst-DNA complex, but the contribution to the fluorescence changes from the overall dynamics of the DNA is also being considered.…”