Analogues of 9-oxo-9H-xanthene-4-acetic acid (XAA) bearing small, lipophilic 5-substituents are among the most dose-potent compounds yet reported with the capability of causing hemorrhagic necrosis of implanted colon 38 tumors in mice. To further extend structure-activity relationships among this class of compound, a series of XAA derivatives bearing two small lipophilic groups at various positions have been prepared and evaluated. The 5,6-disubstituted compounds in particular show consistently high levels of both dose potency and activity, suggesting this is the optimal configuration among substituted 9-oxo-9H-xanthene-4-acetic acids. The 5,6- dimethyl and 5-methyl-6-methoxy are the most effective analogues, showing in vivo colon 38 activity comparable to that of FAA at 10-15-fold lower doses and superior activity to FAA at the respective optimal doses, and the former has been selected for detailed evaluation.

The charge/orbital ordering (COO) of the layered mixed-valence manganites (La,Sr)(n+1)Mn(n)O(3n+1) (n = 1 and 2) is examined by first-principles calculations and discussed in comparison with the La(0.5)Ca(0.5)MnO(3) perovskite phase ([Formula: see text]). The results demonstrated that the layered structural features could yield not only visibly weak coupling between Mn-O layers but also various features in the orbital ordering associated with different types of local structural distortions. In both La(0.5)Sr(1.5)MnO(4) (n = 1) and LaSr(2)Mn(2)O(7) (n = 2) phases, the orbital ordering can be chiefly assigned to the d(x(2)-y(2)) orbital, in contrast with the zigzag-type d(z(2)) orbital ordering in the [Formula: see text] perovskite phase. Our theoretical analysis shows that a variety of essential factors, including the local structural distortions of the MnO(6) octahedra, the on-site Coulomb interaction, and magnetic interaction, have to be properly considered in order to achieve acceptable COO ground states for the layered variants in (La,Sr)(n+1)Mn(n)O(3n+1).