Hamilton Langhoff (rulephone46)

(+)-Digoxin (1) is a well-known cardiac glycoside long used to treat congestive heart failure and found more recently to show anticancer activity. Several known cardenolides (2-5) and two new analogues, (+)-8(9)-β-anhydrodigoxigenin (6) and (+)-17-epi-20,22-dihydro-21α-hydroxydigoxin (7), were synthesized from 1 and evaluated for their cytotoxicity toward a small panel of human cancer cell lines. A preliminary structure-activity relationship investigation conducted indicated that the C-12 and C-14 hydroxy groups and the C-17 unsaturated lactone unit are important for 1 to mediate its cytotoxicity toward human cancer cells, but the C-3 glycosyl residue seems to be less critical for such an effect. Indolelactic acid order Molecular docking profiles showed that the cytotoxic 1 and the noncytotoxic derivative 7 bind differentially to Na+/K+-ATPase. The HO-12β, HO-14β, and HO-3'aα hydroxy groups of (+)-digoxin (1) may form hydrogen bonds with the side-chains of Asp121 and Asn122, Thr797, and Arg880 of Na+/K+-ATPase, respectively, but the altered lactone unit of 7 results in a rotation of its steroid core, which depotentiates the binding between this compound and Na+/K+-ATPase. Thus, 1 was found to inhibit Na+/K+-ATPase, but 7 did not. In addition, the cytotoxic 1 did not affect glucose uptake in human cancer cells, indicating that this cardiac glycoside mediates its cytotoxicity by targeting Na+/K+-ATPase but not by interacting with glucose transporters.In its crystalline state, a dinuclear Cu-based metallocycle discriminates between the three isomers of xylene with liquid-phase selectivity in the order p-xylene ≫ m-xylene ≫ o-xylene. This selectivity holds over a wide concentration range, with p-xylene concentrations as low as 5%. Single-crystal X-ray diffraction and gas chromatography further indicate that the metallocyclic host extracts trace amounts of p-xylene from commercially pure o-xylene (≥99%); using NMR spectroscopy, we show that the metallocycle exhibits exclusive selectivity for p-xylene. Crystallographic studies show that the selectivity is based on the size and shape of the guest in combination with the flexibility of the host.The unsymmetrical coordination of gold(I) by 2,2'-bipyridine (bipy) in some planar, three-coordinate cations has been examined by crystallographic and computational studies. The salts [(Ph3P)Au(bipy)]XF6 (X = P, As, Sb) form an isomorphic series in which the differences in Au-N distances range from 0.241(2) to 0.146(2) Å. A second polymorph of [(Ph3P)Au(bipy)]AsF6 has also been found. Both polymorphs exhibit similar structures. The salts [(Et3P)Au(bipy)]XF6 (X = P, As, Sb) form a second isostructural series. In this series the unsymmetrical coordination of the bipy ligand is maintained, but the gold ions are disordered over two unequally populated positions that produce very similar overall structures for the cations. Although many planar, three-coordinate gold(I) complexes are strongly luminescent, the salts [(R3P)Au(bipy)]XF6 (R = Ph or Et; X = P, As, Sb) are not luminescent as solids or in solution. Computational studies revealed that a fully symmetrical structure for [(Et3P)Au(bipy)]+ is 7 kJ/mol higher in energy than the observed unsymmetrical structure and is best described as a transition state between the two limiting unsymmetrical geometries. The Au-N bonding has been examined by natural resonance theory (NRT) calculations using the "12 electron rule". The dominant Lewis structure is one with five lone pairs on Au and one bond to the P atom, which results in a saturated (12 electron) gold center and thereby inhibits the formation of any classical, 2 e- bonds between the gold and either of the bipy nitrogen atoms. The nitrogen atoms may instead donate a lone pair into an empty Au-P antibonding orbital, resulting in a three-center, four-electron (3c/4e) P-Au-N bond. The binuclear complex, [μ2-bipy(AuPPh3)2](PF6)2, has also been prepared and shown to have an aurophillic interaction be