Dimer

About: Dimer is a research topic. Over the lifetime, 18291 publications have been published within this topic receiving 433645 citations.

Synthesis and X-ray structure of dumb-bell-shaped C 120

Abstract: The discovery and large-scale synthesis of fullerenes have aroused interdisciplinary interest in these closed-cage molecules1,2,3,4,5,6 C60 can be photopolymerized into a form in which the cages are thought to be linked by cyclic C4 units in a [2 + 2] cycloaddition7, provoking theoretical studies of the C60 dimer8,9,10,11,12,13,14,15, the smallest subunit of such a polymer The C60 dimers C120O (refs 16, 17), C121H2( ref 17) and C120O2(ref 18) have been reported, in which the two C60molecules are linked by, respectively, a furan group, a cyclopentane ring and a cyclobutane ring plus two oxygen bridges; but the simplest dimer, C120linked by a cyclobutane ring alone, has not so far been observed We now report that this dumb-bell-shaped molecule can be synthesized by a solid-state mechanochemical reaction of C60 with potassium cyanide Our X-ray structural analysis shows that the C4 ring connecting the cages is square rather than rectangular—the latter is predicted theoretically8,9,13,14,15 The dimer dissociates cleanly into two C60 molecules on heating or one-electron reduction, but in the gas phase during mass-spectrometric measurements it undergoes successive loss of C2 units, shrinking to even-numbered fullerenes such as C118 and C116 in a sequence similar to that seen for other large fullerenes19,20

Small-Molecule Inhibition of TNF-α

Abstract: We have identified a small-molecule inhibitor of tumor necrosis factor alpha (TNF-alpha) that promotes subunit disassembly of this trimeric cytokine family member. The compound inhibits TNF-alpha activity in biochemical and cell-based assays with median inhibitory concentrations of 22 and 4.6 micromolar, respectively. Formation of an intermediate complex between the compound and the intact trimer results in a 600-fold accelerated subunit dissociation rate that leads to trimer dissociation. A structure solved by x-ray crystallography reveals that a single compound molecule displaces a subunit of the trimer to form a complex with a dimer of TNF-alpha subunits.

Human IL-12 p40 homodimer binds to the IL-12 receptor but does not mediate biologic activity.

Abstract: IL-12, a heterodimeric cytokine, consists of two disulfide-linked subunits, p40 and p35. We investigated the role of p40 in ligand binding and signal transduction by expressing this subunit alone in COS cells. Culture media of the transfected COS cells exhibited specific dose-dependent binding to KIT225/K6 cells, a human T cell line that expresses IL-12R. Analysis of the culture media by SDS-PAGE and Western blotting demonstrated the presence of 40-kDa monomers and 80-kDa disulfide-linked homodimers. The two p40 species were purified and identified by N-terminal sequencing and proteolytic peptide mapping. Characterization of the p40 proteins for binding and bioactivity showed that both the p40 monomer and dimer inhibited 125I-labeled IL-12 binding to IL-12R, but the 80-kDa species, having a 50% inhibitory concentration (IC50) of 20 to 70 ng/ml, was at least 20-fold more effective than the monomer. Although neither the monomer nor the dimer stimulated human PHA-blast proliferation, the 80-kDa dimer inhibited IL-12-induced proliferation in a dose-dependent manner with an IC50 of 65 ng/ml. The results suggest that the IL-12 p40 subunit contains the essential epitopes for receptor binding. However, a proper conformation required for high affinity binding is achieved only when p40 is associated with a p35 subunit or another p40 subunit. When p40 is associated with a p35 subunit, the heterodimer acts as an agonist mediating biologic activity. However, when p40 associates with another p40, the homodimer behaves as an antagonist in vitro.

Stability and Lifetime of Quadruply Hydrogen Bonded 2-Ureido-4[1H]-pyrimidinone Dimers

Abstract: 2-Ureido-4[1H]-pyrimidinones are known to dimerize via a strong quadruple hydrogen bond array. A detailed study of the dimerization constant and lifetime of the dimer is presented here. Excimer fluorescence of pyrene-labeled 2-ureido-4[1H]-pyrimidinone 1b was used to determine a dimerization constant Kdim of 6 × 107 M-1 in CHCl3, 1 × 107 M-1 in chloroform saturated with water, and 6 × 108 M-1 in toluene (all at 298 K). Under these conditions, the preexchange lifetime of the similar dimers of both 1d and 1e is 170 ms in CDCl3, 80 ms in wet CDCl3, and 1.7 s in toluene-d8, as determined by dynamic NMR spectroscopy. Association rate constants were calculated from the Kdim values and the preexchange lifetimes. The resulting values are significantly lower than the diffusion-controlled association rate constants calculated using the Stokes−Einstein and the Debeije equations. This difference is ascribed to a tautomeric equilibrium of the monomer between the dimerizing 4[1H]-pyrimidinone and nondimerizing 6[1H]-py...