ABSTRACT
Traditional molecular conductors are composed of more than two chemical species and are characterized by low-dimensional electronic band structures. By contrast, the single-component molecular metals [M(tmdt)(2)] (M = Ni, Pt, Au; tmdt = trimethylenetetrathiafulvalenedithiolate) possess three-dimensional electronic structures that can be widely tuned by exchanging the central transition metal atom (M). In this study, the Cu atom was used to realize a new magnetic single-component molecular conductor exhibiting strong pi-d interactions. The crystal structure of [Cu(tmdt)(2)] was found to be essentially the same as those of the Ni, Pt, or Au-based systems with metallic states down to low temperature, but different from the structure of [Cu(dmdt)(2)] (dmdt = dimethyltetrathiafulvalenedithiolate) with its tetrahedrally coordinated dmdt ligands. A compressed pellet of microcrystals exhibited fairly high room-temperature conductivity (sigma(RT) approximately 7 S.cm(-1)), which increased almost linearly with pressure, reaching 110 S.cm(-1) at 15 kbar. This strongly suggests that the single crystal of [Cu(tmdt)(2)] is metallic at high pressure. Magnetic susceptibility measurements indicated one-dimensional Heisenberg behavior with |J| = 117 cm(-1) and an antiferromagnetic transition at 13 K. Density functional theory molecular orbital calculations revealed that the alpha-spin orbital of pdsigma(-) is distributed at the central part of the complex (CuS(4)), and alpha- and beta-sym-Lpi orbitals have almost the same energies and their spins are distributed mainly in the pdsigma(-) orbital. This is in contrast to the first single-component molecular metal [Ni(tmdt)(2)], which has stable metal bands formed from an almost degenerated sym-Lpi orbital (the highest occupied molecular orbital) and asym-Lpi(d) orbital (the lowest unoccupied molecular orbital). These results suggest that the alpha-pdsigma(-) state of [Cu(tmdt)(2)] exists just around the Fermi energy of the virtual metal band formed from the asym-Lpi(d) and sym-Lpi states. Thus, as expected, [Cu(tmdt)(2)] is a non-trivial single-component molecular conductor with pi-d multifrontier orbitals. In addition, ((n)Bu(4)N)(2)[Cu(tmdt)(2)] was synthesized, and its crystal structure was determined. Its Curie behavior (chi(rt) = 1.2 x 10(-3) emu mol(-1); C = 0.36 emu.K mol(-1)) indicates the existence of an isolated S = 1/2 spin on each dianionic molecule.
ABSTRACT
Zintevir is a single strand DNA that forms an intramolecular quadruplex structure and shows potent anti-human immunodeficiency virus type 1 (HIV-1) activity. Zintevir was discovered as a potent inhibitor for HIV-1 integrase. Recently, the primary molecular target of Zintevir, however, was shown to be the HIV-1 gp120. In fact, in our previous study, Zintevir was shown to inhibit the only processes of the viral adsorption and the entry into the cell. This result suggests that Zintevir is not able to penetrate through the cell membranes. Therefore, we designed and synthesized the complex of D-17mer with HIV-1 tat peptide that has the cell membrane permeability.
Subject(s)
Anti-HIV Agents/chemical synthesis , DNA/chemical synthesis , Anti-HIV Agents/chemistry , Anti-HIV Agents/metabolism , Cell Membrane Permeability , DNA/chemistry , DNA/metabolism , G-Quadruplexes , Oligonucleotides/chemistryABSTRACT
We have synthesized l-type enantiomers (cU and cA) of nucleoside analogues, whose glycosyl bonds are fixed in a low anti conformation (ap glycosyl conformation, [small chi][approximate] 180[degree]), and incorporated them into oligonucleotides to evaluate the hybridization ability with natural DNA and RNA sequences. Although the incorporation of the modified nucleosides into oligonucleotides decreased the hybridization ability with unmodified complementary DNA sequences, the fully-substituted 12mers (cU(12) and cA(12)) still retained the hybridization ability with the complementary unmodified DNA 12mers, regardless of their unnatural l-chirality. In contrast, cU(12) and cA(12) showed different hybridization behavior with complementary unmodified RNA 12mers. cU(12) forms a more stable duplex with rA(12) than the corresponding natural 12mer (dT(12)), whereas cA(12) cannot hybridize with rU(12). Based on the model structure of cU(12)-rA(12), we discuss these experimental results.
Subject(s)
DNA/chemistry , Oligonucleotides/chemistry , RNA/chemistry , Animals , Base Sequence , Carbohydrate Conformation , Circular Dichroism , Drug Stability , Glycosides/chemical synthesis , Glycosides/chemistry , Glycosides/metabolism , Models, Molecular , Nucleic Acid Conformation , Nucleic Acid Denaturation , Nucleic Acid Hybridization , Nucleosides/chemistry , Oligonucleotides/chemical synthesis , Oligonucleotides/metabolism , Phosphoric Diester Hydrolases/metabolism , Snake Venoms , Sodium Chloride/chemistry , Stereoisomerism , TemperatureABSTRACT
Zintevir is an oligonucleotide analogue, which has the phosphorothioate modification at both termini, that forms a K(+)-induced quadruplex structure and shows potent anti-human immunodeficiency virus (HIV)-1 activity. We synthesized the non-modified analogue (D-17mer) of Zintevir and its enantiomer (L-17mer), and compared their anti-HIV-1 activity and molecular mechanism of action. Although L-17mer forms the exact mirror image quadruplex structure of D-17mer, which has a very similar structure with Zintevir, L-17mer showed comparable anti-HIV-1 activity with Zintevir. The results obtained by the time-of-addition experiments and the immunofluorescence binding assay strongly suggest that the primary molecular target of L-17mer is the viral gp120 envelope protein as well as Zintevir, regardless of their reciprocal chirality.
Subject(s)
Anti-HIV Agents/chemistry , Anti-HIV Agents/pharmacology , Oligonucleotides/chemistry , Oligonucleotides/pharmacology , Antibodies, Monoclonal/metabolism , Base Sequence , CD4 Antigens/immunology , Cell Line, Transformed , Circular Dichroism , Drug Stability , Flow Cytometry , Genes, gag/drug effects , Genes, gag/genetics , HIV Envelope Protein gp120/immunology , Humans , Nucleic Acid Conformation , Oligonucleotides/chemical synthesis , Oligonucleotides/metabolism , Phosphodiesterase I/metabolism , Single-Strand Specific DNA and RNA Endonucleases/metabolism , Stereoisomerism , Temperature , Time FactorsABSTRACT
L-Ribose was synthesized by a simple four-step method with overall yield of 76.3% from a protected L-arabinose derivative, which is a compatible intermediate for the synthesis of L-deoxyribose. The key step of this strategy is the Swern oxidation and subsequent stereoselective reduction accompanied by inversion of the 2-hydroxy group of protected L-arabinose.
Subject(s)
Arabinose/chemistry , Ribose/chemical synthesis , Deoxyribose/chemical synthesis , Deoxyribose/chemistry , Nucleosides/chemical synthesis , Nucleosides/chemistry , Ribose/chemistryABSTRACT
Zintevir is a DNA 17mer that forms a quadruplex and shows strong anti-human immunodeficiency virus (HIV)-1 activity. The quadruplex formation is thought to be essential for the anti-HIV-1 activity of Zintevir. We synthesized the enantiomer of Zintevir and evaluated its structure and anti-HIV-1 activity. The results showed that the enantiomer has anti-HIV-1 activity comparable to that of Zintevir although it forms the mirror image quadruplex structure of Zintevir.
