No abstract

Fusion between viral and host cell membranes is the initial step of HIV infection and is mediated by the gp41 protein which is embedded in the viral membrane. The ~20-residue N-terminal fusion peptide (FP) region of gp41 binds to the host cell membrane and plays a critical role in fusion catalysis. Key gp41 fusion conformations include an early pre-hairpin intermediate (PHI) characterized by extended coiled-coil structure in the region C-terminal of the FP and a final hairpin state with compact six-helix bundle (SHB) structure. The large "N70" (gp41 1-70) and "FP-Hairpin" constructs of the present study contained the FP and respectively modeled the PHI and hairpin conformations. Comparison was also made to the shorter "FP34" (gp41 1-34) fragment. Studies were done in membranes with physiologically relevant cholesterol content and in membranes without cholesterol. In either membrane type, there were large differences in fusion function among the constructs with little fusion induced by FP-Hairpin, moderate fusion for FP34, and very rapid fusion for N70. Overall, our findings support acceleration of gp41-induced membrane fusion by early PHI conformation and fusion arrest after folding to the final SHB structure. FP secondary structure at Leu-7 of the membrane-associated constructs was probed by solid-state NMR and showed populations of molecules with either β-sheet or helical structure with greater β-sheet population observed for FP34 than for N70 or FP-Hairpin. The large differences in fusion function among the constructs were not obviously correlated with FP secondary structure. Observation of cholesteroldependent FP structure for fusogenic FP34 and N70 and cholesterol-independent structure for nonfusogenic FP-Hairpin was consistent with membrane insertion of the FP for FP34 and N70 and with lack of insertion for FP-Hairpin. Membrane insertion of the FP may therefore be associated with the early PHI conformation and FP withdrawal with the final hairpin conformation.

The reactions of the samarium(II) complexes Tmp 2 Sm (Tmp = 2,3,4,5-tetramethyl-1H-phosphol-1-yl) and Cp* 2 Sm(THF) 2 (Cp* = 1,2,3,4,5-tetramethyl-2,4-cyclopentadien-1-yl) with pyridine were found to be different, despite the fact that the Cp* and Tmp π-ligands are similar in size. With Tmp 2 Sm, a simple adduct, Tmp 2 Sm(pyridine) 2 is isolated, while with Cp* 2 Sm(THF) 2 pyridine is dimerized with concomitant oxidation of samarium to form [Cp* 2 Sm-(C 5 H 5 N)] 2 [μ-(NC 5 H 5 −C 5 H 5 N)]. However, reaction of Tmp 2 Sm with acridine, a better π-acceptor than pyridine, did result in acridine dimerization and the isolation of [Tmp 2 Sm] 2 [μ-(NC 13 H 9 −C 13 H 9 N)]. DFT calculations on the model structures of Tmp 2 Sm and Cp* 2 Sm, and on the single electron transfer step from Sm to pyridine and acridine in these ligand environments, confirmed that, even though the Sm−πligand bonds are mostly ionic, the different electronic properties of the Tmp ligand versus that of Cp are responsible for the difference in reactivity of Tmp 2 Sm and Cp* 2 Sm.■ EXPERIMENTAL SECTION Computational Details. Calculations were performed with the GAUSSIAN 03 suite of programs. 10 DFT was applied by means of the

The reactivity of the unusual oxyaryl dianionic ligand, (C6H2(t)Bu2-3,5-O-4)(2-), in the Bi(3+) NCN pincer complex Ar'Bi(C6H2(t)Bu2-3,5-O-4), 1, [Ar' = 2,6-(Me2NCH2)2C6H3] has been explored with small molecule substrates and electrophiles. The first insertion reactions of CO2 and COS into Bi-C bonds are observed with this oxyaryl dianionic ligand complex. These reactions generate new dianions that have quinoidal character similar to the oxyaryl dianionic ligand in 1. The oxyarylcarboxy and oxyarylthiocarboxy dianionic ligands were identified by X-ray crystallography in Ar'Bi[O2C(C6H2(t)Bu2-3-5-O-4)-κ(2)O,O'], 2, and Ar'Bi[OSC(C6H2(t)Bu2-3-5-O-4)-κ(2)O,S], 3, respectively. Silyl halides and pseudohalides, R3SiX (X = Cl, CN, N3; R = Me, Ph), react with 1 by attaching X to bismuth and R3Si to the oxyaryl oxygen to form Ar'Bi(X)(C6H2(t)Bu2-3,5-OSiR3-4) complexes, a formal addition across five bonds. These react with additional R3SiX to generate Ar'BiX2 complexes and R3SiOC6H3(t)Bu2-2,6. The reaction of 1 with I2 forms Ar'BiI2 and the coupled quinone, 3,3',5,5'-tetra-tert-butyl-4,4'-diphenoquinone, by oxidative coupling.

The first example of NO insertion into a Bi-C bond has been found in the direct reaction of NO with a Bi(3+) complex of the unusual (C6H2tBu2-3,5-O-4)(2-) oxyaryl dianionic ligand, namely, Ar'Bi(C6H2tBu2-3,5-O-4) [Ar' = 2,6-(Me2NCH2)2C6H3] (1). The oximate complexes [Ar'Bi(ONC6H2-3,5-tBu2-4-O)]2(μ-O) (3) and Ar'Bi(ONC6H2-3,5-tBu2-4-O)2 (4) were formed as a mixture, but can be isolated in pure form by reaction of NO with a Bi(3+) complex of the [O2C(C6H2tBu2-3-5-O-4](2-) oxyarylcarboxy dianion, namely, Ar'Bi[O2C(C6H2tBu2-3-5-O-4)-κ(2)O,O']. Reaction of 1 with Ph3CSNO gave an oximate product with (Ph3CS)(1-) as an ancillary ligand, (Ph3CS)(Ar')Bi(ONC6H2-3,5-tBu2-4-O) (5).

The first crystallographic characterization of bismuth complexes containing benzyl ligands is reported. The NCN pincer ligand complex, Ar′BiCl 2 [Ar′ = 2,6-(Me 2 NCH 2 ) 2 C 6 H 3 ], reacts with (PhCH 2 )MgCl to form Ar′Bi(η 1 -CH 2 Ph) 2 in high yield. X-ray crystallography and spectroscopic studies confirm η 1 -bonding of the benzyl ligands in Ar′Bi(η 1 -CH 2 Ph) 2 as well as in the homoleptic Bi(η 1 -CH 2 Ph) 3 .

3,5-Di-tert-butyl-4-hydroxybenzoic acid can be made under mild conditions in a cyclic process from carbon dioxide and 3,5-di-tert-butyl-4-phenol using bismuth-based C-H bond activation and CO2 insertion chemistry starting with the Bi(3+) complex, Ar'BiCl2, of the NCN pincer ligand, Ar' = 2,6-(Me2NCH2)2C6H3. Complexes of the recently discovered oxyaryl dianion, (C6H2(t)Bu2-3,5-O-4)(2-), and the oxyarylcarboxy dianion, [O2C(C6H2(t)Bu2-3,5-O-4)](2-), are intermediates in the process. Further studies of the oxyarylcarboxy dianion in Ar'Bi[O2C(C6H2(t)Bu2-3,5-O-4)-κ(2)O,O'], show that it undergoes decarboxylation upon reaction with I2 and it reacts with trimethylsilyl chloride to produce the trimethylsilyl ether of the trimethylsilyl ester of 3,5-di-tert-butyl-4-hydroxybenzoic acid and the Ar'BiCl2 starting material.

Review: 217 refs.