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The FK506-FKBP12 binding domain of the kinase FRAP(FRB) forms a classic up-down four-helical bundle and the folding pathway of this protein is investigated using combination of equilibrium and kinetic studies. It is concluded that the four helical bundle proteins FRB populates an intermediate state during folding.

Pyrrolidine enamines derived from three 1,3-dioxan-5-ones have undergone [alpha],[alpha]E-annelation reactions with methyl [alpha]-(bromomethyl)acrylate to produce bridged 2,4-dioxabicyclo[3.3.1]nonane ring systems with complete stereocontrol. Base-mediated ester epimerization has provided the stereochemical array found in the highly oxygenated cyclohexane ring of phyllaemblic acid and glochicoccins B and D.

A chiral ferrocene-based boronic acid was interacted with (R)- and (S)-binol to produce two complexes that exhibited significantly different ferrocene-based electrode potentials. The differences in the redox behavior could be exploited to demonstrate in principle how high levels of enantiomeric excess in a mixture of enantiomers could be quantified and read-out using an electrochemical method.

Halide abstraction is shown to be a good method for the generation of mononuclear cationic complexes containing gallium donor ligands. The ligand properties are compared with related ten valance electron systems such as [N.sub.2], CO and BF.

Changes in the optical properties of an alkynyldigold(I) complex upon reaction with Cu(I) are associated with a complicated structural change to form an unusual Au4Cu4 cluster. This complex involves weak Cu...Cu/Au interactions and pi-alkyne coordination.

Eightdithiolato-, diselenolato-, and mixed S,Se-Fe2(CO)6complexes based on peri-substitutednaphthalene and phenanthrene dichalcogenides are prepared by oxidativeinsertion of Fe3(CO)12into the dichalcogenbonds of 2,7-dimethoxynaphtho[1,8-cd][1,2]dithiole,three naphtho[1,8-cd][1,2]diselenoles, two naphtho[1,8-cd][1,2]thiaselenoles, phenanthro[1,10-cd][1,2]dithiole, and phenanthro[1,10-cd][1,2]diselenole.Complexes are characterized by 1H, 13C NMR,UV/vis, and IR spectroscopy and by X-ray analysis. The effect of replacingsulfur with selenium, incorporating electron-donating groups (2,7-di-tert-butyl, 2,7-dimethoxy) on the naphthalene ring system,and changing the degree of conjugation in the aromatic backbone (naphthalenevs phenanthrene) on the reduction potential is evaluated by cyclicvoltammetry. The electrocatalytic activity of these [FeFe]-hydrogenasesynthetic mimics for proton reduction in the presence of increasingconcentrations of p-TsOH is investigated. Diselenolate-based[FeFe]-complexes show enhanced catalytic activity for proton reductioncompared with their sulfur congeners. [ABSTRACT FROM AUTHOR]

While N2 and CO have played central roles in developing models of electronic structure, and their interactions with transition metals have been widely investigated, the valence isoelectronic diatomic molecules EX (E = group 13 element, X = group 17 element) have yet to be isolated under ambient conditions, either as the "free" molecule or as a ligand in a simple metal complex. As part of a program designed to address this deficiency, together with wider issues of the chemistry of cationic systems [LnM(ER)]+ (E = B, Al, Ga; A = aryl, amido, halide), we have targeted complexes of the type [LnM(GaX)]+ Halide abstraction is shown to be a viable method for the generation of mononuclear cationic complexes containing gallium donor ligands. The ability to isolate tractable two-coordinate products, however, is strongly dependent on the steric and electronic properties of the metal/ligand fragment. In the case of complexes containing ancillary ar-acceptor ligands such as CO, cationic complexes can only be isolated as base-trapped adducts, even with bulky aryl substituents at gallium. Base-free gallylene species such as [Cp*Fe(CO)2(GaMes)]+ can be identified only in the vapor phase by electrospray mass spectrometry experiments. With bis(phosphine) donor sets at the metal, the more favorable steric/electronic environment allows for the isolation of two-coordinate ligand systems, even with halide substituents at gallium. Thus, [Cp*Fe(dppe)(Gal)]+iBArf4]- (9) can be synthesized and shown crystallographically to feature a terminally bound Gal ligand; 9 represents the first experimental realization of a complex containing a valence isoelectronic group 13/group 17 analogue of CO and N2. DFT calculations reveal a relatively weakly bound Gal ligand, which is confirmed experimentally by the reaction of 9 with CO to give [Cp*Fe(dppe)+ (CO)]+[BArf4]-. In the absence of such reagents, 9 is stable for weeks in fluorobenzene solution, presumably reflecting (i) effective steric shielding of the gallium center by the ancillary phosphine and Cp* ligands; (ii) a net cationic charge which retards the tendency toward dimerization found for putative charge neutral systems; and (iii) (albeit relatively minor) population of the LUMOs of the Gal molecule through π overlap with the HOMO and HOMO-2 of the [Cp*Fe(dppe)]+ fragment. [ABSTRACT FROM AUTHOR]

The 6-azabicyclo[3.2.1]octane ring system, prevalent in a range of biologically active molecules, is prepared through a novel semipinacol rearrangement utilizing a cyclic phosphorane or sulfite intermediate. The rearrangement proceeds with exclusive N-acyl group migration of a β-lactam ring and results in carbonyl functionality at the 7- and bridging 8-position of the bicycle. Precursor ring-fused β-lactam diols are prepared through a sequence of 4-exo trig carbamoyl radical cyclization, regioselective dithiocarbamate group elimination, and dihydroxylation.

Pyrrolidine enamines derived from three 1,3-dioxan-5-ones undergo α,α'-annelation reactions with methyl α-(bromomethyl)acrylate to produce bridged 2,4-dioxabicyclo[3.3.1]nonane ring systems with complete stereocontrol. Stereochemical outcomes have been rationalized based on steric and stereoelectronic interactions in intermediate boat-like conformations of the 1,3-dioxane ring and subsequent kinetic protonation to set an axial ester group on the cyclohexanone ring. Base-mediated ester epimerization provides the stereochemical array found in the highly oxygenated cyclohexane ring of phyllaemblic acid and glochicoccins B and D.

Iodine-mediated cyclization of homoallyl amines at room temperature delivered cis-2,4-azetidine through a 4-exo trig cyclization. Isomerization of iodo-azetidines to cis-pyrrolidines could be achieved by heating, with complete stereocontrol. The relative stereochemistry of the iodo-azetidines and pyrrolidines was confirmed by NMR spectroscopy and X-ray crystallography. Further functionalization was achieved through nucleophilic displacement of iodine to deliver substituted azetidines and pyrrolidines. 1,2,3-Triazole-appended azetidines and pyrrolidines were also prepared.

A tricyclic core structure 2 related to gelsemine 1 was synthesized from an oxabicyclo[3.2.1]octanone 4 by a three-step bridge swapping strategy involving elimination of the bridging ether oxygen and intramolecular Michael addition of a tethered cyanoacetamide unit.

Changes in the optical properties of an alkynyldigold(I) complex upon reaction with Cu(I) are associated with a complicated structural change to form an unusual Au4Cu2 cluster with metallophilic interactions as well as pi-alkyne coordination.