Intramolecular dimers: a new design strategy for fluorescence-quenched probes

Fluorogenic probes dual-labeled with reporter and quencher dyes use a change in fluorescence to monitor biochemical events (e.g., substrate binding or enzyme digestion). Such events change the reporter-quencher distance, which affects fluorescence. Recently, it is has been shown that static quenching through intramolecular dimers is an important mechanism that can sometimes be more efficient than F?rster resonance energy transfer (FRET).     

A Mets motif peptide found in copper transport proteins selectively binds Cu(I) with methionine-only coordination

Mets motifs, which refer to methionine-rich sequences found in the high-affinity copper transporter Ctr1, also appear in other proteins involved in copper trafficking and homeostasis, including other Ctrs as well as Pco and Cop proteins isolated from copper-resistant bacteria. To understand the coordination chemistry utilized by these proteins, we studied the copper binding properties of a peptide labeled Mets7-PcoC with the sequence Met-Thr-Gly-Met-Lys-Gly-Met-Ser. By comparing this sequence to a series of mutants containing noncoordinating norleucine in place of methionine, we confirm that all three methionine residues are involved in a thioether-only binding site that is selective for Cu(I). Two independent methods, one based on mass spectrometry and one based on rate differences for the copper-catalyzed oxidation of ascorbic acid, provide an effective K(D) of approximately 2.5 microM at pH 4.5 for the 1:1 complex of Mets7-PcoC with Cu(I). These results establish that a relatively simple peptide containing an MX(2)MX(2)M motif is sufficient to bind Cu(I) with an affinity that corresponds well with its proposed biological function of extracellular copper acquisition.     

Reactions of siliranes with elemental sulfur and with t-butyl mercaptan. Preparation of the 2,3-dithia-1-silacyclopentane ring system

The reaction of 1,1-dimethyl-trans-2,3,-bis(2′,2′-dimethylcyclopropylidene)-1-silirane with S₈ gives a mixture of four isomeric products derived from incorporation of one sulfur atom and a cyclopropylcarbinyl-to-butenyl type rearrangement. This silirane reacts with t-butyl mercaptan to give a product of mercaptan addition in which a cyclopropylcarbinyl-to-butenyl rearrangement also has occurred. Hexamethylsilirane reacts with S₈ to give 1,1,4,4,5,5-hexamethyl-2,3-dithia-1-silacyclopentane in high yield. These reactions are discussed in terms of free radical mechanisms.     

Suzuki-Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols

A simple new protocol for the high yielding Suzuki-Miyaura cross-couplings of aryl chlorides with aryl boronic acids using a palladium/imidazolium salt catalytic system is presented. The first examples of a palladium/imidazolium salt protocol for sp³-sp³ Suzuki-Miyaura couplings of alkyl halides are also disclosed.     

One‐Dimensional,Cofacial Porphyrin Polymers Formed by Self‐Assembly of meso‐Tetrakis(ERE Donor) Zinc(II) Porphyrins

A series of meso‐tetrakis‐(ERE donor) zinc(II) porphyrins n Zn (ERE donor=4‐R‐3,5‐bis[(E)‐methyl]phenyl; 1 Zn: E=NMe₂, R=Br; 2 Zn: E=NMe₂, R=H; 3 Zn: E=OMe, R=Br; 4 Zn: E=OMe, R=H) have been synthesized in excellent yields. As a result of the combination of a Lewis acidic site and eight Lewis basic sites within one molecule, monomeric molecules of n Zn self‐assemble to form one‐dimensional porphyrin polymers [ n Zn]_∞ in the solid state, as confirmed for 1 Zn and 3 Zn by X‐ray crystallography. The coordination environment around the zinc(II) ions in these polymers is octahedral. They are ligated by four equatorial nitrogen atoms of the porphyrin and two apical E atoms (E=N, O) provided by the EBrE donor groups of adjacent n Zn molecules. Complexes 2 Zn and 4 Zn did not form single crystals, but solid‐state UV/Vis analysis points to the formation of similar structures. Solution UV/Vis and ¹H NMR spectroscopy indicated that interactions between 1 Zn and 2 Zn monomers in the polymers are stronger than between 3 Zn and 4 Zn monomers. Interestingly, they also revealed that the presence of a neighboring bromine atom in the EBrE donor groups has a considerable influence on the coordination properties of the benzylic N or O atoms. The zinc(II) ions of the porphyrins most likely adopt only hexacoordination in the solid state, owing to the unique predisposition of Lewis acidic and basic sites in the n Zn molecules. Several parameters of the aggregates, for example, the interplanar separation between porphyrins and the zinc–zinc distances, change as a function of the coordinating E groups. The high degree of modularity in their synthesis makes these zinc(II) porphyrins an interesting new entry in noncovalent multiporphyrin assemblies.     

Quinazolines. VII. Synthesis of 1,3-Diamino-5,6-dihydrobenzo[f]quinazolines

Eighteen new 1,3-diamino-5,6-dihydrobenzo[f] quinazolines ( 6 , R. = alkyl, Cl, MeO) were synthesized via the condensation of appropriate 2-tetralones with cyanoguanidine under fusion conditions. Methods were developed for the preparation of a number of heretofore undescribed 2-tetralones as precursors. The final products can be viewed as conformationally rigid analogs of pyrimethamine ( 2 ), and are of interest as inhibitors of dihydrofolate reductase and as potential antimalarial and antitumor agents.     

Synthesis of the ABC ring system of manzamine A

A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.     

Chiral bidentate aminophosphine ligands: synthesis, coordination chemistry and asymmetric catalysis

Chiral aminophosphines Ph2PN(R)(CH2)nN(R)PPh2 1-4 [n= 2, R = CH(CH3)(Ph) 1; n= 3, R = CH(CH2CH3)(Ph) 2, n= 2, R = CH(CH3)(1-naphthyl) 3; n= 2, R = CH(CH3)(C6H11) 4] were synthesized by the reaction of ClPPh2 with the appropriate easily accessible enantiopure amine building blocks. For compounds 1 and 2, the corresponding selenides 5 and 6 were prepared to determine the electronic character of the phosphine moieties. By reaction of 1 with either PdCl2(cod) or PdCl(CH3)(cod) the cis-complexes 7 and 8 were obtained. The molecular structure for complex 7, cis-[PdCl2(1)], was determined by X-ray crystallography. Reaction of PtCl2(cod) with 1 or 2 yielded the corresponding monomeric cis-isomers 9 and 10. The rhodium derivative [RhCl(CO)(1)] (11) was obtained as a mixture of cis and trans-isomers. Preliminary results in the rhodium catalyzed hydroformylation of styrene and vinyl acetate, with ee's up to 51% and high regioselectivities, showed the potential of these chiral aminophosphines for homogeneous catalysis.