Structure and mechanism of action of isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase

We have obtained the three-dimensional X-ray crystallographic structure of a C67A mutant Escherichia coli isopentenylpyrophosphate-dimethylallylpyrophosphate isomerase (EC 5.3.3.2) complexed with the bromohydrin of isopentenylpyrophosphate, at 1.93 A resolution. The overall backbone fold is very similar to that obtained previously for the wild-type enzyme in the presence of a divalent metal cation (Mn2+ or Mg2+). However, in the new structure, there are two metal binding sites, not just one. The first metal binding site is occupied by Mn2+, coordinated to three histidine and two glutamate residues, while the second is occupied by Mg2+, coordinated to two bromohydrin-ligand phosphate oxygens, the carbonyl oxygen of A67, a carboxyl oxygen of E87, and two water molecules. The C3 hydroxyl group of the bromohydrin inhibitor is involved in a short hydrogen bond to the carboxyl group of E116, one of the two Mn-bound glutamates. The structure obtained is consistent with a mechanism of action of the enzyme in which the carboxyl group of E116 protonates the double bond in isopentenylpyrophosphate, forming a carbocation, followed by removal of a C2 proton by the thiolate of C67, in the wild-type enzyme. The inhibition of the enzyme by a wide variety of other potent inhibitors is also readily explained on the basis of the bromohydrin inhibitor structure.     

Synthesis of a hexaalkoxybenzo[b]triphenylene mesogen

The synthesis of the first mesogenic hexaalkoxybenzo[b]triphenylene derivative is reported; this compound exhibits a broad columnar liquid crystal phase at temperatures only slightly above room temperature.     

Reactions of the ionized enol tautomer of acetanilide: elimination of HNCO via a novel rearrangement

The reactions of ionised acetanilide, C(6)H(5)NH(=O)CH(3)(.+), and its enol, C(6)H(5)NH(OH)=CH(2)(.+), have been studied by a combination of tandem mass spectrometric and computational methods. These two isomeric radical cations have distinct chemistries at low internal energies. The keto tautomer eliminates exclusively CH(2)=C=O to give ionised aniline. In contrast, the enol tautomer loses H-N=C=O, via an unusual skeletal rearrangement, to form predominantly ionised methylene cyclohexadiene. Hydrogen atom loss also occurs from the enol tautomer, with the formation of protonated oxindole. The mechanisms for H-N=C=O and hydrogen atom loss both involve cyclisation; the former proceeds via a spiro transition state formed by attachment of the methylene group to the ipso position, whereas the latter entails the formation of a five-membered ring by attachment to the ortho position. The behaviour of labelled analogues reveals that these two processes have different site selectivities. Hydrogen atom loss involves a reverse critical energy and is subject to an isotope effect. Surprisingly, attempts to promote the enolisation of ionised acetanilide by proton-transport catalysis were unsuccessful. In a reversal of the usual situation for ionised carbonyl compounds, ionised acetanilide is actually more stable than its enol tautomer. The enol tautomer was resistant to proton-transport catalysed ketonisation to ionised acetanilide, possibly because the favoured geometry of the encounter complex with the base molecule is inappropriate for facilitating tautomerisation.     

Solid-phase synthesis and characterization of a novel fullerene-peptide derived from histone H3

A peptide analogue from a histone H3 protein containing the L-fulleropyrrolidino-glutamic acid has been prepared by a solid-phase approach and has been fully characterized. By molecular modelling it was verified that this peptide derivative is able to retain a binding capacity to the MHC (major histocompatibility complex) molecule similar to that of the cognate epitope.     

Application of Horner–Emmons Olefination to the Crown-Ether Derivatives

An effective synthetic approach to the preparation of a new crown-ether vinylogs involving the Horner–Emmons olefination of carbonyl precursors with the use of C₂- and C₅-phosphonates was proposed. The effects of the conjugation chain length and the nature of the terminal polar functions in the phosphonate reagent on the yield and process stereoselectivity were discussed.     

Nanostructured Ion-Selective MCM-48 Membranes

Templated MCM-48 silica was prepared using CTAB as surfactant. The MCM-48 powders and thin films were characterized by different techniques. MCM-48 layers were deposited on macroporous α-alumina supports and silicon nitride microsieves. The water permeability of MCM-48 was compared with the permeability of conventional mesoporous γ-alumina membranes. The applicability of MCM-48 as ion-selective electric field-driven switchable interconnect for microfluidic devices was demonstrated.