High-performance liquid chromatographic separation and dual competitive binding assay of corrinoids in biological material

Corrinoids were extracted with hot ethanol from human plasma and faeces and separated by high-performance liquid chromatography. The corrinoids (cobalamin and cobalamin analogues) were quantified in the eluted fractions by a dual radioisotope assay using as binders intrinsic factor and haptocorrin to detect cobalamin and total corrinoids, respectively. Recoveries ranged from 37.7 +/- 5.1% for hydroxycobalamin to 75.0 +/- 9.1% for cyanocobalamin. In plasma, the main forms of cobalamin were the coenzymes methylcobalamin and 5'-deoxyadenosylcobalamin (32.1 +/- 13.4 and 28.4 +/- 12.3%, respectively, of total corrinoids). The cobalamin analogue fraction of plasma was eluted with a retention time close to that of cobinamide and of deoxyadenosylcobalamin. In the faeces, most of the corrinoids separated were detected better by the haptocorrin assay than by the intrinsic factor assay. One corrinoid peak was eluted with the same retention time as cobinamide. This peak was detected by haptocorrin assay but not by intrinsic factor assay. It could therefore correspond to cobinamide.     

ANTHRALIN-DERIVED TRANSIENTS—II. FORMATION OF THE RADICAL BY SPONTANEOUS FRAGMENTATION OF BOTH SINGLET AND TRIPLET STATES OF THE 10,10''-DEHYDRODIMER: RADICAL PAIR MULTIPLICITY EFFECTS

The singlet and triplet states of the anthralin (1,8-dihydroxy-9-anthrone) dehydrodimer have been produced selectively in benzene via pulsed laser excitation and pulse radiolysis respectively. The lifetime of S1 is less than or equal to 30 ps, that of T1 short but unspecified. Both states fragment spontaneously to yield a pair of anthralin radicals. The singlet radical pair predominantly undergoes geminate recombination within the solvent cage. In contrast, the corresponding triplet radical pair undergoes essentially exclusive cage escape to give the anthralin free radical (lambda max 370, 490 and 720 nm) which recombines under normal diffusive conditions. Both recombination processes lead, at least in part, to one or more species which have been assigned as tautomeric forms of the original dimer. The anthralin free radical in benzene is insensitive to the vitamin E model 6-hydroxy-2,2,5,7,8-pentamethylchroman and reacts only slowly with oxygen.     

Aspects of heterogeneous enantioselective catalysis by metals

Some aspects of metal-catalyzed heterogeneous enantioselective reactions are reviewed with specific reference to four different systems where the phenomena that control enantioselection appear to be very different. In the case of glucose electro-oxidation, it is clear that any intrinsic chirality present at the metal surface plays a vital role. With α-keto hydrogenation, achiral surfaces modified by the adsorption of chiral agents become effective enantioselective catalysts and the formation of extended arrays of chiral species appears not to be of importance: instead a 1:1 docking interaction controlled by hydrogen bonding between the adsorbed chiral modifier and the prochiral reactant determines the outcome. Hydrogen bonding also plays a central role in β-ketoester hydrogenation, but here fundamental studies indicate that the formation of ordered arrays involving the reactant and chiral ligand is of importance. Asymmetric C═C hydrogenation, though relatively little studied, has the potential for major impact in synthetic organic chemistry both on the laboratory scale and in the manufacture of fine chemicals and pharmaceuticals. The structural attributes that determine whether a given chiral ligand is effective have been identified; the ability to form strong covalent bonds with the metal surface while also resisting hydrogenation and displacement by the strongly adsorbing reactant under reaction conditions is an essential necessary condition. Beyond this, ligand rigidity in the vicinity of the chirality center coupled with resistance to SAM formation is a critically important factor whose absence results in racemic chemistry.     

Non-invasive vibrational SFG spectroscopy reveals that bacterial adhesion can alter the conformation of grafted "brush" chains on SAM

Understanding bacterial adhesion on a surface is a crucial step to design new materials with improved properties or to control biofilm formation and eradication. Sum Frequency Generation (SFG) vibrational spectroscopy has been employed to study in situ the conformational response of a self-assembled monolayer (SAM) of octadecanethiol (ODT) on a gold film to the adhesion of hydrophilic and hydrophobic ovococcoid model bacteria. The present work highlights vibrational SFG spectroscopy as a powerful and unique non-invasive biophysical technique to probe and control bacteria interaction with ordered surfaces. Indeed, the SFG vibrational spectral changes reveal different ODT SAM conformations in air and upon exposure to aqueous solution or bacterial adhesion. Furthermore, this effect depends on the bacterial cell surface properties. The SFG spectral modeling demonstrates that hydrophobic bacteria flatten the ODT SAM alkyl chain terminal part, whereas the hydrophilic ones raise this ODT SAM terminal part. Microorganism-induced alteration of grafted chains can thus affect the desired interfacial functionality, a result that should be considered for the design of new reactive materials.     

Tropylium ion mediated α-cyanation of amines

Tropylium ion mediated α-cyanation of amines is described. Even in the presence of KCN, tropylium ion is capable of oxidizing various amine substrates, and the resulting iminium ions undergo salt metathesis with cyanide ion to produce aminonitriles. The byproducts of this transformation are simply cycloheptatriene, a volatile hydrocarbon, and water-soluble potassium tetrafluoroborate. Thirteen total substrates are shown for the α-cyanation procedure, including a gram scale synthesis of 17β-cyanosparteine. In addition, a tropylium ion mediated oxidative aza-Cope rearrangement is demonstrated.     

Optically and thermally induced electron transfer pathways in hexakis[4-(N,N-diarylamino)phenyl]benzene derivatives

The optically and thermally induced electron transfer pathways of highly symmetrical (D(3)) hexaarylbenzene systems with six triarylamine redox sites have been investigated. Owing to slightly different local redox potentials, the radical trication could be selectively generated by electrochemical methods. This trication shows a strong intervalence charge-transfer band in the near infrared (NIR) that was measured by spectroelectrochemistry and analysed using multi-dimensional Mulliken-Hush theory. Quantum chemical AM1 CI calculations indicate that there is no optically induced concerted three-electron transfer that transforms the ground state into a state in which all three positively charged triarylamine moieties change place with their neutral neighbours. The potential energy surface of the ground state was constructed by using quadratic potentials. From this potential surface it is apparent that there is also no thermally allowed concerted three-electron transfer pathway. Instead, three consecutive one-electron transfer steps are necessary for this process.     

Vertical and nonvertical participation by sulfur,selenium, and tellurium

The mechanism of stabilization of positive charge on carbon by sulfur, selenium, or tellurium at the beta-position has been investigated kinetically, by measurement of rate enhancements, and structurally, by variation of the bond strength to the leaving group. Stabilization can occur either nonvertically with formation of a bridged intermediate or vertically through hyperconjugation within an open carbocation. We observed large rate enhancements (10(5) for S, 10(6) for Se) in 97% aqueous trifluoroethanol with trifluoroacetate as the leaving group. These enhancements are consistent with either mechanism. Product structures also are consistent with either mechanism. Nine crystal structures revealed that the bond to the leaving group (C-O) is lengthened by the presence of S or Se at the beta-position, in proportion to the basicity of the leaving group. This lengthening is not accompanied by angle distortions expected for the bridging mechanism. The crystallographic data support vertical (hyperconjugative) character along the reaction coordinate, more so for selenium than sulfur.     

Synthetic studies towards the penicisulfuranols: Synthesis of an advanced spirocyclic diketopiperazine intermediate

The 2,5-diketopiperazine (DKP) moiety is a core feature of many natural products and medicinally relevant scaffolds. As part of our efforts directed towards a total synthesis of penicisulfuranol B, we have developed and report herein: (1) the preparation of an N-hydroxy diketopiperazine intermediate accessible via a molybdenum-mediated oxidation of a parent diketopiperazine, and (2) further synthetic studies leading to a novel spirocyclic dihydrobenzofuran-containing diketopiperazine.     

A rhenium tris-carbonyl derivative as a single core multimodal probe for imaging (SCoMPI) combining infrared and luminescent properties

A rhenium tris-carbonyl derivative has been designed to couple infrared and luminescent detection in cells. Both spectroscopies are consistent with one another; they point out the reliability of the present SCoMPI (for Single Core Multimodal Probe for Imaging) for bimodal imaging and unambiguously indicate a localization at the Golgi apparatus in MDA-MB-231 breast cancer cells.