The diazo route to diazonamide A: studies on the tyrosine-derived fragment

Various approaches to the tyrosine-derived fragment of the marine secondary metabolite diazonamide A are described. Initial efforts were focused on the originally proposed structure of the natural product, and a feasibility study established that a model 4-aryltryptamine could be readily prepared. Protected 4-bromotryptamine underwent Pd0-catalyzed coupling with the boronic acid derived from 2-bromophenyl allyl ether by Claisen rearrangement, O-methylation and lithiation-boration. The resulting biaryl was elaborated into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Z-valinamide gave the desired tryptamine-oxazole following cyclodehydration of the intermediate ketoamide. A potential precursor to the benzofuran ring of the original structure of diazonamide A was prepared in eight steps from N-Z-tyrosine tert-butyl ester. Iodination, O-protection and Stille coupling gave the cinnamyl alcohol 25, converted via the bromide into the allyl aryl ether 27. Subsequent Claisen rearrangement and oxidative cleavage of the alkene gave the lactol 29, converted into the desired benzofuranone 31. The revision in the structure of diazonamide A to 2 resulted in the targeting of an alternative tyrosine-derived model benzofuranone 41 synthesized in four steps from N-Z-tyrosine methyl ester 36 by a route involving Claisen rearrangement of cinnamyl ether 37. Poor yields in this sequence prompted an investigation into the intramolecular Heck reaction as a route to benzofuranone 50. Coupling of 3-iodotyrosine 44 with 2-phenylbutenoic acid 48 gave ester 49 that readily underwent intramolecular Heck reaction to give benzofuranone 50, albeit with poor stereocontrol.     

Participation of Bao2* in chemiluminescence from low-pressure Ba(g) + O2 flames

New spectioscopic and vibronic population data support the essential correctness of BaO₂^* as the nascent polyatomic emitter and as the precursor to BaO (A ¹Σ⁺ → X¹Σ⁺) and (A' ¹Π → X¹Σ⁺) visible chemiluminescence from metal-rich Ba(g) + O₂ (+ Ar) diffusion flames at 2–350 mTorr- Absolute visible photon yields are reported over this pressure regime.     

Pinkment: a synthetic platform for the development of fluorescent probes for diagnostic and theranostic applications

Reaction-based fluorescent-probes have proven successful for the visualisation of biological species in various cellular processes. Unfortunately, in order to tailor the design of a fluorescent probe to a specific application (i.e. organelle targeting, material and theranostic applications) often requires extensive synthetic efforts and the synthetic screening of a range of fluorophores to match the required synthetic needs. In this work, we have identified Pinkment-OH as a unique “plug-and-play” synthetic platform that can be used to develop a range of ONOO⁻ responsive fluorescent probes for a variety of applications. These include theranostic-based applications and potential material-based/bioconjugation applications. The as prepared probes displayed an excellent sensitivity and selectivity for ONOO⁻ over other ROS. In vitro studies using HeLa cells and RAW 264.7 macrophages demonstrated their ability to detect exogenously and endogenously produced ONOO⁻. Evaluation in an LPS-induced inflammation mouse model illustrated the ability to monitor ONOO⁻ production in acute inflammation. Lastly, theranostic-based probes enabled the simultaneous evaluation of indomethacin-based therapeutic effects combined with the visualisation of an inflammation biomarker in RAW 264.7 cells.

Pinkment, a resorufin based ONOO⁻ selective and sensitive ‘plug and play’ fluorescence-based platform for in vitro and in vivo use, enables facile functionalisation for various imaging and theranostic applications.     

Proton transfer reaction ion trap mass spectrometer

Proton transfer reaction mass spectrometry is a relatively new field that has attracted a great deal of interest in the last few years. This technique uses H(3)O(+) as a chemical ionization (CI) reagent to measure volatile organic compounds (VOCs) in the parts per billion by volume (ppbv) to parts per trillion by volume (pptv) range. Mass spectra acquired with a proton transfer reaction mass spectrometer (PTR-MS) are simple because proton transfer chemical ionization is "soft" and results in little or no fragmentation. Unfortunately, peak identification can still be difficult due to isobaric interferences. A possible solution to this problem is to couple the PTR drift tube to an ion trap mass spectrometer (ITMS). The use of an ITMS is appealing because of its ability to perform MS/MS and possibly distinguish between isomers and other isobars. Additionally, the ITMS duty cycle is much higher than that of a linear quadrupole so faster data acquisition rates are possible that will allow for detection of multiple compounds. Here we present the first results from a proton transfer reaction ion trap mass spectrometer (PTR-ITMS). The aim of this study was to investigate ion injection and storage efficiency of a simple prototype instrument in order to estimate possible detection limits of a second-generation instrument. Using this prototype a detection limit of 100 ppbv was demonstrated. Modifications are suggested that will enable further reduction in detection limits to the low-ppbv to high-pptv range. Furthermore, the applicability of MS/MS in differentiating between isobaric species was determined. MS/MS spectra of the isobaric compounds methyl vinyl ketone (MVK) and methacrolein (MACR) are presented and show fragments of different mass making differentiation possible, even when a mixture of both species is present in the same sample. However, MS/MS spectra of acetone and propanal produce fragments with the same molecular masses but with different intensity ratios. This allows quantitative distinction only if one species is predominant. Fragmentation mechanisms are proposed to explain the results.     

Synthesis of a New Bivalent Hirudin Analog (hirufos), which includes a stable 4′-phosphono-L-phenylalanine mimic of (L-tyrosine O4-sulfate)-63

The synthesis on solid phase of a new derivative of the anticoagulant protein hirudin is described (see Scheme and Fig.1, I ). The henicosapeptide is a bivalent conjugate of the C-terminus of hirudin and of the active-site-binding tetrapeptide D -Phe-Pro-Arg-Pro linked via a tetraglycine spacer. The peptide, for which the name hirufos was coined, incorporates a stable phosphono derivative of L -phenylalanine which, combined with the other structural modifications, leads to a potent anticoagulant agent. Synthesis was readily achieved by the (9H-fluoren-9-yl)-methoxycarbonyl (Fmoc) strategy followed by acidolytic cleavage from the resin and deprotection, including the liberation of the crucial phosphonic group on L -phenylalanine.     

Approximate solutions of the Bloch-McConnell equations for two-site chemical exchange.

Approximate formulas for the transverse-relaxation rate constant and resonance frequency have been derived for nuclear spins subject to two-site chemical exchange. The new results are more accurate than previous approximations when chemical exchange does not approach the fast-exchange limit or when site populations are not highly asymmetric. Results are derived from an effective average evolution operator that contains contributions from both exact eigenvalues of the Bloch-McConnell equations. These expressions are useful for interpretation of chemical exchange processes in NMR spectroscopy.     

Pigment-Protein Interactions in the Antenna-Reaction Center Complex of Heliobacillus mobilis

Membrane fragments of Heliobacillus (Hc.) mobilis were characterized using resonance Raman (RR) spectroscopy in order to determine the configuration of the neurosporene carotenoid, the pigment-protein interactions of the bacteriochlorophyll (BChl) g molecules, and the Chl a-like chlorin pigments present in the antenna-reaction center complex constituting the photosynthetic apparatus. Using 363.8 nm excitation, the Raman contributions of the BChl g molecules were selectively resonantly enhanced over those of the carotenoid and the Chl a-like chlorin pigments. The RR spectrum of BChl g in these membranes excited at 363.8 nm exhibits bands at 1614 and 1688 cm^?1, which correspond to a C_aC_m methine bridge stretching mode and a keto carbonyl group stretching mode, respectively. Both of these bands are 16 cm^?1 wide (full width at half maximum, FWHM), indicating that a sole population of BChl g molecules is being enhanced at this excitation wavelength. The observed frequency of the C_aC_m stretching mode (1614 cm^?1) indicates that the bulk of BChl g molecules is pentacoordinated with only one axial ligand to the central Mg atom while that of the keto carbonyl stretching mode (1668 cm^?1) indicates that these groups are engaged in a hydrogen bond. This homogeneous population of BChl g molecules bound to the heliobacterial core polypeptides is in contrast to the heterogeneous population of Chl a molecules bound to the core polypeptides of the reaction center of photosystem I of Synechocystis 6803 as observed by the inhomogeneously broadened C₉ keto carbonyl band in its RR spectrum. The RR spectrum of the Chl a-like chlorin pigments in Hc. mobilis excited at 441.6 nm exhibits a broad keto carbonyl band (43 cm^?1 FWHM) with components at 1665, 1683 and 1695 cm^?1, indicating several populations of these pigments differing in their protein interactions at the level of the keto carbonyl group. Fourier transform (FT) pre-RR spectroscopic measurements of intact whole cells and membrane fragments at room temperature using 1064 nm excitation indicate that high quality vibrational spectra of the BChl g molecules can be obtained with no photodegradation. Low-temperature FT Raman spectra excited at 1064 nm reveals an inhomogeneously broadened 1665 cm^?1 band corresponding to the C₉ keto carbonyl stretching mode. Spectral deconvolution and second derivative analysis of this band reveal that it is comprised of components at 1665, 1682 and 1695 cm^?1, the latter two most likely arising from BChl g photoconversion products. Excitation using 885 nm to enhance the preresonance effect of the BChl g molecules yields an FT Raman spectrum where the keto carbonyl band at 1665 cm^?1 is narrow, as is the case in the Soret RR spectra, reflecting a sole population of BChl g molecules, which are engaged in an H bond. The RR spectrum of the neurosporene molecule in Hc. mobilis membranes excited at 496.5 nm is compared to that of 1,2-dihydroneurosporene bound in a cis configuration in reaction centers of Rhodopseudomona viridis and to that of the same carotenoid in its all-trans configuration extracted from these reaction centers in the presence of light. The similarity of this latter RR spectrum with that of neurosporene in the Hc. mobilis membranes indicates that it is bound in an all-trans configuration.     

Oxidation of secondary alcohols byN-methylmorpholine-N-oxide (NMO) catalyzed by atrans-dioxo ruthenium(VI) complex or perruthenate complex: A kinetic study

Thetrans-dioxo ruthenium (VI) complex, [P(C₆H₅)₃C₆H₅CH₂]⁺[Ru(O)₂OAcCl₂] or tetrapropylammonium perruthenate catalyzes the oxidation of secondary alcohols to ketones byN-methylmorpholine-N-oxide (NMO). Kinetic studies showed the formation of a complex between catalyst and substrate (alcohol) as the first step in the mechanism.     

Volumes of activation for the reactions of Pentacyanocobaltate(III) Complexes in aqueous solution

The volumes of activation in cm³ mol^?1 for the aquation of Co(CN)₅X^3? were determined at 40°C and μ = 1 M (NaClO₄) to be + 7.8 ± 0.5 for X = Cl^?, + 7.6 ± 0.6 for X = Br^?, + 14.0 ± 0.7 for X = I^?, and + 16.8 ± 0.5 for X = N₃^? (0.1 M HClO₄), respectively. The volumes of activation for the aquation of Co(CN)₅Cl^3? at μ = 0.1 M are + 10.0 ± 0.6 cm³ mol^?1 and ± 9.1 ± 0.3 cm³ mol^?1 at 40°C and 25°C, respectively. The corresponding values for the anation of Co(CN)₅OH₂^2? (at 40°C) and μ = 1 M by Br^?, I^?, and NCS^? are +8.4 ± 1.0, +9.4 ± 1.6, and +8.2 ± 0.9 cm³ mol^?1, respectively. These data are discussed in terms of a dissociative (D) mechanism.