Furan-based Polysemiacylcarbazides by Polyaddition of Bis(furanic hydrazide)s with Diisocyanates

A solution polyaddition procedure was applied to prepare furanic polyacylsemicarbazides based on 2,2′-isopropylidene-bis(5-(2-furoyl) hydrazide) and aliphatic or aromatic diisocyanates. Model compounds were prepared to facilitate the synthesis and the characterization of the polymers. A systematic study of reaction parameters (the nature of the organic phase, the temperature, the reaction time, and the concentration of monomers) was carried out. High MW polymers were obtained after 12 h reaction at 20°C with 0.2 M monomer solutions in dimethylacetamide. In fact, the polyacylsemicarbazides obtained had inherent viscosities ranging from 0.63 to 0.85 dL/g. There showed good solubility in aprotic polar solvents. The ¹H and ¹³C-NMR spectra were consistent with the expected structures. These furan-based polyacylsemicarbazides are thermally stable up to 290°C, but exhibit a complex thermal behavior. This was explained by the cyclohydration of acylsemicarbazide groups into NH-substituted oxadiazoles, resulting in rigid and high melting polymers, less stable, however, than conventional aromatic polyoxadiazoles.     

Unusual mixed solvent supramolecular crystal framework formed of a new tecton-like tetracarboxylic building block

A new tecton-like tetracarboxylic compound 1 featuring two isophthalic acid groups attached to both ends of a rigid 1,3-butadiyne spacer unit is synthesised using acetylene blocking/deblocking and coupling techniques. Crystallisation of 1 from DMSO-chloroform solution gives rise to the formation of an unusual mixed solvent crystalline framework structure 1a containing DMSO and chloroform as secondary and tertiary components in 1:2:1 stoichiometric ratio. The X-ray crystal structure of 1a shows interesting stacking mode and hydrogen-bonded, 3D network architecture with the two solvent species being involved in different behaviour pattern.     

Synthesis, characterisation, and mass spectrometric detection of a pegylated EPO-mimetic peptide for sports drug testing purposes

Erythropoietin (EPO) and other erythropoiesis‐stimulating agents possess a high misuse potential in elite sport due to their ability to increase the oxygen transport capacity, which plays a vital role in enhancing endurance performance. Currently, a new generation of EPO‐mimetic peptides is under development from which peginesatide (also referred to as Hematide?), a pegylated homodimeric peptide of approximately 45 kDa with no structural relationship to erythropoietin, is the most advanced drug candidate undergoing phase‐III clinical trials. Since preventive doping research aims at the development of detection methods before a drug receives clinical approval, a selective and sensitive assay has to be established knowing that conventional doping control assays for EPO will not succeed in detecting peginesatide. Thus, a pegylated EPO‐mimetic peptide simulating the structure and properties of the lead drug candidate peginesatide was synthesised as a model compound for this new class of emerging drugs and characterised by means of gel electrophoresis, matrix‐assisted laser desorption/ionisation (MALDI) mass spectrometry, as well as liquid chromatography/electrospray ionisation tandem mass spectrometry (LC/ESI‐MS/MS) after proteolytic digestion. Based on these results, a mass spectrometric detection method of the product in plasma was developed targeting a pentapeptide fragment after protein precipitation and subtilisin digestion. Its fitness for purpose was evaluated by the determination of selected method characteristics focusing particularly on specificity, recovery (ca. 60%), and limit of detection (1 ng/mL). Copyright © 2011 John Wiley & Sons, Ltd.     

Acid-base and electrochemical properties of manganese meso(ortho- and meta-N-ethylpyridyl)porphyrins: potentiometric, spectrophotometric and spectroelectrochemical study of protolytic and redox equilibria

The difference in electrostatics and reduction potentials between manganese ortho-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP) and manganese meta-tetrakis(N-ethylpyridinium-3-yl)porphyrin (MnTE-3-PyP) is a challenging topic, particularly because of the high likelihood for their clinical development. Hence, a detailed study of the protolytic and electrochemical speciation of Mn(II-IV)TE-2-PyP and Mn(II-IV)TE-3-PyP in a broad pH range has been performed using the combined spectrophotometric and potentiometric methods. The results reveal that in aqueous solutions within the pH range ～2-13 the following species exist: (H(2)O)Mn(II)TE-m-PyP(4+), (HO)Mn(II)TE-m-PyP(3+), (H(2)O)(2)Mn(III)TE-m-PyP(5+), (HO)(H(2)O)Mn(III)TE-m-PyP(4+), (O)(H(2)O)Mn(III)TE-m-PyP(3+), (O)(H(2)O)Mn(IV)TE-m-PyP(4+) and (O)(HO)Mn(IV)TE-m-PyP(3+) (m = 2, 3). All the protolytic equilibrium constants that include the accessible species as well as the thermodynamic parameters for each particular protolytic equilibrium have been determined. The corresponding formal reduction potentials related to the reduction of the above species and the thermodynamic parameters describing the accessible reduction couples were calculated as well.     

Complexation of diazaperylene and bisisoquinoline with transition metal ions in the gas phase studied by electrospray ionization mass spectrometry

The complex formation of the ligands 1,12-diazaperylene (dap), 1,1'-bisisoquinoline (bis), 2,2'-bipyridine (bpy) and 1,10-phenanthroline (phen) with transition metal ions (M = Fe, Co, Ni, Cu, Zn, Ru, Os, Re, Pd, Pt, Ag and Cd) in the gas phase has been studied by electrospray ionization mass spectrometry. With the exception of Ru, Os, Fe, Ni and Cu, singly charged complexes [MLn](+) (n = 1,2) were observed. The complexes of dap and bis with Ru, Os, Fe and Ni ions, and the mixed ligand complexes with bpy and phen, are preferably of the doubly charged type [ML3]2+. In addition, collision-induced dissociation (CID) measurements were employed to evaluate the relative stabilities of these complexes. The CID experiments of mixed-ligand complexes which contain both dap and phen or dap and bpy exhibit preferential elimination of bpy, indicating that bpy is a weaker ligand than phen and dap.     

Ultrafast pump-probe study of excited-state charge-transfer dynamics in umecyanin from horseradish root

We have applied femtosecond pump-probe spectroscopy to investigate the excited-state dynamics of umecyanin from horseradish roots, by exciting its 600-nm ligand-to-metal charge-transfer band with a 15-fs pulse and probing over a broad range in the visible region. The decay of the pump-induced ground-state bleaching is modulated by clearly visible oscillations and occurs exponentially with a time constant depending on the observed spectral component of the transmission difference signal, ranging from 270 fs up to 700 fs. The slower decaying process characterizes the spectral component corresponding to the metal-to-ligand charge-transfer transition. The excited-state decay rate is significantly lower than in other blue copper proteins, probably because of the larger energy gap between ligand- and metal-based orbitals in umecyanin. Wavelength dependence of the recovery times could be due to either the excitation of several transitions or the occurrence of intramolecular vibrational relaxation within the excited state. We also find evidence of a hot ground-state absorption, at 700 nm, persisting for several picoseconds. The vibrational coherence induced by the ultrashort pump pulse allows vibrational activity to be observed, mainly in the ground state, as expected in a system with fast excited-state decay. However, we find evidence of a rapidly damped oscillation, which we assign to the excited state. Finally, the Fourier transform of the oscillatory component of the signal presents additional bands in the low-frequency region which are assigned to collective motions of the protein.     

New examples of indefinite hyper-Kähler symmetric spaces

Following the approach to pseudo-Riemannian symmetric spaces developed in [I. Kath, M. Olbrich, On the structure of pseudo-Riemannian symmetric spaces, arXiv:math.DG/0408249, 2004] we exhibit examples of indefinite hyper-Kähler symmetric spaces with non-abelian holonomy. Moreover, we classify indecomposable hyper-Kähler symmetric spaces whose metric has signature (4,4n)$(4,4n)$. Such spaces exist if and only if n∈{0,1,3}$n\in \{0,1,3\}$.     

Adriadysiolide,the First Monoterpenoid Isolated from a Marine Sponge

Spectra and chemical transformations allow to establish the gross structure 6,7-epoxy-4,7-dimethyl-l-oxa-spiro[4.4]non-3-en-2-one for adriadysiolide ( 1 ), the first monoterpenoid isolated from a marine sponge, a Dysidea sp. of the Adriatic Sea. Its configuration 5R*, 6S*, 7S* as given in 1a is derived from diastereoselective total syntheses of both 1a and its diastereoisomer 1b via stereochemically predictable peracid epoxidations of olefinic precursors. Thus, OH assistance in allylic alcohol 8 leads to oxirane 13 which is subjected to methyl cuprate conjugate addition to give epiadriadysiolide ( 1b ), whilst electronic deactivation by a neighboring heterocyclic O-atom in intermediate 5 , derived from 8 mainly leads to adriadysiolide ( 1a ). Comparative ¹H-NMR shift-reagent effects with 1a and 1b , evaluated with the aid of molecular-mechanics calculations, support these conclusions.     

Modular Medical Imaging Agents Based on Azide–Alkyne Huisgen Cycloadditions: Synthesis and Pre-Clinical Evaluation of 18F-Labeled PSMA-Tracers for Prostate Cancer Imaging

Since the seminal contribution of Rolf Huisgen to develop the [3+2] cycloaddition of 1,3-dipolar compounds, its azide–alkyne variant has established itself as the key step in numerous organic syntheses and bioorthogonal processes in materials science and chemical biology. In the present study, the copper(I)-catalyzed azide–alkyne cycloaddition was applied for the development of a modular molecular platform for medical imaging of the prostate-specific membrane antigen (PSMA), using positron emission tomography. This process is shown from molecular design, through synthesis automation and in vitro studies, all the way to pre-clinical in vivo evaluation of fluorine-18- labeled PSMA-targeting ‘F-PSMA-MIC’ radiotracers (t_1/2=109.7 min). Pre-clinical data indicate that the modular PSMA-scaffold has similar binding affinity and imaging properties to the clinically used [⁶⁸Ga]PSMA-11. Furthermore, we demonstrated that targeting the arene-binding in PSMA, facilitated through the [3+2]cycloaddition, can improve binding affinity, which was rationalized by molecular modeling. The here presented PSMA-binding scaffold potentially facilitates easy coupling to other medical imaging moieties, enabling future developments of new modular imaging agents.