Fabiane M. Nachtigall

Charge-tagged N-heterocyclic carbenes

The interception, formation and characterization of the first stable, long lived charge-tagged N-heterocyclic carbenes of the general type 4x+ (x = 1–3) and analogues is reported. Via ESI(+)-MS of solutions of bromine salts of doubly, triply and quadruply charged imidazolium ion IL (3.Brn, n = 2–4), the isolated 4x+ as well as charged aggregates [3.Br(n−x)]x+ likely to be participating in the [3.Br(n−x)]x+ ⇌ 4x+ + HBr solution equilibrium could be transferred and characterized in the gas phase. Mimicking the solution equilibrium, the gaseous [3.Br(n−x)]x+ were found to dissociate nearly exclusively viaHBr loss during thermal activationvia collisions to form gaseous 4x+, which were found to add to acrolein and acetone.

TBAI/TBHP-catalyzed [3 + 2]cycloaddition/oxidation/aromatization cascade and online ESI-MS mechanistic studies: synthesis of pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles

A facile [3 + 2]cycloaddition/oxidation/aromatization cascade reaction for the synthesis of pyrrolo[2,1-a]isoquinolines and indolizino[8,7-b]indoles has been developed. This tandem approach was accomplished by employing tert-butyl hydroperoxide (TBHP) as the environmentally benign stoichiometric oxidant, with the catalysis of non-toxic tetrabutylammonium iodide (TBAI) and isopropanol as the green solvent. Gratifyingly, this protocol is highly versatile, as the construction of polycyclics could be tailored by readily available dipolarophiles. Only a catalytic amount of TBAI was required, as the hypervalent electrophilic iodine species (IOH) can be recovered in situ by oxidation with TBHP. Furthermore, for the first time, the mechanistic aspects and the putative intermediates associated with this cascade have been intercepted and characterized by online monitoring of the reaction by using ESI-MS/MS.

In situ and in silico evaluation of amine- and folate-terminated dendrimers as nanocarriers of anesthetics

The search for new nano-systems for targeted biomedical applications and controlled drug release has attracted significant attention in polymer chemistry, pharmaceutics, and biomaterial science. Controlled drug delivery has many advantages over conventional drug administration, such as reduction of side effects, maintaining a stable plasma level concentration and improving the quality of life of patients. In this study, PAMAM G5 dendrimers and PAMAM G5-folic acid conjugates (PAMAM G5-FA) are synthesized and characterized by mass spectrometry (MALDI-MS). Controlled release studies at different pH values show that PAMAM G5-FA is a good candidate as a carrier for tramadol and morphine, while mathematical modeling is conducted, suggesting that the release process is governed by a diffusion mechanism. In addition, using molecular dynamics simulations, we investigate the structural and energetic properties that facilitate the encapsulation of tramadol and morphine by unmodified and functionalized PAMAM-G5 dendrimers at low, neutral and high pH. Our results correlate well with experimental data, confirming that tramadol and morphine may be encapsulated both by functionalized PAMAM dendrimers and unmodified PAMAM. Moreover, the simulations further reveal that hydrogen-bond and electrostatic interactions govern the affinity the dendrimers for both drugs. This information is envisioned to prove useful for the encapsulation of other drugs and for the design of novel functionalized dendrimers.

Natural AD-Like Neuropathology in Octodon degus: Impaired Burrowing and Neuroinflammation

Alzheimers disease (AD) is the most common cause of dementia, affecting more than 36 million people worldwide. Octodon degus, a South American rodent, has been found to spontaneously develop neuropathological signs of AD, including amyloid-β (Aβ) and tau deposits, as well as a decline in cognition with age. Firstly, the present work introduces a novel behavioral assessment for O. degus - the burrowing test - which appears to be a useful tool for detecting neurodegeneration in the O. degus model for AD. Such characterization has potentially wide-ranging implications, because many of these changes in species-typical behaviors are reminiscent of the impairments in activities of daily living (ADL), so characteristic of human AD. Furthermore, the present work characterizes the AD-like neuropathology in O. degus from a gene expression point of view, revealing a number of previously unreported AD biomarkers, which are found in human AD: amyloid precursor protein (APP), apolipoprotein E (ApoE), oxidative stress-related genes from the NFE2L2 and PPAR pathway, as well as pro-inflammatory cytokines and complement proteins, in agreement with the known link between neurodegeneration and neuroinflammation. In summary, the present results confirm a natural neuropathology in O. degus with similar characteristics to AD at behavioral, cellular and molecular levels. These characteristics put O. degus in a singular position as a natural rodent model for research into AD pathogenesis and therapeutics against AD.

Synthesis and characterization of an insoluble polymer based on polyamidoamine: applications for the decontamination of metals in aqueous systems.

We present a novel, insoluble, low-generation polyamidoamine (PAMAM)-based polymer. The monomer and polymer were characterized by fourier transform infrared spectroscopy, electrospray ionization mass spectrometry and thermogravimetric measurement, revealing that G0 acryloyl-terminated PAMAM were synthesized and polymerized using ammonium persulfate as an initiator, producing a high-density PAMAM derivative (PAMAM-HD). PAMAM-HD was tested for its ability to remove Na(I), K(I), Ca(II), Mg(II), Cu(II), Mn(II), Cd(II), Pb(II) and Zn(II) ions from acidic, neutral and basic aqueous solutions. PAMAM-HD efficiently removed metals ions from all three solutions. The greatest absorption efficiency at neutral pH was observed against Cu(II), Cd(II) and Pb(II), and the experimental data were supported by the calculated Kd values. Our data could have a significant impact on water purification by providing an inexpensive and efficient polymer for the removal of metal ions.

Monitoring of β-blockers ozone degradation via electrospray ionization mass spectrometry

The structures of intermediate products of ozone degradation of different pharmaceutical compounds have been studied. Under the conditions employed, complete ozone degradation of nadolol was achieved after 100 min. The degradation products obtained in aqueous solution were characterized by electrospray ionization mass (and tandem mass) spectrometry (ESI-MS and ESI-MS/MS). The proposed mechanism for degradation, ozone attacks at the aniline amino group giving rise to nitro compounds and further degradation occurs via a series of oxidative processes. Continuous online monitoring by ESI-MS(/MS) with high accuracy mass measurements showed that ozone degradation of atenolol (ATE) and acebutolol (ACE) occurs via mechanisms similar to that of nadolol

Fast detection of Piscirickettsia salmonis in Salmo salar serum through MALDI-TOF-MS profiling.

Piscirickettsia salmonis is a pathogenic bacteria known as the aetiological agent of the salmonid rickettsial syndrome and causes a high mortality in farmed salmonid fishes. Detection of P. salmonis in farmed fishes is based mainly on molecular biology and immunohistochemistry techniques. These techniques are in most of the cases expensive and time consuming. In the search of new alternatives to detect the presence of P. salmonis in salmonid fishes, this work proposed the use of MALDI-TOF-MS to compare serum protein profiles from Salmo salar fish, including experimentally infected and non-infected fishes using principal component analysis (PCA). Samples were obtained from a controlled bioassay where S. salar was challenged with P. salmonis in a cohabitation model and classified according to the presence or absence of the bacteria by real time PCR analysis. MALDI spectra of the fish serum samples showed differences in its serum protein composition. These differences were corroborated with PCA analysis. The results demonstrated that the use of both MALDI-TOF-MS and PCA represents a useful tool to discriminate the fish status through the analysis of salmonid serum samples.

Chemotaxonomic Fingerprinting of Chilean Lichens Through Maldi and Electrospray Ionization Mass Spectrometry

The aim of this work was to study a fast, new, sensitive, and simple method for the chemotaxonomic classification of Chilean lichens (Teloschistes chrysophthalmus, Ramalina farinacea, Usnea pusilla, Ramalina chilensis and Stereocaulon ramulosum) using MALDI-TOF-MS and UPLC-ESI(-)-MS data. Lichens soluble proteins fingerprints were acquired by MALDI-TOF-MS and they were analyzed by chemometric (PCA). Lichens organic extracts fingerprints were obtained by UPLC-ESI(-)-MS. MALDI-TOF-MS associated with chemometric analysis was used to detect new m/z patterns of soluble proteins that were compared with Protein Data Bank of UnitPro. These data also permitted the satisfactory distinction among the families and species. UPLC-ESI(-)-MS fingerprints analyses of the organic extracts showed the presence of five major lichen compounds (atranorin, parietin, teloschistin, ramalinolic and usnic acids). In contrast to other techniques, MALDI-TOF-MS associated with chemometric analysis and UPLC-ESI(-)-MS provided a new, fast and sensitive method for chemotaxonomic characterization of lichens.

Polymer-supported (-)-8-phenylmenthyl Auxiliary as an Effective Solidphase Chiral Inductor in the Addition of Nucleophiles to N-acyliminium Ions

AIM AND OBJECTIVE According to our interest in developing new methods for the construction of intricate molecules, a reliable polymer-supported (-)-8-phenylmenthyl chiral auxiliary for the addition of different nucleophiles to chiral-supported N-acyliminium precursors were developed. MATERIALS AND METHODS Merrifield resin was employed to anchor (-)-8-phenylmenthol, which was prepared by nitration of (-)-8-phenylmenthyl chloroacetate followed by reduction of nitro group and subsequent Merrifield resin coupling. Treatment of a suspension of polymer-supported chloroformate and piperidinone in the presence of Et3N resulted in attachment of the substrate onto the solid-support. Treatment of the resulting resin with LiEt3BH/MeOH afforded methoxypiperidine in 87% yield. Then, the addition of allyltrimethylsilane, TMSCN, 2-(trimethylsiloxy)propene and triisopropylsilyloxyfuran and others to the N-acyliminium ion derived from chiral 2- methoxypiperidine carbamate was studied. RESULTS The stereochemical outcome of the addition of nucleophiles to the supported N-acyliminium ion derived from 2-methoxypiperidine carbamate was proposed through the Si-face, affording after resin cleavage 2-substituted piperidines in 70%-84% yields and selectivities ranging from 4:1-11.1. Moreover, the key intermediates of chiral piperidines have been employed for the synthesis of simple chiral alkaloids such as (R)-pipecolic acid, (R)-pelletierine, (S)-coniine and (R,R)-myrtine. CONCLUSION The proposed supported-chiral auxiliary for asymmetric approach may be expected to result not only in efficient solid-phase syntheses of a wide range of alkaloids but also in the development of useful new solid-phase methodologies, particularly for the asymmetric additions to iminium precursors. This work describes the first example of solid-phase synthesis by using supported (-)-8-phenylmenthyl as an effective chiral inductor and would be useful for the synthesis of chiral building block libraries.

Effect of Sulfamic Acid on 1,3-Dipolar Cycloaddition Reaction: Mechanistic Studies and Synthesis of 4-Aryl-NH-1,2,3-triazoles from Nitroolefins

A facile and new metal-free 1,3-dipolar cycloaddition reaction for the synthesis of 4-aryl-NH-1,2,3-triazoles from nitroolefins and NaN3 employing NH2SO3H has been developed. Sulfamic acid proved to be an efficient additive in this transformation by inhibiting the formation of triaryl benzene. Mechanistic aspects and key intermediates associated with this transformation have also been characterized by online monitoring of the reaction using electrospray ionization tandem mass spectrometry method (ESI-MS/MS). The protocol emphasizes broad substrate scope for many functionalities, simple reaction conditions such as stability to open air, less reaction time, easy work-up, eco-friendly and with good to excellent yields.