Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine-tetrazoles. Thirty-one compounds were synthesized and evaluated for their triple reuptake inhibition of serotonin, norepinephrine and dopamine. Triple reuptake inhibitor, compound 2q, in particular, showed potent serotonin reuptake inhibition, validating our design approach.
The MS analysis was carried out using Advion Expression® CMS ESI.
Harrison C. Daly, Gonzalo Sampedro, Corentin Bon, Dan Wu, Ghazi Cahill, Roman A. Cahill, Donal F. O’Shea
The use of near-infrared fluorescence for in vivo research and intraoperative clinical imaging is rapidly expanding, with new applications being proposed and developed. While imaging hardware and software have significantly progressed in recent times, the molecular fluorescent agents remain a limiting factor. In this report, the design, synthesis, photophysical characterization and bio-medical imaging assessment of two new NIR-fluorophores based on the BF2-azadipyrromethene fluorophore class are described. Inclusion of dimethylamino substituents on these BF2-azadipyrromethene probes results in very large bathochromic shifts with photophysical measurements showing absorption and emission maxima between 757 and 818 nm within the desired NIR spectra region. Testing of the probes shows that they are suitable for fluorescence imaging with both research and clinical instrumentation. Preclinical imaging assessment shows their suitability as fluorescent markers (tattoos) of lesions for intraoperative identification and lymphatic mapping in ex vivo human colonic tissue. These new clinical wavelength-compatible fluorophores may contribute towards the on-going expansion of medical uses for NIR-fluorescence.
The LC/MS analysis was carried out using Advion Expression® CMS.
Martin Doert, Stephanie Krüger, Gertrud E. Morlock, Lothar W. Kroh
Ternary mixtures of lecithins, vitamin C and vitamin E are powerful antioxidants for the stabilization of polyunsaturated (n-3 fatty acid) oils. In this study, the chemistry of the antioxidant synergistic effect was investigated in ethyl linoleate (EL) containing α-tocopherol (α-Toc) or in linoleate rich vegetable oils at 110 °C using mixtures of phosphatidylethanolamine (PE) and either l-ascorbic acid (AA) or l-dehydroascorbic acid (DHA). The highest stabilization effects in EL were similar in both systems and were found in the molar mixtures of PE and AA or DHA. The thermal formation of reaction products between PE and AA (PE–AA) or DHA (PE–DHA) were investigated by HPTLC/ESI-MS. When α-tocopherylquinone (α-TQ) was used instead of α-Toc, nearly the same antioxidant effect was observed in the EL system. It was shown that molar mixtures of PE and AA, or PE and DHA, can regenerate α-TQ to α-Toc at elevated temperatures. PE–AA was synthesized and tested as antioxidants in EL containing α-Toc and in vegetable oils at room temperature. An improved stabilization was observed with the synthesized derivative compared to the physical mixture of the compounds, which demonstrated that PE–AA is a potential new antioxidant. A mechanism for the synergistic action between PE, AA and α-Toc through an acid-catalysed regeneration of α-TQ is suggested. PE–AA is an active apolar antioxidant, which is involved in the reduction of α-TQ.
The MS analysis was carried out using Advion Expression® CMS TLC and ESI.
Rajesh H. Vekariya, Kinjal D. Patel, Dhanji P. Rajani, Smita D. Rajani, Hitesh D. Patel
A convenient, one-pot, multi-component protocol for the preparation of 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide derivatives has been achieved. Here, firstly we have reported the synthesis of 3-acetyl-2H-chromen-2-one using starch sulfuric acid and cellulose sulfuric acid as biodegradable catalysts. Subsequently, we also carried out the reaction of isothiocynates, hydrazine hydrate and 3-acetyl-2H-chromen-2-one in the presence of catalytic amount of glacial acetic acid in refluxing ethanol to afford corresponding 2-(1-(2-oxo-2H-chromen-3-yl)ethylidene)hydrazinecarbothioamide derivatives in high to excellent yields. All synthesized compounds were screened for antimicrobial activity. All compounds were found to show good to excellent activity against Escherichia coli MTCC 443.
A: We provide our expertise, combining chromatography and mass spectrometry, as well as other Analytical techniques within the Facility. This facilitates and assists in the characterization of compounds synthesized in the Chemistry Department and a number of other departments within the University of Birmingham in addition to work for industrial collaborators.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: We needed a system capable of analysing reaction mixtures to assist in the identification of compounds of interest with minimal sample isolation required and provide a relatively quick identification of the compounds. The Advion TLC-MS has fully met these requirements, in terms of the ease of use as a walk-up instrument. This has greatly assisted in providing separation conditions in purification method development, as well as, a useful tool in simple reaction monitoring. The system has enabled us to directly obtain good quality data from complex mixtures of compounds. This has been of great benefit to research students across Chemistry, Chemical Engineering, Biochemistry and Pharmacology Departments who have all used the Advion TLC-MS. The major advantage of the Advion TLC-MS is the ability for the users to visualise the spot on the TLC that is being analysed by the mass spectrometer. If the sample requires further clean-up, the TLC conditions provide the initial starting point for upscaling purification using preparative columns.
Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?
A: The Advion TLC-MS system is setup using an HPLC pump plumbed directly into the TLC sampler which is then plumbed back through the HPLC autosampler and finally into the Advion expression CMS. This setup has benefitted users to simply run a TLC and perform the MS analysis which takes just a few minutes and they have a lot of useful information about their reaction, product identity, impurities etc. The HPLC autosampler act as a method of directly delivering fractions collected from preparative HPLC allowing the users to quickly identify the fraction of interest. The feedback we have had is that by using the Advion TLC-MS the users are now spending significantly more time running reactions, increasing research output by spending less time isolating and characterizing each component in their reaction mixtures.
A: Our group is interested in bacterial natural product chemistry, with projects ranging from the directed discovery of new natural products by genome mining and heterologous pathway expression, the elucidation of individual biocatalytic reactions by in vitro studies and the application of the respective biosynthetic enzymes in organic synthesis. This also involves significant synthetic work, for example to prepare enzyme substrates, validate natural product structure elucidation, or to realize chemo-enzymatic natural product total syntheses.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: While NMR spectroscopy is an analytical tool that is meanwhile accessible to chemical research practically at any time, making standard 1H NMR experiments available within minutes to few hours after a reaction work up, MS spectrometry can sometimes be challenging to conduct sufficiently fast to allow for an efficient work flow: MS equipment in academia is typically located in service units with relatively few machines for whole departments, often leading to waiting times of one to several days for an analysis. While MS would be the perfect tool to directly monitor the success of a chemical reaction in situ or to quickly evaluate the outcome of enzymatic transformations, above restrictions prevent this tool from being regularly and efficiently used.
Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?
A: We integrated the expression CMS into our analytical equipment to obtain fast information on our synthetic and biocatalytic reactions, as well as on the content of whole bacterial raw extracts. While the machine is usually used for direct injections and for recording of MS spectra from TLC reaction controls using the Plate Express system, LC-MS measurements of enzymatic reaction set-ups and raw extracts are run overnight. To our surprise, even the detection of post-translational modifications on small proteins can accurately be detected with the CMS, providing us with an additional tool even for protein characterization. This now gives us fast initial MS data for all applications important to our lab, thus significantly streamlining our research work.
Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION CMS?
A: The expression CMS is the perfect MS system for any research laboratory involved in synthetic organic chemistry and chemical analytics of small molecules to proteins. The system is easy to use and maintain and can thus be used by many individuals. It is therefore particularly well-suited for academic research laboratories.
Ana A. Folgueiras-Amador, Kai Philipps, Sébastien Guilbaud, Jarno Polacker, Prof. Dr. Thomas Wirth
Flow electrochemistry is an efficient methodology to generate radical intermediates. An electrochemical flow microreactor has been designed and manufactured to improve the efficiency of electrochemical flow reactions. With this device only little or no supporting electrolytes are needed, making processes less costly and enabling easier purification. This is demonstrated by the facile synthesis of amidyl radicals used in intramolecular hydroaminations to produce isoindolinones. The combination with inline mass spectrometry facilitates a much easier combination of chemical steps in a single flow process.
The in-line MS analysis was carried out using Advion Expression® CMS (Atmospheric Pressure Ionisation Techniques (APCI)) and an MRA® valve.
TLC/CMS, the atmospheric liquids and solids probe (ASAP), and the volatile APCI source provide direct analysis without sample preparation – even for air-sensitive compounds.
With the daily need to analyze a variety of samples, these techniques are indispensable in a busy lab.
Learn how a single instrument can be adapted to each of these sample requirements and rapidly changed to accommodate back-to-back assays. Listen to users in the field speak about the innovative sample inlets that have cut down on sample prep and streamlined their everyday work flow.
During this webinar you will:
Learn how the CMS offers real-time results and decision making right at the bench. This allows chemists to optimize reactions, know when to quench, and know when they have failed and to move on
Learn several novel sample techniques that can streamline workflow in your lab
Find fast analysis methods for liquids, solids and vapor-phase compounds
Hear from leaders in mass spectrometry including:
Dr. Jack Henion, Advion Scientific Founder
Matthew Turner, Experimental Officer in Mass Spectrometry, Department of Chemistry, Loughborough University
Tao Yongfeng, Post Doctorate, The Romo Group, Baylor University
Sean M. Kerwin, PhD, Associate Professor, Department of Chemistry & Biochemistry, Texas State University
The preparation and full characterization of an iridium complex of the monocarba-closo-dodecaborate anion is reported. It was prepared by B–H bond activation using a tosyl amide directing group.
Analysis by spectroscopic methods and X-ray crystallography revealed the presence a direct B–Ir interaction. The carborane acts as aB,N chelating ligand towards the Ir(Cp*)(solvent) fragment, resulting in a monomeric complex that is inert in solution and the solid state.
Treatment with N-chlorosuccinimide resulted in selective monochlorination of the B–Ir position. In addition, its structure, spectroscopic features and reactivity were investigated by DFT calculations.
Quant Express, an addition to Advion’s user-friendly Mass Express 4.0 software suite, features quantitation to create a fully integrated software system for expression CMS users.
