Purdue University

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

A: My research focuses on developing small molecule modulators to pharmacologically validate potential antibiotic, cancer, and chronic pain therapeutic targets.

Q: WHAT WAS YOUR PREVIOUS WORKFLOW AND SOME OF THE CHALLENGES YOU EXPERIENCED?

A: Purdue’s campus has not had easy access to walk-up mass spec instruments. To get reliable mass spec data for small molecules, one would typically have to submit a request to a central mass spec core. This was not conducive to reaction monitoring or small molecule characterization.

Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?

A: The university research office acknowledged this need and purchased three CMSL instruments with the Plate Express™ and ASAP® capability for walk-up mass spec at three locations on campus. This provided easy access to mass spec data to monitor reactions and characterize molecules. We have even confirmed covalent modification of a protein with a small molecule ligand using this instrument. I was so impressed with the user-friendly interface and instrument set up, that I applied for and received a grant to purchase a 4th instrument to be used in the undergraduate organic teaching lab in the course I teach. We have now incorporated this instrument into the workflow of lab modules for students to collect and analyze their own mass spec data. Something else that stuck out as a positive with Advion is that the data processing software, Data Express™, is free to download for any user. We can have our students analyze data off-site on their own computers. We look forward to incorporating this instrument into more organic lab modules and other courses.

Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION® CMS?

A: I recommend this instrument for both research labs and teaching labs. The ASAP® probe is especially convenient and easy to use for mass spec data.

Q: DO YOU HAVE ANY PUBLICATIONS OR PRESENTATIONS USING THE EXPRESSION® CMS?

A: Not yet, but we have one in review for my research, and another that will be written to publish the laboratory module in the Journal of Chemical Education.

Minimally-destructive atmospheric ionisation mass spectrometry authenticates authorship of historical manuscripts

University of Glasgow, University of Edinburgh

Authentic historic manuscripts fetch high sums, but establishing their authenticity is challenging, relies on a host of stylistic clues and requires expert knowledge. High resolution mass spectrometry has not, until now, been applied to guide the authentication of historic manuscripts. Robert Burns is a well-known Scottish poet, whose fame, and the eponymous ‘Burns Night’ are celebrated world-wide. Authenticity of his works is complicated by the ‘industrial’ production of fakes by Alexander Smith in the 1890s, many of which were of good quality and capable of fooling experts. This study represents the first analysis of the inks and paper used in Burns poetry, in a minimally destructive manner that could find application in many areas. Applying direct infusion mass spectrometry to a panel of selected authenticated Burns and Smith manuscripts, we have produced a Support Vector Machine classifier that distinguishes Burns from Smith with a 0.77 AUC. Using contemporary recipes for inks, we were also able to match features of each to the inks used to produce some of Burns’ original manuscripts. We anticipate the method and classifier having broad application in authentication of manuscripts, and our analysis of contemporary inks to provide insights into the production of written works of art.

ETH, Laboratory of Organic Chemistry, Zurich, Switzerland

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

A: Our laboratory focuses on the development of small molecules with functions that are fulfilled in nature by large macromolecules. We utilize the power of organic synthesis to access functionalities that nature might not have in the repertoire of building blocks. The focus is both on practical applications and an understanding of the properties on the molecular level. This scope includes the development of bioinspired asymmetric catalysts and functionalisable collagen, molecular scaffolds for applications in supramolecular and biological chemistry (e.g., cell-penetrating peptides and tumor targeting) and the controlled formation of metal nanoparticles.

Q: WHAT WAS YOUR PREVIOUS WORKFLOW OR CHALLENGES?

A: For the synthesis of building blocks and target molecules it is important to efficiently analyze and confirm their chemical structures. We routinely do this by, e.g., NMR spectroscopic analysis of the isolated and purified products. This involves the analysis of small molecules in our asymmetric catalysis projects as well as molecules with molecular weights of up to 2000 Da in our chemical biology and materials science projects. In particular for new reactions, fast and straightforward analysis methods for the newly formed compounds are important but challenging at the same time.

Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?

A: The expression® CMS allows us to efficiently analyze the mass of newly formed compounds in (almost) real time. We particularly value that the instrument allows us to monitor the reaction progress of crude mixtures. Separated on a TLC, products and potential side products can be identified, which results in an optimized and faster down-stream-processing, e.g. column chromatography, and only desired products are isolated on a preparative scale. Furthermore, the ASAP mode is very helpful and extremely fast, when looking for expected product masses, e.g. in the fractions of preparative HPLC separations – just dip it in and measure the MS… it takes 30 seconds per fraction. The possibility to easily switch between the ionization modes ESI and APCI as well to measure MS spectra in positive and negative mode in parallel is very helpful for a fast and reliable analysis.

Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION® CMS?

A:  We recommend the expression® CMS in combination with the TLC-Reader Plate Express™ to any group working in the field of synthetic organic chemistry. The reliable and fast identification of molecules is extremely helpful to monitor reactions, to identify the desired products and potential side products, and to simplify downstream processing.

Eberhard Karls University, Institute of Pharmaceutical Sciences, Tübingen, Germany

 

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

A: We are a Medicinal Chemistry laboratory with a major focus on kinase inhibitors. Within the last decade, we have developed highly potent and selective chemical probes such as Skepinone L, a specific p38 MAP kinase inhibitor suitable for in vivo use. Our strategies involve the reversible targeting of kinases via ATP-competitive type I or less competitive type II inhibitors as well as intermediate type 11/2 inhibitors. More recently, we turned towards covalent kinase targeting by addressing non-catalytic cysteines. This strategy furnished excellent probes for JNK3 and JAK3. For example, we developed FM-381, an extremely isoform-selective JAK3 inhibitor, which is now available as a high-quality probe from the Chemical Probes Portal and the chemical probes program of the Structural Genomics Consortium.

Q: WHAT WAS YOUR PREVIOUS WORK EXPERIENCE?

A: Since our work mainly relies on organic synthesis, we have an urgent need for accurate and rapid characterization of novel compounds. While our group owns two NMR spectrometers and several HPLC systems, mass spectrometry was usually done at a shared service unit, which caused additional costs and delays. Although we were also equipped with several LC-MS devices, these were routinely used for biological samples or metabolism studies, thus adapting the workflows for chemical samples was always tedious. Consequently, a more practical solution was required.

Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?

A: As mentioned, mass spectrometry was one of the bottlenecks in our synthesis endeavors. The purchase of an LC-MS system exclusively for reaction monitoring and compound analysis would have been an option. However, especially when dealing with crude mixtures, LC-MS devices are typically quite vulnerable and require a lot of maintenance. Moreover, if you do not have a UPLC system, LC-MS runs are time-consuming, limiting the number of samples to a maximum of a few dozens a day, which is a serious problem with respect to the size of our group.

Therefore, Advion’s expression CMS in combination with the Plate Express™ TLC plate reader was the perfect solution for us. It is easy to use, quite robust, offers a high throughput, and is suitable for almost the entire mass range of our compounds. Needless to say, the device is especially suited for reaction monitoring and the rapid assignment of product fractions from column chromatography.

Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION CMS?

A: The expression CMS/Plate Express™ couple can be recommended to Organic or Medicinal Chemistry groups in general since it seamlessly integrates into organic synthesis workflows. Due to the affordable pricing, it is also a great solution for chemists in academia. Especially laboratories with high turnover of masters students and research interns will appreciate the robustness of the system.

Toluene-Assisted APCI and Elemental Composition Prediction Using a Compact Mass Spectrometer

OVERVIEW

  • Toluene-assisted APCI (TAPCI) can generate (M)+· and (M+H)+ ions from analytes that cannot be ionized by ESI or APCI.
  • Elemental formula prediction at 250 ppm accuracy and isotope distribution matching by TAMI (Tal Aviv Molecule Identifier) supports analyte identification.
  • Combining both TAPCI and TAMI on the expression compact mass spectrometer (CMS) provides a cost-effective analysis platform for a wide range of compounds.

INTRODUCTION

Many compounds in organic synthetic chemistry either have no functional group, a C=O carbonyl group, or protected functional groups and are difficult to ionize by ESI or APCI for detection by mass spectrometry. TAPCI has been shown to ionize compounds to (M)+· and (M+H)+ protonated molecules not accessible by ESI or APCI MS analysis. The ionization is believed to include a charge transfer reaction in the APCI plasma region of the source. Elemental formula prediction using TAMI allows analyte identification on a single quadrupole mass spectrometer with mass accuracy in the 250 ppm range, isotope pattern analysis and auto comparison to NIST databases. Here, we investigate the use of both techniques on the expression CMS as an attractive and cost-effective solution for analyte identification covering an increased compound space.

Urinary Cortisol Quantitation Using Ultra High Pressure Liquid Chromatography/Compact Mass Spectrometry

Introduction

Cortisol is an important steroid hormone produced from cholesterol in the adrenal cortex. Its secretion is closely regulated by Adrenocorticotropic hormone (ACTH). Most cortisol is protein-bound, and only unbound cortisol is excreted in urine. Measurement of cortisol in urine is typically used in the diagnosis of Cushing’s syndrome, a disorder of hypercortisolism.

Although immunoassay methods have extremely high sensitivity, they are subject to variable interferences from other steroids and their conjugates. Liquid chromatography with tandem mass spectrometry is increasingly used in clinical analysis because of its higher specificity and selectivity than immunoassay methods. A simple and robust UHPLC/MS method will be introduced for urinary cortisol analysis and the dynamic range and sensitivity (LOD and LLOQ) of the UHPLC/CMS method will be evaluated.

Rapid Screening for Fentanyl in Urine Using a Compact Mass Spectrometer (CMS) with an Open Port Sampling Interface (OPSI)

Introduction

Fentanyl, a fast-acting synthetic painkiller about 100 times stronger than morphine, is also the most widely used synthetic opioid medicine in 2017.1 Its abuse is becoming a public health problem. A quick and easy analysis method for this drug is in high demand from health practitioners and law enforcement agencies.

The Touch Express™ Open Port Sampling Interface (OPSI),2,3 is designed for simple sampling of solids, liquids, sample preparation tips and fibers. Paired with the ESI of the expression® CMS, the product incorporates an open port of continuous low-volume solvent, flowing directly into the ESI for MS analysis. Any soluble sample touching the open port will be analyzed by the mass spectrometer in just seconds.

Here, a simple and quick analysis method for fentanyl in urine using Touch Express™ OPSI on the Advion expression® CMS is presented.

Toluene-Assisted APCI Using a Compact Mass Spectrometer

Overview

  • Toluene-assisted APCI (TAPCI) can generate (M)+· and (M+H)+ molecules from analytes not MS accessible by ESI or APCI.
  • Elemental formula prediction at 250 ppm accuracy and isotope distribution matching by TAMI (Tal Aviv Molecule Identifier) supports analyte identification.
  • Combining both TAPCI and TAMI on a compact single quadrupole mass spectrometer (CMS) provides a cost-effective analysis platform for a wide compound space.

Monitoring Synthetic Reactions Using an (inert) Atmospheric Solids Analysis Probe (iASAP)

Introduction

Metal based compounds have found utility in various fields such as clinical, energy, food safety and environmental to name a few. Creating the metal complex is the last step in a synthetic process when ligands are bound to the metal center. Once made, these metal complexes can be used anywhere from stereospecific synthesis to anti-cancer drugs. It is critical that reaction conditions are providing the desired product and that side products are kept to a minimum to maximize yield. Presented here is the use of an inert atmospheric solid analysis (iASAP) probe to quickly sample and measure the reaction via mass spectrometry.

University of Leeds Webinar: Self-Optimizing Continuous Flow Reactors

Chemical processes can be performed in two ways; in batch or in flow, each method having set advantages and disadvantages associated with them.

Flow chemistry has gathered increasing attention over the past decade and is being readily adopted into academia to help improve synthetic routes, which maybe undesirable in batch, where outputs such as yield, productivity, E-factor or selectivity maybe improved via various methods of optimisation. On-line analytics within continuous flow chemistry allow reactions to be monitored in real-time ultimately allowing immediate characterisation and the ability to optimise in the easiest possible way.

Hosted by Jack Henion, Advion’s Chief Scientific Founder, Chris Horbaczewskyj of the University of Leeds outlines the work carried out within the Bourne group for process development applications:

  • Use of flow chemistry with online HPLC in the self-optimisation of reactions,
  • Use of online mass spectrometry for the optimisation of continuous flow reactions using an experimental design approach,
  • The development of new algorithms for multiple variable optimisation in chemical systems.