The immediate environment of a molecule can have a profound influence on its properties. Benzocaine, the ethyl ester of para-aminobenzoic acid that finds an application as a local anesthetic, is found to adopt in its protonated form at least two populations of distinct structures in the gas phase, and their relative intensities strongly depend on the properties of the solvent used in the electrospray ionization process. Here, we combine IR-vibrational spectroscopy with ion mobility-mass spectrometry to yield gas-phase IR spectra of simultaneously m/z and drift-time-resolved species of benzocaine. The results allow for an unambiguous identification of two protomeric species: the N- and O-protonated forms. Density functional theory calculations link these structures to the most stable solution and gas-phase structures, respectively, with the electric properties of the surrounding medium being the main determinant for the preferred protonation site. The fact that the N-protonated form of benzocaine can be found in the gas phase is owed to kinetic trapping of the solution-phase structure during transfer into the experimental setup. These observations confirm earlier studies on similar molecules where N- and O-protonation have been suggested.
14Cellular Biology, University of Leeds, LS2 9JT, UK Electrospray ion mobility-mass spectrometry (IM-MS) data show that for some small 21 molecules, two (or even more) ions with identical sum formula and mass, but distinct drift 22
Breath research has almost invariably focussed on the identification of endogenous volatile organic compounds (VOCs) as disease biomarkers. After five decades, a very limited number of breath tests measuring endogenous VOCs is applied to the clinic. In this perspective article, we explore some of the factors that may have contributed to the current lack of clinical applications of breath endogenous VOCs. We discuss potential pitfalls of experimental design, analytical challenges, as well as considerations regarding the biochemical pathways that may impinge on the application of endogenous VOCs as specific disease biomarkers. We point towards several lines of evidence showing that breath analysis based on administration of exogenous compounds has been a more successful strategy, with several tests currently applied to the clinic, compared to measurement of endogenous VOCs. Finally, we propose a novel approach, based on the use of exogenous VOC (EVOC) probes as potential strategy to measure the activity of metabolic enzymes in vivo, as well as the function of organs, through breath analysis. We present longitudinal data showing the potential of EVOC probe strategies in breath analysis. We also gathered important data showing that administration of EVOC probes induces significant changes compared to previous exposures to the same compounds. EVOC strategies could herald a new wave of substrate-based breath tests, potentially bridging the gap between research tools and clinical applications.
The hydrolysis of melphalan is studied in the scope of a phase II clinical trial (isolated lung perfusion, ILuP). Patient samples were screened for the presence of all documented and novel melphalan hydrolysis products. This study reports the formation of a new class of oligomeric compounds in both in vivo and in vitro samples.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.