Gilles Frache

A series of bis-phenolate saturated N-heterocyclic carbene (NHC) group 4 complexes ([κ³-O,C,O]-NHC)­M­(OiPr)­Cl­(THF) (M = Ti, 1; Zr, 2; Hf, 3) in the presence of [PPN]Cl as cocatalyst were investigated and showed high activity in the tandem terpolymerization of phthalic anhydride (PA), cyclohexene oxide (CHO) with CO₂. The resultant terpolymers revealed a diblock pattern leading selectively to poly­(ester-b-carbonate). Subsequently, other titanium complexes ([κ³-O,C,O]-NHC)­TiX₂ bearing various coligands (X = Cl, 4; OiPr, 5; OAc, 6; OAc^F, 7) also displayed high activity with a turnover frequency (TOF) up to 460 h^–1 that is comparable to 1. Using the same tandem approach, the nature of terpolymers was modulated with other mono- and tricyclic anhydrides alongside CHO with CO₂. Intrigued by the high rates of PA conversion observed experimentally in terpolymerization, complexes 1–3 as well as benzannulated and unsaturated NHC analogues of complex 1 were investigated as a stand-alone reaction for the copolymerization of PA and CHO. Complex 1/[PPN]Cl displayed excellent catalytic activity (TOF ∼ 1600 h^–1) and high selectivity (≥99%) toward polyesters comparable to other highly active heteronuclear (Al/K and Fe/K) catalysts and binary (salen)­MX systems. Kinetic studies performed on complexes 1 and 3 determined activation barriers (E _a) consistent with the observed catalytic trend, i.e., E _a: Ti < Hf.

Professor Jean‐François Muller, a distinguished figure in the field of mass spectrometry, made significant contributions to the advancement of analytical chemistry and its applications. As the founding director of the Laboratory of Mass Spectrometry and Laser Chemistry at the University of Metz, Muller played a pivotal role in establishing Metz as a leading center for mass spectrometry research. His pioneering work, particularly in the development of matrix‐assisted laser desorption/ionization (MALDI) instrumentation and Fourier transform ion cyclotron resonance mass Spectrometry (FTICR MS), has had a profound impact on various scientific disciplines. This article commemorates Professor Muller's illustrious career and highlights his collaborative efforts with industrial partners such as Total, which led to groundbreaking advancements in MS analysis. I will delve into the key findings of my thesis which focused on instrumental developments for MALDI analysis and imaging, as well as personal reminiscences and the impact of his inspiring mentorship.

Professor Jean-François Muller, a distinguished figure in the field of mass spectrometry, made significant contributions to the advancement of analytical chemistry and its applications. As the founding director of the Laboratory of Mass Spectrometry and Laser Chemistry at the University of Metz, JF Muller played a pivotal role in establishing Metz as a leading centre for mass spectrometry research. His pioneering work, particularly in the development of matrix-assisted laser desorption/ionization (MALDI) instrumentation and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry (FTICR MS), has had a profound impact on various scientific disciplines. This article commemorates Pr. JF Muller’s illustrious career and highlights his collaborative efforts with industrial partners such as TOTAL, which led to groundbreaking advancements in MS analysis. I will delve into the key findings of my thesis which focused on instrumental developments for MALDI analysis and imaging, as well as personal reminiscences and the impact of his inspiring mentorship.

Using our earlier developed protocol, mass spectrometry imaging of small endogenous peptides (and a selection of small metabolites) can be successfully performed directly in tissue sections of formaldehyde-fixed paraffin-embedded (FFPE) samples, such as those available in Homo sapiens biobanks. In analogy with immunohistochemistry (IHC) which employs antibodies as detection probes, this method was designated mass spectrometry histochemistry (MSHC) as it solely relies on (top-down) mass spectrometry for analyte detection. We demonstrate that MSHC enables the localization of cystine-containing neuropeptides in histological sections of human FFPE biobanked tissue and illustrate this on pituitary adenomas and non-diseased pituitary tissues archived for several years in an academic hospital pathology biobank. The instrumental setup consists of high-resolution mass spectrometers (several orbitrap systems and one dedicated hybrid TOF instrument) fitted with atmospheric pressure (AP) scanning matrix-assisted laser desorption/ionization MALDI. Currently, the best spatial resolution routinely achievable with such (MALDI) apparatus is 5m. The high mass spectrometric resolution obtained allows revealing the full isotope envelopes of the peptides. As such both reduced and oxidized cysteine-containing proteoforms of e.g., the neurosecretory nonapeptides vasopressin and oxytocin can be visualized in biobanked FFPE tissue, demonstrating yet a novel application of MSHC.

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has become an important tool for skin analysis, as it allows the simultaneous detection and localization of diverse molecular species within a sample. The use of in vivo and ex vivo human skin models is costly and presents ethical issues; therefore, reconstructed human epidermis (RHE) models, which mimic the upper part of native human skin, represent a suitable alternative to investigate adverse effects of chemicals applied to the skin. However, there are few publications investigating the feasibility of using MALDI MSI on RHE models. Therefore, the aim of this study was to investigate the effect of sample preparation techniques, i.e., substrate, sample thickness, washing, and matrix recrystallization, on the quality of MALDI MSI for lipids analysis of the SkinEthic RHE model. Images were generated using an atmospheric pressure MALDI source coupled to a high-resolution mass spectrometer with a pixel size of 5 μm. Masses detected in a defined region of interest were analyzed and annotated using the LipostarMSI platform. The results indicated that the combination of (1) coated metallic substrates, such as APTES-coated stainless-steel plates, (2) tissue sections of 6 μm thickness, and (3) aqueous washing before HCCA matrix spraying (without recrystallization), resulted in images with a significant signal intensity as well as numerous m/z values. This refined methodology using AP-MALDI coupled to a high-resolution mass spectrometer should improve the current sample preparation workflow to evaluate changes in skin composition after application of dermatocosmetics.

Nowadays, matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) is routinely implemented as the reference method for the swift and straightforward identification of microorganisms. However, this method is not flawless and there is a need to upgrade the current methodology in order to free the routine lab from incubation time and shift from a culture-dependent to an even faster independent culture system. Over the last two decades, mass spectrometry imaging (MSI) gained tremendous popularity in life sciences, including microbiology, due to its ability to simultaneously detect biomolecules, as well as their spatial distribution, in complex samples. Through this literature review, we summarize the latest applications of MALDI-MSI in microbiology. In addition, we discuss the challenges and avenues of exploration for applying MSI to solve current MALDI-TOF MS limits in routine and research laboratories.

Mass spectrometry imaging is a technique uniquely suited to localize and identify lipids in a tissue sample. Using an atmospheric pressure (AP-) matrix-assisted laser desorption ionization (MALDI) source coupled to an Orbitrap Elite, numerous lipid locations and structures can be determined in high mass resolution spectra and at cellular spatial resolution, but careful sample preparation is necessary. We tested 11 protocols on serial brain sections for the commonly used MALDI matrices CHCA, norharmane, DHB, DHAP, THAP, and DAN in combination with tissue washing and matrix additives to determine the lipid coverage, signal intensity, and spatial resolution achievable with AP-MALDI. In positive-ion mode, the most lipids could be detected with CHCA and THAP, while THAP and DAN without additional treatment offered the best signal intensities. In negative-ion mode, DAN showed the best lipid coverage and DHAP performed superiorly for gangliosides. DHB produced intense cholesterol signals in the white matter. One hundred fifty-five lipids were assigned in positive-ion mode (THAP) and 137 in negative-ion mode (DAN), and 76 peaks were identified using on-tissue tandem-MS. The spatial resolution achievable with DAN was 10 μm, confirmed with on tissue line-scans. This enabled the association of lipid species to single neurons in AP-MALDI images. The results show that the performance of AP-MALDI is comparable to vacuum MALDI techniques for lipid imaging.