Gloves represent an essential feature for hand protection because it is a requirement in the professional framework to comply with both hand hygiene standards and the principles of good laboratory practice. Despite their wide use, there is a knowledge gap regarding their composition, including phthalates. The purpose of the present study was to develop two orthogonal methods, GC–MS and HPLC–DAD, for the screening of plasticizers in gloves. Performances of these two methods were compared in terms of ease of use, number of analyzed plasticizers, and sample preparation. The two methods were validated and applied for the identification and quantification of plasticizers in ten gloves made with different materials (vinyl, nitrile, latex, and neoprene). Results revealed the presence of three main ones: DEHP, DEHT, and DINP. Additionally, the contents of plasticizers were extremely variable, depending on the glove material. As expected, the results point out a predominant use of plasticizers in vinyl gloves with an amount that should be of concern. While DEHP is classified as a toxic substance for reproduction 1B, it was, however, quantified in the ten different glove samples studied. This study provides new data regarding the plasticizers’ content in protective gloves, which could be useful for risk assessment.

Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders.

Edaravone is an antioxidant drug used for the treatment of amyotrophic lateral sclerosis. Edaravone has been shown to react with aldehydes, such as 6formylpterin. We investigated the reaction of edaravone with vanillin (used as a model aromatic aldehyde) to evidence the reaction products formed in an aqueous solution. Mono-and bis-adducts vanillin-(edaravone) 1-2 were characterized by high-performance liquid chromatography coupled to high-resolution mass spectrometry. Kinetic analysis revealed that the bis-adduct vanillin-(edaravone) 2 formed more intensely and more rapidly than the mono-adduct vanillin-(edaravone) 1 . Decay rates of 2.4 and 3.4 μM/min were calculated for vanillin and edaravone, respectively. The Michael addition of a second edaravone molecule onto the vanillin-(edaravone) 1 hybrid corresponds to a facile reaction compared to the initial Knoevenagel-type condensation between edaravone and vanillin. However, the bis-adduct vanillin-(edaravone) 2 can decompose in solution to provide the mono-adduct and regenerate small amounts of edaravone and vanillin. The regeneration of vanillin from vanillin-(edaravone) 2 was kinetically characterized. We compared the condensation of edaravone with fifteen aromatic aldehydes, to show that only vanillin and 3-methoxy-benzaldehyde can react easily with edaravone, the other aromatic aldehydes being less or not reactive. The study opens perspectives to apprehend the reactivity of edaravone with biologically relevant aldehydes.

DOI: https://doi.org/10.1002/sscp.202200031 The cover picture shows how the reactivity of the phenyl‐pyrazolone drug edaravone in the presence of vanillin, used here as a model aromatic aldehyde. Edaravone (EDA) is an injectable drug commonly used to treat amyotrophic lateral sclerosis, acting as a free radical scavenger to reduce oxidative damages in cells. In addition, EDA can form adducts with aromatic aldehydes, such as 6‐formylpterin and vanillin, for example. Here, the mono‐ and bis‐adducts formed in the presence of vanillin in an aqueous solution have been separated and fully identified. The kinetic of the reaction has been analyzed and, for the first time, a partial reversibility of the reaction has been evidenced.

Orally-active anticancer small molecules targeting the PD-1/PD-L1 immune checkpoint are actively searched. Phenyl-pyrazolone derivatives with a high affinity for PD-L1 have been designed and characterized. In addition, the phenyl-pyrazolone unit acts as a scavenger of oxygen free radicals, providing antioxidant effects. The mechanism is known for the drug edaravone (1) which is also an aldehyde-reactive molecule. The present study reports the synthesis and functional characterization of new molecules (2–5) with an improved anti-PD-L1 activity. The leading fluorinated molecule 5 emerges as a potent checkpoint inhibitor, avidly binding to PD-L1, inducing its dimerization, blocking PD-1/PD-L1 signaling mediated by phosphatase SHP-2 and reactivating the proliferation of CTLL-2 cells in the presence of PD-L1. In parallel, the compound maintains a significant antioxidant activity, characterized using electron paramagnetic resonance (EPR)-based free radical scavenging assays with the probes DPPH and DMPO. The aldehyde reactivity of the molecules was investigated using 4-hydroxynonenal (4-HNE), which is a major lipid peroxidation product. The formation of drug-HNE adducts, monitored by high resolution mass spectrometry (HRMS), was clearly identified and compared for each compound. The study leads to the selection of compound 5 and the dichlorophenyl-pyrazolone unit as a scaffold for the design of small molecule PD-L1 inhibitors endowed with antioxidant properties.