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The application of biocatalysis has become essential in both academic and industrial domains for the asymmetric synthesis of chiral amines, and it serves as an alternative tool to transition-metal catalysis and complements traditional chemical methods. It relies on the swift expansion of available processes, primarily as a result of advanced tools for enzyme discovery, combined with high-throughput laboratory evolution techniques for optimizing biocatalysts. This concept paper explores the utilization of non-conventional media such as ether-type solvents, deep eutectic solvents, and micellar catalysis to enhance biocatalytic reactions for chiral amine synthesis. Each section focuses on the unique properties of these media, including their ability to stabilize enzymes, alter substrate solubility, and modulate enzyme selectivity. The paper aims to provide insights into how these innovative media can overcome traditional limitations, offering new avenues for sustainable and efficient chiral amine production through biocatalytic processes., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

The first enantioselective reduction of 2-substituted cyclic imines to the corresponding amines (pyrrolidines, piperidines, and azepines) by imine reductases (IREDs) in non-conventional solvents is reported. The best results were obtained in a glycerol/phosphate buffer 1 : 1 mixture, in which heterocyclic amines were produced with full conversions (>99 %), moderate to good yields (22-84 %) and excellent S-enantioselectivities (up to >99 % ee). Remarkably, the process can be performed at a 100 mM substrate loading, which, for the model compound, means a concentration of 14.5 g L -1 . A fed-batch protocol was also developed for a convenient scale-up transformation, and one millimole of substrate 1 a was readily converted into 120 mg of enantiopure amine (S)-2 a with a remarkable 80 % overall yield. This aspect strongly contributes to making the process potentially attractive for large-scale applications in terms of economic and environmental sustainability for a good number of substrates used to produce enantiopure cyclic amines of high pharmaceutical interest., (© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Crystalline silica (CS) is a well-known hazardous material that causes severe diseases including silicosis, lung cancer, and autoimmune diseases. However, the hazard associated to crystalline silica is extremely variable and depends on some specific characteristics, including crystal structure and surface chemistry. The crystalline silica polymorphs share the SiO 2 stoichiometry and differentiate for crystal structure. The different crystal lattices in turn expose differently ordered hydroxyl groups at the crystal surface, i.e., the silanols. The nearly free silanols (NFS), a specific population of weakly interacting silanols, have been recently advanced as the key surface feature that governs recognition mechanisms between quartz and cell membrane, initiating toxicity. We showed here that the nearly free silanols occur on the other crystalline silica polymorphs and take part in the molecular interactions with biomembranes. A set of crystalline silica polymorphs, including quartz, cristobalite, tridymite, coesite, and stishovite, was physico-chemically characterized and the membranolytic activity was assessed using red blood cells as model membranes. Infrared spectroscopy in highly controlled conditions was used to profile the surface silanol topochemistry and the occurrence of surface nearly free silanols on crystalline silica polymorphs. All crystalline silica polymorphs, but stishovite were membranolytic. Notably, pristine stishovite did not exhibited surface nearly free silanols. The topochemistry of surface silanols was modulated by thermal treatments, and we showed that the occurrence of nearly free silanols paralleled the membranolytic activity for the crystalline silica polymorphs. These results provide a comprehensive understanding of the structure-activity relationship between nearly free silanols and membranolytic activity of crystalline silica polymorphs, offering a possible clue for interpreting the molecular mechanisms associated with silica hazard and bio-minero-chemical interfacial phenomena, including prebiotic chemistry., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pavan, Escolano-Casado, Bellomo, Cananà, Tomatis, Leinardi, Mino and Turci.)

Inhaled crystalline silica causes inflammatory lung diseases, but the mechanism for its unique activity compared to other oxides remains unclear, preventing the development of potential therapeutics. Here, the molecular recognition mechanism between membrane epitopes and "nearly free silanols" (NFS), a specific subgroup of surface silanols, is identified and proposed as a novel broad explanation for particle toxicity in general. Silica samples having different bulk and surface properties, specifically different amounts of NFS, are tested with a set of membrane systems of decreasing molecular complexity and different charge. The results demonstrate that NFS content is the primary determinant of membrane disruption causing red blood cell lysis and changes in lipid order in zwitterionic, but not in negatively charged liposomes. NFS-rich silica strongly and irreversibly adsorbs zwitterionic self-assembled phospholipid structures. This selective interaction is corroborated by density functional theory and supports the hypothesis that NFS recognize membrane epitopes that exhibit a positive quaternary amino and negative phosphate group. These new findings define a new paradigm for deciphering particle-biomembrane interactions that will support safer design of materials and what types of treatments might interrupt particle-biomembrane interactions., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)