Biocatalytic routes to anti-viral agents and their synthetic intermediates.

With recent outbreaks of COVID-19 and Ebola, health and healthcare have once more shown to be heavily burdened by the lack of generally effective anti-viral therapies. Initial scientific ventures towards finding anti-viral agents are soon to be followed by challenges regarding their mass production. Biocatalysis offers mild, highly selective, and environmentally benign synthetic strategies for the production of pharmaceuticals in a sustainable fashion. Here we summarise biocatalytic methods that have been applied to the production of FDA-approved anti-viral drugs and their intermediates. Exemplary are the enzymatic asymmetric synthesis of amino acid components, the fermentative production of structurally complex intermediates of anti-influenza drugs and the fully enzymatic, large-scale synthesis of a potential block-buster HIV drug. With many enzyme classes being uncharted with regards to the synthesis of anti-viral agents, there is still a large unopened toolbox waiting to be unlocked. Additionally, by discussing biocatalytic strategies towards potential anti-viral agents against SARS-CoV-2, we hope to contribute to the development of novel synthetic routes to aid in the mass production of a future treatment of COVID-19.

One-Step Generation of Reactive Superhydrophobic Surfaces via SiHCl3-Based Silicone Nanofilaments.

Superhydrophobic surfaces gain ever-growing attention because of their applicability in many (consumer) products/materials as they often display, among others, antifouling, anti-icing, and/or self-cleaning properties. A simple way to achieve superhydrophobicity is through the growth of silicone nanofilaments. These nanofilaments, however, are very often nonreactive and thus difficult to utilize in subsequent chemistries. In response, we have developed a single-step procedure to grow (SiHCl3-based) silicone nanofilaments with selective reactivity that are intrinsically superhydrophobic. The silicone nanofilaments could be further functionalized via Pt-catalyzed hydrosilylation of exposed Si-H moieties. These surfaces are easily obtained using mild conditions and are stable under hydrolytic conditions (neutral water, 24 h at 80 °C) while remaining highly transparent, which makes them well suited for optical and photochemical experiments.

Elucidating the mechanism behind the laccase-mediated modification of poly(ethersulfone).

Laccase-mediated oligomerisation of 4-hydroxybenzoic acid (4-HBA) derivatives and simultaneous in situ surface modification has proven to be a cost-effective, easily applicable and eco-friendly strategy for preventing biofouling of poly(ethersulfone) (PES) water filtration membranes. Modification of the membrane surface has previously been hypothesised to occur through covalent bonding of enzymatically generated phenolic radicals to the polymeric membrane. The current study shows, however, that in situ formation of soluble phenolic oligomers does not result in covalent membrane modification. We studied in situ laccase-mediated oligomerisation of custom-synthesised positively charged and commercially available negatively charged monomeric phenols, and demonstrated that their mode of binding to PES is not covalent. In addition, soluble, non-soluble and on-resin PES model compounds were synthesised and used in the laccase-mediated oligomerisation of 4-HBA. Covalent bond formation between these model compounds and (oligomeric) 4-HBA could not be observed either. Furthermore, extensive washing of PES membranes modified through laccase-mediated oligomerisation of 4-HBA resulted in substantial discolouration of the membrane surface, showing that the layer of oligomerised phenolics could easily be removed. Altogether, it was concluded that laccase-assisted modification of PES membranes resulted from strong physical adsorption of phenolic oligomers and polymers rather than from covalent bonding of those.

Laccase-Mediated Grafting on Biopolymers and Synthetic Polymers: A Critical Review.

Laccase-mediated grafting on lignocelluloses has gained considerable attention as an environmentally benign method to covalently modify wood, paper and cork. In recent decades this technique has also been employed to modify fibres with a polysaccharide backbone, such as cellulose or chitosan, to infer colouration, antimicrobial activity or antioxidant activity to the material. The scope of this approach has been further widened by researchers, who apply mediators or high redox potential laccases and those that modify synthetic polymers and proteins. In all cases, the methodology relies on one- or two-electron oxidation of the surface functional groups or of the graftable molecule in solution. However, similar results can very often be achieved through simple deposition, even after extensive washing. This unintended adsorption of the active substance could have an adverse effect on the durability of the applied coating. Differentiating between actual covalent binding and adsorption is therefore essential, but proves to be challenging. This review not only covers excellent research on the topic of laccase-mediated grafting over the last five to ten years, but also provides a critical comparison to highlight either the lack or presence of compelling evidence for covalent grafting.