Chitin and chitosan, abundant biopolymers derived from the shells of crustaceans and the cell walls of fungi, have garnered considerable attention in pharmaceutical circles due to their ...biocompatibility, biodegradability, and versatile properties. Deep eutectic solvents (DESs), emerging green solvents composed of eutectic mixtures of hydrogen bond acceptors and donors, offer promising avenues for enhancing the solubility and functionality of chitin and chitosan in pharmaceutical formulations. This review delves into the potential of utilizing DESs as solvents for chitin and chitosan, highlighting their efficiency in dissolving these polymers, which facilitates the production of novel drug delivery systems, wound dressings, tissue engineering scaffolds, and antimicrobial agents. The distinctive physicochemical properties of DESs, including low toxicity, low volatility, and adaptable solvation power, enable the customization of chitin and chitosan-based materials to meet specific pharmaceutical requirements. Moreover, the environmentally friendly nature of DESs aligns with the growing demand for sustainable and eco-friendly processes in pharmaceutical manufacturing. This revision underscores recent advances illustrating the promising role of DESs in evolving the pharmaceutical applications of chitin and chitosan, laying the groundwork for the development of innovative drug delivery systems and biomedical materials with enhanced efficacy and safety profiles.
Biocatalysis has emerged as a powerful and useful strategy for the synthesis of active pharmaceutical ingredients (APIs). The outstanding developments in molecular biology techniques allow nowadays ...the screening, large-scale production, and designing of biocatalysts, adapting them to desired reactions. Many enzymes can perform reactions both in aqueous and non-aqueous media, broadening even further the opportunities to integrate them in complex pharmaceutical multi-step syntheses.
This paper showcases several examples of biocatalysis in the pharmaceutical industry, covering examples of different enzymes, such as lipases, oxidoreductases, and transaminases, to deliver active drugs through complex synthetic routes. Examples are critically discussed in terms of reaction conditions, motivation for using an enzyme, and how biocatalysts can be integrated in multi-step syntheses. When possible, biocatalytic routes are benchmarked with chemical reactions.
The reported enzymatic examples are performed with high substrate loadings (>100 g L
−1
) and with excellent selectivity, making them inspiring strategies for present and future industrial applications. The combination of powerful molecular biology techniques with the needs of the pharmaceutical industry can be aligned, creating promising platforms for synthesis under more sustainable conditions.
Dextran aldehyde (dexOx), resulting from the periodate oxidative cleavage of 1,2-diol moiety inside dextran, is a polymer that is very useful in many areas, including as a macromolecular carrier for ...drug delivery and other biomedical applications. In particular, it has been widely used for chemical engineering of enzymes, with the aim of designing better biocatalysts that possess improved catalytic properties, making them more stable and/or active for different catalytic reactions. This polymer possesses a very flexible hydrophilic structure, which becomes inert after chemical reduction; therefore, dexOx comes to be highly versatile in a biocatalyst design. This paper presents an overview of the multiple applications of dexOx in applied biocatalysis, e.g., to modulate the adsorption of biomolecules on carrier surfaces in affinity chromatography and biosensors design, to serve as a spacer arm between a ligand and the support in biomacromolecule immobilization procedures or to generate artificial microenvironments around the enzyme molecules or to stabilize multimeric enzymes by intersubunit crosslinking, among many other applications.
Agarose-vinyl sulfone (VS) beads have proven to be a good support to immobilize several enzymes. However, some enzymes are hardly immobilized on it. This is the case of penicillin G acylase (PGA) ...from Escherichia coli, which is immobilized very slowly on this support (less than 10% in 24 h). This enzyme is also not significantly adsorbed in aminated MANAE-agarose beads, an anionic exchanger. In this study, MANAE-agarose beads were modified with divinyl sulfone (DVS) to produce MANAE-vinyl sulfone (VS) agarose beads. When PGA was immobilized on this support, the enzyme was fully immobilized in less than 1.5 h. PGA cannot be released from the support by incubation at high ionic strength, suggesting that the enzyme was rapidly immobilized in a covalent fashion. Considering that the amount of reactive VS groups was only marginally increased, the results indicated some cooperative effect between the anion exchange on the amine groups of the support, probably as the first step of the process, and the covalent attachment of the previously adsorbed PGA molecules. The covalent reaction of the previously adsorbed enzyme molecules proceeds much more efficiently than that of the free enzyme, due to the proximity of the reactive groups of the support and the enzyme. Finally, the steps of immobilization, incubation, and blocking with different agents were studied to determine the effects on final activity/stability. The stability of PGA immobilized on this new catalyst was improved with respect to the VS-agarose prepared at low ionic strength.
INTRODUCTIONAlzheimer's disease is a multifactorial neurodegenerative disorder characterized by beta-amyloid accumulation and tau protein hyperphosphorylation. The disease involves interconnected ...mechanisms, which can be clustered into two target-packs based on the affected proteins. Pack-1 focuses on beta-amyloid accumulation, oxidative stress, and metal homeostasis dysfunction, and Pack-2 involves tau protein, calcium homeostasis, and neuroinflammation. Against this background heterocyclic system, there is a powerful source of pharmacophores to develop effective small drugs to treat multifactorial diseases like Alzheimer's.AREAS COVEREDThis review highlights the most promising heterocyclic systems as potential hit candidates with multi-target capacity for the development of new drugs targeting Alzheimer's disease. The selection of these heterocyclic systems was based on two crucial factors: their synthetic versatility and their well-documented biological properties of therapeutic potential in neurodegenerative diseases.EXPERT OPINIONThe synthesis of small drugs against Alzheimer's disease requires a multifactorial approach that targets the key pathological proteins. In this context, the utilization of heterocyclic systems, with well-established synthetic processes and facile functionalization, becomes a crucial element in the design phases. Furthermore, the selection of hit heterocyclic should be guided by a full understanding of their biological activities. Thus, the identification of promising heterocyclic scaffolds with known biological effects increases the potential to develop effective molecules against Alzheimer's disease.
Invited for this month′s cover is the Working Group Sustainable Chemistry of the European Society of Applied Biocatalysis (ESAB). The image shows the significant contributions of Biocatalysis to ...science, industry, society, and environment as a technology of first choice for Sustainable Chemistry in the 21st century. The Perspective itself is available at 10.1002/cssc.202102709.
“A “Golden Age” of biocatalysis is on the horizon…” This and more about the story behind the research that inspired the Cover image is presented in the Cover Profile. Read the full text of the corresponding research at 10.1002/cssc.202102709. View the Front Cover here: 10.1002/cssc.202200707.
In their Editorial for the Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry, Guest Editors Andrés Alcántara, Pablo Domínguez de María, Jennifer Littlechild, and Roland ...Wohlgemuth and their co‐workers on the European Society of Applied Biocatalysis’ (ESAB) Working Group on Sustainable Chemistry Martin Schürmann and Roger Sheldon discuss the Special Issue and the importance of biocatalysis in carrying out cutting‐edge industrial chemistry in a sustainable way, as well as the future prospects for the field.
Putting biocatalysts to work: In their Editorial for the Special Issue on Biocatalysis as Key to Sustainable Industrial Chemistry, the Guest Editors and their co‐workers on the European Society of Applied Biocatalysis’ Working Group on Sustainable Chemistry discuss the importance of biocatalysis in carrying out industrial chemistry in a sustainable way.
Dynamic kinetic resolution (DKR) of a series of sterically hindered allylic alcohols has been conducted with Candida antarctica lipase B (CALB) and ruthenium catalyst 1. The optically pure allylic ...acetates obtained were subjected to oxidative cleavage to give the corresponding acylated acyloins in high yields without loss of chiral information.
This review mainly focuses on the use of glucose oxidase in the production of d -gluconic acid, which is a reactant of undoubtable interest in different industrial areas. The enzyme has been used in ...numerous instances as a model reaction to study the problems of oxygen supply in bioreactors. One of the main topics in this review is the problem of the generated side product, hydrogen peroxide, as it is an enzyme-inactivating reagent. Different ways to remove hydrogen peroxide have been used, such as metal catalysts and use of whole cells; however, the preferred method is the coupling glucose oxidase with catalase. The different possibilities of combining these enzymes have been discussed (use of free enzymes, independently immobilized enzymes or co-immobilized enzymes). Curiously, some studies propose the addition of hydrogen peroxide to this co-immobilized enzyme system to produce oxygen in situ . Other cascade reactions directed toward the production of gluconic acid from polymeric substrates will be presented; these will mainly involve the transformation of polysaccharides (amylases, cellulases, etc. ) but will not be limited to those ( e.g. , gluconolactonase). In fact, glucose oxidase is perhaps one of most successful enzymes, and it is involved in a wide range of cascade reactions. Finally, other applications of the enzyme have been reviewed, always based on the production of d -gluconic acid, which produces a decrease in the pH, a decrease in the oxygen availability or the production of hydrogen peroxide; in many instances, cascade reactions are also utilized. Thus, this review presents many different cascade reactions and discusses the advantages/drawbacks of the use of co-immobilized enzymes.
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