Rationalizing and Adapting Water-Accelerated Reactions for Sustainable Flow Organic Processes.

Water-accelerated reactions, wherein at least one organic reactant is not soluble in water, are an important class of organic reactions, with a potentially pivotal impact on sustainability of chemical manufacturing processes. However, mechanistic understanding of the factors controlling the acceleration effect has been limited, due to the complex and varied physical and chemical nature of these processes. In this study, a theoretical framework has been established to calculate the rate acceleration of known water-accelerated reactions, giving computational estimations of the change to ΔG‡ which correlate with experimental data. In-depth study of a Henry reaction between N-methylisatin and nitromethane using our framework led to rationalization of the reaction kinetics, its lack of dependence on mixing, kinetic isotope effect, and different salt effects with NaCl and Na2SO4. Based on these findings, a multiphase flow process which includes continuous phase separation and recycling of the aqueous phase was developed, and its superior green metrics (PMI-reaction = 4 and STY = 0.64 kg L-1 h-1) were demonstrated. These findings form the essential basis for further in silico discovery and development of water-accelerated reactions for sustainable manufacturing.

Algorithm-driven activity-directed expansion of a series of antibacterial quinazolinones.

Activity-directed synthesis (ADS) is a structure-blind, function driven approach that can drive the discovery of bioactive small molecules. In ADS, arrays of reactions are designed and executed, and the crude product mixtures are then directly screened to identify reactions that yield bioactive products. The design of subsequent reaction arrays is then informed by the hit reactions that are discovered. In this study, algorithms for reaction array design were developed in which the reactions to be executed were selected from a large set of virtual reactions; the reactions were selected on the basis of similarity to reactions known to yield bioactive products. The algorithms were harnessed to design arrays of photoredox-catalysed alkylation reactions whose crude products were then screened for inhibition of growth of S. aureus ATCC29213. It was demonstrated that the approach enabled expansion of a series of antibacterial quinazolinones. It is envisaged that such algorithms could ultimately enable fully autonomous activity-directed molecular discovery.

Enhancing the Potential Exploitation of Food Waste: Extraction, Purification, and Characterization of Renewable Specialty Chemicals from Blackcurrants ( Ribes nigrum L.).

Natural colorants were extracted from renewable botanical sources, specifically waste epicarp from the blackcurrant fruit pressing industry. A process was developed which used acidified water extraction followed by a solid-phase extraction (SPE) purification stage which allowed the production of an anthocyanin-rich extract in good yields (ca. 2% w/ w based on dry weight of raw material). The components in the extracts were extensively characterized by HPLC, mass spectrometry, IR, NMR, and UV-vis spectroscopy. HPLC confirmed presence of four anthocyanins: delphinidin-3- O-rutinoside (45%), cyanidin-3- O-rutinoside (31%), and the corresponding glucosides at 16% and 8%, respectively. On sequential liquid-liquid aqueous-organic partitioning of the post-SPE sample, monomeric anthocyanins (54.7%) and polymeric anthocyanins (18%) were found in the aqueous layer with 3- O-rutinosides of myricetin (3.1%) and quercetin (3.2%), while isopropylacetate achieved selective extraction of caffeic acid (3%), p-coumaric acid (5%), and myricetin (2.5%) and quercetin (3.2%) aglycons. 3- O-Glucosides of myricetin (3.1%) and quercetin (2%), along with nigrumin- p-coumarate (1%) and nigrumin ferulate (0.5%) were selectively extracted from the remaining aqueous fraction using ethyl acetate. This allowed for near total quantification of the blackcurrant extract composition.

Revisiting unexploited antibiotics in search of new antibacterial drug candidates: the case of γ-actinorhodin.

Of the thousands of natural product antibiotics discovered to date, only a handful have been developed for the treatment of bacterial infection. The clinically unexploited majority likely include compounds with untapped potential as antibacterial drugs, and in view of the ever-growing unmet medical need for such agents, warrant systematic re-evaluation. Here we revisit the actinorhodins, a class that was first reported 70 years ago, but which remains poorly characterized. We show that γ-actinorhodin possesses many of the requisite properties of an antibacterial drug, displaying potent and selective bactericidal activity against key Gram-positive pathogens (including Staphylococcus aureus and enterococci), a mode of action distinct from that of other agents in clinical use, an extremely low potential for the development of resistance, and a degree of in vivo efficacy in an invertebrate model of infection. Our findings underscore the utility of revisiting unexploited antibiotics as a source of novel antibacterial drug candidates.