engleski

Rational design of natural deep eutectic solvents for biocatalytic preparation of chiral drugs

Natural deep eutectic solvents (NADES) and biocatalysis's synergistic use fit logically to the efficient and sustainable production of enantiomerically pure compounds. The biotechnological approach ensures catalysing otherwise difficult transformations in high regio-, chemo- and enantioselective, at mild and economic conditions. NADES can serve as the green support for modulating/directing the reaction route to obtain the desired product. Papers dealing with the use of NADES as a medium for enantiopure compounds preparation/recovery implied that the unique properties of these solvents make them a promising candidate for reactions catalysed either by isolated enzymes or whole-cells through improved substrate/product solubility ; enhanced enzyme activity, and stability ; enhanced reaction yield ; possibility to tailor reaction enantioselectivity and regioselectivity ; the possibility of solvent NADES recycle and reuse [1, 2] The abundance of possible NADES formulations, makes it impossible to prepare and characterize all of them, pointing out the need to develop predictive NADES structure-activity mathematical models. Approaches used so far for screening appropriate/ideal NADES (out of an enormous pool of structural possibilities) have been governed by time- consuming empirical methods. The systematic investigation in NADES structure-activity relationship, as a backbone for these solvents' rational design, is still lacking. Current literature suggests COSMOtherm, software that can predict thermodynamic properties and phase equilibrium, which would help design the best possible solvent for a specific application. Thus, the trial-and-error method of NADES preparation can be avoided. Based on those mentioned above, this work aims to apply COSMOtherm in NADES screening for application in Saccharomyces cerevisiae - catalysed asymmetric reduction of prochiral ketones for chiral building block synthesis. By using COSMOtherm, the most suitable NADES for biocatalytic reaction is selected among 100 different NADES from our database. Further steps in rational design include optimization of reaction conditions, development of downstream protocol and scale-up.

chiral drugs ; biocatalysis ; natural deep eutectic solvents ; Saccharomyces cerevisiae

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