Abstract
Significant inroads have been made using biocatalysts to perform new-to-nature reactions with high selectivity and efficiency. Meanwhile, advances in organosilicon chemistry have led to rich sets of reactions holding great synthetic value. Merging biocatalysis and silicon chemistry could yield new methods for the preparation of valuable organosilicon molecules as well as the degradation and valorization of undesired ones. Despite silicon’s importance in the biosphere for its role in plant and diatom construction, it is not known to be incorporated into any primary or secondary metabolites. Enzymes have been found that act on silicon-containing molecules, but only a few are known to act directly on silicon centers. Protein engineering and evolution has and could continue to enable enzymes to catalyze useful organosilicon transformations, complementing and expanding upon current synthetic methods. The role of silicon in biology and the enzymes that act on silicon-containing molecules are reviewed to set the stage for a discussion of where biocatalysis and organosilicon chemistry may intersect.
Highlights
Silicon is found in copious amounts on Earth, where it comprises ∼28% of the lithosphere, is the second most abundant element after oxygen, and is present in teramole quantities in the oceans.[1,2] It holds a privileged position as one of the key elements of human enterprise
We review the enzymes that act on silicon-containing molecules and how biocatalysis has been used to perform organosilicon chemistry, including using reactivities not found in Nature
Advances in molecular biology and protein engineering techniques combined with the ever-increasing diversity of known protein sequences have expanded the ability to access biocatalysts with new-to-nature reactivities
Summary
Silicon is found in copious amounts on Earth, where it comprises ∼28% of the lithosphere, is the second most abundant element after oxygen, and is present in teramole quantities in the oceans.[1,2] It holds a privileged position as one of the key elements of human enterprise. The “sila-substitution” of drugs is not a new strategy.[89] Silicon has long been used as a bioisostere of carbon, and syntheses of sila-substituted compounds go back over 50 years.[90] One recent study compared loperamide, an antidiarrheal, with sila-loperamide, a sila-substituted analogue.[91] A comparison of these compounds’ pharmacokinetic and pharmacodynamic properties revealed that, despite major differences in their in vitro properties (including clearance and permeability), their in vivo pharmacokinetic profiles are nearly identical Thorough studies like this example underscore how the ability to access sila-substituted compounds can lead to novel molecules with unique pharmaceutical properties. The inorganic Si−O−Si backbone of silsesquioxanes is stable, enabling the construction of polymeric compounds, while the functional groups allow installation of potentially diverse reactivities to meet applications in nanocomposites, optoelectronics, catalysis, high-temperature composites, and biomaterials (Figure 6E).[104] Controlling the functional substituents on silsesquioxanes remains an outstanding challenge and is an area where the chemo- and regioselectivity of enzymes may aid in precisely functionalizing silicon centers en route to designer silsesquioxanes
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