Biocatalytic Transformations of Silicon—the Other Group 14 Element

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.

Biocatalysis as Key to Sustainable Industrial Chemistry

“…[82,83] The development of new-to-nature biocatalytic reactions [84] enables biocatalysis to enter completely new fields, such as sustainable silicon chemistry. [85] Biocatalytic reaction platforms, metabolic engineering and synthetic biology can be valuable in a systems biocatalysis approach [86] to biocatalytic route design to convert raw materials or waste materials, such as carbon dioxide, [87] into useful products. Emphasis on combining the use of biocatalysis and biobased starting materials is also useful for a sustainable virtuous cycle in a biorefinery-like approach.…”

“…The development of new‐to‐nature biocatalytic reactions [84] enables biocatalysis to enter completely new fields, such as sustainable silicon chemistry [85] …”

Silicon switch: Carbon–silicon Bioisosteric replacement as a strategy to modulate the selectivity, physicochemical, and drug‐like properties in anticancer pharmacophores

“…This subtle change in bond polarization can lead to a more favorable hydrogen bond donor capability, while the increase in lipophilicity can result in a rise in volume of distribution, bringing about an enhanced membrane penetration for the entire molecule (Franz & Wilson, 2013; Gately & West, 2007; Meanwell, 2011; Mills & Showell, 2004; Patani & LaVoie, 1996; Pooni & Showell, 2006; Ramesh & Reddy, 2018; Showell & Mills, 2003; Zhou et al, 2022). Nevertheless, with the exception of oxygen, silicon tends to form thermodynamically stable but kinetically labile bonds with many non‐metallic elements from the periodic table, which can easily be cleaved in aqueous or acidic conditions to form the corresponding silanol (Si–OH) bond, depending on the steric environment around the silicon atom (Bains & Tacke, 2003; Franz & Wilson, 2013; Sarai et al, 2021; Tacke & Zilch, 1986). These properties can affect the metabolic clearance of the resulting molecules in some cases.…”

“…However, notwithstanding their strong resemblance, silicon possesses slightly different intrinsic properties from its carbon counterpart. Unlike carbon, which can form long‐chain hydrocarbons and is at the center of a large diversity of biochemical and metabolic transformations, with an entire branch of study, namely organic chemistry, dedicated to carbon‐containing molecules, silicon occurs in nature primarily as silicates and silica, owing to the higher stability of Si–O bond (368 kJ/mol) as compared to Si–Si bond (230 kJ/mol) (Bertrand, 2004; Marschner & Tilley, 2017; Petkowski et al, 2020; Sarai et al, 2021). Furthermore, silicon has a larger covalent radius than carbon and forms noticeably longer bonds, with Si–C bond being about 20% longer when compared to C–C bond (Bertrand, 2004; Marschner & Tilley, 2017; Petkowski et al, 2020; Sarai et al, 2021).…”

“…Illustration of the typical bond lengths and bond dissociation energies for carbon and silicon (Si covalent radius = 1.17 Å, and C covalent radius = 0.77 Å) (Petkowski et al, 2020; Sarai et al, 2021). …”