Binary Cu/boron enhanced graphene quantum dots as a biomimetic nanocatalyst for Trp catabolism to indole-3-aldehyde: mechanism and specificity

Abstract

Multienzyme-mimetic nanocatalysts, which emulate natural enzyme cascades, offer a useful platform for studying complex biochemical transformations. Tryptophan catabolism to indole-3-carbaldehyde (IAld) is a multienzyme biochemical process which impacts key physiological processes. Here, a Cu/boron co-functionalized graphene quantum dot (Cu/B–GQD) catalyst was developed, which selectively catalyzed Trp conversion to IAld through a pathway resembling that of the native enzymatic mechanism. Cu/B–GQD was extensively characterized using several analytical techniques featuring a GQD-based nanoarchitecture. A detailed study on the reaction mechanism demonstrated a close resemblance between the nanocatalytic and natural enzymatic pathways of Trp conversion to IAld. Indole-3-acetamide (IAM), for instance, is an on-pathway intermediate in both the mechanisms. Notably, it was found that during the mimetic catabolism of Trp, indole-3-acetonitrile (IAN) was converted to IAM, a step that has not been observed in the enzymatic catabolism to date. Furthermore, our studies suggest that cooperative radical and hydrolytic chemistry is responsible for this in situ nitrile-to-amide conversion. These studies also reveal that hydroxylation of the adjacent benzylic hydrogens is critical for the subsequent transformation of IAM to IAld. The specificity of the nanocatalyst for Trp was shown using identical reaction conditions with phenylalanine and tyrosine substrates. While phenylalanine yielded benzeneacetamide, no conversion was detected with tyrosine. This study not only provides new insights into the Trp catabolism but also highlights the potential of enzyme-mimetic nanocatalysts for probing complex biochemical cascades.