Catalytic mechanism of superoxide dismutation nanoenzymes to be elucidated

Nanozymes are a class of nanomaterials with enzymatic properties, capable of catalyzing substrates of enzymes under physiological or extreme conditions, with enzymatic reaction kinetics similar to natural enzymes, and can be used in human health
as an alternative to enzymes.
Since it was first reported in 2007, 420 studies in 55 countries around the world have reported the nanozyme activity of nearly 1200 different nanomaterials, with catalytic types covering oxidoreductases, hydrolases, lyases and isomerases
.
Nanozymes are a model of multidisciplinary cross-integration and were rated as one of the top ten emerging chemical technologies
by IUPAC in 2022.
After more than ten years of development, under the joint promotion of scientists engaged in chemistry, enzymology, materials, biology, medicine, theoretical calculation and other fields, nanozymes have become a new research hotspot
.
With the in-depth study of the catalytic mechanism and structure-activity relationship of nanoenzymes, nanozymes have gradually evolved from random synthesis to rational design
.
In particular, peroxide nanoenzymes have surpassed natural peroxidases
in catalytic activity.

However, nanoenzymes with other catalytic types, such as superoxide dismutase (SOD), still face the challenges
of unclear structure-activity relationship and low catalytic activity.
Therefore, based on the systematic study of the structure-activity relationship of carbon dot nanoenzymes, the researchers prepared a carbon dot SOD nanoenzyme
with catalytic activity comparable to that of natural SOD enzymes.
Through selective chemical modification and theoretical calculations, the researchers have deeply elucidated
its catalytic mechanism and structure-activity relationship.
The research results were published online in the journal
Nature Communications on January 11, 2023.

Carbon dots (C-dots) have received great attention
over the past decade as a class of photoluminescent nanomaterials due to their unique properties.
The carbon dot has the advantages of small particle size, easy preparation and low cost, and its surface is rich in oxygen-containing functional groups, such as carbonyls, carboxyl groups, hydroxyl groups, etc.
, so that the carbon dots have good water solubility and easy functionalization
.
Therefore, carbon dots show great application potential
in sensing, biological imaging, light-emitting diodes, disease treatment and other aspects.
In addition, carbon dots exhibit catalytic activity due to their small size effect and abundant active sites, but previously reported carbon dot nanoenzymes mainly focus on their peroxidase activity, and reports on the design of carbon dot nanoenzymes with high antioxidant activity are rare
.

In this work, the researchers designed a carbon dot nanoenzyme (active > 10000 U/mg) with ultra-high SOD-like activity, and revealed its catalytic mechanism
using surface structure-oriented regulation strategies and theoretical calculations.
The results show that the hydroxyl group and carboxyl group of the carbon point SOD nanoenzyme can bind to the superoxide anion through hydrogen bonding, and the carbonyl group conjugated with the π-system captures an electron of the superoxide anion to produce oxygen and reduced carbon dots
.
The reduced carbon dot is oxidized back to its initial state by another superoxide anion and hydrogen peroxide is produced
.
In vitro experimental results show that carbon dot nanoenzymes can selectively target oxidatively damaged cells and localize to mitochondria, which is very beneficial
for removing intracellular ROS from the source.
Combined with its high catalytic activity, the researchers successfully applied carbon-dot SOD nanoenzymes to resist oxidative stress caused by ischemic stroke in vivo and achieved good therapeutic effects
.
In addition, carbon point SOD nanoenzymes have the advantages of high stability, easy preparation, low cost and easy large-scale production, overcome the limitations of natural enzymes, and show great application potential
in industry, medicine, biology and other fields.

Figure: (a) Preparation and catalytic mechanism of carbon dot SOD nanoenzyme and (b) its application in the treatment of ischemic stroke

Academician Yan Xiyun and Professor Fan Kelong of the Institute of Biophysics, Chinese Academy of Sciences, Professor Pang Daiwen of Nankai University, Researcher Zhang Mingzhen and Associate Professor Liu Cui of Xi'an Jiaotong University are co-corresponding authors of this paper, and Gao Wenhui of Xi'an Jiaotong University, Dr.
He Jiuyang and Dr.
Chen Lei of the Institute of Biophysics, Chinese Academy of Sciences are co-first authors
.
The research was supported
by the National Natural Science Foundation of China, the Key R&D Program of the Ministry of Science and Technology, the Innovation Interdisciplinary Team of the Chinese Academy of Sciences, the Youth Innovation Promotion Association of the Chinese Academy of Sciences, and the Young Top Talents Program of Xi'an Jiaotong University.

Article link: https://doi.
org/10.
1038/s41467-023-35828-2

(Contributed by: Fan Kron's research group)