Integrated Computational and Experimental Framework for Inverse Screening of Candidate Antibacterial Nanomedicine.

Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli. is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future.

eg Occupancy as a Predictive Descriptor for Spinel Oxide Nanozymes.

Functional nanomaterials offer an attractive strategy to mimic the catalysis of natural enzymes, which are collectively called nanozymes. Although the development of nanozymes shows a trend of diversification of materials with enzyme-like activity, most nanozymes have been discovered via trial-and-error methods, largely due to the lack of predictive descriptors. To fill this gap, this work identified eg occupancy as an effective descriptor for spinel oxides with peroxidase-like activity and successfully predicted that the eg value of spinel oxide nanozymes with the highest activity is close to 0.6. The LiCo2O4 with the highest activity, which is finally predicted, has achieved more than an order of magnitude improvement in activity. Density functional theory provides a rationale for the reaction path. This work contributes to the rational design of high performance nanozymes by using activity descriptors and provides a methodology to identify other descriptors for nanozymes.

Two-Dimensional Tin Selenide (SnSe) Nanosheets Capable of Mimicking Key Dehydrogenases in Cellular Metabolism.

While dehydrogenases play crucial roles in tricarboxylic acid (TCA) cycle of cell metabolism, which are extensively explored for biomedical and chemical engineering uses, it is a big challenge to overcome the shortcomings (low stability and high costs) of recombinant dehydrogenases. Herein, it is shown that two-dimensional (2D) SnSe is capable of mimicking native dehydrogenases to efficiently catalyze hydrogen transfer from 1-(R)-2-(R')-ethanol groups. In contrary to susceptible native dehydrogenases, lactic dehydrogenase (LDH) for instance, SnSe is extremely tolerant to reaction condition changes (pH, temperature, and organic solvents) and displays extraordinary reusable capability. Structure-activity analysis indicates that the single-atom structure, Sn vacancy, and hydrogen binding affinity of SnSe may be responsible for their catalytic activity. Overall, this is the first report of a 2D SnSe nanozyme to mimic key dehydrogenases in cell metabolism.

Converting organosulfur compounds to inorganic polysulfides against resistant bacterial infections.

The use of natural substance to ward off microbial infections has a long history. However, the large-scale production of natural extracts often reduces antibacterial potency, thus limiting practical applications. Here we present a strategy for converting natural organosulfur compounds into nano-iron sulfides that exhibit enhanced antibacterial activity. We show that compared to garlic-derived organosulfur compounds nano-iron sulfides exhibit an over 500-fold increase in antibacterial efficacy to kill several pathogenic and drug-resistant bacteria. Furthermore, our analysis reveals that hydrogen polysulfanes released from nano-iron sulfides possess potent bactericidal activity and the release of polysulfanes can be accelerated by the enzyme-like activity of nano-iron sulfides. Finally, we demonstrate that topical applications of nano-iron sulfides can effectively disrupt pathogenic biofilms on human teeth and accelerate infected-wound healing. Together, our approach to convert organosulfur compounds into inorganic polysulfides potentially provides an antibacterial alternative to combat bacterial infections.

Theoretical study on the ground state structure of uranofullerene U@C82.

Despite its experimental characterization, the detailed geometry and electronic structure of actinide metallofullerene U@C(82) have been rarely studied. We predict that (#5)C(82) and (#8)C(82) are the best cages for the encapsulation of monovalent and tetravalent U (i.e., U(+) and U(4+)), respectively; while (#9)C(82) is the best cage for divalent, trivalent, pentavalent, and hexavalent U cations (i.e., U(2+), U(3+), U(5+), and U(6+)). U@(#9)C(82) is the thermodynamically most stable one among all the isomers and thus corresponds to the most experimentally isolable isomer of U@C(82). The calculated spin density explicitly suggests that the endohedral metallofullerene U@(#9)C(82) is a trivalent ion-pair with an electronic configuration of U(3+)@C(82)(3-). The proposed geometry and electronic structure of U(3+)@(#9)C(82)(3-) are in good agreement with the experimental observation.