The outbreak of antibiotic-resistant bacteria, or "superbugs", poses a global public health hazard due to their resilience against the most effective last-line antibiotics. Identifying potent antibacterial agents capable of evading bacterial resistance mechanisms represents the ultimate defense strategy. This study shows that -the otherwise essential micronutrient- manganese turns into a broad-spectrum potent antibiotic when coordinated with a carboxylated nitrogen-doped graphene. This antibiotic material (termed NGA-Mn) not only inhibits the growth of a wide spectrum of multidrug-resistant bacteria but also heals wounds infected by bacteria in vivo and, most importantly, effectively evades bacterial resistance development. NGA-Mn exhibits up to 25-fold higher cytocompatibility to human cells than its minimum bacterial inhibitory concentration, demonstrating its potential as a next-generation antibacterial agent. Experimental findings suggest that NGA-Mn acts on the outer side of the bacterial cell membrane via a multimolecular collective binding, blocking vital functions in both Gram-positive and Gram-negative bacteria. The results underscore the potential of single-atom engineering toward potent antibiotics, offering simultaneously a long-sought solution for evading drug resistance development while being cytocompatible to human cells.

• Keywords
• antibiotic, cytocompatibility, manganese, multi‐drug resistance, single‐atom,
• MeSH
• Anti-Bacterial Agents * pharmacology   chemistry   MeSH
• Drug Resistance, Bacterial * drug effects   MeSH
• Nitrogen chemistry   MeSH
• Graphite chemistry   pharmacology   MeSH
• Humans MeSH
• Manganese chemistry   MeSH
• Microbial Sensitivity Tests * MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Nitrogen MeSH
• Graphite MeSH
• Manganese MeSH

Nanostructured materials with antibacterial activity face the same threat as conventional antibiotics - bacterial resistance, which reduces their effectiveness. However, unlike antibiotics, research into the emergence and mechanisms of bacterial resistance to antibacterial nanomaterials is still in its early stages. Here we show how Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli bacteria develop resistance to silver nanoparticles, resulting in an increase in the minimum inhibitory concentration from 1.69 mg/L for S. aureus and 3.38 mg/L for E. coli to 54 mg/L with repeated exposure over 12 and 6 cultivation steps, respectively. The mechanism of resistance is the same for both types of bacteria and involves the aggregation of silver nanoparticles leading to the formation of black precipitates. However, the way in which Gram-positive and Gram-negative bacteria induce aggregation of silver nanoparticles is completely different. Chemical analysis of the surface of the silver precipitates shows that aggregation is triggered by flagellin production in E. coli and by bacterial biofilm formation in S. aureus. However, resistance in both types of bacteria can be overcome by using pomegranate rind extract, which inhibits both flagellin and biofilm production, or by stabilizing the silver nanoparticles by covalently binding them to a composite material containing graphene sheets, which protects the silver nanoparticles from aggregation induced by the bacterial biofilm produced by S. aureus. This research improves the understanding of bacterial resistance mechanisms to nanostructured materials, which differ from resistance mechanisms to conventional antibiotics, and provides potential strategies to combat bacterial resistance and develop more effective antimicrobial treatments.

• MeSH
• Anti-Bacterial Agents * pharmacology   chemistry   MeSH
• Drug Resistance, Bacterial * drug effects   MeSH
• Biofilms drug effects   growth & development   MeSH
• Escherichia coli * drug effects   MeSH
• Metal Nanoparticles * chemistry   MeSH
• Microbial Sensitivity Tests * MeSH
• Staphylococcus aureus * drug effects   MeSH
• Silver * pharmacology   chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Silver * MeSH

A strategy for the synthesis of a gold-based single-atom catalyst (SAC) via a one-step room temperature reduction of Au(III) salt and stabilization of Au(I) ions on nitrile-functionalized graphene (cyanographene; G-CN) is described. The graphene-supported G(CN)-Au catalyst exhibits a unique linear structure of the Au(I) active sites promoting a multistep mode of action in dehydrogenative coupling of organosilanes with alcohols under mild reaction conditions as proven by advanced XPS, XAFS, XANES, and EPR techniques along with DFT calculations. The linear structure being perfectly accessible toward the reactant molecules and the cyanographene-induced charge transfer resulting in the exclusive Au(I) valence state contribute to the superior efficiency of the emerging two-dimensional SAC. The developed G(CN)-Au SAC, despite its low metal loading (ca. 0.6 wt %), appear to be the most efficient catalyst for Si-H bond activation with a turnover frequency of up to 139,494 h-1 and high selectivities, significantly overcoming all reported homogeneous gold catalysts. Moreover, it can be easily prepared in a multigram batch scale, is recyclable, and works well toward more than 40 organosilanes. This work opens the door for applications of SACs with a linear structure of the active site for advanced catalytic applications.

• Publication type
• Journal Article MeSH

Anchoring single metal atoms on suitable substrates is a convenient route towards materials with unique electronic and magnetic properties exploitable in a wide range of applications including sensors, data storage, and single atom catalysis (SAC). Among a large portfolio of available substrates, carbon-based materials derived from graphene and its derivatives have received growing concern due to their high affinity to metals combined with biocompatibility, low toxicity, and accessibility. Cyanographene (GCN) as highly functionalized graphene containing homogeneously distributed nitrile groups perpendicular to the surface offers exceptionally favourable arrangement for anchoring metal atoms enabling efficient charge exchange between the metal and the substrate. However, the binding characteristics of metal species can be significantly affected by the coordination effects. Here we employed density functional theory (DFT) calculations to analyse the role of coordination in the binding of late 3d cations (Fe2+, Fe3+, Co2+, Ni2+, Cu2+, Cu+, and Zn2+) to GCN in aqueous solutions. The inspection of several plausible coordination types revealed the most favourable arrangements. Among the studied species, copper cations were found to be the most tightly bonded to GCN, which was also confirmed by the X-ray photoelectron spectroscopy (XPS), atomic absorption spectroscopy (AAS), and isothermal titration calorimetry (ITC) measurements. In general, the inclusion of coordination effects significantly reduced the binding affinities predicted by implicit solvation models. Clearly, to build-up reliable models of SAC architectures in the environments enabling the formation of a coordination sphere, such effects need to be properly taken into account.

• MeSH
• Graphite * MeSH
• Cations MeSH
• Metals chemistry   MeSH
• Copper chemistry   MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Graphite * MeSH
• Cations MeSH
• Metals MeSH
• Copper MeSH

Single-atom catalysts (SACs) based on graphene derivatives are an emerging and growing class of materials functioning as two-dimensional (2D) metal-coordination scaffolds with intriguing properties. Recently, owing to the rich chemistry of fluorographene, new avenues have opened toward graphene derivatives with selective, spacer-free, and dense functionalization, acting as in-plane or out-of-plane metal coordination ligands. The particular structural features give rise to intriguing phenomena occurring between the coordinated metals and the graphene backbone. These include redox processes, charge transfer, emergence, and stabilization of rare or otherwise unstable metal valence states, as well as metal-support and metal-metal synergism. The vast potential of such systems has been demonstrated as enzyme mimics for cooperative mixed-valence SACs, ethanol fuel cells, and CO2 fixation; however, it is anticipated that their impact will further expand toward diverse fields, e.g., advanced organic transformations, electrochemical energy storage, and energy harvesting.

• Publication type
• Journal Article MeSH
• Review MeSH

The number of antibiotic-resistant bacterial strains is increasing due to the excessive and inappropriate use of antibiotics, which are therefore becoming ineffective. Here, we report an effective way of enhancing and restoring the antibacterial activity of inactive antibiotics by applying them together with a cyanographene/Ag nanohybrid, a nanomaterial that is applied for the first time for restoring the antibacterial activity of antibiotics. The cyanographene/Ag nanohybrid was synthesized by chemical reduction of a precursor material in which silver cations are coordinated on a cyanographene sheet. The antibacterial efficiency of the combined treatment was evaluated by determining fractional inhibitory concentrations (FIC) for antibiotics with different modes of action (gentamicin, ceftazidime, ciprofloxacin, and colistin) against the strains Escherichia coli, Pseudomonas aeruginosa, and Enterobacter kobei with different resistance mechanisms. Synergistic and partial synergistic effects against multiresistant strains were demonstrated for all of these antibiotics except ciprofloxacin, which exhibited an additive effect. The lowest average FICs equal to 0.29 and 0.39 were obtained for colistin against E. kobei and for gentamicin against E. coli, respectively. More importantly, we have experimentally confirmed for the first time, that interaction between the antibiotic's mode of action and the mechanism of bacterial resistance strongly influenced the combined treatment's efficacy.

• MeSH
• Anti-Bacterial Agents * chemistry   pharmacology   MeSH
• Ciprofloxacin pharmacology   MeSH
• Escherichia coli MeSH
• Gentamicins pharmacology   MeSH
• Colistin * pharmacology   MeSH
• Microbial Sensitivity Tests MeSH
• Pseudomonas aeruginosa MeSH
• Drug Synergism MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Anti-Bacterial Agents * MeSH
• Ciprofloxacin MeSH
• Gentamicins MeSH
• Colistin * MeSH