{"doi":"10.26434/chemrxiv.14582913","title":"Gold Nanoclusters as Nano-Antibiotic Auranofin Analogues","abstract":"Auranofin, a gold(I)-complex with tetraacetylated thioglucose and triethylphosphine ligands, is an FDA-approved drug used as an anti-inflammatory aid in the treatment of rheumatoid arthritis. In repurposing auranofin for other diseases, it was found that the drug showed significant activity against Gram-positive bacteria but was inactive against Gram-negative bacteria. Herein, we report the design and synthesis of gold nanoclusters (AuNCs) based on the structural motif of auranofin. Phosphine-capped AuNCs were synthesized and glycosylated, yielding auranofin AuNC analogues with mixed phosphine/thioglucose ligand shells. These AuNCs were active against both Gram-negative and Gram-positive bacteria, including a panel of resistant ESKAPE pathogens. Notably, an auranofin analogue, a mixed-ligand 1.6 nm AuNC (<strong>4b</strong>) was ~4 times more active than auranofin against <em>Pseudomonas aeruginosa</em>, while exhibiting 24 times lower toxicity against human A549 cells. The enhanced antibacterial activity of these AuNCs was characterized by a greater uptake of Au by the bacteria compared to Au<sup>I</sup>-complexes (20% for AuNC <strong>4b</strong>). Additional factors include increased oxidative stress, moderate inhibition of thioredoxin reductase (TrxR), and DNA damage. Most intriguingly, the AuNCs were not affected by the bacterial outer membrane (OM) barrier or by extracellular proteins. This contrasts with Au<sup>I</sup>-complexes like auranofin that are susceptible to protein binding and hindered by the OM barrier.","journal":"ChemRxiv","year":2021,"id":229480,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":675717,"name":"N. G. Hasitha Raviranga","orcid":"0000-0002-0002-6126","position":1,"is_corresponding":false},{"id":676303,"name":"Jingzhe Lao","orcid":null,"position":2,"is_corresponding":false},{"id":675718,"name":"Olof Ramström","orcid":"0000-0002-1533-6514","position":3,"is_corresponding":false},{"id":463185,"name":"Mingdi Yan","orcid":"0000-0003-1121-4007","position":4,"is_corresponding":false},{"id":675716,"name":"William Ndugire","orcid":"0000-0001-7818-4274","position":0,"is_corresponding":true}],"reference_count":2,"raw_metadata":null,"created_at":"2026-07-18T23:54:57.922333Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}