Ruthenium-centred glycoclusters as inhibitors for biofilm formation

• Published in: RSC advances 2021-05, Vol.11 (27), p.16318-16325
• Main Authors: O'Reilly, Ciaran, Blasco, Salvador, Parekh, Bina, Collins, Helen, Cooke, Gordon, Gunnlaugsson, Thorfinnur, Byrne, Joseph P
• Format: Article
• ISSN: 2046-2069
• DOI: 10.1039/d0ra05107a

Carbohydrate-decorated clusters (glycoclusters) centred on a Ru( ii ) ion were synthesised and tested for their activity against Pseudomonas aeruginosa biofilm formation. These clusters were designed by conjugating a range of carbohydrate motifs (galactose, glucose, mannose and lactose, as well as galactose with a triethylene glycol spacer) to a btp (2,6-bis(1,2,3-triazol-4-yl)pyridine) scaffold. This scaffold, which possesses a C 2 symmetry, is an excellent ligand for d-metal ions, and thus the formation of the Ru( ii )-centred glycoclusters 7 and 8Gal was achieved from 5 and 6Gal ; each possessing four deprotected carbohydrates. Glycocluster 8Gal , which has a flexible spacer between the btp and galactose moieties, showed significant inhibition of P. aeruginosa bacterial biofilm formation. By contrast, glycocluster 7 , which lacked the flexible linker, didn't show significant antimicrobial effects and neither does the ligand 6Gal alone. These results are proposed to arise from carbohydrate-lectin interactions with LecA, which are possible for the flexible metal-centred multivalent glycocluster. Metal-centred glycoclusters present a structurally versatile class of antimicrobial agent for P. aeruginosa , of which this is, to the best of our knowledge, the first example. Ruthenium-centred glycoclusters based on carbohydrate-functionalised bis(triazolyl)pyridine ligands show Pseudomonas aeruginosa biofilm inhibition, with activity that is dependent on ligand structure.