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We describe the synthesis and characterisation of two symmetrical bis\u2010amide derivatives of <jats:bold>EDTA<\/jats:bold>, featuring glycyl or pyridyl substituents: <jats:bold>AmGly<jats:sub>2<\/jats:sub><\/jats:bold> and <jats:bold>AmPy<jats:sub>2<\/jats:sub><\/jats:bold>. Metal ion affinities (log<jats:italic>K<\/jats:italic>) have been evaluated for a range of metals (Mg<jats:sup>2+<\/jats:sup>, Ca<jats:sup>2+<\/jats:sup>, Fe<jats:sup>3+<\/jats:sup>, Mn<jats:sup>2+<\/jats:sup>, Zn<jats:sup>2+<\/jats:sup>), revealing less avid binding compared to <jats:bold>EDTA<\/jats:bold>. The solid\u2010state structures of <jats:bold>AmGly<jats:sub>2<\/jats:sub><\/jats:bold> and of its Mg<jats:sup>2+<\/jats:sup> complex have been determined crystallographically. The latter shows an unusual 7\u2010coordinate, capped octahedral Mg<jats:sup>2+<\/jats:sup> centre. The antibacterial activities of the two ligands and of <jats:bold>EDTA<\/jats:bold> have been evaluated against a range of health\u2010relevant bacterial species, three Gram negative (<jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Pseudomonas aeruginosa<\/jats:italic> and <jats:italic>Klebsiella pneumoniae<\/jats:italic>) and a Gram positive (<jats:italic>Staphylococcus aureus<\/jats:italic>). The <jats:bold>AmPy<jats:sub>2<\/jats:sub><\/jats:bold> ligand is the only one that displays a significant inhibitory effect against <jats:italic>K.\u2005pneumoniae<\/jats:italic>, but is less effective against the other organisms. <jats:bold>AmGly<jats:sub>2<\/jats:sub><\/jats:bold> exhibits a more powerful inhibitory effect against <jats:italic>E. coli<\/jats:italic> at lower concentrations than <jats:bold>EDTA<\/jats:bold> (&lt;3\u2005m<jats:sc>m<\/jats:sc>) or <jats:bold>AmPy<jats:sub>2<\/jats:sub><\/jats:bold>, but loses its efficacy at higher concentrations. The growth inhibition of <jats:bold>EDTA<\/jats:bold> and <jats:bold>AmGly<jats:sub>2<\/jats:sub><\/jats:bold> on mutant <jats:italic>E.\u2005coli<\/jats:italic> strains with defects in outer\u2010membrane lipopolysaccharide (LPS) structures has been assessed to provide insight into the unexpected behaviour. Taken together, the results contradict the assumption of a simple link between metal ion affinity and antimicrobial efficacy.<\/jats:p>","DOI":"10.1002\/chem.201800026","type":"journal-article","created":{"date-parts":[[2018,3,23]],"date-time":"2018-03-23T15:11:52Z","timestamp":1521817912000},"page":"7137-7148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["On the Antibacterial Activity of Azacarboxylate Ligands: Lowered Metal Ion Affinities for Bis\u2010amide Derivatives of EDTA do not mean Reduced Activity"],"prefix":"10.1002","volume":"24","author":[{"given":"Raminder S.","family":"Mulla","sequence":"first","affiliation":[{"name":"Department of Chemistry Durham University  Durham DH1 3LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marikka S.","family":"Beecroft","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University  Durham DH1 3LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Pal","sequence":"additional","affiliation":[{"name":"Department of Chemistry Durham University  Durham DH1 3LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan A.","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Department of Chemistry Durham University  Durham DH1 3LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Pitarch\u2010Jarque","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular Universidad de Valencia  C\/ Catedr\u00e1tico Jos\u00e9 Beltr\u00e1n 2 46980 Paterna, Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrique","family":"Garc\u00eda\u2010Espa\u00f1a","sequence":"additional","affiliation":[{"name":"Instituto de Ciencia Molecular Universidad de Valencia  C\/ Catedr\u00e1tico Jos\u00e9 Beltr\u00e1n 2 46980 Paterna, Valencia Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Lurie\u2010Luke","sequence":"additional","affiliation":[{"name":"Procter and Gamble Technical Centres Limited, Rusham Park  Whitehall Lane Egham, Surrey TW20 9NW UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary J.","family":"Sharples","sequence":"additional","affiliation":[{"name":"Department of Biosciences Durham University  Durham DH1 3LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4688-3000","authenticated-orcid":false,"given":"J. 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