Synthesis, characterisation and antimicrobial activity of copper(II) and manganese(II) complexes of coumarin-6,7-dioxyacetic acid (cdoaH2) and 4-methylcoumarin-6,7-dioxyacetic acid (4-MecdoaH2): X-ray crystal structures of [Cu(cdoa)(phen)2].8.8H(2)O and [Cu(4-Mecdoa)(phen)2].13H2O (phen=1,10-phenanthroline).
Two novel coumarin-based ligands, coumarin-6,7-dioxyacetic acid (1) (cdoaH(2)) and 4-methylcoumarin-6,7-dioxyacetic acid (2) (4-MecdoaH(2)), were reacted with copper(II) and manganese(II) salts to give [Cu(cdoa)(H(2)O)(2)].1.5H(2)O (3), [Cu(4-Mecdoa)(H(2)O)(2)] (4), [Mn(cdoa)(H(2)O)(2)] (5) and [Mn(4-Mecdoa)(H(2)O)(2)].0.5H(2)O (6). The metal complexes, 3-6, were characterised by elemental analysis, IR and UV-Vis spectroscopy, and magnetic susceptibility measurements and were assigned a polymeric structure. 1 and 2 react with Cu(II) in the presence of excess 1,10-phenanthroline (phen) giving [Cu(cdoa)(phen)(2)].8.8H(2)O (7) and [Cu(4-Mecdoa)(phen)(2)].13H(2)O (8), respectively. The X-ray crystal structures of 7 and 8 confirmed trigonal bipyramidal geometries, with the metals bonded to the four nitrogen atoms of the two chelating phen molecules and to a single carboxylate oxygen of the dicarboxylate ligand. The complexes were screened for their antimicrobial activity against a number of microbial species, including methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Candida albicans. The metal-free ligands 1 and 2 were active against all of the microbes. Complexes 3-6 demonstrated no significant activity whilst the phen adducts 7 and 8 were active against MRSA (MIC(80)=12.1microM), E. coli (MIC(80)=14.9microM) and Patonea agglumerans (MIC(80)=12.6microM). Complex 7 also demonstrated anti-Candida activity (MIC(80)=22microM) comparable to that of the commercially available antifungal agent ketoconazole (MIC(80)=25microM).
Creaven
Bernadette S
BS
Centre for Pharmaceutical Research and Development, Institute of Technology Tallaght, Dublin, Dublin 24, Ireland. bernie.creaven@it-tallaght.ie
Egan
Denise A
DA
Karcz
Dariusz
D
Kavanagh
Kevin
K
McCann
Malachy
M
Mahon
Mary
M
Noble
Andy
A
Thati
Bhumika
B
Walsh
Maureen
M
D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D002704:Chlorates / Q000737:chemistry; D003300:Copper / Q000737:chemistry; D003460:Crystallization; D018360:Crystallography, X-Ray; D004875:Ergosterol / Q000037:antagonists & inhibitors / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D008345:Manganese / Q000737:chemistry; D010618:Phenanthrolines / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D014468:Umbelliferones / Q000138:chemical synthesis* / Q000494:pharmacology; D014867:Water / Q000737:chemistry
D000890:Anti-Infective Agents; D002704:Chlorates; D010618:Phenanthrolines; D014468:Umbelliferones; D014867:Water; D008345:Manganese; C096882:6,7-dihydroxy-4-methylcoumarin; D003300:Copper; C025205:1,10-phenanthroline; D004875:Ergosterol