Synthesis and Structure of Silver Complexes with Nicotinate-Type Ligands Having Antibacterial Activities against Clinically Isolated Antibiotic Resistant Pathogens Morsy A. M. Abu-Youssef,* ,† Raja Dey, ‡ Yousry Gohar, § Alshima’a A. Massoud, † Lars O 2 hrstro 1 m,* ,‡ and Vratislav Langer ‡ Department of Chemical and Biological Engineering, Chalmers UniVersity of Technology, SE-412 96 Gothenburg, Sweden, Department of Chemistry, Faculty of Science, Alexandria UniVersity, P.O. Box 426 Ibrahimia, 21321 Alexandria, Egypt, and Department of Microbiology, Faculty of Science, Alexandria UniVersity, P.O. Box 426 Ibrahimia, 21321 Alexandria, Egypt Received November 14, 2006 The synthesis and low-temperature X-ray crystal structures of five new silver complexes, [Ag 2 -µ-O,O′(2- aminonicotinium) 2 (NO 3 ) 2 ] n (7), [Ag(isonicotinamide) 2 -µ-O,O′(NO 3 )] 2 (8), [Ag(ethyl nicotinate) 2 ](NO 3 )(9), [Ag(ethyl isonicotinate) 2 (NO 3 )] (10), and [Ag(methyl isonicotinate) 2 (H 2 O)](NO 3 )(11), are presented and fully characterized by spectral and elemental analysis. The antimicrobial activities of these complexes were screened using 12 different clinical isolates belonging to four pathogenic bacteria, S. aureus, S. pyogenes, P. mirabilis, and Ps. Aeruginosa, all obtained from diabetic foot ulcers. These tested bacteria were resistant for at least 10 antibiotics commonly used for treatment of diabetic foot ulcers. Compounds 7 and 8 had considerable activity against Ps. Aeruginosa (MIC values 2-8 µg/mL), compound 9 against S. aureus (MIC 4-16 µg/mL) and S. pyogenes (MIC 2-4 µg/mL), and also 9 and 11 against P. mirabilis (MIC 1-16 µg/mL). All complexes were non-toxic for daphnia at concentrations above 512 µg/mL overnight. Introduction Currently we are seeing a revival of silver in the medical practice, principally in the addition of silver to medical instruments and in wound dressings (especially burns and chronic wounds) to avoid infections. 1,2 There is also much interest in investigating and applying new more sophisticated Ag(I) compounds for their antimicrobial activity. 1,3-7 One approach to such compounds is to combine known biologi- cally benign molecules with suitable donor groups with Ag- (I) and investigate their properties. 1b One attractive class of ligands comprises nicotinic acid, 1, and nicotinamide (vitamin B3, 3) and their derivatives; * To whom correspondence should be addressed. E-mail: morsy5@ link.net (M.A.M.A.-Y.), ohrstrom@chalmers.se (L.O ¨ ). Fax: +46 31 772 3858 (L.O ¨ ). Phone: +31 772 2871 (L.O ¨ ). † Department of Chemistry, Alexandria University. E-mail: shimo@ chalmers.se (A.A.M.). ‡ Chalmers University of Technology. E-mail: rdey@usc.edu (R.D.), langer@chalmers.se (V.L.). § Department of Microbiology, Alexandria University. E-mail: ymgohar@yahoo.com (Y.G.). (1) (a) Melaiye, A.; Sun, Z. H.; Hindi, K.; Milsted, A.; Ely, D.; Reneker, D. H.; Tessier, C. A.; Youngs, W. J. J. Am. Chem. Soc. 2005, 127, 2285-2291. (b) Kascatan-Nebioglu, A.; Melaiye, A.; Hindi, K.; Durmus, S.; Panzner, M. J.; Hogue, L. A.; Mallett, R. J.; Hovis, C. E.; Coughenour, M.; Crosby, S. D.; Milsted, A.; Ely, D. L.; Tessier, C. A.; Cannon, C. L.; Youngs, W. J. J. Med. Chem. 2006, 49, 6811- 6818. (2) (a) Melaiye, A.; Youngs, W. J. Expert Opin. Ther. Pat. 2005, 15, 125-130. (b) Strohal, R.; Schelling, M.; Takacs, M.; Jurecka, W.; Gruber, U.; Offner, F. J. Hosp. 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